Anticipating Persistent Infection

We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual within a given range. We focus on the role of synchronization in the persistence of contagion. Our key result is that higher degree of synchronization, both globally in the population and locally in the neighborhoods, hinders persistence of infection. Importantly, we find that early short-time asynchrony appears to be a consistent precursor to future persistence of infection, and can potentially provide valuable early warnings for sustained contagion in a population patch. Thus transient synchronization can help anticipate the long-term persistence of infection. Further we demonstrate that when the range of influence of an infected individual is wider, one obtains lower persistent infection. This counter-intuitive observation can also be understood through the relation of synchronization to infection burn-out.Comment: 6 pages, 9 figures, accepted in EPL (March 2018

Drug utilization evaluation of antibiotics in district hospital Rudraprayag

Drug utilization is very important for antibiotics as they are widely used in hospitals and their in appropriate use may lead to resistance. To check this irrational use of antibiotics and promote rational use the present retrospective study was conducted to access drug utilization evaluation of antibiotics in in patient department of District Hospital Rudraprayag for a period of three months. Overall 126 patients records were encountered in the study in which male female ratio .was 1 2. Prominent age range was 21-40. Overall 1064 drugs were prescribed average number of drug per prescription was 8.44. Percentage of drug by generic name was 33. Percentage of antibiotic prescribed was 82.74. Percentage of drugs with EDL was 66.16. Study results revealed poly-pharmacy, brand prescribing as common trends. Study showed need to promote prescribers to follow generic prescribing and use injectable and antibiotics rationally to prevent development of resistance in hospital and community. Keywords: Antibiotic resistance, Drug utilization, Antibiotic

Instance-Level Semantic Maps for Vision Language Navigation

Humans have a natural ability to perform semantic associations with the surrounding objects in the environment. This allows them to create a mental map of the environment which helps them to navigate on-demand when given a linguistic instruction. A natural goal in Vision Language Navigation (VLN) research is to impart autonomous agents with similar capabilities. Recently introduced VL Maps \cite{huang23vlmaps} take a step towards this goal by creating a semantic spatial map representation of the environment without any labelled data. However, their representations are limited for practical applicability as they do not distinguish between different instances of the same object. In this work, we address this limitation by integrating instance-level information into spatial map representation using a community detection algorithm and by utilizing word ontology learned by large language models (LLMs) to perform open-set semantic associations in the mapping representation. The resulting map representation improves the navigation performance by two-fold (233\%) on realistic language commands with instance-specific descriptions compared to VL Maps. We validate the practicality and effectiveness of our approach through extensive qualitative and quantitative experiments

An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation

Protein Arginine Methyltransferases: Catalytic Mechanisms and Crosstalk in Epigenetics

Over the last decade, protein arginine methyltransferases (PRMTs) have emerged as key regulators in epigenetic processes and have been shown to be crucial targets for drug therapies in various types of cancers. As drug-development is progressing, however, it is vital to understand the biochemical nature of these enzymes and what makes them different from other posttranslational modifiers in the epigenetic landscape. To that end, the studies conducted in this work provide novel insights into how PRMTs specify the products they make, how one of the mammalian PRMTs—PRMT7—exhibits a peculiar preference for sub-physiological temperatures, and the first evidence of positive cooperativity observed in PRMTs and potential crosstalk among them. Specifically, a model has been developed which describes the unique aspects of PRMT active sites in way that highlights the role of sterics and overall volume differences between the different types of PRMTs and allows them to produce different methylarginine derivates. Secondly, biophysical techniques in this work show that human PRMT7 preference for colder, sub-physiological temperatures may be caused due to incredibly minute structural changes that need to be more finely measured in vivo and replicated in vitro. Finally, as the field of epigenetic research expanded and the general knowledge of enzymes in this area has grown, more and more evidence for the regulation of these regulators in the way of enzyme crosstalk has been documented. In the case of PRMTs, however, this work shows for the first time that both PRMT1 and PRMT5 display positive cooperativity when methylating histone H4 N-terminal peptides; furthermore, PRMT5’s ability to methylate histone H4 R3 seems to be greatly affected by a prior methylation of H4 R17—a modification carried out by PRMT7

PRMT7 as a unique member of the protein arginine methyltransferase family: A review

Protein arginine methyltransferases (PRMTs) are found in a wide variety of eukaryotic organisms and can regulate gene expression, DNA repair, RNA splicing, and stem cell biology. In mammalian cells, nine genes encode a family of sequence-related enzymes; six of these PRMTs catalyze the formation of ω-asymmetric dimethyl derivatives, two catalyze ω-symmetric dimethyl derivatives, and only one (PRMT7) solely catalyzes ω-monomethylarginine formation. Purified recombinant PRMT7 displays a number of unique enzymatic properties including a substrate preference for arginine residues in R-X-R motifs with additional flanking basic amino acid residues and a temperature optimum well below 37 °C. Evidence has been presented for crosstalk between PRMT7 and PRMT5, where methylation of a histone H4 peptide at R17, a PRMT7 substrate, may activate PRMT5 for methylation of R3. Defects in muscle stem cells (satellite cells) and immune cells are found in mouse Prmt7 homozygous knockouts, while humans lacking PRMT7 are characterized by significant intellectual developmental delays, hypotonia, and facial dysmorphisms. The overexpression of the PRMT7 gene has been correlated with cancer metastasis in humans. Current research challenges include identifying cellular factors that control PRMT7 expression and activity, identifying the physiological substrates of PRMT7, and determining the effect of methylation on these substrates