Biology subjects

Pawar, S.

Publications and source records attributed to Pawar, S..

45 records · Page 3Linked to original sources

bioRxiv2020

The effect of resource limitation on the temperature dependence of mosquito population fitness

Laboratory-derived temperature dependencies of life history traits are increasingly being used to make mechanistic predictions for how climatic warming will affect vector-borne disease dynamics, partially by affecting abundance dynamics of the vector population. These temperature-trait relationships are typically estimated from populations reared on optimal resource supply, even though natural populations of vectors are expected to experience variation in resource supply, including intermittent resource limitation. Using laboratory experiments on the mosquito Aedes aegypti, a principal arbovirus vector, combined with stage-structured population modelling, we show that low-resource supply significantly depresses the vectors maximal population growth rate across the entire temperature range (22-32{degrees}C) and causes it to peak at a lower temperature than at high-resource supply. This effect is primarily driven by an increase in juvenile mortality and development time, combined with an exaggerated decrease in adult size with temperature at low-resource supply. Our study suggests that projections of vector abundance and disease transmission based on laboratory studies are likely to substantially underestimate how resource supply can modulate the temperature-dependency of population-level fitness through its influence on juvenile survival and development time. Our results provide compelling evidence for future studies to consider resource supply when predicting the effects of climate and habitat change on disease vectors and transmission.

ecology↗

bioRxiv2020

DNA Encoded Glycan Libraries as a next-generation tool for the study of glycan-protein interactions

Interactions between glycans and glycan-binding proteins (GBPs) mediate diverse cellular functions, and therefore are of diagnostic and therapeutic significance. Current leading strategies for studying glycan-GBP interactions require specialized knowledge and instrumentation. In this study, we report a strategy for studying glycan-GBP interactions that uses PCR, qPCR and next-generation sequencing (NGS) technologies that are more routinely accessible. Our headpiece conjugation-code ligation (HCCL) strategy couples glycans with unique DNA codes that specify glycan sugar moieties and glycosidic linkages when sequenced. We demonstrate the technology by synthesizing a DNA encoded glycan library of 50 biologically relevant glycans (DEGL-50) and probing interactions against 25 target proteins including lectins and antibodies. Data show glycan-GPB interactions in solution that are consistent with lower content, lower throughput ELISA assays. Data further demonstrate how monovalent and multivalent headpieces can be used to increase glycan-GPB interactions and enrich signals while using smaller sample sizes. The flexibility of our modular HCCL strategy has potential for producing large glycan libraries, facilitating high content-high throughput glycan binding studies, and increasing access to lower cost glyco-analyses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/017012v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@fb1c1dorg.highwire.dtl.DTLVardef@1f2c3ceorg.highwire.dtl.DTLVardef@11546e7org.highwire.dtl.DTLVardef@1e21a83_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2019

Therapeutic efficacy of an immune stimulatory gene therapy strategy in a mouse model of high grade brainstem glioma

PurposeDiffuse intrinsic pontine glioma (DIPG) bears a dismal prognosis. A genetically engineered brainstem glioma model harboring the recurrent DIPG mutation, ACVR1-G328V (mACVR1), was developed for testing an immune-stimulatory gene therapy. Experimental DesignWe utilized the Sleeping Beauty transposase system to generate an endogenous mouse model of mACVR1 brainstem glioma. Histology was used to characterize and validate the model. We performed RNAseq analysis on neurospheres (NS) harboring mACVR1. mACVR1 NS were implanted into the pons of immune competent mice to test the therapeutic efficacy and toxicity of immune stimulatory gene therapy using adenoviruses expressing thymidine kinase (TK) and fms-like tyrosine kinase 3 ligand (Flt3L). mACVR1 NS expressing the surrogate tumor antigen ovalbumin were generated to investigate if TK/Flt3L treatment induces the recruitment of tumor-antigen specific T cells. ResultsHistological analysis of mACVR1 tumors indicates that they are localized in the brainstem and have increased downstream signaling of bone morphogenetic pathway as demonstrated by increased phospho-smad1/5 and Id1 levels. Transcriptome analysis of mACVR1 NS identified an increase in the transforming growth factor beta (TGF-{beta}) signaling pathway and the regulation of cell differentiation. Adenoviral delivery of TK/Flt3L in mice bearing brainstem gliomas resulted in anti-tumor immunity, recruitment of anti-tumor specific T cells and increased median survival. ConclusionsThis study provides insights into the phenotype and function of the tumor immune microenvironment in a mouse model of brainstem glioma harboring mACVR1. Immune stimulatory gene therapy targeting the hosts anti-tumor immune response inhibits tumor progression and increases median survival of mice bearing mACVR1 tumors. Translational RelevanceThe therapeutic efficacy of anti-DIPG immune responses is limited due to a low number of immune cells in the tumor microenvironment. We have uncovered a novel treatment strategy that utilizes adenoviral delivery of therapeutic genes, thymidine kinase (TK) and fms tyrosine kinase 3 ligand (Flt3L) into the tumor, eliciting a reprograming of the hosts own immune system to recognize and kill tumor cells. We demonstrate that TK/Flt3L therapy generates an effective anti-tumor response and can be safely delivered into the brainstem. This treatment approach could provide a novel translational approach towards potentiating an anti-DIPG immune response to overcome the current limitations in the treatment of patients with DIPG.

cancer biology↗

bioRxiv2019

Adaptive evolution explains the present-day distribution of the thermal sensitivity of population growth rate

Developing a thorough understanding of how ectotherm physiology adapts to different thermal environments is of crucial importance, especially in the face of global climate change. A key aspect of an organisms thermal performance curve--the relationship between fitness-related trait performance and temperature--is its thermal sensitivity, i.e., the rate at which trait values increase with temperature within its typically-experienced thermal range. For a given trait, the distribution of thermal sensitivities across species, often quantified as "activation energy" values, is typically right-skewed. Currently, the mechanisms that generate this distribution are unclear, with considerable debate about the role of thermodynamic constraints vs adaptive evolution. Here, using a phylogenetic comparative approach, we study the evolution of the thermal sensitivity of population growth rate across phytoplankton (Cyanobacteria and eukaryotic microalgae) and prokaryotes (bacteria and archaea), two microbial groups that play a major role in the global carbon cycle. We find that thermal sensitivity across these groups is moderately phylogenetically heritable, and that its distribution is shaped by repeated evolutionary convergence throughout its parameter space. More precisely, we detect bursts of adaptive evolution in thermal sensitivity, increasing the amount of overlap among its distributions in different clades. We obtain qualitatively similar results from evolutionary analyses of the thermal sensitivities of two physiological rates underlying growth rate: net photosynthesis and respiration of plants. Furthermore, we find that these episodes of evolutionary convergence are consistent with two opposing forces: decrease in thermal sensitivity due to environmental fluctuations and increase due to adaptation to stable environments. Overall, our results indicate that adaptation can lead to large and relatively rapid shifts in thermal sensitivity, especially in microbes where rapid evolution can occur at short time scales. Thus, more attention needs to be paid to elucidating the implications of rapid evolution in organismal thermal sensitivity for ecosystem functioning. Author summaryChanges in environmental temperature influence the performance of biological traits (e.g., respiration rate) in ectotherms, with the relationship between trait performance and temperature (the "thermal performance curve") being single-peaked. Understanding how thermal performance curves adapt to different environments is important for predicting how organisms will be impacted by climate change. One key aspect of the shape of these curves is the thermal sensitivity near temperatures typically experienced by the species. Whether and how thermal sensitivity responds to different environments is a topic of active debate. To shed light on this, here we perform an evolutionary analysis of the thermal sensitivity of three key traits of prokaryotes, phytoplankton, and plants. We show that thermal sensitivity does not evolve in a gradual manner, but can differ considerably even between closely related species. This suggests that thermal sensitivity undergoes rapid adaptive evolution, which is further supported by our finding that thermal sensitivity varies weakly with latitude. We conclude that variation in thermal sensitivity arises partly from adaptation to environmental factors and that this may need to be accounted for in ecophysiological models.

evolutionary biology↗

bioRxiv2019

Metabolic rates of prokaryotic microbes may inevitably rise with global warming

Understanding how the metabolic rates of prokaryotes respond to temperature is fun-damental to our understanding of how ecosystem functioning will be altered by climate change, as these micro-organisms are major contributors to global carbon efflux. Ecological metabolic theory suggests that species living at higher temperatures evolve higher growth rates than those in cooler niches due to thermodynamic constraints. Here, using a global prokaryotic dataset, we find that maximal growth rate at thermal optimum increases with temperature for mesophiles (temperature optima [lsim] 45{degrees}C), but not thermophiles ({gtrsim} 45{degrees}C). Furthermore, short-term (within-day) thermal responses of prokaryotic metabolic rates are typically more sensitive to warming than those of eukaryotes. Given that climatic warming will mostly impact ecosystems in the mesophilic temperature range, we conclude that as microbial communities adapt to higher temperatures, their metabolic rates and therefore, carbon efflux, will inevitably rise. Using a mathematical model, we illustrate the potential global impacts of these findings.

ecology↗

bioRxiv2018

More than a flying syringe: Using functional traits in vector borne disease research

Many important endemic and emerging diseases are vector-borne. The functional traits of vectors affect not just pathogen transmission rates, but also the fitness and population dynamics of these animals themselves. Increasing empirical evidence suggests that vector traits vary significantly at time scales relevant to transmission dynamics. Currently, an understanding of how this variation in key traits impacts transmission is hindered by a lack of both empirical data and theoretical methods for mechanistically incorporating traits into transmission models. Here, we present a framework for incorporating both intrinsic and environment-driven variation in vector traits into empirical and theoretical vector-borne disease research. This framework mechanistically captures the effect of trait variation on vector fitness, the correlation between vector traits, and how these together determine transmission dynamics. We illustrate how trait-based vector-borne disease modelling can make novel predictions, and identify key steps and challenges in the construction, empirical parameterisation and validation of such models, as well as the organization and prioritization of data collection efforts.

ecology↗

bioRxiv2018

Phytoplankton thermal responses adapt in the absence of hard thermodynamic constraints

To better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related traits to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can--at least partly--overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curves of growth rate of phytoplankton--a globally important functional group--, controlling for environmental effects (habitat type and thermal regime). We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of maximum performance with the temperature at which the curve peaks, suggesting a weak "hotter-is-better" constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we find that all aspects of the thermal performance curve evolve along the phylogeny. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.

evolutionary biology↗

bioRxiv2018

Minimum Information for Reusable Arthropod Abundance Data (MIReAAD)

Introduction Introduction Discussion Conclusion References Arthropods play a dominant role in the dynamics of practically all natural and human-modified terrestrial ecosystems1-3, and have significant economic and health effects. For example, certain insects provide significant economic benefits (e.g. pollination) exceeding $57 billion a year to the United States alone4. Meanwhile, invasive insects cost an estimated $70 billion dollars per year globally5 and insect pests may reduce agricultural harvests by up to 16%, with an equal amount of further losses of harvested goods6. Particularly noteworthy is a subset of arthropods that are disease vectors, transmitting pathogens to and between animals as well as plan ...

ecology↗

bioRxiv2017

Metabolic traits predict the effects of warming on phytoplankton competition

Understanding how changes in temperature affect interspecific competition is critical for predicting changes in ecological communities as the climate warms. Here we develop a simple theoretical model that links interspecific differences in metabolic traits, which capture the temperature-dependence of resource acquisition, to the outcome of pairwise competition in phytoplankton. We parameterised our model with metabolic traits derived from six species of freshwater phytoplankton and tested its ability to predict the outcome of competition in all pairwise combinations of the species in a factorial experiment, manipulating temperature and nutrient availability. The model correctly predicted the outcome of competition in 71% of the pairwise experiments. These results demonstrate that metabolic traits play a key role in determining how changes in temperature influence interspecific competition and lay the foundation for developing theory to predict the effects of warming in complex, multi-species communities.

ecology↗