cord-000445-2x7dfl1q	2011	brucei rhodesiense than the corresponding 2,5-substituted isomers (compounds 1-10, figure 4a), while among the 2, 5-substituted dications, the compounds possessing cationic substituents adjacent to nitrogen atoms in pyridine rings displayed superior activities against parasites compared to pentamidine as evident from compound 6 (figure 4b) which showed promising anti-trypanosomal activity (0.001µM) and lower cytotoxicity (4.90µM) than pentamidine and melarsoprol, but had poor in vivo activity giving only 1/4 cures in the STIB900 mouse model. Structure of two phenylbenzofuran dications with promising anti-trypanosomal activity Tidwell RR et al found that the in vitro anti-trypanosomal activities of bisbenzofuran derivatives against Trypanosoma brucei rhodesiense, and cytotoxicity against mammalian cells depended on the position and the type of cationic substituents as well as the length of the carbon linker between aromatic moieties. Thus promising in vitro, anti-trypanosomal activity, excellent potency in the acute mouse model of trypanosomiasis and the reduced cytotoxicity (1.9 µM) of compound 1 compared to pentamidine warrants further pre-clinical and clinical trials of this molecule.
cord-000884-zq8kqf6h	2013	This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. To simplify cell membrane systems, model membranes such as monolayers, bilayers, liposomes and nanodiscs have been developed, enabling detailed investigation of membrane protein structure in lipid membranes. There are a number of approaches used to create a model membrane in order to mimic properties of the native cell membrane, and we will review these various approaches for reconstituting membrane proteins into different types of model membrane-monolayers [5] , supported planar lipid bilayer [6] and liposomes [7] as shown in Figure 1A -C. By using this approach, it appears that both PLA2 and PLC are active at the monolayer model membrane, indicating that the kinetics of phospholipid hydrolysis at the air-water interface can be monitored by biophysical characterization techniques in situ such as PM-IRRAS and infrared reflection adsorption spectroscopy [22] .
cord-001835-0s7ok4uw	2015	Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues.
cord-004879-pgyzluwp	1994	Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins.
cord-004948-ad3i9wgj	2001	Specific CTL were derived by immunization of HHD mice with tumor peptide extracts loaded on antigen presenting cells and with HHD transfected human tumor cell lines CTL induced against peptides from various tumors recognized tumor peptides more effectively than peptides extracted from normal tissues and also reacted with a serie of peptides derived from overexpressed candidate proteins, identified by differential display methods (SAGE, Microarrays) Comparison of CTL derived from HHD mice to CTL induced from patient''s PBMC showed overlapping recognition of many candidate peptides. By comparison of pro-teomic cell maps from normal controls and individuals affected with lysosomal transport disorders we have selected and identified several candidate disease-causing proteins, which have to be further studied by mutation analysis and functional expression. The results of the in vitro studies available to date strongly suggest that its effects on neuronal amino acid transport processes is mediated via some novel extracellular mechanism controlling the H Ï© (and/or other ionic) concentrations of neurones.
cord-005337-3f6pwyy3	2013	title: Recent development of highly sensitive protease assay methods: Signal amplification through enzyme cascades Various methods have been developed to analyze protease activity, among which, protease assays based on resonance energy transfer are currently used most widely. In this review, we briefly summarize the protease assay methods based on resonance energy transfer, and then elaborate the efforts to develop sensitive protease assays through signal amplification by using enzyme cascades. FRET methods have been widely used to assay protease activities because of its advantages, especially coming from the fact the signal is based on fluorescence [17, 18] . For instance, a highthroughput FRET-based method for assaying OmpT endopeptidase activity was used for engineering the substrate specificity of the enzyme [23, 24] . Detection and characterization of SUMO protease activity using a sensitive enzyme-based reporter assay
cord-006230-xta38e7j	2012	Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure.
cord-006860-a3b8hyyr	1996	Dept of Pediatrics, University Hospitals Kiel and Mtinster, Germany Resistance to activated protein C (APCR), in the majority of cases associated with the Arg 506 Gin point mutation in the factor V gene is present in more than 50 % of patients < 60 years of age with unexplained thrombophilia. The regular APC resistance test is not applicable to plasma from Orally anticoagulated (OAC) or heparinized patients due to decreased levels of vitamin K-dependent clotting factors and to thrombin inhibition by antithrombin, respectively. On admission an extensive coagulation screen yielded the following results (n/normal, t/elevated, I/reduced, +/positive, -/negative): PT t, aPTT t, Tr n, factor II, V, VIII n, factor VII, IX, XI, XII /,, fibrinogan t, ATIII n, protein C, S *, activated protein C sensitivity ratio 1.92 ($), FV-Leidenmutation PCR -, fibrinolytic system n, TAT t, Ft÷2 t, lupus anticoagulant +, heparin induced platelet antibodies +; no diagnosis of a specific autoimmuna disorder could be made.
cord-007084-4niom5mw	1987	Cholesterol side-chain cleavage enzyme activity, the rate-limiting enzyme in corticosterone biosynthesis, was measured in adrenal mitochondria isolated from 2-, 12-, and 18-month-old male Sprague-Dawley rats. Under basal conditions (without 25-hydroxycholesterol), cholesterol side-chain cleavage activity (expressed as nanomoles of pregnenolone produced per min mg protein" 1 ) increased (P < 0.001) from a mean (±SE) of 0.43 ± 0.06 in 2-month-old rats to 1.26 ± 0.11 and 1.51 ± 0.06 in the 12-and 18-month-old rats, respectively. Accordingly, we measured cholesterol side-chain cleavage, 3/3-HSD, 21-hydroxylase, 11/3-hydroxylase activities, and cytochrome P450 contents in appropriate mitochondrial and microsomal fractions of adrenals from 2-, 12-, and 18-month-old rats. Results of the present study also suggest that the decline in steroidogenesis observed in adrenocortical cells isolated from senescent rats is not related to a reduction in cholesterol side-chain cleavage activity or other steroidogenic responses, as measured in vitro in isolated subcellular components.
cord-007682-01iom9al	2016	An alternative to classical activity probes containing a full ubiquitin or ubiquitin-like polypeptide is based on the use of small molecule inhibitors to label the catalytic site of desumoylating enzymes (sentrin-specifi c proteases, SENPs ). Indeed, the complexity of the recognition site of DUBs, which requires the binding of full-length ubiquitin in the catalytic site as well as the challenges in the characterization of potent and selective DUB inhibitors , has hindered production of ABPs for DUBs. However, following on from the ground-breaking evolution of cell-permeable and in vivo-compatible activity-based imaging probes developed for other proteases such as caspases or cathepsins [ 69 , 70 ] , the next generation of probes for DUBs will certainly be agents that enable direct visualization and quantifi cation of DUB activity in vivo.
cord-008777-i2reanan	2005	Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins.
cord-011038-5t8az1hf	2019	title: Synthesis, Type II diabetes inhibitory activity, antimicrobial evaluation and docking studies of indeno[1,2-c]pyrazol-4(1H)-ones We report a convenient and efficient synthesis of indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) by the reaction of a variety of 2-acyl-(1H)-indene-1,3(2H)-diones (1) and 2-hydrazinylbenzo[d]thiazole/2-hydrazinyl-6-substitutedbenzo[d]thiazoles (2) in the presence of glacial acetic acid in good yields. All the synthesized indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) were assayed for their in vitro Type II diabetes inhibitory activity by using Acarbose as standard drug and in vitro antimicrobial activity utilizing Streptomycin and Fluconazole as reference drugs. 2017; Huang and Huang 2019) and sulfur as heteroatoms and their biological activities herein, we report the synthesis, characterization, α-amylase and α-glucosidase inhibition, antimicrobial evaluation and docking studies of several benzothiazole tethered indeno [1,2-c] pyrazol-4(1H)ones (4a-o). In conclusion, the present study describe the synthesis and characterization of heterocyclic frameworks i.e., indeno [1,2-c] pyrazoles (4), and their biological evaluation as inhibitor of α-glucosidase and α-amylase related to Type II diabetes, and antimicrobial activity.
cord-012623-bc9fj29h	2019	title: Participant-reported priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia: a qualitative analysis OBJECTIVES: The purpose of this qualitative study was to explore perceptions and priorities of persons with spinal cord injury (SCI) for physical activity and to incorporate their feedback to inform future development of a physical activity program delivered via a telemonitoring platform. Another study measured the effects of a home-based exercise program in persons with chronic SCI, including outcome measures of metabolism, body composition, physical activity, energy intake, measures of health and wellbeing, resting metabolic rate, heart rate, and blood pressure, aerobic capacity, immune function, and adipose gene expression [23] . Here, we report the results of a qualitative study of priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia.
cord-013176-6ckuya1w	2020	Quercetin, extracted from Embelia ribes (Mirsinaceae), exhibited antiviral effects against HCV, exerted through activity inhibition of the viral protease Non-Structural protein 3 (NS3), leading to a decrease in HCV replication [36] . The natural extract of Tetrastigma hemsleyanum (Vitaceae) contains many flavonoids, including vitexin, vitexin-2-O-rhamnoside, isorhamnetin, rutin, kaempferol, astragalin, quercitrin, quercetin and iso-quercetin, which were shown to be able to exert anti-influenza virus activity, with different efficiency, through the reduction of the number of plaques induced by the influenza virus in infected Madin-Darby Canine Kidney (MDCK) cells [21] . In future perspective, this approach could be considered in order to possibly improve the antiviral activity of some flavonoids, like baicalin, that was able, like fludarabine [65] , to act against HIV-1 chronic infection of human monocytes and macrophages, inhibiting the fusion of HIV virus envelope proteins with these cells [73] .
cord-016089-h122of8q	2015	Among them, chlorogenic acid is received considerable attention for its part in the human diet with potential biological effects [5] , and is used as a standard compound for evaluation of the quality of Jinyinhua and related pharmaceutical or natural health product containing the herb. Chlorogenic acid and luteoloside, officially used as the indicator compound to characterize the quality of this herb and its related preparations, were shown to have beneficial effects in the aspects of anti-oxidation and antitumor [1, 13] . Meanwhile, luteolin, another major flavonoid in Jinyinhua, and volatile oil also showed significant anti-inflammatory activity. They are mainly used for the treatment of fever, cough, sore throat, acute and chronic tonsillitis, acute and chronic pharyngitis through its function clearing away the heat and toxic material, antibacterial, anti-inflammatory and antiviral effects. Because Jinyinhua is an edible herb and commonly used as raw material in health food, clinical reports on the toxicity or side effects were done to determine its safety at least 10 years ago.
cord-016362-d3cpy37g	2007	As shown in Table 1 , none of the compounds had the ability to inhibit HSV, while only quercetin-3,7-O-α-L-dirhamnoside had inhibitory activity against PI-3 in the range 8-32 µg/mL of maximum and minimum cytopathogenic effect (CPE) inhibitory concentrations, respectively. In one of our recent studies, five diterpenoid-derivative alkaloids, lycoctonine (9), 18-O-methyllycoctonine (10), delcosine (11), 14acetyldelcosine (12), and 14-acetylbrowniine (13) (as shown in Fig. 3) were screened for their antibacterial, antifungal, and antiviral activities [39] . The most active alkaloid with anti-PI-3 effect was shown to be protopine (1-32 µg/mL), followed by fumarophycine (2-32 µg/mL), chelidimerine, (+)-bulbocapnine, and (-)ophiocarpine (4-32 µg/mL), as well as β-allocriptopine and oxosarcocapniA number of antimicrobial, antiviral, antitumoral, antimalarial, and cytotoxicity studies have been so far reported on various derivatives of natural or synthetic isoquinoline alkaloids [51] [52] [53] [54] [55] [56] [57] .
cord-016575-bn15006x	2019	Terpenes have a wide range of medicinal uses among which antiplasmodial activity is notable as its mechanism of action is similar to the popular antimalarial drug in use—chloroquine. Terpenes and terpenoids are terms that are often used interchangeably but the two terms have slight differences; terpenes are an arrangement of isoprene units that are naturally occurring, volatile, unsaturated 5-carbon cyclic compounds that give off a scent or a taste to defend itself from organisms that feed off of certain types of plants (see footnote 1). This plant contains many medicinal properties like anticancer, antimicrobial, antifungal, antiviral, antihyperglycemic, analgesic, anti-inflammatory, and antiparasitic (Franklin et al. Beta-myrcene from Cannabis sativa, the plant which is high in terpenes, does not show an anti plasmodial effect but extracts from stem, leaves, and seeds of clove basil showed a good antiplasmodial activity (Small 2017; Kpoviessi et al. The results revealed that terpenes formed a major part of the extracts of medicinal plants that exerted antidepressant effects (Saki et al.
cord-017131-rx1z4orm	2012	Although numerous studies have been conducted in vitro and in vivo in the recent years on the efficacy of plant phytochemicals as antimicrobial agents, this chapter provides an overview of the antimicrobial properties of some major group of phytochemicals, namely, different phenolic compounds, alkaloids, saponins, iridoids and secoiridoids, polyacetylenes, glucosinolates, terpenoids, sulfinate, limonoids (tetranortepenoids) and anthranoids against pathogenic bacteria, fungi, viruses and commensal bacteria in the intestinal tracts of humans and animals. This chapter also discusses their antimicrobial mechanisms of action, the efficiency of different groups of phytochemicals against multiple-drug resistant bacteria, the effect of active dietary phytometabolites on the beneficial and pathogenic microbes of the gastrointestinal tracts and the outcomes of combination of phytofactors and drugs interactions. Although, phenolic acids are effective against Gram-negative bacteria, their antimicrobial effect is strain dependent (e.g. different strains of Escherichia coli ; Cueva et al.
cord-017504-rtg7fs82	2012	The results suggested that the aril juice the major and tasty part of pomegranate fruit, did not contain ellagic acid and punicalagin (i.e. the polyphenols highly represented in the rind which appeared to be responsible for the antioxidant capacity) in amounts suf fi cient to exert cytoprotection in oxidatively injured, living cells. After consumption of pomegranate juice, fruit peel, aril and fl ower extracts the atherosclerotic lesion area in atherosclerotic apolipoprotein e-de fi cient (E 0) mice was signi fi cantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while pomegranate seed oil had no effect. Further in-vitro studies showed that Punica granatum fl ower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. In-vitro studies using normal human epidermal keratinocytes, showed that pre-treatment with pomegranate fruit extract rich in anthocyannins and hydrolyzable tannins protected against the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPK) pathways (Afaq et al.
cord-020010-q58x6xb0	2006	In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression.
cord-021419-nypnib0h	2020	In this review, the following classes of compounds are considered as scaffolds for the synthesis of new antibiotics: polycyclic glycopeptides of the vancomycin ± teicoplanin group, classical macrolides, macrolides of the amphotericin B ± oligomycin group, anthracyclines, aureolic acid derivatives, heliomycin, synthetic benzoxaboroles and some other antibiotics. 42 Antibacterial activity of derivatives 52 ± 55 modified at the C(11)7OH group of the aglycone was evaluated compared to the starting antibiotics vancomycin (1) and azithromycin (30) on a panel of Gram-positive and Gramnegative bacterial strains (8 and 3 strains, respectively). In order to improve antifungal properties, cytotoxic and therapeutic characteristics and to study the mechanisms of action, series of new semi-synthetic derivatives based on AmB (63a) and bioengineered analogues S44HP (64a), BSG005 (65a), BSG022 (66a), BSG019 (67), BSG003 (68a) and BSG018 (69) were synthesized (in collaboration with the company BIOSERGEN, Norway) (Scheme 17).
cord-021897-yeih3tfo	2011	• tourism is a discretionary activity (people are not required to undertake it as a basic need to survive, unlike consuming food and water) • tourism is of growing economic significance at a global scale, with growth rates in excess of the rate of economic growth for many countries • many governments see tourism as offering new employment opportunities in a growing sector that is focused on service industries and may assist in developing and modernizing the economy • tourism is increasingly becoming associated with quality of life issues as it offers people the opportunity to take a break away from the complexities and stresses of everyday life and work -it provides the context for rest, relaxation and an opportunity to do something different • tourism is becoming seen as a basic right in the developed, Westernized industrialized countries and it is enshrined in legislation regarding holiday entitlement -the result is many people associate holiday entitlement with the right to travel on holiday • in some less developed countries, tourism is being advocated as a possible solution to poverty (described as ''pro-poor'' tourism) • holidays are a defining feature of non-work for many workers • global travel is becoming more accessible in the developed world for all classes of people with the rise of low-cost airlines and cut-price travel fuelling a new wave of demand for tourism in the new millennium.
cord-022779-himray6q	2005	Here we present a novel strategy to synthesize proteins through a chemical ligation using unprotected peptide segments. Using short portions (7-11 amino acid) rich in positively charged residues from either human lactoferricin or the MARCKS protein as templates, a panel of 70 peptides each possessing a specific chemical structure was synthesized. Subsequent functionalization of such azide groups via Staudinger or "Click" chemistry should provide a convenient method for linking proteins with a diverse array of probes, biomolecules, surfaces and other materials under mild conditions. Moreover, the advantages of peptide and protein chemical synthesis over recombinant-DNA methods are increasingly being used to provide rapid structure-activity information of complex bioactive peptides, small proteins and functional receptor domains. Thus, these new peptides bear all of the requirements which are necessary for formation of cooperatively interacting helical structures and, furthermore, contain domains for cooperative sheet aggregation as well.
cord-022940-atbjwpo5	2016	We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment.
cord-022955-vy0qgtll	2005	In order to understand the molecular basis of the enzyme-substrate binding mechanism, we employ the synthetic peptide and mass spectrometry-based approaches to investigate the significance of selected amino acid residues that are flanking both sides of the SARS-CoV 3CL pro cleavage site. To contribute to the assignment of a physiological role to genomic-derived peptidases and to make them more accessible for the drug discovery process, we have undertaken a program consisting of mRNA expression profiling, full-length recombinant expression in insect cells, purification and determination of the catalytic activity for the human proteolytic enzymes. This comprehensive analysis of the local backbone properties of SGTI in the free and in the complex form made possible to identify conformational similarities and differences responsible for its efficient binding to the enzyme, and provides a good basis for further studying the structural aspects of protease inhibitor specificity.
cord-023208-w99gc5nx	2006	In order to develop a synthetic protocol by an automated instrumentation, increasing yield, purity of the crude, and reaction time, a microwave-assisted solid phase peptide synthesis was validated comparing the use of the new generation of Triazine-Based Coupling Reagents (TBCRs) with a series of commonly used ones. Ubiquitinium is a well known mechanism in protein degredation of Eukaryotic cells ,in which many obsolte and corrupted three dimentional structure protein ,become marked by covalent attachment of ubuquitin through a multi-step enzymatic pathway.Ubiquitin is a small ,8.5 kDa peptide of 76 amino acid residues that targets such substrtes for proteolysis in proteasome .Recnt studies showed that an extra cellular ubiquitination process also taking place in the epididymes of humans and other animals marks protein on the surface of the defective sperm .it appears that structurally and functionally defective sperm become surface ubiquitinated by epididymal epithelial cells. This head-to-tailcyclized 14-amino-acid peptide contains one disulfide bridge and a lysine residue (Lys5) present in the P1 position, which is responsible for inhibitor specificity.As was reported by us and other groups, SFTI-1 analogues with one cycle only retain trypsin inhibitory activity.
cord-023209-un2ysc2v	2008	Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds.
cord-023225-5quigar4	2012	To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues.
cord-024652-4i6kktl0	2020	
cord-027712-2o4svbms	2020	We present the grounding approach, deployment and preliminary validation of the elementary devised model of physical well-being in urban environments, summarizing the heterogeneous personal Big Data (on physical activity/exercise, walking, cardio-respiratory fitness, quality of sleep and related lifestyle and health habits and status, continuously collected for over a year mainly through wearable IoT devices and survey instruments in 7 global testbed cities) into 5 composite domain indicators/indexes convenient for interpretation and use in predictive public health and preventive interventions. In the first approach, daily and intra-daily underlying measurements (Table 1 ) are used to estimate levels of adherence to rule-and range-based recommendations matured from institutional knowledge of relevant authorities and population-significant studies in the field, accumulated for over decades in the stated four example domains of motility, physical activity, sleep quality and cardio-respiratory fitness [8, 10, 11] .
cord-027713-8ohchx8p	2020	In this work, we perform the recognition of the human activity based on the combined Weighted SVM and HMM by taking advantage of the relative strengths of these two classification paradigms. The basic procedure for mobile activity recognition involves i) collection of labelled data, i.e., associated with a specific class or activity from users that perform sample activities to be recognized ii) classification model generation by using collected data to train and test classification algorithms iii) a model deployment stage where the learnt model is transferred to the mobile device for identifying new contiguous portions of sensor data streams that cover various activities of interest. In this work, we adopted a new method for physical activity recognition using mobile phones that uses labels outputting WSVM in HMM. One also notices for HAR dataset that the multi-class WSVM method improves the classification results over MC-SVM, MC-HF-SVM and HMM classifiers used alone.
cord-034066-fsp7e5x5	2020	2 And in 2008, the Agency for Healthcare Research and Quality of the HHS came out with an Evidence-Based/Technology Assessment entitled "The Effectiveness of Weight Management Programs in Children and Adolescents." 3 In addition to these government-sponsored guidelines, recommendations for management of overweight and obesity in this population have been issued by multiple other organizations. One 12month technology-based program for adolescents with Type 2 diabetes "was not sufficient to produce weight loss with the combination of web intervention and group sessions and telephone follow up, but improvements in sedentary behavior and use of behavior change strategies expected to lead to behavior change was evidenced." 32 Telemedicine, in theory, should be able to compensate for some of the barriers that prevent access to and utilization of family based comprehensive behavioral interventions for child and adolescent obesity.
cord-102632-yazl9usb	2020	To assemble these different elements -biological vocabulary, observation, active learning and gamification -in a comprehensive learning activity, we created a large scale biological treasure hunt for our students. Educators also have the possibility to define specific game parameters, such as specific geographic regions in which the game takes place or restriction on the number of submissions in each quest group (adding for instance a point penalty below a certain number of "animal" or "plant" submissions). Once pictures are stored on the web interface, students can assign them to a specific quest and submit it for evaluation. The web application allows users to follow their progress in detail (which picture was submitted for which quest, what is the evaluation status, etc.) as well as the global progress of the other groups (the total number of collected points). More precisely, in the photo quiz module, students are presented with pictures submitted by other groups and validated by the educators (see below "Expert evaluation).
cord-252108-04xr5xdl	2013	The screening of antitrypanosomal and antiviral activities of 5-(3-naphthalen-2-yl-5-aryl-4,5-dihydropyrazol-1-yl)-thiazolidine-2,4-diones was carried out with the promising influence of the mentioned compounds on Trypanosoma brucei, but minimal effect on SARS coronavirus and influenza types A and B viruses. The most promising compound in series of aryl-4-oxothiazolylhydrazones was shown to be very active at non-cytotoxic concentrations in in vitro assays against Trypanosoma cruzi cell cultures and exhibited potency comparable with the reference compounds (IC 50 (Y strain) ¼ 0.3 mM) [9] . Aiming at the detailed elaboration of SAR, especially the influence of the linking group of thiazolidinoneepyrazoline conjugates on the anticancer activity, 5-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-2oxoethylidene]-thiazolidine-2,4-diones (4ae4f) were synthesized by the method, described previously [29] . The cytotoxic and/or growth inhibitory effects of the most active selected compounds were tested in vitro against the full panel of human tumor cell lines at concentrations ranging from 10 À4 to 10 À8 M.
cord-253276-mqcwk2ow	2013	The structure activity relationship revealed that the presence of electron withdrawing groups at para position of phenyl ring remarkably enhanced the antibacterial activity of synthesized compounds. From the results of the antimicrobial activity of the synthesized compounds 5ael, the following structure activity relationships can be derived: the antibacterial activity was considerably affected by substitution pattern on the phenyl ring and the most active compounds contain electron withdrawing substituent at para and meta positions of the phenyl ring (p > m > o). Compounds 5c and 5i, substituted with inductively electron withdrawing fluoro and nitro groups, respectively at para position showed the highest antibacterial activity (F > NO 2 ). While, substituting the phenyl ring with fluoro and nitro group at ortho position resulted in noticeable decrease in the antibacterial activity of compounds 5a and 5g respectively. The contrasting nature of substitution pattern at para position of the phenyl ring of most active antibacterial and antifungal agents indicate that the structural requirements are different for binding of drug to bacterial or fungal targets, respectively [43] .
cord-256992-rwy0n01l	2020	Polyphenols are a wide group of plant-derived molecules resulting from secondary metabolism, ubiquitously distributed in vegetable kingdom where they display different activities such as protective effect against UV rays, bacteria, virus and fungi infections, modulation of plant hormones, enzyme inhibition and pollinator attraction [1] . [101] reported the in vitro effect of myricetin on high glucose-induced β-cell apoptosis, possibly via cyclin-dependent kinase 5 (CDK5) inhibition. Anti-angiogenic effects of myricetin (5 to 20 μM) assessed through in vitro (HUVEC) and in vivo (CAM) models revealed that this compound significantly inhibits angiogenesis induced by OVCAR-3 cells. In SKOV3 human ovarian cancer cells, myricetin inhibited viability and induced apoptosis (40 μg/mL, time-dependent manner) through endoplasmic reticulum stress and DNA double-strand breaks [130] . Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo
cord-257167-rz4r5sj7	2006	SY1-3-11-3 SAD: A novel kinase implicated in phosphoproteome at the presynaptic active zone Toshihisa Ohtsuka Department of Clinical and Molecular Pathology, Faculty of Medicine/Graduate School of Medicine, University of Toyama, Toyama, Japan SAD is a serine/threonine kianse, which has been shown to regulate various neuronal functions during development, including clustering synaptic vesicles, maturation of synapses, and axon/dendrite polarization: these have recently been revealed by genetic studies in C. The results suggest that EAAT4 plays a major role in regulating the concentration of CF transmitters, possibly glutamate, in the route of its extrasynaptic diffusion, and determining the degree of CF-induced inhibition of GABA release from BCs depending on the regional difference of EAAT4 expression in postsynaptic PCs. Chitoshi Takayama 1 , Yoshiro Inoue 1 1 Department of Molecular Neuroanatomy, Hokkaido University School of Medicine, Sapporo, Japan GABA mediates inhibitory transmission in the adult central nervous system (CNS).
cord-257494-242k58ll	2017	
cord-257749-eyhsc8q8	2019	These bioactive compounds belong to different chemical classes, including flavonoids, coumarins, furanocoumarins, chalcones, quinines, terpenoids and some others due to which these species exhibit significant anti-oxidant, anti-bacterial, anti-fungal, anti-viral, anti-helmintic, anti-diabetic, diuretic, hepatoprotective, anti-cancer and anti-tumor activities. The active compound, bakuchiol (155) is a monoterpene phenol, has been obtained in a pure state and named after Sanskrit name of the plant (Mehta et al., 1973) and possess the potent anti-bacterial property (Satyavati et al., 1987) . corylifolia, several bioactive compounds such as bakuchiol (155), psoralen (92), isopsoralen (2), corylin (187), corylifolin (185) and psoralidin (228) were screened for their anti-oxidant potential. Studies on extraction and isolation of active constituents from Psoralea corylifolia and the anti-tumor effect of the constituents in vitro Anti-fungal activity of aqueous and solvent extracts of seeds of Psoralea corylifolia L.
cord-258239-7xyqlz0u	2020	To this end, we established an approach to determine the proteolytic activity of CatG on the cell surface of neutrophils, NK cells, B cells, and T cells in peripheral blood mononuclear cells (PBMCs) by combining the activity-based probe MARS116-Bt and the antibiotin-150 Nd antibody with CyTOF analysis. Therefore, MARS116-Bt-anti-biotin-150 Nd antibodies are useful to profile a vast panel of different cell subsets in order to evaluate catalytically active CatG, its regulation, or inhibition on the cell surface. The next-generation flow cytometry CyTOF setup in combination with MARS116-Bt-anti-biotin-150 Nd antibodies allows us to analyze and gate distinct cell subsets and simultaneously determine the proteolytic activity of CatG. Furthermore, MARS116-Bt-anti-biotin-150 Nd antibodies can be added to a vast panel of activation markers in CyTOF analysis to characterize immune cells during inflammation, inducing a pathologic effect, in homeostasis, or when stimulated with different substances.
cord-260674-a0ejus6m	2020	CONCLUSIONS: COVID-19 marginally improved the eating behaviour, yet one-third of participants gained weight as physical activity declined significantly coupled with an increase in screen and sitting time. A web-based cross-sectional study was conducted on the general population to assess the impact of COVID-19 on daily lifestyle-related practices such as dietary, activity and sleep pattern using a validated questionnaire. The electronic survey questionnaire was designed to assess changes in multiple lifestyle-related behaviors such as eating, physical activity, sleep and other health related behaviours during the COVID-19 outbreak. Part A (A1 to A24) assesses the baseline lifestylerelated behaviours and Part B (B1 to B24) evaluates changes in different lifestyle related behaviors such as eating habits, physical activity and sleep pattern during the pandemic.
cord-261170-arnwk287	2017	Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. To gain an understanding of the importance of marine natural products chemistry in drug development G To be able to map the process involved in drug development from marine natural products G To gain an appreciation of the range of biological activities associated with compounds isolated from micro-and macroorganisms G To identify the marine-derived drugs which are undergoing clinical evaluation Biological activities identified in extracts and metabolites of algal origin include anticancer, antiobesity, neuroprotective, and antioxidant activity and Scheme 18.2 shows chemical structures of representative bioactive compounds isolated from the macroalgae. Biologically active compounds from marine bacteria also include Streptomyces species from sediment and fish gut from which anticancer (e.g., halichomycin and δ-indomycinone) and antibacterial agents (e.g., phenazines) have been obtained [58À60].
cord-262950-zv6qerhg	2020	In the current article, we provide a task analysis for creating both simple and complex digital activity schedules using Google Slides, a freely available, web-based technology that operates on a variety of digital platforms. Thus, the purpose of this article is to provide a detailed task analysis that both behavior analysts and parents can use to create and modify digital activity schedules using Google Slides, a freely available, web-based program that works on a variety of digital devices and platforms. 7. "Turn the page" on the digital schedule to display the next activity by touching or clicking on the arrow in the bottom-right corner of the screen. If the slide linked to the rectangle is incorrect, click "Remove link." Return to Step 5 in the section "Creating Navigation for Choice Pages." 9. In the left navigation bar, select the second choice page (the first slide with a large toy picture in the lower rectangle; Fig. 18 ) and paste the arrow.
cord-265764-h4zg0q8x	2013	On the other hand, pyrimidine-based compounds are well known for their wide range of promising antiviral [22] , antitubercular [23] , anti-AIDS [24] , antinociceptive [25] , antifungal [26] , antitumor [27] and antimalarial activities [28] apart from their role in the nucleic acid synthesis. The in vitro antimalarial screening of the new synthesized compounds 5aeg revealed good to moderate activities in nM range against both the tested Dd2 (CQ S ) and D10 strains (CQ R ) of P. Analysis of the activity of the compounds recorded in Table 1 reveals that replacing C-5 ethyl ester of the previously reported [29] decrease in antimalarial activity against both the chloroquine sensitive and chloroquine resistant strains of P. In this study, we have evaluated the mechanism of antimalarial activity of the most potent compound 5b of the series by studying its binding with heme (Fig. 4) .
cord-267284-3uz0v29k	2014	
cord-269943-g77qe5ml	2020	
cord-270037-tq82srhn	2012	
cord-270424-8yhsjbmi	2016	27 In this context, in view of the above fact and to discover completely new anti-vaccinia and adenovirus agents with a novel skeleton and unique mode of action, a relatively small library of 6-(1-benzyl-1H-1,2,3-triazol-4-yl)-3-hydroxyquinazoline-2,4(1H,3H)-dione compounds (the general formula in Scheme 1) was constructed via the copper(I)-catalyzed azidealkyne cycloaddition (CuAAC) reaction 28 and the biological significance of the novel synthesized quinazolines was highlighted by evaluating them in cell culturebased antiviral high-throughput screening (HTS) assays against a broad panel of DNA viruses, retroviruses and several RNA viruses. The newly synthesized 1,2,3-triazole-linked 3-hydroxy-quinazoline-2,4 (1H,3H)-diones were performed to evaluate against their antiviral activity against a broad panel of DNA virus, including Herpes simplex virus-1 (KOS), Herpes simplex virus-2 (G), Herpes simplex virus-1 TKKOS ACVr, vaccinia virus and Adeno virus-2 (evaluated in infected human embryonic lung fibroblast (HEL) cells). In conclusion, a series of novel 1,2,3-triazole-containing 3hydroxy-quinazoline-2,4(1H,3H)-diones has been synthesized using CuAAC reaction, and was firstly identified as potent and specific vaccinia and adenovirus inhibitors in vitro.
cord-270602-599vweqe	2003	Although many marine-product clinical trials are for cancer chemotherapy, drug resistance, emerging infectious diseases, and the threat of bioterrorism have all contributed to the interest in assessing natural ocean products in the treatment of infectious organisms. Many marine natural products have successfully advanced to the late stages of clinical trials, including dolastatin 10, ecteinascidin-743, kahalalide F, and aplidine, and a growing number of candidates have been selected as promising leads for extended preclinical assessment. Many marine natural products have successfully advanced to the late stages of clinical trials, including dolastatin 10, ecteinascidin-743, kahalalide F, and aplidine, and a growing number of candidates have been selected as promising leads for extended preclinical assessment. 6 In this review, we focus on the pharmacologically tested marine leads that have shown in-vivo efficacy or potent invitro activity against infectious and parasitic diseases, including malaria, toxoplasmosis, trypanosomiasis, and viral, bacterial, and fungal infections.
cord-270892-ycc3csyh	2010	[79] [80] [81] [82] Taken together, the results of natural cold studies as well as of experimental infection in human volunteers clearly demonstrate that HRV are able to replicate in the upper as well as in the lower airways. Such an anti-HRV drug would have to be (i) with broad spectrum activity because of the high number of HRV serotypes, (ii) administered very early in infection to demonstrate a good antiviral effect because of the fast infection kinetics, (iii) very safe because of the broad application by millions of people, and (iv) directed against a highly conserved target with low risk of resistance development. The HRV-induced CPE, infectious virus titers, viral protein expression, and RNA synthesis can be chosen as parameters to evaluate the anti-HRV activity of compounds in cell-culture based assays. Due to the lack of a small-animal model for HRV infection until 2008, the experimental human challenge model has to be used to approve effects of potential antiviral drugs under controlled conditions in preclinical studies.
cord-271068-rwx171oj	2010	
cord-272943-q09i8fqu	2014	Surprisingly, the use of fluoroquinolones in indications other than bacterial infections has never been exploited, although not only nalidixic acid and its congener chloroquine exerts pleiotropic actions but, e.g., β-lactams and aminoglycosides are characterized by a broad range of biological activities too [47, 48] , so that a multitude of antimicrobial effects would not have been unusual. Fluoroquinolones inhibit not only enzymic activity of viral topoisomerases/helicases, but inhibit in vitro human immunodeficiency virus (HIV) reverse transcriptase as well; complete inhibition was observed at concentrations of ciprofloxacin and ofloxacin of 3 μM and norfloxacin of 1 μM, respectively [71] [72] [73] . Fluoroquinolones like ciprofloxacin, amifloxacin, enoxacin, norfloxacin, ofloxacin, pefloxacin, grepafloxacin, trovafloxacin, and 16 additional commercially available quinolones exhibit marked in vitro activity and in vivo efficacy against Plasmodium spp.
cord-274101-vm9nh8lc	2012	The separation occurs because of highly specific biochemical interactions between the peptide and the ligand Used when a high degree of specificity is required, for example, isolation of a target protein present in low concentration in a biological fluid or a cell extract Capillary electrophoresis Based on the migration of the peptide according to its charge in solution, depending on the application of an electric field. Peptides have shown various bioproperties, among them antimicrobial activity, leading to the application of these compounds in the food preservation area by either direct addition or incorporation into packaging materials (Table 8) . Active packaging materials incorporated with antimicrobial peptides have shown effectiveness in inhibiting pathogenic microorganisms, an improvement in food safety. Several studies have indicated significant changes in mechanical properties and surface morphology of the films incorporated with antimicrobial peptides.
cord-274506-fzcuu4ma	2019	While PLpro cuts the first three cleavage sites of its polyprotein, 3CLpro is responsible for cleavage of the remaining eleven locations resulting in release of a total of 16 non-structural proteins (nsp) in both SARS-and MERS-CoVs. The homodimeric form of 3CLpro is active in the presence of substrates. In this study, we used a proteolytic method to probe MERS-CoV 3CLpro inhibitory compounds with a synthetic peptide labelled with the EDANS-DABCYL FRET (Fluorescence resonance energy transfer) pair (Liu et al., 2005) . The proteolytic assay using MERS-CoV 3CLpro in the presence of Triton X-100 has been performed to differentiate artificial inhibitory activity of chemicals through non-specific binding with proteases by forming aggregate or complexation. The four compounds showed the severely reduced fluorescent intensity and thus represented their MERS-CoV 3CLpro inhibitory activity. In this study, we assayed the inhibitory activity of various flavonoids against MERS-CoV 3CLpro. The analysis of the four compounds with their homologs using an induced-fit docking study provided an insight of flavonoid scaffolds required to bind with MERS-CoV 3CLpro.
cord-276166-b1e0bbrp	2017	Previous studies showed that glycosylated IFN-ω + ribavirin (RBV) had a synergistic effect in terms of its antiviral activity in hepatitis C virus (HCV)-infected patients [43] . [49] showed that interleukin (IL)-6 production was affected considerably in feline immunodeficiency virus (FIV)-infected cats treated with recombinant feline IFN-ω (rFeIFN-ω) by subcutaneous or oral protocols. Because of its antiviral, immunomodulatory, anti-proliferation, and antitumor activities, IFN-ω has been explored as a treatment option for some diseases and viral infections in humans and other animals. Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega Limited efficacy of topical recombinant feline interferon-omega for treatment of cats with acute upper respiratory viral disease Oral recombinant feline interferon-omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation
cord-277077-kwaiorp8	2020	The main purpose of this paper is to create a yoghurt with high antioxidant capacity, using only raw materials from Romania; (2) Methods: The bioactive components used to enrich the cow milk yoghurt were extracted as volatile oils out of four aromatic plants: basil, mint, lavender and fennel. The 2,2-diphenyl-1-picrylhy-drazyl (DPPH) method was used to determine the antioxidant activity; (3) Results: The results show that cow milk yoghurt enhanced with volatile oils of basil, lavender, mint and fennel, encapsulated in sodium alginate has an antioxidant and antimicrobial effect as a staple food with multiple effects in increasing the body''s immunity. The antioxidant and antimicrobial activity of volatile fennel oil is offered by the high content of trans-anethole (63.30%), pinene (11.11%) and fenchone (8.32%) [20] [21] [22] [23] [24] [25] Basil (Ocimum basilicum) is an aromatic plant that belongs to the Lamiaceae family and is considered a rich source of essential oils.
cord-277541-ieex2xwx	2010	title: Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv "White Cloud Bean" A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv "White Cloud Bean". They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 μM. The objective of the present study was to isolate and characterize proteins with protease inhibitory activity from white cloud beans. The present study disclosed the production of two trypsin inhibitors with closely related N-terminal sequences chromatographic behavior and bioactivities by the white cloud bean variety of Phaseolus vulgaris. White cloud bean trypsin inhibitors demonstrate antiproliferative activity against tumor cells but do no inhibit mycelial growth or HIV-1 reverse transcriptase.
cord-277802-f8pyn3rx	2015	Aminomethylated derivatives of hydroxycarbazoles have been also mentioned in a different study [60] , which described the synthesis of a small series of phenolic Mannich bases 47 (Fig. 8 ) obtained from 5-substituted 2-hydroxy-5H-benzo[b]carbazole-6,11-diones along with their in vitro anticancer evaluation at National Cancer Institute (NCI) using an in-house developed screening panel of approximately 60 cell lines derived from nine different types of cancer. Recently, Mannich bases 132 ( Fig. 24 ) obtained using Schiff bases derived from 5-fluoroisatin and 4-arylideneaminoanilines as substrates and ciprofloxacin as amine reagent were shown to be generally less potent antibacterials than reference drug ciprofloxacin, although some candidates had MIC values comparable to those of ciprofloxacin against the investigated bacteria [164] . Both types of Mannich bases 133l and 134l, featuring a 1,2,4-triazole moiety at position 5 of the triazolethione scaffold, showed good antibacterial activity, but compounds 134l were generally more potent than 133l, and two of candidates 134l actually had MIC values comparable to those of reference drug ciprofloxacin [177] .
cord-278513-ajfpghze	1980	Sectioning of the villus-crypt unit in a cryostat enabled direct comparison of the distribution of lactase and sucrase enzyme activities in the adult rat. Sectioning of the villus-crypt unit in a cryostat enabled direct comparison of the distribution of lactase and sucrase enzyme activities in the adult rat. Differences in localization of enzyme activity in turn might help explain the decrease in the ratio of lactase to sucrase (0), and acid &alactosidase (A) along the villus-crypt unit. This is the first report that directly compares distribution of lactase and sucrase activities along the crypt-villus unit of the adult rat. The more apical localization of lactase activity compared to sucrase activity on the crypt-villus unit may help to explain the vulnerability of this enzyme to acute mucosal injury (e.g., acute gastroenteritis). Although it is not stated that the activities of all enzymes were assayed on the same villus-crypt unit, the authors report a more apical distribution of jejunal lactase activity when compared to sucrase and maltase.
cord-278654-dxx6z2fj	2013	the reduction in plasma ACE2 activity reported in ESRD patients treated by dialysis, particularly in female subjects, could limit Ang II degradation leading to increased levels of this peptide, which could contribute to the high prevalence of hypertension and cardiovascular morbidity that afflicts the dialysis population When compared with historic samples from healthy subjects, however, all CKD groups examined, i.e. predialysis, transplant patients and even subjects on dialysis, seemed to have increased levels of plasma ACE2 activity. What the study shows, in our opinion, is that while plasma ACE2 activity tends to increase in CKD patients, perhaps as a compensatory mechanism to attenuate Ang II overactivity, at the time that ESRD is reached and dialysis initiated a relative deficiency in plasma ACE2 activity ensues. This abnormally expressed endothelial protein could be shed into the circulation and could be the source of increased plasma ACE2 activity in certain conditions such as myocardial infarction, kidney disease or diabetes.
cord-280795-wtrt13ij	2007	
cord-281137-j81fgnld	2017	Methanolic extracts were evaluated for total phenolic contents (TPC), total flavonoids contents (TFC), DPPH free radical scavenging activity, reducing power and total anti-oxidant assays were performed. Total phenolic contents and total flavonoids contents varies among all the bacterial extracts respectively in which Bacillus subtilis showed high phenolic contents 243 µg/mg of gallic acid equivalents (GAE) and Stenotrophomonas maltophilia showed high flavonoids contents 15.9 µg/mg quercitin equivalents (QA), total antioxidant capacity (TAC) 37.6 µg/mg of extract, reducing power (RP) 206 µg/mg of extract and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity with 98.7 μg/mL IC(50) value. Ascorbic acid was taken as standard and percent DPPH free radical scavenging activity of each endophytic bacterial extracts are shown in Table 2 . dispersa showed the highest values indicating their electron donating ability for Table 6 Protein kinase (PK) inhiation (i.e. zone''s diameter in mm ± SD) during Streptomyces hyphae formation of isolated bacterial extracts (bald zone indicates PK inhibition while clear zone shows cytotoxicity) Surfactin stabilizing free radicals and showed the similar reductive potential as reported above.
cord-281597-x53ni6q1	2020	Here, we used multiplexed, sequencing-based assays to measure the effects of 2,695 VKOR missense variants on abundance and 697 variants on activity in cultured human cells. Finally, 25% of human VKOR missense variants show reduced abundance or activity, possibly conferring warfarin sensitivity or causing disease. To understand the effect of human variants and to define the vitamin K and warfarin binding sites, VKOR variant activity has been extensively studied in cell-based assays (Czogalla et al., 2017; Shen et al., 2017; Tie et al., 2013) . We recombined a library of VKORC1 variants into the HEK293 activity reporter cell line and sorted recombinant cells into quartile bins based on carboxylation-specific antibody binding. Using these contacts, we computationally folded human VKOR, yielding a modeled structure similar to the bacterial structure (RMSD = 2.58 Å over 97/143 C alpha , Figure 3 Comparison of our abundance data to the energy required to insert different amino acids into the membrane yielded additional evidence for the four transmembrane domain model.
cord-283301-adjjkqt2	2020	
cord-285856-0sw3wt1i	2009	We here report on the chemical synthesis, anti-influenza virus activity and structure-activity relationship of novel glycopeptide compounds carrying a hydrophobic side chain on an aglycoristocetin backbone ( Fig. 1) . b HPLC conditions: instrument: Waters 600 with UV230nm detection; column: Lichrospher RP-8 (4 mm × 250 mm; 10 m); injection volume: 20 l (corresponding to 2 g compound); solvents: Table 2 , several asymmetric squaric diamides derived from aglycoristocetin exerted marked activity against influenza virus, the most potent compounds being the phenylbenzyl derivative 8e [average antiviral EC 50 : 0.4 M; selectivity index (SI), defined as the ratio of MCC to EC 50 : 50]; the hexanol deriva-tive 8a (EC 50 : 1 M; SI: 14) and the naphthyl derivative 8f (EC 50 : 1.4 M; SI: 10). With regard to the antiviral mode of action, time-of-addition studies suggested that 8e blocks the viral entry process, since optimal anti-influenza virus activity was obtained when the compound was added to MDCK cells 30 min prior to or simultaneously with virus infection.
cord-286136-gm6w590s	2019	
cord-286303-wo6356vq	2019	In the current study, we present a machine learning based method for predicting novel mouse TLR9 (mTLR9) agonists based on features including count and position of motifs, the distance between the motifs and graphically derived features such as the radius of gyration and moment of Inertia. We therefore selected RF with the 20-fold cross-validation scheme, having maximum mean balanced accuracy and MCC and minimum standard deviation on both measures, to perform the Fig. 2 The effect of top 20 motifs in the high (a) and low (b) mTLR9 activity group of ODNs in the dataset. Our RF model predicted 545 of these 6000 random ODNs to be of high activity and we selected the top 100 for chemical synthesis, and then experimental tested them for mTLR9 activity using the RAW-Blue reporter cell line that expresses mTLR. The test dataset used to evaluate the performance of a model was composed of 46 ODNs (23 each from the two groups of high and low mTLR9 activity).
cord-287348-00yaxpkp	2005	Although many compounds with potent antiviral activity in cell cultures and in experimental animals have been detected, at present only several molecules and a-interferon have been approved by the health authorities for therapy of viral infections in humans. Furthermore, several soluble derivatized dextrans with different percentages of carbomethyl, benzylamide and sulphonate/sulphate groups were also evaluated for possible inhibitory effects on HIV-1 infection, and from the results obtained, their use as anti-HIV therapeutic agents can be proposed [56] . Carrageenans and fucoidan are sulphated PS extracted from red seaweed and brown algae, which have shown potent inhibitory activity against different viruses including HIV. These compounds act as potent inhibitors of different enveloped viruses, including members of Herpesviridae, and their activity is linked to the anionic features of the molecule which hinder the attachment of viral particles to host cells.
cord-291559-h6czy5bh	2017	
cord-292286-ygomb3oi	2017	Flavonoids are widely distributed as secondary metabolites produced by plants and play important roles in plant physiology, having a variety of potential biological benefits such as antioxidant, anti-inflammatory, anticancer, antibacterial, antifungal and antiviral activity. The antiviral activity of flavones is known from the 1990s, when it was showed that the simultaneous application of apigenin with acyclovir resulted in an enhanced antiviral effect on herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in cell culture [92] . Besides these DNA viruses, apigenin was found to exert antiviral effect against African swine fever virus (ASFV), by suppressing the viral protein synthesis and reducing the ASFV yield by 3 log [46]. Besides these viruses, EGCG has been found to exert antiviral activity against HCV by preventing the attachment of the virus to the cell surface and suppressing RNA replication steps [8, 15] . Antiviral activity of baicalin against influenza A (H1N1/ H3N2) virus in cell culture and in mice and its inhibition of neuraminidase
cord-293867-c4wnr5xe	2019	Besides the wide biological activity spectrum of imidazo[2,1-b] thiazole derivatives, also the compounds bearing hydrazide, acyl-hydrazone and spirothiazolidinone moiety, have been reported in the literature with their various effects such as antibacterial [21] , antifungal [22] , antitubercular [23] , antiviral [24] , anticonvulsant [25] and antidepressant [26] . In this study, we further explored the scaffold containing the imidazo [2,1-b] thiazole ring as the aromatic moiety, that is linked by an amide to a spirothiazolidinone ring system as the aliphatic cyclic moiety and from this point forward, novel derivatives were synthesized (Table 1) , and broadly evaluated for their antiviral and antimycobacterial activity (Fig. 2) . General procedure for the synthesis of 6-(4-bromophenyl)-N 2 -(substituted/non-substituted cycloalkylidene)imidazo[2,1-b]thiazole-3-acetohydrazides (4a-d) 0,005 mol of 3 was boiled in a water bath under reflux with 30 mL of ethanol until a clear solution was obtained.
cord-293974-jcpkla55	2020	The aims of this review are to showcase the extensive research and application of silver nanoparticles (AgNPs) and other metal nanoparticles (MNPs) as antimicrobial agents. The fact that NTM share many infectious traits with the causing agents of tuberculosis (TB) allows them to be used in many research studies as model organisms of infection for this disease, with the advantage of being less pathogenic and faster growing species [7, 9] . Mycogenic synthesis of AgNPs combines the best of both worlds: the most effective MNPs that nanotechnology has developed together with the green production process mediated by fungi [80] . So far, little has been explored combining the use of mycogenic AgNPs and the fight against TB and other mycobacterioses, but the efforts presented in Table 4 show the potential to exert some control over this infection and its increasing resistance. Green synthesis of silver nanoparticles and their activity against Mycobacterium tuberculosis
cord-294897-29diwyoe	2017	In this connection, marine algae are emerging as a new generation of potential preservatives, macro-and microalgae extracts, or pure ingredients with health benefits and demonstrated antibacterial, antifungal, and antiviral activities (Dai & Mumper, 2010; Devi et al., 2008) . Although intensive study of the antimicrobial potential of algae has begun [2005] [2006] [2007] [2008] [2009] [2010] [2011] [2012] [2013] [2014] [2015] [2016] , most of the studies that have been published are about therapeutic and antibacterial/antiviral capabilities of algae compounds, their ability to inhibit or kill clinical bacteria (Mehadi et al., 2015; Rajeshkumar et al., 2014; Rhimou, Hassane, José, & Nathalie, 2010) , but not about the effect of these bioactive molecules against foodborne pathogens and spoilage microorganisms commonly found in food matrices. Nowadays, the antimicrobial potential of algae against the main foodborne pathogens and spoilage microorganisms is one of the most interesting fields of research regarding the use of marine vegetables as sources of staple food and bioactives for human nutrition.
cord-295335-oa4twg2z	2018	In vivo-double-blind clinical trial in human patients Reduction of erythema, oedema, and itching scores (Halder & Richards, 2004) -In vitro-topical treatments in human patients during 4 weeks Lighten hand solar lentigines (Nerya et al., 2003) Glycyrrhetinic acid; glabridin 0-120 μM In vitro-human keratinocyte culture Prevention of oxidative DNA fragmentation and activation of apoptosis-associated proteins in human keratinocyte (Grippaudo & Di Russo, 2016) (Continues) In vitro-Vero cells In vivo-ducks Stimulation of immune and antiviral effect against DHV (Soufy et al., 2012) 0.1 μg/ml (extract) In vitro-human foreskin cell line Protection of host cells against EV71 infection (Kuo, Chang, Wang, & Chiang, 2009) In vivo-oral administration to humans (LDL isolation) (Carmeli & Fogelman, 2009) Licochalcone 2-20 μg/ml DPPH, superoxide anion, lipid peroxidation, red blood cells Inhibition of the microsomal lipid peroxidation (Haraguchi, Ishikawa, Mizutani, Tamura, & Kinoshita, 1998) Hepatoprotective activity Liquorice aqueous extract 100-300 mg/kg 15 days In vivo-oral administration to Wistar rats Stimulation of the antioxidant enzymes and arrest of inflammatory cytokine production (Huo, Wang, Liang, Bao, & Gu, 2011) G.
cord-295543-nj4a640t	2020	Conclusion: The Spanish adult population, especially young people, students and very active men, decreased daily self-reported PA and increased ST during COVID-19 confinement. While the disease spreads around the world, healthy people are being requested to stay at home for prolonged periods of time and, as a consequence, COVID-19 has radically modified the determining factors (individual, interpersonal, environmental, regional or national policies and global) [11] of both types of behavior Thus, due to isolation and limitations in engaging in regular and common activities, fulfilling PA recommendations and reducing sedentary behavior during lockdown may pose a significant challenge, especially during the first weeks when the population has limited chances to find alternatives to ensure they remain active even at home. Therefore, the aim of this study was to analyze self-reported PA and sedentary behavior before and during lockdown caused by COVID-19 in a Spanish healthy adult population.
cord-296769-xnjmk4pm	2020	The mechanism of anti-inflammatory and antioxidant effects of aspirin on hyperoxia-induced acute lung injury was studied in NF-κB-luciferase transgenic mice. Fetească neagră tendrils and leaves extracts, intended to be used in oral hygiene products recommended in periodontal disease, displayed a cytoprotective effect against nicotine-induced cytotoxicity and anti-inflammatory activity in human gingival fibroblasts [19] . opulus fruit fresh juice and a phenolic-rich fraction were able to decrease intracellular oxidative stress in mice insulinoma MIN6 cells, induced glucagon-like peptide-1 secretion in the presence of an elevated glucose concentration, and inhibited in vitro activity of the dipeptidyl peptidase-4 [21] . Moreover, their anti-inflammatory activity was studied in macrophages and multidrug resistance modulation as inhibition of P-glycoprotein and sensitization of doxorubicin-resistant ovarian carcinoma cells overproducing P-glycoprotein was detected and the effect on related gene expression revealed a distinct mechanism of action for the individual compounds [23, 24] .
cord-299007-5m6lk409	2008	
cord-300522-okbupw61	2020	Given the ability of various algal molecules—mainly sulfated polysaccharides—to inhibit viral infection at Stage I (adsorption and invasion of cells), we envisage a need to further investigate the antiviral ability of algae, and their mechanisms of action. Oxidative stress-a loss in the balance between the production of free radicals including reactive oxygen species (ROS) and antioxidant cell signaling pathways [2] -can be a key factor of the pathogenesis in many acute or chronical human diseases [3] . For that, we explore the relationship between oxidative stress and viral infections, looking for solutions through the deciphering of cell signaling pathways that can inhibit virus replication and infections, and the mechanisms of action of potential antiviral molecules. Three polysaccharides extracted from marine microalgae, naviculan from the diatom Navicula directa, and two others (named A1 and A2) from the dinoflagellate Cochlodinium polykrikoides also displayed antiviral activities against several enveloped viruses, such as HIV-1, HSV-1 or influenza virus type A (IFV-A) [71] .
cord-300872-blycbi4u	2020	Some of these strains have even become resistant to many antibiotics and chemotherapeutic agents; These prepared compounds were subjected to bioactivity screening against the highly pathogenic H5N1 avian influenza viruses, with the results expressed as percentages of growth inhibition, and to cytotoxicity evaluation against the A549 cell line. A synthetic procedure (Scheme 13) involved a condensation reaction between the amino group (NH2) in 49 and the carbonyl group in salicylic aldehyde (50), followed by intramolecular cyclization under a These prepared compounds were screened for potential anticancer activity against MCF-7, HCT 116, HepG-2, and A549 using the MMT assay. This compound was screened against MCF-7 and Hela cancer cell lines using MMT assay, giving IC50 values of 21.02 and 27.73 mM, respectively In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives (Scheme 14) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [36] .
cord-303468-95btvr1v	2020	This short communication describes three public engagement activities hosted by the authors, focused on biofilm control: hand hygiene, plaque control and an externally applied antimicrobial coating. Thus, as part of a PhD project investigating the activity of photocatalytic surfaces, one of the external walls of the University was used to illustrate the effectiveness of titanium dioxide paints in terms of self-cleaning and reduction of the formation of biofilm on the wall material. Our aim was to inform the passing public about our research (an interpretation panel was affixed to the wall), and on occasion, we encouraged passers-by to participate in a longitudinal subjective assessment of the impact of titanium dioxide-containing paint on the perceived cleanliness of the panel.
cord-303646-uxewsyli	1999	Recently, we have shown that in childre n with chole stasis of diffe ring e tiologie s incre ase d se rum met-enkephalin occurs concom itantly with highly ele vate d se rum aminope ptidase -M activity and that both parame ters were appare ntly not affe cted by a short-te rm treatment with ursode oxycholic acid (39, 40) . There fore , in this study we attempted to furthe r characterize and compare the serum aminope ptidase -M activity in he althy childre n, childre n with chole static live r dise ase , and childre n with chronic or acute he patitis due to hepatitis B virus (HBV) infe ction. As shown in Figure 2a , the e nzyme activity increased from 45 6 5 (undilute d se rum, pH 7.4) up to maxim al value s of 880 6 90 pg/min/ml (80-fold dilute d serum; value s are means 6 SEM) .
cord-303879-3hug5hj3	2005	Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Although there have been comparatively few studies into the mechanisms underlying flavonoid antibacterial activity, information from published literature indicates that different compounds within this class of phytochemicals may target different components and functions of the bacterial cell [137] [138] [139] . The cytoplasmic membrane activity detected for quercetin by Mirzoeva and co-workers may represent one of the additional mechanisms of antibacterial action that was suspected to be present among the seven DNA gyrase-inhibiting flavonoid compounds tested by Ohemeng and colleagues [68] . In addition to the structural alteration of weak and moderately active antimicrobial flavonoids, investigation into the mechanisms of action of these compounds is likely to be a productive area of research.
cord-304375-l5gvpat3	2012	Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In this communication, we report synthesis of a set of compounds that possess basic, hydrophobic as well as hydrogen bonding substituents, required for targeting either or both heme as well as DNA, thus providing new antimalarial agents active against chloroquine resistant strains of P. We have evaluated their anti-plasmodial activity, cytotoxicity and cytostatic activity, binding studies with DNA and heme (monomeric as well as m-oxo dimeric) using UVevisible, fluorescence spectrophotometry as well as NMR analysis. The comparison of association constants of 10r and 10c for monomeric and m-oxo heme reveals that both compounds bind strongly with m-oxo heme than monomeric heme and inhibit hemozoin formation by blocking the growing face of heme resulting in the observed anti-plasmodial activity.
cord-307983-gjdza9bh	2020	Thus, while more motivated offenders being online is likely to elevate rates of cybervictimization, the overall patterns are likely more affected by changes in target suitability and guardianship that result from the pandemic. These "dangerous" online routines would include surfing the dark web, playing online video games, online shopping, and visiting social media sites as all of these activities have been reported to increase cybervictimization (Bossler & Holt, 2009; Bossler et al., 2012; Costello et al., 2016; Hawdon et al., 2014; Leukfeldt & Yar, 2016; Navarro & Jasinski, 2012; Reyns et al., 2011; van Wilsem, 2011) . Taking all of these factors together, we would anticipate an increase in cybervictimization amid the COVID-19 pandemic due to more motivated offenders, a change in some "dangerous" online routines, and perhaps less target-hardening.
cord-309052-3h0g7s9v	2017	
cord-315918-12rbbe8c	2019	
cord-318528-yc0jw3s1	2020	In the group analysis, differences were observed in relation to gender, year of study, BMI, alcohol consumption, tobacco use, symptoms of anxiety/depression, Mediterranean diet, living situation and stage of change. To broaden our approach, as a secondary aim, we also wanted to look at changes in physical activity and sedentary behaviour resulting from other factors such as alcohol and tobacco consumption, adherence to a Mediterranean diet, motivation, symptoms of anxiety/depression and sociodemographic characteristics. This study aimed to evaluate physical activity and sedentary behaviour in health sciences students before and during the lockdown. In the analysis by group, minutes of physical activity increased significantly during lockdown among the following groups: women; all years of study except final year; normal or low BMI; those who did not eat a Mediterranean diet; and those in the preparation or action stage of change.
cord-318854-xaus3bma	2016	In this review, we discuss the antitumor-promoting, antiinflammatory, cytotoxic, antimicrobial, antiinfluenza, and antiherpes simplex-1 virus activities of diarylheptanoids isolated from galangal resulting from our own and other research groups'' investigation. Compound 6 showed the strongest activity among the four diarylheptanoids (IC 50 : 10 μM), and it also inhibited the mRNA expression of tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2, as well as protein levels of microphthalmia-associated transcription factor (MITF) [52] . Compounds 2, 6, 15, 16, 47, and 48 were tested for their inhibitory effects on NO production in the LPS-activated macrophage cell line RAW 264.7 [15] . Thus, the reports cited above suggest that diarylheptanoids possess inhibitory effects against inflammatory and tumor-promoting activities. Compound 4 was also active against influenza virus with an EC 50 value of <10 μg/mL [61] , which suggests that 4 is an effective diarylheptanoid against both RSV and influenza virus in vitro.
cord-320693-de1lmzl1	2019	METHODS: In this study, we evaluated the activities of five broad-spectrum antimicrobial peptides (AMPs) against several important swine-origin pathogenic viruses by TCID(50) assay. The pathogenic viruses isolated from pigs including pseudorabies virus (PRV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and rotavirus (RV) are commonly observed in China. In this study, we investigated the activity of five AMPs including piscidin, caerin, maculatin, lactoferricin B, and indolicidin against several porcine-origin viruses. The antiviral effects of the peptides (maculatin, caerin, piscidin, lactoferricin B, indolicidin) were investigated in vitro against several viral pathogens that severely threaten the porcine industry. Three peptides (caerin, piscidin, maculatin) exhibited inhibitory activity against PRV, PEDV, TGEV, PRRSV, and rotavirus. Our plaque reduction assay result indicated that piscidin, caerin, and maculatin could inhibit PRV by directly interacting with the virus.
cord-321985-w84wwkgi	2014	RESULTS: Main constituents of WESB remain unchanged during the incubation with simulated gastric juice (pH=1.5) and intestinal juice (pH=6.8), whereas four flavones, baicalin, wogonoside, oroxyloside and norwogonoside were metabolized into their respective aglycons by human intestinal bacteria. In this study, the water extract of Huangqin, the root of Scutellaria baicalensis (WESB) was incubated with simulated gastric and intestinal juices, and human fecal microflora, their metabolites were identified and the in vitro anticomplementary activity was evaluated. The inhibitory activity of main compounds in Huangqin as well as their metabolites against the standard strains of methicillin-resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), Enterococcus faecalis (gram-positive bacteria), Escherichia coli, Pseudomonas aeuroginosa (gram-negative bacteria) was determined to understand the role of gastrointestinal tract conditions on pharmacological effects of Huangqin. According to the content changes as well as the chemical structure of the eight ingredients in WESB, we concluded that four flavone glycosides, baicalin, wogonoside, oroxyloside and norwogonoside were converted to their respective aglycons, i.e. baicalein, wogonin, oroxylin A and norwogonin by intestinal bacteria.
cord-324217-secnz2ta	2016	The present chapter reviews natural traditional remedies used in the treatment of respiratory infections with the emphasis on antibacterial, antiviral, and antiinflammation activities of the volatile natural compounds (essential oils, etc.), and provides a brief view in some of structural activity relationships between antibacterial potencies and chemical structures of the essential oil''s constituents. 10 Besides the antimicrobial activity of the essential oils in natural products, other characteristics such as high vapor pressure, low toxicity, and antiinflammatory potential create a worthwhile theme for using of these natural compounds for new drug development in respiratory infections. As a member of the phytochemicals, terpenoids have been observed as a model of lipid soluble agents, which have an impact on the activities of membrane catalyzed enzymes; for 3 SCREENING OF THE ANTIbACTERIAL EFFECTS OF ESSENTIAL OILS example, enzymes involved in respiratory pathways. 98 Among the natural chemical compounds, significant antiinflammatory activities of plant-based essential oil have been reported by many researchers, which showed the basis for folk and traditional uses of these herbs for treatment of inflammatory diseases.
cord-324335-eoabmyg7	2020	Considering the enormous quantity of results and scientific data concerning the validation of medicinal and biological properties, the international scientific community included neem on the list of the top 10 plants to investigate and use for the sustainable development of the planet and the health of mankind (Tewari, 1992; Foster and Moser, 2000) . The plant drug is usually utilized exsiccated, or as a derived product, like an extract, resin or oil, which can be obtained as such, or be enriched in one or more constituents, which are considered responsible for the activity. In particular, considering insect-borne diseases, in vivo activity of neem seed oil (NSO) against malaria Plasmodium has also been reported (Dahiya et al., 2016; Trapanelli et al., 2016) .
cord-327521-g5vefajw	2020	In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. The recent discovery of the complexity of the human intestinal microbiota, composed of bacteria, fungi and viruses, and its intricate pathophysiological relationships with the immune system and the enteric nervous system, makes EOs truly interesting for their antimicrobial activities, often selective for the different microbial components. Recent studies have shown that geraniol administration reduced the intestinal inflammation induced by DSS [7] , but these anti-inflammatory effects could be also linked to its antioxidant activity, since its administration resulted in a decreased iNOS activity and a decreased lipid peroxidation, in a rat model of colitis [22] . Geraniol antibacterial activity seems to be linked to his property to destabilize bacterial cell wall and damage transmembrane efflux pumps, thus restoring drug-sensitivity in different bacterial antibiotic-resistant strains, such as Enterobacter aerogenes, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii [29] .
cord-328176-fck2ktxi	2013	This study examined the cytostatic and antiviral activity of twelve methyl-2-arylidene hydrazinecarbodithioates reported by many researchers as intermediates for the synthesis of thiosemicarbazides and the preparation of their metal complexes. Compounds IIc, IIi, and IIl with tridentate ligand features were found to have the lowest IC(50) value (6.5 μM, ≈ 1 μM, and 0.8 μM, respectively) against HL60 human promyelocytic leukemia cells. Compound IIc and IIl show antiviral activity against wild-type herpes simplex virus (HSV), varicella zoster virus (VZV), and acyclovirresistant HSV; however, these activities were observed at concentrations at which the compounds also markedly inhibit HL60 and HEL cell proliferation. It is interesting to note that preferably compounds with tridentate ligand characteristics (IIl, IIi, and IIc) showed potent anti-proliferative activity against the HL60 cells (Table 3 ). The compounds investigated are known as intermediates in the synthesis of many thiosemicarbazones but their usefulness as medicinally active agents has not yet been studied.
cord-328834-yetnlb2j	2020	Upon in vitro evaluation, compound 10 ( Fig. 3) showed prominent activity (87% growth inhibition) against colon cancer cell line (HCT-116) as compared to fluorouracil (67% inhibition). Derivatives bearing electron withdrawing groups at positions # 5, # 6 and # 7 of chromone scaffold showed better activity. Upon evaluation as anticancer agents by MTT assay, compounds 22 (IC 50 = 1.42 ± 0.13 mM) and 23 (IC 50 = 2.92 ± 0.94 mM) showed prominent in vitro activity versus breast cancer cell line (T47D) as compared to doxorubicin (IC 50 = 0.33 ± 0.05 mM). Incorporation of methyl and ethyl group in the heterocyclic ring showed comparable activity to unsubstituted derivatives [47] . Attachment of methyl group with chromone core also produced less active derivatives [51] . synthesized fluorine-containing chromone and tetrazole hybrid molecules by Ugi-azide reaction [63] These derivatives displayed moderate antimicrobial activity as is evident by compound 51 (MIC = 20 mg/mL) activity versus Pseudomonas aeruginosa (P.
cord-330660-tx20im6w	2020	Molecular docking simulations of the synthesized compounds into leucyl-tRNA synthetase editing domain of Candida albicans suggested that most formazan analogues can fit deeply forming stable complexes in the active site. Inspired by the promising previously reported antimicrobial and antiviral activities of formazans and the urgent need of new effective antimicrobial agent and antiviral drugs to act mainly against COVID-19 and in continuation of our research work in synthesis of bioactive compounds [27] [28] [29] [30] [31] [32] , we synthesized herein a new series of nano-sized formazan analogues to study their potential as antibacterial and antifungal agents in vitro. In this study, molecular docking study of the newly synthesized formazan analogues 3a-f, 5a-h and 7a,b have been performed onto the active site of Candida albicans editing domain of cytosolic leucyl-tRNA synthetase to demonstrate their binding affinity and orientation.
cord-336165-if8uxqha	2020	The definition most used by the experts in this area is the one elaborated by Richards and Raymond (2000) , who define creative tourism as offering tourists the opportunity to develop their creative potential through active participation in courses and learning experiences that are the characteristics of the destination in which they are carried out. Tourism Management Perspectives 36 (2020) 100746 In the early 2000s, Raymond (2003) , based on a case study in New Zealand (Table 1) , presented a proposal to segment and profile creative tourism seekers based on general demographic profiles, proposing three groups: baby-boomers and retired, tourists under 30 (e.g., students and backpackers) and New Zealanders who are interested in learning more about different aspects of the culture of their country. The research presented here segmented the tourists based on their motivation to participate in creative tourism activities and analysed the resulting profiles.
cord-336578-5qzpd890	2020	The increasing incidence, limited efficacy of current treatment options, and significant risk of drug-resistance in NTM infections suggest an urgent need for new antimycobacterial agents. Even though mycolic acids are found in all mycobacterial pathogens and provide similar cellular protection, structural integrity, and virulence, The increasing incidence, limited efficacy of current treatment options, and significant risk of drug-resistance in NTM infections suggest an urgent need for new antimycobacterial agents. Recently developed compounds targeting the MmpL3 transporter, a new and promiscuous target recognizing many structurally unique chemotypes, have proven to be effective in both TB and NTM infections. From the second series, the compound with the highest potency contained a cyclooctyl ring and 4,6-dimethyl indole (1, Table 1 ), having an activity ranging from 0.0039 to 0.6 µg/mL against RGM. From the second series, the compound with the highest potency contained a cyclooctyl ring and 4,6-dimethyl indole (1, Table 1 ), having an activity ranging from 0.0039 to 0.6 µg/mL against RGM.
cord-338727-1kodz527	2014	Many ribonucleases (RNases) are able to inhibit the reproduction of viruses in infected cell cultures and laboratory animals, but the molecular mechanisms of their antiviral activity remain unclear. Therefore, the formation of RNA fragments enhanced by RNase L, followed by their interaction with RIG I and MDA5, activates transcription factor NF κB and triggers transcription of interferon β gene, which prevents virus replication and stimulates the growth of immune system cells [9] . Previously, onconase, an RNases from oocytes of the leopard frog Rana pipiens, efficiently suppresses the replication of HIV 1 due to the selective degrada tion of viral RNA, which exhibits no pronounced cytotoxic effect on infected human cells [22] . At the first stage, when binase meets the virus outside cell, its catalytic activity is not inhibited by the natural RNase and it may destroy viral RNA (Fig. 3, C) . Ribonucleases in HIV type 1 inhibition: Effect of recombinant RNases on infection of primary T cells and immune activation induced RNase gene and protein expression
cord-339227-2i9q9c8u	2010	Pentagalloylglucose [1], 3-galloyl-gallic acid and 4-galloyl-gallic acid isomers isolated from Galla chinensis are reported to be the primary bioactive gallotannins, possessing numerous medicinal activities and health benefi ts Sakai et al., 1990; Bhimani et al., 1993; Feldman et al., 2001; . Two terpene compounds, moronic acid [8] and betulonic acid [9], were separated from Rhus chinensis and their subsequent anti-HSV activities were assessed in vitro and in vivo . (2004) screened 112 Chinese medicinal plants for antioxidant activity; the results showed that the aqueous extract of Galla chinensis contained the highest antioxidant concentration of 17674 μmol TEAC/100 g. (2003) tested the inhibitory effect of an aqueous extract from the gall of Rhus chinensis on α-glucosidase activity in in vitro and in vivo models. Anti-HIV-1 activities of extracts from the medicinal plant Rhus chinensis Anti-HIV-1 activities of compounds isolated from the medicinal plant Rhus chinensis
cord-339716-1khdh9nf	2020	RESULTS: After the implementation of physical distancing measures in NSW, there were significant decreases in physical activity (odds ratio [OR] = .53, 95% confidence interval [CI] = .34–.83), increases in social media and Internet use (OR = 1.86, 95% CI = 1.15–3.00), and increased screen time based on participants'' smartphone screen state. Comparisons of participant characteristics between (1) those who completed baseline and follow-up, (2) those who completed EMAs pre-and post-implementation of the physical distancing policy, and (3) those who provided or did not provide sensor are provided in Supplementary Tables 1 and 2 Descriptive plots of trajectories of physical activity were examined over the 22-week follow period, based on daily pedometer data, MBAR, and weekly self-report EMAs. Trajectories of self-reported fruit, vegetable, and fast food consumption were also examined based on weekly EMAs, as were trajectories of psychological well-being based on distress, well-being, and sleep duration.
cord-340879-gu91cact	2017	title: Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells The intent of the present study was to isolate a trypsin inhibitor from the gold bean and to test it for inhibitory action on tumor cells, viral enzymes, and fungal growth. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. A lectin, an antifungal protein and a trypsin inhibitor can be isolated from the gold bean [24, 25] . A homodimeric sporamin-type trypsin inhibitor with antiproliferative, hiv reverse transcriptase-inhibitory and antifungal activities from wampee (clausena lansium) seeds The isolation of two proteins, glycoprotein i and a trypsin inhibitor, from the seeds of kidney bean (Phaseolus vulgaris)
cord-342634-4ouhdjsr	2010	In brief, the group of proteins with RNA chaperone activity includes proteins that, first, open up misfolded structures without requirement of ATP and that, second, are dispensable once the RNA has been folded. coli showed that 1/3 of the tested proteins possesses strong RNA chaperone activity in vitro in the trans-splicing assay [21] . E. coli contains nine members of the csp family and CspA, the major cold-shock protein and CspE were identified to interact non-specifically with RNA molecules and to possess nucleic acid melting activities [44] [45] [46] . Later, a detailed study on possible functions of Ro RNPs, which are Ro ribonucleoprotein complexes, composed of a small noncoding cytoplasmic RNA, termed Y RNA and its protein partners was conducted: besides the permanently associated proteins Ro60 and La, subpopulations of Ro-RNPs also contain hnRNP I and hnRNP K, both of which exhibited strong RNA chaperone activity in vitro in the transsplicing and the cis-splicing assay [22] .
cord-344902-bittqpyo	2020	title: A systematic review of the physical activity levels of acutely ill older adults in Hospital At Home settings: an under-researched field PURPOSE: The purpose of this review was to identify, evaluate and synthesise existing evidence reporting the physical activity levels of acutely ill older patients in a ''Hospital At Home'' setting and compare this to patients with similar characteristics treated in a traditional hospital inpatient setting. CONCLUSION: There is a lack of published research on the physical activity levels of acutely-ill older adults in Hospital at Home settings. The aim of this review was to identify, evaluate and synthesise the evidence on the physical activity levels of acutely ill older patients undergoing treatment in an HaH vs inpatient setting. This review has provided an indication of the baseline activity levels of inpatients suitable for a Hospital at Home service, however primary objective research is needed in this treatment setting.
cord-345695-5vi9wibk	2020	From these data, we developed site-specific prediction models for bat activity to account for seasonal and annual temperature variation prior to known occurrence of WNS. We propose this model-based method for future monitoring efforts that could be used to trigger targeted sampling of individual bats or hibernacula for WNS, in areas where traditional disease surveillance approaches are logistically difficult to implement or because of human-wildlife transmission concerns from COVID-19. We predicted that bat populations in the western U.S. would have low levels of activity during winter months, high levels of activity during the summer, and that acoustic monitoring could be used as an effective approach for disease surveillance in remote areas of the Intermountain West. The model was fit to data from all 41 sites to estimate among-site and among-year variation in activity, but we use the results to generate prediction intervals for four forest sites to depict how a landowner might implement this approach for WNS surveillance monitoring.
cord-346060-ns6v76rb	2020	After the first 2 weeks of lockdown with limited structure and free reinforcement access, in some of our first cohort families we observed the following during our online meetings: high levels of escape from simple instructions, the loss of independence and communication skills (appropriate mands), satiation (significant reduction in the time children spent with favorite items), an increase in problematic interactions between parents and all children, and unmanageable levels of mands for attention (both appropriate and inappropriate). Although, in general, the daily structure centered on adult-led or shared activities alternated with periods of solitary reinforcement, all parents learned to interact with their children and siblings in a way that worked for them and maintained low rates of problem behavior. We wished to create a mutually reinforcing situation for both the adults and the children, where parents could experience success in delivering instructions and interacting with their child, given that they would need to engage in this behavior daily in a confined space, over extended periods of time without a break.
cord-351932-dn60t7qa	2019	As reported by Jesus et al., 2016 , diosgenin (3-β-hydroxy-5spirostene) is the primary furostanol saponin found in several plants, including Dioscorea species, and is described as a promising bioactive compound with several medicinal properties, i.e. hypolipidemic, antioxidant, anti-inflammatory, hypoglycaemic, and antiproliferative activities (5) . A new furostanol glycoside namely 26-O-β -D-glucopyranosyl-3β,26-dihydroxy-20,22-seco-25(R)-furost-5en-20,22-dione-3-O-α-L-rhamnopyranosyl-(1→4)-α -L-rhamnopyranosyl-(1→4)-[ α -L -r h a m n o p y r a n o s y l -( 1 → 2 ) ] -β -Dglucopyranoside was isolated from the methanolic extract of the rhizome of Dioscorea cayenensis growing in Cameroon, together with the known spirostanol saponins described as methyl protodioscin, asperoside and prosapogenin A of dioscin (12) . Concerning the phytochemical profile, twelve cyclic diarylheptanoids were isolated from the rhizomes of Dioscorea nipponica (20) , among which two new cyclic diarylheptanoids, diosniponol A and B; moreover, as reported by the same authors, these compounds were evaluated for their effects on nitric oxide production without cell toxicity in lipopolysaccharide-activated BV-2 cells.
cord-352668-qjlqsb2k	2020	Sexual activity offers numerous advantages for physical and mental health but maintains inherent risks in a pandemic situation, such as the current one caused by SARS-CoV-2. A group of experts from the Spanish Association of Sexuality and Mental Health (AESexSAME) has reached a consensus on recommendations to maintain lower-risk sexual activity, depending on one''s clinical and partner situations, based on the current knowledge of SARS-CoV-2. In all other cases (for those under quarantine, those with some clinical symptoms, health professionals in contact with COVID-19 patients, and during pregnancy), abstaining from coital/oral/anal sex, substituting it with masturbatory or virtual sexual activity to provide maximum protection from the contagion, and increasing the benefits inherent to sexual activity are recommended. Due to the ease of contagion and the lack of information about the possible transmission of SARS-CoV-2, a group of experts from the Spanish Association for Sexuality and Mental Health, covering the fields of sexology, psychiatry, psychology and medicine reached a consensus.
cord-352844-wggg3ynb	2020	Again, the coumarin derivative showed inhibitory activity on 15-LOX-1 in PC3 and DU145 cell lines, thus inducing apoptosis of the cancer cell, with the same mechanism of The results represent a good starting point for the design of novel derivatives, because most of the examined compounds exhibited selective toxicity on HeLa cells (IC 50 values between 136.4 ± 1.90 µM and 172.2 ± 1.80 µM after 24 h), whereas no negative effects on HDF normal cell''s growth was detected. Since tacrine is a well-known inhibitor of the catalytic site of AChE, whereas coumarins showed affinity for the peripheral anionic site (PAS) [161] , this new compounds may be potential dual-and therefore more powerful -inhibitors of ChEs. The in vitro AChE and BuChE inhibitory activity was evaluated using the Ellman''s method [159] ; among all the tested molecules, compound 105 resulted the best in AChE inhibition (IC 50 Thanks to their simple structural architecture and chemical stability, coumarins can be easily synthesized and modified in order to produce more active and selective compounds.
cord-353815-w35spqqt	2020	This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. Tryptophan (Trp), as a non-polar amino acid, has a remarkable effect on the interface region of the lipid bilayer, whereas Arg, as a basic amino acid, confers peptide charge and hydrogen bond interactions, which are essential properties to combine with the bacterial membrane''s abundant anionic component. And it seems that Trp residues play the role of natural aromatic activators of Arg-rich AMPs by ion-pair-π interactions (Walrant et al., 2020) , thereby promoting enhanced peptide-membrane interactions (Chan et al., 2006) . Furthermore, L4H4, which is designed based on the linear cationic amphiphilic peptide magainin, also shows good antibacterial activity and cell penetration properties by inserting four histidine sequences in leucine and alanine (Lointier et al., 2020) .
cord-354044-3ugc7odq	2020	Therefore, in order to provide relevant information regarding the potential benefits of SLns in preventing Abbreviations: ACE, angiotensin I-converting enzyme; AMPK, activated protein kinase; APOC3, apolipoprotein C3; AT, adipose tissue; CAT, catalase; COX-2, cyclooxygenase 2; CVD, cardiovascular disease; FFA, free fatty acids; FN, fibronectin; G6Pase, glucose-6-phosphatase; GK, glucokinase; GPx, glutathione peroxidase; GSH, reduced glutathione; HDL-C, high-density lipoproteins-cholesterol; IFN-g, interferon gamma; IL-1b, interleukin 1 beta; IL-6, interleukin 6; iNOS, inducible nitric oxide synthase; IR, insulin resistance; JNK, c-Jun N-terminal kinases; LDL-C, low-density lipoprotein-cholesterol; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinases; MCP-1, monocyte chemoattractant protein 1; MetS, metabolic syndrome; NF-kB, nuclear factor kappa B; NO, nitric oxide; ROS, reactive oxygen species; SLns, sesquiterpene lactones; SOD, superoxide dismutase; STAT1, signal transducer and activator of transcription 1; STZ, streptozotocin; T2DM, type 2 diabetes mellitus; TBARS, thiobarbituric acid reactive substances; TC, total cholesterol; TG, triglycerides; TGF-b1, transforming growth factor beta; TLRs, Toll-like receptor; TNF-a, tumor necrosis factor alpha; VLDL, very-low-density lipoprotein and managing MetS, this review addresses plant-derived SLns that are potentially responsible for the positive effect in improving risk factors associated with MetS.
cord-356062-7q5n4t97	2005