Biology subjects

Ray, S.

Publications and source records attributed to Ray, S..

8 recordsLinked to original sources

bioRxiv2018

millepattes micropeptides are an ancient developmental switch required for embryonic patterning

Small open reading frames (smORFs) that code for \"micropeptides\" (10-100 amino acids) exhibit remarkable evolutionary complexity. Conserved micropeptides encoded by the millepattes (mlpt) gene are essential in Tribolium for embryogenesis but in Drosophila, function only in leg and cuticle differentiation. We find that a module identified in Drosophila trichome patterning, comprising Mlpt, UBR3, and Shaven-baby (Svb), coordinates early embryo patterning in several insect orders. Intriguingly, Mlpt segmentation function can be re-awakened in the Drosophila blastoderm, demonstrating the potency of an ancestral developmental switch retained despite evolving embryonic patterning modes. smORFs like millepattes thus illustrate plasticity of micropeptide functions despite constraints of essential genetic networks.\n\nOne sentence summaryA module comprising the small ORFs mlpt/pri/tal, the transcription factor Svb, and the ubiquitin ligase UBR3, possesses an ancestral function in insect embryo patterning which is lost in flies but reactivated when Svb expression is restored.

developmental biology↗

bioRxiv2017

Predicting resistance of clinical Abl mutations to targeted kinase inhibitors using alchemical free-energy calculations

The therapeutic effect of targeted kinase inhibitors can be significantly reduced by intrinsic or acquired resistance mutations that modulate the affinity of the drug for the kinase. In cancer, the majority of missense mutations are rare, making it difficult to predict their impact on inhibitor affinity. This complicates the practice of precision medicine, pairing of patients with clinical trials, and development of next-generation inhibitors. Here, we examine the potential for alchemical free-energy calculations to predict how kinase mutations modulate inhibitor affinities to Abl, a major target in chronic myelogenous leukemia (CML). We find these calculations can achieve useful accuracy in predicting resistance for a set of eight FDA-approved kinase inhibitors across 144 clinically-identified point mutations, achieving a root mean square error in binding free energy changes of [Formula] kcal/mol (95% confidence interval) and correctly classifying mutations as resistant or susceptible with [Formula] accuracy. Since these calculations are fast on modern GPUs, this benchmark establishes the potential for physical modeling to collaboratively support the rapid assessment and anticipation of the potential for patient mutations to affect drug potency in clinical applications.

cancer biology↗

bioRxiv2017

Cross talk between photo-pigments and graphene electron cloud - Designing a biodiode

We report emergence of a new electrical material by growing photosynthetic biofilm on a Dirac material, graphene. The material showed new conducting as well as semiconducting properties. Frequency dependent capacitive spectra further indicated presence of electrical isosbestic points(at 0.8 and 9MHz), implying two state dieletric transitions at critical frequencies. A notable reult was a Schottky diode like behavior in the IV curve. Voltage dependent conductance with conductance peaks near the Schottky diode threshold was observed. We obtained facilitated growth of photosynthetic biofilm in presence of graphene. Lastly higher bacterial metabolism was seen in graphene incorporated biofilm. For this zero band gap Dirac material this can only be interpreted as coupling of the electron transport chain of the bacterial biofilm and the graphene electron cloud.

biophysics↗

bioRxiv2017

Non-canonical circadian oscillations in Drosophila S2 cells drive gene-expression cycles coupled to metabolic oscillations

Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 hours. Current models propose that transcriptional feedback loops are the principal mechanism for the generation of circadian oscillations. In these models, Drosophila S2 cells are generally regarded as non-rhythmic cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products are rhythmically expressed in a 24-hour cycle. Metabolomics analyses extended these findings and illustrated that central carbon metabolism and amino acid metabolism are the main pathways regulated in a rhythmic fashion. We thus demonstrate that daily genome-wide oscillations, coupled to metabolic cycles, take place in eukaryotic cells without the contribution of known circadian regulators.

systems biology↗

bioRxiv2017

Switchable amplification of fluoresence from a photosynthetic microbe

One known attribute of the photosynthetic apparatus is photon capture and generation of metabolic energy. The thermodynamic implications of fluorescence, invariably associated with the photosynthetic components is however poorly understood. In this paper we report a density dependent amplification of such fluorescence which can be interpreted as a thermodynamic strategy of controlled energy release by the cell. We show in support of this hypothesis that prolonged photo-exitation of cell free extract of Rhodobacter capsulatus SB1003 at 395 nm, induces fluorescence emission amplifying with time as long as the fluorophore density is above a critical level. The fact that the amplification disappears at low temperature and at dilute condition, is in accordance with the thermodynamic interpretation that energy is released as per requirement. Live cell imaging is also validation of the phenomenon even at the cellular level. Single cells of Rhodobacter capsulatus SB1003 shows time dependent loss of fluorescence, the process being reversed for cellular clusters. To explain the mechanism of this bistable fluorescence (F) amplification, variation of the scale free kinetic constant k=1/F (dF/dt) is studied at varying temperatures in presence and absence of static magnetic field. The sign of k shifts from positive to negative if T is lowered or if the system is diluted. But at low T, k again switches from negative to positive value, if static magnetic field is applied. The chain of events can be explained by a simple model assuming excretion of a porphyrin by the microbe and possible photon dependent aggregation behavior of such porphyrin complex, differential temperature and magnetic field sensitivity of the monomeric or aggregated forms of porphyrin being reported earlier.

biophysics↗

bioRxiv2017

Light Amplification By Biofilm And Its Polarization Dependence

We report amplified, transmitted light intensity, compared to input, when photosynthetic biofilms were placed in the path of Rayleigh scattered, monochromatic light. Enhancement spectrum shows peak at around 505 nm, which corresponds to the pore wall thickness in biofilm ultra-structure, suggesting role of resonant Mie scattering. Enhancement factors differed when biofilms from different stages of growth were used. Enhancement factors were found to depend on the nature of Rayleigh scattering liquid. Polarizing Rayleigh scattered light by the use of polarizers affected the percentage of enhancement. Amplified output is achievable with constructive interference arising out of coherent forward light scattering, a theoretically predicted outcome of Anderson localization of photons. Possible uses of photosynthetic biofilms in organic material based photonic devices have been discussed.

bioengineering↗

bioRxiv2017

Bistability In Fluorescence From A Purple Non-Sulfur Bacteria

Bistable optical emission has been observed for photosynthetic purple non-sulfur bacteria Rhodobacter capsulatus SB1003. The microbes respond to UV excitation (at 395nm) in a bifurcating way one branch corresponding to increase and the other corresponding to diminishing fluorescent emission in the range 590-685nm.The switching between such bifurcating branches can be observed when parameters like concentration, temperature are varied or static magnetic field is applied. Thus switching from amplification to reduction occurs if fluorophore concentration lowered. Again if temperature is lowered a steady quenching (instead of amplification) of fluorescence is observed. However presence of magnetic field of the order of 0.5 T reverts this and once again the systems resumes its fluoresence amplifying state. We propose that aggregation of bacterial porphyrin and regulation of such aggregation by photon excitation may explain this bistablity. Possible ecological implication of the photosynthetic bistability is suggested.

systems biology↗

bioRxiv2017

Emerging Electrical Properties of Graphene incorporated Photosynthetic Biofilms

We report emergence of a new electrical material by growing photosynthetic biofilm on a Dirac material, graphene. The material showed new conducting as well as semiconducting properties. Frequency dependent capacitive spectra further indicated presence of electrical isosbestic points(at 0.8 and 9MHz), implying two state dieletric transitions at critical frequencies. A notable reult was a Schottky diode like behavior in the IV curve. Voltage dependent conductance with conductance peaks near the Schottky diode threshold was observed. We obtained facilitated growth of photosynthetic biofilm in presence of graphene. Lastly higher bacterial metabolism i was seen in the biofilm in contact with graphene as compared to its normal growth condition. For this zero band gap Dirac material this can only be interpreted as coupling of the electron transport chain of the bacterial biofilm and the graphene electron cloud.

biophysics↗