Fine‐scale ecological and anthropogenic variables predict the habitat use and detectability of sloth bears in the Churia habitat of east Nepal

Once widespread throughout the tropical forests of the Indian Subcontinent, the sloth bears have suffered a rapid range collapse and local extirpations in the recent decades. A significant portion of their current distribution range is situated outside of the protected areas (PAs). These unprotected sloth bear populations are under tremendous human pressures, but little is known about the patterns and determinants of their occurrence in most of these regions. The situation is more prevalent in Nepal where virtually no systematic information is available for sloth bears living outside of the PAs. We undertook a spatially replicated sign survey‐based single‐season occupancy study intending to overcome this information gap for the sloth bear populations residing in the Trijuga forest of southeast Nepal. Sloth bear sign detection histories and field‐based covariates data were collected between 2 October and 3 December 2020 at the 74 randomly chosen 4‐km² grid cells. From our results, the model‐averaged site use probability (ψ ± SE) was estimated to be 0.432 ± 0.039, which is a 13% increase from the naïve estimate (0.297) not accounting for imperfect detections of sloth bear signs. The presence of termite mound and the distance to the nearest water source were the most important variables affecting the habitat use probability of sloth bears. The average site‐level detectability (p ± SE) of sloth bear signs was estimated to be 0.195 ± 0.003 and was significantly determined by the index of human disturbances. We recommend considering the importance of fine‐scale ecological and anthropogenic factors in predicting the sloth bear‐habitat relationships across their range in the Churia habitat of Nepal, and more specifically in the unprotected areas.     

The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes Is Consistent with Adaptations to the Human Host

Depletion of CpG dinucleotides in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes has been linked to virus evolution, host-switching, virus replication, and innate immune responses. Temporal variations, if any, in the rate of CpG depletion during virus evolution in the host remain poorly understood. Here, we analyzed the CpG content of over 1.4 million full-length SARS-CoV-2 genomes representing over 170 million documented infections during the first 17 months of the pandemic. Our findings suggest that the extent of CpG depletion in SARS-CoV-2 genomes is modest. Interestingly, the rate of CpG depletion is highest during early evolution in humans and it gradually tapers off, almost reaching an equilibrium; this is consistent with adaptations to the human host. Furthermore, within the coding regions, CpG depletion occurs predominantly at codon positions 2-3 and 3-1. Loss of ZAP (Zinc-finger antiviral protein)-binding motifs in SARS-CoV-2 genomes is primarily driven by the loss of the terminal CpG within the motifs. Nonetheless, majority of the CpG depletion in SARS-CoV-2 genomes occurs outside ZAP-binding motifs. SARS-CoV-2 genomes selectively lose CpGs-motifs from a U-rich context; this may help avoid immune recognition by TLR7. SARS-CoV-2 alpha-, beta-, and delta-variants of concern have reduced CpG content compared to sequences from the beginning of the pandemic. In sum, we provide evidence that the rate of CpG depletion in virus genomes is not uniform and it greatly varies over time and during adaptations to the host. This work highlights how temporal variations in selection pressures during virus adaption may impact the rate and the extent of CpG depletion in virus genomes.     

Evidence for photosynthetic independence of viral multiplication in cyanophage LPP-1 infected cyanobacterium Phormidium uncinatum

Abstract Pigment decomposition, oxygen evolution and CO₂ fixation were measured in the cyanobacterium Phormidium uncinatum after infection with cyanophage LPP-1, under light and dark conditions. A gradual decrease in para benzoquinone supported O₂ evolution, chlorophyll a and phycocyanin level were noticed after 6 h of infection. These results demonstrated decreased photosynthetic activity of the host P. uncinatum prior to the start of LPP-1 multiplication. Metabolic inhibitor investigations confirmed that the cyanophage LPP-1 multiplication was independent of host photosynthesis.     

IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate. We first describe the architecture of IQCELL. Next, we apply IQCELL to scRNA-seq datasets from early mouse T-cell and red blood cell development, and show that the platform can infer overall over 74% of causal gene interactions previously reported from decades of research. We will also show that dynamic simulations of the generated GRN qualitatively recapitulate the effects of known gene perturbations. Finally, we implement an IQCELL gene selection pipeline that allows us to identify candidate genes, without prior knowledge. We demonstrate that GRN simulations based on the inferred set yield results similar to the original curated lists. In summary, the IQCELL platform offers a versatile tool to infer, simulate, and study executable GRNs in dynamic biological systems.     

How do plants defend themselves against pathogens-Biochemical mechanisms and genetic interventions

In agro-ecosystem, plant pathogens hamper food quality, crop yield, and global food security. Manipulation of naturally occurring defense mechanisms in host plants is an effective and sustainable approach for plant disease management. Various natural compounds, ranging from cell wall components to metabolic enzymes have been reported to protect plants from infection by pathogens and hence provide specific resistance to hosts against pathogens, termed as induced resistance. It involves various biochemical components, that play an important role in molecular and cellular signaling events occurring either before (elicitation) or after pathogen infection. The induction of reactive oxygen species, activation of defensive machinery of plants comprising of enzymatic and non-enzymatic antioxidative components, secondary metabolites, pathogenesis-related protein expression (e.g. chitinases and glucanases), phytoalexin production, modification in cell wall composition, melatonin production, carotenoids accumulation, and altered activity of polyamines are major induced changes in host plants during pathogen infection. Hence, the altered concentration of biochemical components in host plants restricts disease development. Such biochemical or metabolic markers can be harnessed for the development of “pathogen-proof” plants. Effective utilization of the key metabolites-based metabolic markers can pave the path for candidate gene identification. This present review discusses the valuable information for understanding the biochemical response mechanism of plants to cope with pathogens and genomics-metabolomics-based sustainable development of pathogen proof cultivars along with knowledge gaps and future perspectives to enhance sustainable agricultural production.     

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.     

Selective secretion of protein kinase C isozymes by thrombin-stimulated human platelets

The protein kinase C (PKC) was secreted from thrombin-stimulated human platelets in a time- and dose-dependent manner. The PKC specific inhibitors Ro31-8220 (0.05 microM) and GF 109203X (0.5 microM) totally inhibited the secreted kinase activity. Western blot analysis of the secretory components showed reactivity to PKCalpha, PKCbetaII, and PKCdelta antibodies, but not to PKCbetaI, and p42/44 MAPK, although they were present in lysed platelets. The fractionation of platelets secreted components showed that PKC activity increased in both soluble and microparticle fractions after thrombin treatments. This is the first report demonstrating that activated human platelets selectively secrete protein kinase C isozymes. Protein kinase C secreted by platelets in this unique manner may have an extracellular role in the plasma, and may regulate cellular functions, including remodeling of vascular endothelial cells.     

The murine homolog (Mph) of human herpesvirus entry protein B (HveB) mediates entry of pseudorabies virus but not herpes simplex virus types 1 and 2

A mouse member of the immunoglobulin superfamily, originally designated the murine poliovirus receptor homolog (Mph), was found to be a receptor for the porcine alphaherpesvirus pseudorabies virus (PRV). This mouse protein, designated here murine herpesvirus entry protein B (mHveB), is most similar to one of three related human alphaherpesvirus receptors, the one designated HveB and also known as poliovirus receptor-related protein 2. Hamster cells resistant to PRV entry became susceptible upon expression of a cDNA encoding mHveB. Anti-mHveB antibody and a soluble protein composed of the mHveB ectodomain inhibited mHveB-dependent PRV entry. Expression of mHveB mRNA was detected in a variety of mouse cell lines, but anti-mHveB antibody inhibited PRV infection in only a subset of these cell lines, indicating that mHveB is the principal mediator of PRV entry into some mouse cell types but not others. Coexpression of mHveB with PRV gD, but not herpes simplex virus type 1 (HSV-1) gD, inhibited entry activity, suggesting that PRV gD may interact directly with mHveB as a ligand that can cause interference. By analogy with HSV-1, envelope-associated PRV gD probably also interacts directly with mHveB during viral entry.     

Potential Role of Cerebral Glutathione in the Maintenance of Blood-Brain Barrier Integrity in Rat

Using the model of glutathione (GSH) depletion, possible role of GSH in the maintenance of blood-brain barrier (BBB) integrity was evaluated in rats. Administration (ip) of GSH depletors, diethyl maleate (DEM, 1–4 mmol/kg), phorone (2–3 mmol/kg) and 2-cyclohexene-1-one (CHX, 1 mmol/kg), to male adults was found to deplete brain and liver GSH and increase the BBB permeability to micromolecular tracers (sodium fluorescein and [¹⁴C]sucrose) in a dose-dependent manner at 2h. However, BBB permeability to macromolecular tracers such as horseradish peroxidase and Evan's blue remained unaltered. It was also shown that observed BBB permeability dysfunction was associated with brain GSH depletion. A lower magnitude of BBB increase in rat neonates, as compared to adults, indicated a possible bigger role of GSH in the BBB function of mature brain. The treatment with N-acetylcysteine, methionine and GSH provided a partial to full protection against DEM-induced brain (microvessel) GSH depletion and BBB dysfunction; however, the treatment with -tocopherol, ascorbic acid and turmeric were not effective. Our studies showed that cerebral GSH plays an important role in maintaining the functional BBB integrity.     

Opto-electrical processes in a conducting polymer-bacteriorhodopsin system

In this report, we highlight the opto-electrical processes at a conducting polymer-bacteriorhodopsin (bR) interface in presence of a voltage bias. Oriented bR on a conducting polymer substrate forms a unique hybrid system where the oxidation state of the polymer controls the optically activated proton gradient in the bR side. The internal conversion of the intermediate deprotonated M-state and the proton transfer/transport of bR at the interface can be controlled by the electrostatic environment and leads to interesting device features in this process.