An annotated checklist of Culicoides Latreille, 1809 (Insecta: Ceratopogonidae: Diptera) with incorporation of a vector species list from India

Culicoides Latreille, 1809 (Insecta : Diptera : Ceratopogonidae) are small nematocerous biological vectors of a wide range of pathogens of veterinary and medical importance. They are distributed worldwide but prefer warm, damp, and muddy areas. Female midges require blood for egg maturation. Studies on taxonomy, proper identification keys, and distribution patterns of these flies across different geographical regions of India of these flies are limited. This article provides an updated checklist of Culicoides spp. from India collected from various scattered publications, along with their synonyms and details on their subgenera, geographical distribution, and type locality. A compiled list of different Culicoides vectors from India has also been included separately in this article, along with the type of the diseases spread.     

Chemical constituents and energy content of two milkweeds,Asclepias speciosa andA. curassavica

Asclepias speciosa and A. curassavica were evaluated as potential renewable sources of chemicals for use as fuel and/or chemical feedstock. Leaves and stems of both plants were analyzed for acid-detergent fiber, acid-detergent lignin, cellulose and ash. Bomb calorimetry was performed onA. curassavica (leaves 4,590 cal/g; stems 4,219 cal/g; and latex 4,663 cal/g), andA. speciosa (leaves 4,404 cal/g; stems 4,514 cal/g; and latex 9,005 cal/g). Organic carbon inA. curassavica (leaves 41.20%; stems 41.18%; latex 48.03%) andA. speciosa (stems 45.71%; leaves 42.51%; latex 67.30%) were also determined. Major differences between the 2 plant species were in the chemical composition of the latex; A. speciosa latex contained primarily α- and β-amyrin and their acetates, and a small amount of rubber, whileA. curassavica latex is known to contain at least 50% cardiac glycoside.     

Genome-Wide DNA Methylation Profiles Indicate CD8+ T Cell Hypermethylation in Multiple Sclerosis

Objective

Determine whether MS-specific DNA methylation profiles can be identified in whole blood or purified immune cells from untreated MS patients.

Methods

Whole blood, CD4+ and CD8+ T cell DNA from 16 female, treatment naïve MS patients and 14 matched controls was profiled using the HumanMethylation450K BeadChip. Genotype data were used to assess genetic homogeneity of our sample and to exclude potential SNP-induced DNA methylation measurement errors.

Results

As expected, significant differences between CD4+ T cells, CD8+ T cells and whole blood DNA methylation profiles were observed, regardless of disease status. Strong evidence for hypermethylation of CD8+ T cell, but not CD4+ T cell or whole blood DNA in MS patients compared to controls was observed. Genome-wide significant individual CpG-site DNA methylation differences were not identified. Furthermore, significant differences in gene DNA methylation of 148 established MS-associated risk genes were not observed.

Conclusion

While genome-wide significant DNA methylation differences were not detected for individual CpG-sites, strong evidence for DNA hypermethylation of CD8+ T cells for MS patients was observed, indicating a role for DNA methylation in MS. Further, our results suggest that large DNA methylation differences for CpG-sites tested here do not contribute to MS susceptibility. In particular, large DNA methylation differences for CpG-sites within 148 established MS candidate genes tested in our study cannot explain missing heritability. Larger studies of homogenous MS patients and matched controls are warranted to further elucidate the impact of CD8+ T cell and more subtle DNA methylation changes in MS development and pathogenesis.     

Broad-range Glycosidase Activity Profiling

Plants produce hundreds of glycosidases. Despite their importance in cell wall (re)modeling, protein and lipid modification, and metabolite conversion, very little is known of this large class of glycolytic enzymes, partly because of their post-translational regulation and their elusive substrates. Here, we applied activity-based glycosidase profiling using cell-permeable small molecular probes that react covalently with the active site nucleophile of retaining glycosidases in an activity-dependent manner. Using mass spectrometry we detected the active state of dozens of myrosinases, glucosidases, xylosidases, and galactosidases representing seven different retaining glycosidase families. The method is simple and applicable for different organs and different plant species, in living cells and in subproteomes. We display the active state of previously uncharacterized glycosidases, one of which was encoded by a previously declared pseudogene. Interestingly, glycosidase activity profiling also revealed the active state of a diverse range of putative xylosidases, galactosidases, glucanases, and heparanase in the cell wall of Nicotiana benthamiana. Our data illustrate that this powerful approach displays a new and important layer of functional proteomic information on the active state of glycosidases.Carbohydrates are present in all kingdoms of life and are particularly prominent in plants (1). Plants produce carbohydrates as one of their major constituents through their photosynthetic activity. The simplest synthesized forms of carbohydrates are monosaccharide sugars such as glucose, which provides energy for various cellular activities. Carbohydrates also exist in very complex forms. Monosaccharide sugars are attached to one another through covalent glycosidic linkage, which generates di-, oligo-, and polysaccharides. Carbohydrates also attach to non-carbohydrate species (lipids, proteins, hormones) through a glycosidic linkage to form glycoconjugates (2).Glycosidic bonds are hydrolyzed by a group of enzymes termed glycosyl hydrolases (GHs)¹ or glycosidases (3). Because of the tremendous carbohydrate diversity, there are a vast variety of glycosidases, including glucosidases, xylosidases, and galactosidases, that preferentially hydrolyze their respective glycoside substrates. In general, the number of glycosidase-related genes in plants (for instance, Arabidopsis) is relatively high when compared with that in other sequenced organisms (for instance, human) (4). This signifies the unique importance of glycosidases in plants as opposed to other organisms. Based on protein sequence similarities, glycosidases are classified into different GH families. Members of the same GH family share a common mechanism of glycosidic bond cleavage (5).Mechanistically, glycosidases are classified as retaining or inverting enzymes (6). To hydrolyze the glycosidic bond, both retaining and inverting enzymes carry two catalytic glutamate or aspartate residues (or both) (7). Of these two catalytic residues, one acts as a proton donor and the other as a nucleophile/base. The distance between these catalytic residues in the active site of the glycosidases determines the mechanism of hydrolysis. Retaining enzymes have two catalytic residues separated by a distance of ∼5.5 Å, and their hydrolysis mechanism retains the net anomeric configuration of the C1 atom in the sugar molecule. In contrast, inverting enzymes have catalytic residues that are ∼10 Å apart, and these enzymes invert the overall anomeric configuration of the C1 carbon atom in the released sugar (8).Both retaining and inverting glycosidases are present abundantly in plants. The genome of Arabidopsis thaliana encodes for 400 glycosidases, of which 260 are retaining enzymes and 140 are inverting enzymes. Genetic, molecular, and biochemical approaches revealed that glycosidases are localized in different cellular compartments and are important for various biological processes. The majority of plant glycosidases reside in the cell wall, and these enzymes can play major roles in cell wall restructuring (9). Other characterized glycosidases reside in other compartments to regulate glycosylation of proteins and hormones. Despite the importance of GH enzymes, physiological and biochemical functions are assigned to only a few glycosidases (9).Activity-based protein profiling (ABPP) is a powerful tool for monitoring the active state of multiple enzymes without knowledge of their natural substrates (10, 11). ABPP involves chemical probes that react with active site residues in an activity-dependent manner. Thus ABPP displays the availability and reactivity of active site residues in proteins, which are hallmarks for enzyme activity (12). ABPP is particularly attractive because the profiling can be done without purifying the enzymes and can be performed in cell extracts or in living cells. Another key advantage of ABPP is that the activities of large multigene enzyme families can be monitored using broad-range probes. ABPP has had a significant impact on plant science. After the introduction of probes for papain-like cysteine proteases (13, 14), these probes revealed increased protease activities in the tomato and maize apoplasts during immune responses (15, 16) and that these immune proteases are targeted by unrelated inhibitors secreted by fungi, oomycetes, and nematodes (17–24). Likewise, probes for the proteasome displayed unexpected increased proteasome activity during immune responses (25) and revealed that the bacterial effector molecule syringolin A targets the nuclear proteasome (26). We anticipate that more regulatory mechanisms will be discovered through the use of probes introduced for serine hydrolases, metalloproteases, vacuolar processing enzymes, ATP binding proteins, and glutathione transferases (27–32).Cyclophellitol-aziridine-based probes were previously used in animal proteomes to target retaining glucosidases (33). Here we established and applied glycosidase profiling in plants. We discovered that cyclophellitol-aziridine-based probes targeted an unexpectedly broad range of glycosidases representing members of at least seven different GH families. We used these probes to study the active state of glycosidases present in living cells, in different organs and plant species, and in the apoplast of Nicotiana benthamiana.     

Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion

Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P < 0.001) but not cross trainers (to 5.3 ± 0.6%; P = NS) after acute hypertension. FMD was decreased in SED (to 5.7 ± 0.4%; P = 0.019). Dilation to nitroglycerin was similar among groups. These data suggest that endothelial responses are maintained after exposure to a single bout of weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.     

Antipyretic activity of Caesalpinia digyna (Rottl.) leaves extract along with phytoconstituent’s binding affinity to COX-1, COX-2, and mPGES-1 receptors: In vivo and in silico approaches

Caesalpinia digyna (Rottl.) (Family: Fabaceae) is well known for its numerous medicinal values against several human disorders including fever, senile pruritis, diarrhea, tuberculosis, tonic disorder, diabetes, etc. The current study is intended to investigate the in vivo antipyretic activity of the methanol extract of C. digyna leaves (MECD) and its carbon-tetrachloride (CTCD) and butanol fraction (BTCD). Besides, in silico molecular docking and ADME/T profiling of the selective identified bioactive compounds of C. digyna has been also studied to validate the experimental outcomes and establish a better insight into the possible receptor-ligand interaction affinity. In vivo antipyretic activity of MECD, CTCD and BTCD were evaluated by employing yeast induced pyrexia technique in mice model and in silico analysis of the identified compounds of C. digyna has been implemented using PyRx autodock vina, Discovery Studio 2020, UCSF Chimera software and ADME/T online tools. MECD and BTCD unveiled significant antipyretic activity in dose dependent manner whereas, CTCD failed to exhibit significant antipyretic activity. Comparing to other test sample, MECD (400 mg/kg; b.w) (p < 0.001) displayed maximum inhibition of pyrexia. In molecular docking approach, docking score between −6.60 to −10.20 kcal/mol have been revealed. Besides, in ADME/T analysis, no compound violated the lipiniski’s 5 rules and displayed any toxicity. Biological and computational approaches ascertain the ethno-botanical use of C. digyna as a good agent against pyrexia and the compounds of C. digyna are primarily proved as safe. Hereafter, further analysis is suggested to validate this research.     

Subunit‐selective proteasome activity profiling uncovers uncoupled proteasome subunit activities during bacterial infections

The proteasome is a nuclear‐cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions, but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit‐selective inhibitors and dual‐color fluorescent activity‐based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant–microbe interactions. Our data reveal that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both β1 and β5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1‐1 [PtoDC3000(ΔhQ)] whilst the activity profile of the β1 subunit changes. Infection with wild‐type PtoDC3000 causes proteasome activities that range from strongly induced β1 and β5 activities to strongly suppressed β5 activities, revealing that β1 and β5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community, and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species.     

Biological and computational studies provide insights into Caesalphinia digyna Rottler stems

Caesalpinia digyna (Rottl.) (Family: Fabaceae) is an essential medicinal plant for it's conventional uses against a kind of human disorders. This research aims to investigate the antidiarrheal, antibacterial and antifungal properties of the methanol extract of the stems extracts of the C. digyna (MECD). The in vivo antidiarrheal activity of the stem extracts were evaluated by using castor oil-induced diarrhea, castor oil-induced enteropooling and charcoal induced intestinal transit in mice model. Besides, in vitro antimicrobial potentiality of MECD was investigated by the disc diffusion method. In silico activity of the isolated compounds were performed by Schrödinger-Maestro (Version 11.1) software. In addition, The ADME/T analysis and PASS prediction were implemented by using pass online tools. In the antidiarrheal investigation, the MECD exhibited a notable inhibition rate in all test approaches which were statistically significant (p < 0.05, p < 0.1, p < 0.01). MECD 400 mg/kg showed the maximum antidiarrheal potency in all the test methods. In vitro antimicrobial analysis unveiled that, MECD revealed higher potentiality against almost all pathogens and indicates dose-dependent activity against almost all the bacteria and fungi. In the case of in silico evaluation of anti-diarrheal, anti-bacterial and anti-fungal activity, all three isolated compounds met the pre-conditions of Lipinski's five rules for drug discovery. Pass predicted study also employed for all compounds. However, The chemical constituents of the C. digyna can be a potent source of anti-diarrheal, anti-bacterial and anti-fungal medicine and further modification and simulation studies are required to establish the effectiveness of bioactive compounds.     

Chronic Administration of Thymoquinone Enhances Adult Hippocampal Neurogenesis and Improves Memory in Rats Via Regulating the BDNF Signaling Pathway

Neurochemical Research - Thymoquinone is a pharmacologically active component of Nigella sativa Linn. seeds. Despite the diverse neuropharmacological attributes of TQ, limited reports related to...