Biology subjects

Jain, K.

Publications and source records attributed to Jain, K..

42 records · Page 3Linked to original sources

bioRxiv2020

Dynein collective behavior in mitotic nuclear positioning of Saccharomyces cerevisiae

1Positioning the nucleus at the bud-neck prior during Saccharomyces cerevisiae mitosis during anaphase involves pulling forces of cytoplasmic dynein localized in the daughter cell. While genetic analysis has revealed a complex network positioning the nucleus, quantification of the forces acting on the nucleus and dyneins numbers driving the process has remained difficult. In order to better understand the role of motor-microtubule mechanics during nuclear positioning and the role of dynein, we have used a computational model of nuclear mobility in S. cerevisiae and reconciled it to the mobility of labelled spindle pole bodies (SPBs) measured by quantifying fluorescence microscopy time-series. We model the apparent random-walk mobility of SPBs by combining diffusion of the nucleus and active pushing of MTs at the cell membrane. By minimizing the deviation between tracks of fluorescently tagged SPBs and simulations, we estimate the effective cytoplasmic viscosity to be 0.5 Pa s. The directed transport of nuclei during the budding process is similarly quantified by tracking the daughter SPB (SPB-D) in experiment. Using force-balance, we find 2 to 8 motors are required to pull the nucleus to the bud-neck. Simulations of the cytoplasmic MT (cMT) search and capture by dynein suggest single motor binding is followed by a rapid saturation of number of bound motors. The short time and length of MT interactions with the cortex and minimal collective dynein force required, predict a functional role for dynein clustering in nuclear positioning.

cell biology↗

bioRxiv2020

Dominance patterns in dynamic environments

Natural environments are seldom static and therefore it is important to ask how a population adapts in a changing environment. We consider a finite, diploid population with intermediate dominance evolving in a periodically changing environment and study how the fixation probability of a rare mutant depends on its dominance coefficient and the rate of environmental change. We find that in slowly changing environments, the dominance patterns are the same as in the static environment, that is, if a mutant is beneficial (deleterious) when it arrives, it is more (less) likely to fix if it is dominant. But in fast changing environments, these patterns depend on the mutants fitness on arrival as well as that in the time-averaged environment. We find that in a rapidly varying environment that is neutral or deleterious on-average, an initially beneficial (deleterious) mutant that arises while selection is decreasing (increasing) has a fixation probability lower (higher) than that for a neutral mutant leading to a reversal in the standard dominance patterns. We also find that recurrent mutations decrease the phase lag between the environment and the allele frequency, irrespective of the level of dominance.

evolutionary biology↗

bioRxiv2019

openPrimeR for multiplex amplification of highly diverse templates

To study the diversity of immune receptors and pathogens, multiplex PCR has become a central approach in research and diagnostics. However, insufficient primer design against highly diverse templates often prevents amplification and therefore limits the correct understanding of biological processes. Here, we present openPrimeR, an R-based tool for evaluating and designing multiplex PCR primers. openPrimeR provides a functional and intuitive interface and uses either a greedy algorithm or an integer linear program to compute the minimal set of primers that performs full target coverage. As proof of concept, we used openPrimeR to find optimal primer sets for the amplification of highly mutated immunoglobulins. Comprehensive analyses on specifically generated immunoglobulin variable gene segment libraries resulted in the composition of highly effective primer sets (oPR-IGHV, oPR-IGKV and oPR-IGLV) that demonstrated to be particularly suitable for the isolation of novel human antibodies.

immunology↗

bioRxiv2018

Emergence of the East-Central-South-African genotype of Chikungunya virus in Brazil and the city of Rio de Janeiro may have occurred years before surveillance detection

Brazil, which is hyperendemic for dengue virus (DENV), has had recent Zika (ZIKV) and (CHIKV) Chikungunya virus outbreaks. Since March 2016, CHIKV is the arbovirus infection most frequently diagnosed in Rio de Janeiro. In the analysis of 1835 syndromic patients, screened by real time RT-PCR, 56.4% of the cases were attributed to CHIKV, 29.6% to ZIKV, and 14.1% to DENV-4. Sequence analyses of CHIKV from sixteen samples revealed that the East-Central-South-African (ECSA) genotype of CHIKV has been circulating in Brazil since 2013 [95% bayesian credible interval (BCI): 03/2012-10/2013], almost a year before it was detected by arbovirus surveillance program. Brazilian cases are related to Central African Republic sequences from 1980s. To the best of our knowledge, given the available sequence published here and elsewhere, the ECSA genotype was likely introduced to Rio de Janeiro early on 2014 (02/2014; BCI: 07/2013-08/2014) through a single event, after primary circulation in the Bahia state at the Northestern Brazil in the previous year. The observation that the ECSA genotype of CHIKV was circulating undetected underscores the need for improvements in molecular methods for viral surveillance.

genomics↗

bioRxiv2017

‘Switch-like’ transition from random to directed motility of microtubules by a yeast dynein

Processive transport by multiple molecular motors that step stochastically, requires a form of mechanical coupling. In a quantitative microtubule (MT) gliding assay with yeast cytoplasmic dynein, we investigate the nature of this coupling by examining the effect of MT length and motor density on transport. We find speed and velocity have a length dependence for low motor numbers, but are independent of MT length for high motor densities. The dependence of speed, velocity and degree of randomness of MT transport is best understood when evaluated in terms of the numbers of motors bound to a filament. A model of collective transport of MTs, based on stochastic stepping and asymmetric detachment rates, reproduces the experimental trends of decreasing diffusivity with increasing number of motors. Additionally, the model predicts a switch-like increase in directionality of MT transport above a threshold number of motors. Such a rapid transition from random to directed motility with increasing numbers of yeast dyneins, could play a role in vivo during mitosis in the search and orientation of the Saccharomyces cerevisiae nucleus.

biophysics↗

bioRxiv2017

Rob And MarA Alter Susceptibility Of Escherichia coli To Antibiotics In Presence Of Salicylate

When exposed to stress, bacterial cells launch a diverse response to enhance their chances of survival. This response involves modulation of expression of a large number of proteins which help the cell counter stress. This modulation is facilitated by several transcription factors in bacteria and in E. coli three homologous regulators, MarA, Sox, and Rob are known to launch a coordinated response to combat various stress environments. MarA and SoxS are known to control multiple antibiotic resistance and superoxide regulon respectively. Rob has been observed to control similar downstream targets as MarA and SoxS. However, physiological relevance of Rob in not understood. We show that Rob along with MarA, in presence of inducer salicylate, can help cell survive in presence of lethal concentration of wide range of antibiotics.

microbiology↗