Biology subjects

Paul, M.

Publications and source records attributed to Paul, M..

43 records · Page 3Linked to original sources

bioRxiv2020

Altered food habits? Understanding the feeding preference of free-ranging Grey langur (Semnopithecus entellus) within an urban settlement.

Urbanization affects concurrent human-animal movements as a result of altered resource availability and land use pattern, which leads to considerable ecological consequences. While some animals find themselves adrift, homeless with the uncertainty of resources resulting from the urban encroachment, few of them manage to survive by altering their natural behavioural patterns, and co-exist with humans. Folivorous colobines, such as grey langur, whose feeding repertoire largely consists of plant parts, tend to be more attuned to the urban high-calorie food sources to attain maximum fitness benefits within the concrete jungle having an insignificant green cover. However, such a mismatch between their generalized feeding behaviour and specialized gut physiology reminds us of the Liems paradox and demands considerable scientific attention which could tell us the story behind colobines successful co-existence within human settlements. Besides understanding their population dynamics, the effective management of these urbanized, free-ranging, non-human primate populations also depends on their altered feeding preferences, altogether which could lead us to the development of an ecologically sound urban ecosystem. Here, we have used a field-based experimental set up which allows langurs to choose between natural and urban food options, being independent of any inter-specific conflicts over resources due to food scarcity. The multinomial logit model reveals the choice-based decision making of these free-ranging grey langurs in an urban settlement of West Bengal, India, where they have not only learned to approach the human-provisioned urban food items but also shown a keen interest in it. While urbanization imposes tremendous survival challenges to these animals, it also opens up for various alternative options for human-animal co-existence which is reflected in this study, and could guide us for the establishment of a sustainable urban ecosystem in the future. HIGHLIGHTSO_LIThe feeding repertoire of free-ranging grey langurs at Dakshineswar largely consists of urban food items in contrast to the langurs of Nangi, and Nalpur who mostly depend on natural food sources. C_LIO_LIHigh human-langur interactions together with the scarcity of natural plant-based food sources could be considered as an intriguing driving force behind langurs altered feeding habits in Dakhineswar. C_LIO_LIThe field-based experimental set up allows free-ranging langurs to choose between natural and urban food options in an urban settlement like Dakhineswar. C_LIO_LIUrban food items outperformed natural food items as the most chosen one, indicating langurs altered feeding preferences which facilitate their successful co-existence within an urban ecosystem. C_LI

animal behavior and cognition↗

bioRxiv2020

Gradual development of non-adjacent dependency learning during early childhood

In order to become proficient native speakers, children have to learn the morpho-syntactic relations between distant elements in a sentence, so-called non-adjacent dependencies (NADs). Previous research suggests that NAD learning in children comprises different developmental stages, where until 2 years of age children are able to learn NADs associatively under passive listening conditions, while starting around the age of 3 to 4 years children fail to learn NADs during passive listening. To test whether the transition between these developmental stages occurs gradually, we tested childrens NAD learning in a foreign language using event-related potentials (ERPs). We found ERP evidence of NAD learning across the ages of 1, 2 and 3 years. The amplitude of the ERP effect indexing NAD learning, however, decreased with age. These findings might indicate a gradual transition in childrens ability to learn NADs associatively. Cognitively, this transition might be driven by childrens increasing knowledge of their native language, hindering NAD learning in novel contexts. Neuroanatomically, maturation of the prefrontal cortex might play a crucial role, promoting top-down learning, affecting bottom-up, associative learning. In sum, our study suggests that NAD learning under passive listening conditions undergoes a gradual transition between different developmental stages during early childhood. Research HighlightsO_LITransition between developmental stages of non-adjacent dependency (NAD) learning C_LIO_LIChildren between 1 and 3 years of age showed learning of NADs in a foreign language C_LIO_LIBrain responses revealed associative NAD learning, triggered by passive listening C_LIO_LIGradual decrease of the strength of associative non-adjacent dependency learning C_LI

neuroscience↗

bioRxiv2020

A histone-like motif in yellow fever virus contributes to viral replication

The mimicry of host proteins by viruses contributes to their ability to suppress antiviral immunity and hijack host biosynthetic machinery1. Host adaptation to evade this exploitation depends on host protein functional redundancy2. Non-redundant, essential host proteins have limited potential to adapt without severe consequences3. Histones, which are essential for genome architecture and control of gene expression, are among the most evolutionary conserved proteins4. Here we show that the capsid protein of the flavivirus yellow fever virus (YFV), mimics histone H4 and interferes with chromatin gene regulation by BRD4, a bromodomain and extraterminal domain (BET) protein. Two acetyl-lysine residues of YFV capsid are embedded in a histone-like motif that interacts with the BRD4 bromodomain, affecting gene expression and influencing YFV replication. These findings reveal histone mimicry as a strategy employed by an RNA virus that replicates in the cytosol5 and define convergent and distinct molecular determinants for motif recognition of the viral mimic versus histone H4.

microbiology↗

bioRxiv2020

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden

Despite recent advances in lung cancer immunotherapy, a major obstacle to the progress in the field is the lack of preclinical models that recapitulate the genetic and immunologic complexity of human disease. Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor the common oncogenic mutations of the disease, but these models possess low tumor mutational burden (TMB), which limits their utility in immunotherapy studies. Here, we establish novel Kras-mutant murine models of NSCLC bearing common genetic alterations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K), KrasG12DTp53-/- (KP), KrasG12DTp53+/-Lkb1-/- (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU). Increased TMB was associated with enhanced anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models, across all genetic backgrounds. However, anti-PD-1 efficacy was comparatively modest in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This phenotype is consistent with findings in human NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novel Kras-mutant murine NSCLC models bearing common co-occurring mutations with increased TMB possess clinically relevant TMEs and recapitulate the genetic complexity and therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of novel immunotherapies in NSCLC.

cell biology↗

bioRxiv2020

Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase

The recombinase RAD51, and its meiosis-specific paralog DMC1 localize at DNA double-strand break (DSB) repair sites in meiotic prophase nuclei. While both proteins are required during meiotic homologous recombination, their spatial organization during meiotic DSB repair is not fully understood. Using super-resolution microscopy on mouse spermatocyte nuclei, we aimed to define their relative position at DSB foci, and how these vary in time. We show that a large fraction of meiotic DSB repair foci (38%) contained a single RAD51 cluster and a single DMC1 cluster (D1R1 configuration) that were partially overlapping (average center-center distance around 70 nm). The majority of the rest of the foci had a similar combination of a major RAD51 and DMC1 cluster, but in combination with additional clusters (D2R1, D1R2, D2R2, or DxRy configuration) at an average distance of around 250 nm. As prophase progressed, less D1R1 and more D2R1 foci were observed, where the RAD51 cluster in the D2R1 foci elongated and gradually oriented towards the distant DMC1 cluster. This correlated with more frequently observed RAD51 bridges between the two DMC1 clusters. D1R2 foci frequency was more constant, and the single DMC1 cluster did not elongate, but was observed more frequently in between the two RAD51 clusters in early stages. D2R2 foci were rare (<10%) and nearest neighbour analyses also did not reveal pair formation between D1R1 foci. In the absence of the transverse filament of the synaptonemal complex (connecting the chromosomal axes of homologs), early configurations were more prominent, and RAD51 elongation occurred only transiently. This in-depth analysis of single cell landscapes of RAD51 and DMC1 accumulation patterns at DSB repair sites at super-resolution thus revealed the variability of foci composition, and defined functional consensus configurations that change over time. AUTHOR SUMMARYMeiosis is a specific type of cell division that is central to sperm and egg formation in sexual reproduction. It forms cells with a single copy of each chromosome, instead of the two copies that are normally present. In meiotic prophase, homologous chromosomes must connect to each other, to be correctly distributed between the daughter cells. This involves the formation and repair of double-strand breaks in the DNA. Here we used super-resolution microscopy to elucidate the localization patterns of two important DNA repair proteins: RAD51 and DMC1. We found that repair sites most often contain a single large cluster of both proteins, with or without one additional smaller cluster of either protein. RAD51 protein clusters displayed lengthening as meiotic prophase progressed. When chromosome pairing was disturbed, we observed changes in the dynamics of protein accumulation patterns, indicating that they actually correspond to certain repair intermediates changing in relative frequency of occurrence. These analyses of single meiotic DNA repair foci reveal the biological variability in protein accumulation patterns, and the localization of RAD51 and DMC1 relative to each other, thereby contributing to our understanding of the molecular basis of meiotic homologous recombination.

developmental biology↗

bioRxiv2019

Seven-year-olds’ recollection of non-adjacent dependencies after overnight retention

Becoming a successful speaker depends on acquiring and learning grammatical dependencies between neighboring and non-neighboring linguistic elements (non-adjacent dependencies; NADs). Previous studies have demonstrated childrens and adults ability to distinguish NADs from NAD violations right after familiarization. However, demonstrating NAD recall after retention is crucial to demonstrate a lasting effect of NAD learning. We tested 7-year-olds NAD learning in a natural, non-native language on one day and NAD recall on the next day by means of event-related potentials (ERPs). Our results revealed ERPs with a more positive amplitude to NAD violations than correct NADs after familiarization on day one, but ERPs with a more negative amplitude to NAD violations on day two. This change from more positive to more negative ERPs to NAD violations possibly indicates that childrens representations of NADs changed during an overnight retention period, potentially associated with childrens NAD learning. Indeed, our descriptive analyses showed that both ERP patterns (i.e., day one: positive, day two: negative) were related to stronger behavioral improvement (i.e., more correct answers on day two compared to day one) in a grammaticality judgment task from day one to day two. We suggest these findings to indicate that children successfully built associative representations of NADs on day one and then strengthened these associations during overnight retention, revealing NAD recall on day two. The present results suggest that 7-year-olds readily track NADs in a natural, non-native language and are able to recall NADs after a retention period involving sleep, providing evidence of a lasting effect of NAD learning. HighlightsO_LI7-year-olds non-adjacent dependency learning in a foreign language tested C_LIO_LIChildren gave grammaticality judgments while electroencephalography was recorded C_LIO_LIBrain responses revealed childrens learning of non-adjacent dependencies C_LIO_LIBrain responses after overnight retention showed different polarity C_LIO_LIChildrens recall of dependencies after sleep associated with representation change C_LI

neuroscience↗

bioRxiv2018

A New Family of Similarity Measures for Scoring Confidence of Protein Interactions using Gene Ontology

The large-scale protein-protein interaction (PPI) data has the potential to play a significant role in the endeavor of understanding cellular processes. However, the presence of a considerable fraction of false positives is a bottleneck in realizing this potential. There have been continuous efforts to utilize complementary resources for scoring confidence of PPIs in a manner that false positive interactions get a low confidence score. Gene Ontology (GO), a taxonomy of biological terms to represent the properties of gene products and their relations, has been widely used for this purpose. We utilize GO to introduce a new set of specificity measures: Relative Depth Specificity (RDS), Relative Node-based Specificity (RNS), and Relative Edge-based Specificity (RES), leading to a new family of similarity measures. We use these similarity measures to obtain a confidence score for each PPI. We evaluate the new measures using four different benchmarks. We show that all the three measures are quite effective. Notably, RNS and RES more effectively distinguish true PPIs from false positives than the existing alternatives. RES also shows a robust set-discriminating power and can be useful for protein functional clustering as well.

bioinformatics↗