Biology subjects

Watve, M.

Publications and source records attributed to Watve, M..

10 recordsLinked to original sources

bioRxiv2022

Evolution of new variants of SARS-COV-2 during the pandemic: mutation limited or selection limited?

The recent pandemic caused by SARS-Cov-2 has witnessed an evolving succession of variants of the virus. While the phenomenon of invasion by immunity evading variants is known for other viruses such as influenza, the dynamics of the ecological and evolutionary process in the succession is little known. Since during the Covid-19 pandemic, large scale epidemiological data were collected and made available in the public domain, it is possible to seek answers to a number of evolutionary questions, which will also have public health implications. We list multiple alternative hypotheses about the origin and invasion of the variants and evaluate them in the light of epidemiological data. Our analysis shows that invasion by novel variants is selection limited and not mutation limited. Further novel variants are not the necessary and sufficient causes of the repeated waves during the pandemic. Rather there is substantial overlap between the conditions leading to a wave and those favoring selection of a partial immune evading variant. This is likely to lead to an association between invasion by new variant and the rise of a new wave. But the association is not sufficiently strong and does not support a causal role of the new variant. The dynamics of interaction between epidemiological processes and selection on viral variants have many public health implications that can guide future policies for effective control of infectious epidemics.

evolutionary biology↗

bioRxiv2022

Hyperglycemia in type 2 diabetes: physiological and clinical implications of a brain centered model.

Classically type 2 diabetes is believed to be a result of insulin resistance and relative insulin deficiency. However, evidences have been accumulating against the insulin resistance centered models. Absence of fasting hyperglycemia by insulin receptor knockouts or insulin suppression, evidence for hyperinsulinemia preceding insulin resistance, the perplexing hyperinsulinemic normoglycemic state, reduced glucose transport to the brain preceding hyperglycemia, signs of vasculopathy preceding hyperglycemia, absent or poor correlation between fasting glucose and insulin, very strong positive correlation between indices of insulin resistance and {beta} cell function in population data are some of the anomalous findings which glucose homeostasis models have not addressed so far. With increasing evidence for neuronal involvement in glucose regulation, we propose a refined model of glucose regulation that considers brain glucose and insulin levels as the ultimate target of homeostasis and combines central and peripheral mechanisms of regulation. A model considering reduced rate of blood to brain transportation of glucose and insulin as primary pathology explains most of the patterns, with or without insulin resistance. Apart from resolving multiple anomalies the model also accounts for the limited and inconsistent success of glucose normalization in effectively reducing diabetic complications and mortality.

physiology↗

bioRxiv2020

The ratio versus difference optimization and its implications for optimality theory

Among the classical models of optimization, some models maximize the ratio of returns per investment, others maximize the difference between returns and investment. However, the question under what conditions use of the ratio model is appropriate and under what conditions a difference model should be used remained unaddressed until recently. The question is important because the strategies indicated by ratio optimum can be substantially different than the ones suggested by difference optimum. We make a general case here for the set of conditions for appropriate use of ratio versus difference optimum. When the investable amount is perceived as limiting but not the investment opportunities a ratio optimum is appropriate and when the investment opportunities are perceived to be limiting but not the investable amount, difference optimum is appropriate. Taking examples of Concorde fallacy, parental investment, r and K selection, nectar production, pollinator behavior, protein synthesis and stability, viral burst size and human economic behavior we show that the ratiodifference distinction in optimization models resolves many long standing debates and conundrums in evolution, behavior and economics.

evolutionary biology↗

bioRxiv2020

Phylogenetic diversity and activity screening of cultivable actinobacteria isolated from marine sponges and associated environments from the western coast of India

Phylogenetic diversity of cultivable actinobacteria isolated from sponges (Haliclona spp.) and associated environments of intertidal zones, along the northern parts of west coast of India, were studied using 16S rRNA gene sequences. A subset of actinobacteria were screened for three activities, namely predatory behavior, antibacterial activity and enzyme inhibition. We recovered 237 isolates of actinobacteria belonging to 19 families and 28 genera, which could be attributed to 95 putative species using maximum likelihood partition and 100 putative species using Bayesian partition in Poisson Tree Processes. Although the trends in the discovery of actinobacterial genera isolated from sponges was consistent with previous studies from different study areas, we provide first report of nine actinobacterial species from sponges. We observed widespread non-obligate epibiotic predatory behavior in eight actinobacterial genera and we provide first report of predatory activity in Brevibacterium, Glutamicibacter, Micromonospora, Nocardiopsis, Rhodococcus and Rothia. Sponge associated actinobacteria showed significantly more predatory behavior than environmental isolates. While antibacterial activity by actinobacterial isolates mainly affected Gram-positive target bacteria with little to no effect on Gram-negative bacteria, predation targeted both Gram-positive and Gram-negative prey with equal propensity. Actinobacterial isolates from both sponge and associated environment produced inhibitors of serine proteases and angiotensin converting enzyme. Predatory behavior was strongly associated with inhibition of trypsin and chymotrypsin. Our study suggests that sponge and associated environment of western coast of India are rich in actinobacterial diversity with widespread predatory activity, antibacterial activity and production of enzyme inhibitors. Understanding diversity and associations among various actinobacterial activities, with each other and the source of isolation, can provide new insights in marine microbial ecology and provide opportunities to isolate novel therapeutic agents.

microbiology↗

bioRxiv2019

Predator prey and the third beneficiary

All bacterial epibiotic predators are rich in secondary metabolites and most genera rich in secondary metabolites have demonstrable predatory abilities. Therefore it is likely that an antibiotic resistant and thereby predation resistant species may benefit not only by escaping predation but also by utilizing nutrients released by lysis of prey cells by predatory bacteria. The resistant organisms may enjoy greater fitness benefits than the predator since they get the benefit without investing in the predation machinery. In our experiment, a marine isolate of Streptomyces atrovirens showed good predatory activity on a range of species including Staphylococcus aureus and Proteus vulgaris. Escherichia coli was resistant to predation by this species. On slide culture with water agar when the predator, S. aureus and E. coli were grown together S. aureus population declined whereas the predation resistant E. coli increased their population as compared to controls. However the growth of E. coli did not affect growth of the predator unfavorably. This strengthens the possibility that evolution of antibiotic resistance not only gave a selective advantage of escaping predation, it also would have increased the fitness of the resistant organism by promoting growth on nutrients released from the prey cells lysed by the predator. When the predator was grown with S. aureus and P. vulgaris as prey, S. aureus declined rapidly whereas P. vulgaris was spared. This suggests that the predator appears to show preference towards prey and in that case even a partial or relative resistance may give substantial advantage to a population.

microbiology↗

bioRxiv2019

A multidimensional functional fitness score is a stronger predictor of type 2 diabetes than obesity parameters in cross sectional data.

ObjectiveWe examine here whether multidimensional functional fitness is a better predictor of type 2 diabetes as compared to morphometric indices of obesity such as body mass index (BMI) and waist to hip ratio (WHR).\n\nResearch design and methodWe analysed retrospective data of 663 volunteer participants (285 males and 378 females between age 28 and 84), from an exercise clinic in which every participant routinely undergoes a health related physical fitness (HRPF) assessment consisting of 15 different tasks examining 8 different aspects of functional fitness.\n\nResultsThe odds of being diabetic in the highest quartile of BMI were not significantly higher than that in the lowest quartile in either of the sexes. The odds of being a diabetic in the highest WHR quartile were significantly greater than the lowest quartile in females (OR = 4.54 (1.95, 10.61) as well as in males (OR = 3.81 (1.75, 8.3). In both sexes the odds of being a diabetic were significantly greater in the lowest quartile of HRPF score than the highest (males OR = 10.52 (4.21, 26.13); females OR = 10.50 (3.53, 31.35)). HRPF was not correlated with BMI in both sexes but was negatively correlated with WHR. After removing confounding, the predictive power of HRPF was significantly greater than that of WHR.\n\nConclusionMultidimensional functional fitness score was a better predictor of type 2 diabetes than obesity parameters in the Indian population.

epidemiology↗

bioRxiv2019

Does insulin signalling decide glucose levels in the fasting steady state?

Recent work has suggested that altered insulin signalling may not be central and as critical to the pathophysiology of type 2 diabetes as classically believed. We critically re-examine the role of insulin in glucose homeostasis using five different approaches namely (i) systematic review and meta-analysis of tissue specific insulin receptor knock-out experiments in rodents, (ii) systematic review and meta-analysis of insulin suppression and insulin enhancement experiments in rodents and humans, (iii) differentiating steady-state and post-meal state glucose levels in streptozotocin treated rats in primary experiments (iv) mathematical and theoretical considerations and (v) glucose insulin relationship in human epidemiological data. All the approaches converge on the inference that although insulin action is needed to reach a homeostatic steady-state of glucose in fasting condition, there is no evidence that insulin action determines the steady-state level of glucose. A wider scale implication of the analysis is in emphasizing the need to differentiate steady state causality from perturbed state causality or on a broader scale driver causality from navigator causality in biology. A driver cause is a factor which is necessary to attain a destination but does not by itself decide the destination. A navigator cause, on the other hand, is one which by itself may not be sufficient to drive the system to a destination but which plays a role in deciding the destination or direction. Insulin appears to be a driver but not a navigator for glucose homeostasis. All evidence suggests that insulin action is required for reaching a homeostatic steady state, but it does not determine the steady-state level of glucose.

physiology↗

bioRxiv2019

Context-dependent selection as the keystone in somatic evolution of cancer

Somatic evolution of cancer involves a series of mutations, and attendant changes, in one or more clones of cells. A \"bad luck\" type model assumes chance accumulation of mutations. The clonal expansion model assumes, on the other hand, that any mutation leading to partial loss of regulation of cell proliferation will give a selective advantage to the mutant. However, a number of experiments show that an intermediate pre-cancer mutant has only a conditional selective advantage. Given that tissue microenvironmental conditions differ across individual organisms, this selective advantage to a mutant could be widely distributed over the population of organisms. We evaluate three models, namely \"bad luck\", context-independent, and -dependent selection, in a comparative framework, on their ability to predict patterns in total incidence, age-specific incidence, and their ability to explain Peto's paradox. Results show that context dependence is necessary and sufficient to explain observed epidemiological patterns, and that cancer incidence is largely selection-limited, rather than mutation-limited. A wide range of physiological, genetic and behavioural factors influence the tissue micro-environment, and could therefore be the source of this context dependence in somatic evolution of cancer. The identification and targeting of these micro-environmental factors that influence the dynamics of selection offer new possibilities for cancer prevention.

cancer biology↗

bioRxiv2018

Foraging theory and the propensity to be obese: an alternative to thrift

The evolutionary origin of obesity is classically believed to be genetic or developmentally induced thrift, as an adaptation to ancestral feast and famine conditions. However, recently the thrift family of hypotheses have attracted serious criticism necessitating alternative thinking. Optimization of foraging behaviour is an important aspect of behavioural evolution. For a species evolved for optimizing nutritional benefits against predation or other foraging risks, reduction in foraging risk below a threshold dramatically increases the steady-state body weight. In modern life where feeding is detached from foraging, the behavioural regulation mechanisms are likely to fail resulting into escalation of adiposity. At a proximate level the signalling pathways for foraging optimization involve fear induced signal molecules in the brain including Cocaine and Amphetamine Regulated Transcript (CART) interacting with adiposity signals such as leptin. While leptin promotes the expression of the fear peptides, the fear peptides promote anorectic action of leptin. This interaction promotes foraging drive and risk tolerance when the stored energy is low and suppresses hunger and foraging drive when the perceived risk is high. The ecological model of foraging optimization and the molecular model of interaction of these peptides converge in the outcome that the steady state adiposity is an inverse square root function of foraging risk. The foraging optimization model is independent of thrift or insurance hypotheses, but not mutually exclusive. We review existing evidence and suggest testable predictions of the model. Understanding obesity simultaneously at proximate and ultimate levels is likely to suggest effective means to curb the obesity epidemic.

evolutionary biology↗

bioRxiv2018

Inferring causal pathways among three or more variables from steady-state correlations in a homeostatic system

Cross-sectional correlations between two variables have limited implications for causality. We show here that in a homeostatic system with three or more inter-correlated variables, it is possible to make causal inferences from steady-state data. Every putative pathway between three variables makes a set of differential predictions that can be tested with steady state data. For example, among 3 variables, A, B and C, the coefficient of determination, [Formula] is predicted by the product of [Formula] and [Formula] for some pathways, but not for others. Residuals from a regression line are independent of residuals from another regression for some pathways, but positively or negatively correlated for certain other pathways. Different pathways therefore have different prediction signatures, which can be used to accept or reject plausible pathways. We apply these principles to test the classical pathway leading to a hyperinsulinemic normoglycemic insulin-resistant, or pre-diabetic state using four different sets of epidemiological data. Currently, a set of indices called HOMA-IR and HOMA-{beta} are used to represent insulin resistance and glucose-stimulated insulin response by {beta} cells respectively. Our analysis shows that if we assume the HOMA indices to be faithful indicators, the classical pathway must in turn, be rejected. Among the populations sampled, the classical pathway and faithfulness of the HOMA indices cannot be simultaneously true. The principles and tools described here can find wide application in inferring plausible regulatory mechanisms in homeostatic systems based on epidemiological data.

physiology↗