Biology subjects

Ghosh, S.

Publications and source records attributed to Ghosh, S..

384 records · Page 22Linked to original sources

bioRxiv2017

Discovery of global regulators of 3’ untranslated region processing in cancers with KAPAC

3 UTR length is regulated in relation to cellular state. To uncover key regulators of poly(A) site (PAS) use in specific conditions, we have developed PAQR, a method for quantifying PAS use from RNA sequencing data and KAPAC, an approach that infers activities of oligomeric sequence motifs on PAS choice. Application of PAQR and KAPAC to RNA sequencing data from normal and tumor tissue samples uncovered sequence motifs that can explain changes in cleavage and polyadenylation in specific cancers. In particular, our analysis points to Polypyrimidine tract binding protein 1 as a regulator of PAS choice in glioblastoma.

systems biology↗

bioRxiv2017

Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein

Aggregation of alpha synuclein has strong implications in Parkinsons disease. The heterogeneity of folding/aggregation landscape and transient nature of the early intermediates result in difficulty in developing a successful therapeutic intervention. Here we used fluorescence measurements at ensemble and single molecule resolution to study how the late and early events of alpha synuclein aggregation modulate each other. The in-vitro aggregation data was complemented using measurements inside live neuroblastoma cells by employing a small molecule labeling technique. An inhibitor molecule (arginine), which delayed the late event of amyloidosis, was found to bind to the protein, shifting the early conformational fluctuations towards a compact state. In contrast, a facilitator of late aggregation (glutamate), was found to be excluded from the protein surface. The presence of glutamate was found to speed up the oligomer formation at the early stage. We found that the effects of the inhibitor and facilitator were additive and as a result they maintained a ratio at which they cancelled each others influence on different stages of alpha synuclein aggregation.

biophysics↗

bioRxiv2017

Speed breeding: a powerful tool to accelerate crop research and breeding

The growing human population and a changing environment have raised significant concern for global food security, with the current improvement rate of several important crops inadequate to meet future demand [1]. This slow improvement rate is attributed partly to the long generation times of crop plants. Here we present a method called speed breeding, which greatly shortens generation time and accelerates breeding and research programs. Speed breeding can be used to achieve up to 6 generations per year for spring wheat (Triticum aestivum), durum wheat (T. durum), barley (Hordeum vulgare), chickpea (Cicer arietinum), and pea (Pisum sativum) and 4 generations for canola (Brassica napus), instead of 2-3 under normal glasshouse conditions. We demonstrate that speed breeding in fully-enclosed controlled-environment growth chambers can accelerate plant development for research purposes, including phenotyping of adult plant traits, mutant studies, and transformation. The use of supplemental lighting in a glasshouse environment allows rapid generation cycling through single seed descent and potential for adaptation to larger-scale crop improvement programs. Cost-saving through LED supplemental lighting is also outlined. We envisage great potential for integrating speed breeding with other modern crop breeding technologies, including high-throughput genotyping, genome editing, and genomic selection, accelerating the rate of crop improvement.

plant biology↗

bioRxiv2017

Activity based checkpoints ensure circuit stability in the olfactory system

Olfactory circuits function at birth, yet are continuously remodeled through the integration of adult-born interneurons into the olfactory bulb in a manner that preserves olfactory perceptual stability throughout adult life. The mechanisms that ensure appropriate circuit stability in this dynamic context remain poorly understood. Since interneurons sculpt the excitatory output of mitral and tufted (MT) neurons to the olfactory cortex, we predicted that MT neurons might instruct interneuron wiring in the adult brain. By blocking synaptic transmission from MT neurons we show that MT neuronal activity is critical to maintain olfactory bulb integrity and interneuron survival. Blocking interneuron death uncovered a second activity-dependent checkpoint regulating dendrite branching. In contrast, cortical circuits and MT neurons remain stable in the face of these silent and degenerating olfactory circuits. These studies identify a circuit-specific role for non-sensory activity in regulating integration of neurons into the adult brain, as predicted by previous computational models.

neuroscience↗

bioRxiv2017

Nitric oxide sensing by chlorophyll a

Nitric oxide (NO) acts as a signalling molecule that has direct and indirect regulatory roles in various functional processes in biology, though in plant kingdom its role is relatively unexplored. One reason for this is the fact that sensing of NO is always challenging. There are very few probes that can classify the different NO species. The present paper proposes a simple but straightforward way for sensing different NO species using chlorophyll, the source of inspiration being hemoglobin that serves as a NO sink in most mamalian system. The proposed method is able to classify NO from DETA-NONOate or (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1,2-diolate, nitrite, nitrate and S-nitrosothiol or SNO. This discrimination is carried out by chlorophyll a (chl a) at nano molar (nM) order of sensitivity and at 293K to 310K. Molecular docking reveals the differential binding behaviour of NO and SNO with chlorophyll, the predicted binding affinity matching with the experimental observation. Additional expreiments with diverse range of cyanobacteria reveals that apart from spectroscopic approach the proposed sensing module can be used in microscopic inspection of NO speices. Binding of NO is sensitive to tempertaure and static magnetic field. This provides additional support to the involvement of the porphyrin ring structure to the NO sensing process. This also broadens the scope of the sensing methods as hinted in the text.

bioengineering↗

bioRxiv2017

Repression of YdaS Toxin is Mediated by Transcriptional Repressor RacR in the cryptic rac prophage of Escherichia coli K12

AbstractHorizontal gene transfer is a major driving force behind the genomic diversity seen in prokaryotes. The rac prophage in E.coli K12 encodes a putative transcription factor RacR, whose deletion is lethal. We have shown that the essentiality of racR in E.coli K12 is attributed to its role in transcriptionally repressing a toxin gene called ydaS, which is coded adjacent and divergently to racR.

genetics↗