Biology subjects

Mukherjee, J.

Publications and source records attributed to Mukherjee, J..

18 recordsLinked to original sources

bioRxiv2026

Down syndrome postmortem brains exhibit reduction in nifene binding to α4β2* nicotinic acetylcholinergic receptors

Alzheimer's disease (AD) pathology including amyloid beta (A{beta}) plaques and tau tangles accumulate with age in Down Syndrome (DS). Cholinergic abnormalities such as expression of nicotinic acetylcholine receptors (nAChRs) adversely contribute to cognitive decline and neurodegeneration in AD with similar features possible in DSAD. As a radiotracer for 4{beta}2* nAChRs, [18F]nifene was quantitatively evaluated in the frontal cortex (FCX) and temporal cortex (TCX) of DSAD, AD, and cognitively normal (CN) brain tissue using autoradiography. Anti-tau and anti-A{beta} immunostaining in adjacent sections confirmed the presence of tau tangles and A{beta} plaques. [18F]Nifene binding in brain sections demonstrated significantly more binding in gray matter (GM) than white matter (WM), with FCX exhibiting more binding than TCX (OptiQuant). Nicotine substantially displaced [18F]nifene binding in adjacent sections, resulting in average GM/nicotine ratios (DSAD=9.74, AD=10.5, CN=17; suggesting a 38% decrease in AD and a 43% decrease in DSAD) and WM/nicotine ratios (DSAD=2.73, AD=3.31, CN=5.62; suggesting a 41% decrease in AD and a 51% decrease in DSAD). [18F]Nifene was correlated with [125I]IBETA (A{beta}), showing a strong positive relationship between 4{beta}2* nAChRs and A{beta} in DSAD. [18F]Nifene GM/nicotine and WM/nicotine ratios were positively correlated with age in TCX and FCX. The findings of this study suggest that [18F]nifene has potential use in diagnostic investigations of the cholinergic system in DSAD using positron emission tomography. The study also points to a possible need for earlier therapeutic interventions to address the 4{beta}2* nAChRs deficit in DSAD.

neuroscience↗

bioRxiv2026

Increased Binding of Nifene, a PET Imaging Probe for α4β2* Nicotinic Acetylcholinergic Receptors in Hippocampus-Subiculum of Postmortem Human Parkinsons Disease Brain

Non-motor symptoms in Parkinsons disease (PD) may be influenced by the 4{beta}2* subtype of nicotinic acetylcholine receptors (nAChR) present in the hippocampus and subiculum. To continue efforts in PET diagnostics for PD, autoradiographic [18F]nifene binding to 4{beta}2* nAChR was quantitively assessed in the hippocampus-subiculum (HP-SUB) of PD (n = 27; 14 males, 13 females) and cognitively normal (CN) (n = 32; 16 males, 16 females) cases. Anti-ubiquitin for Lewy body and anti--synuclein immunostaining on adjacent slices were analyzed in QuPath and [18F]nifene binding was quantified in OptiQuant. Subiculum had greater [18F]nifene binding (51% to 85%) compared to HP in all subjects. Significantly higher [18F]nifene binding (>250%) was seen in PD SUB and PD HP compared to CN in both males and females. The grey matter (GM) to white matter (WM) ratio in PD=3.53 while CN=1.33, a >150% increase in PD. Binding of [18F]nifene to GM and WM individually was >250% greater in PD compared to CN. Male CN exhibited an increase while and male PD exhibited a significant decrease in [18F]nifene binding with aging, while females did not exhibit significant differences. In summary, 4{beta}2* nAChR measured by [18F]nifene is significantly upregulated in the PD HP and SUB. This increased [18F]nifene binding may be of diagnostic value using PET imaging.

neuroscience↗

bioRxiv2026

Imaging FDG PET/CT Study of Nicotinic Acetylcholinergic Receptor α2 Knock-Out Mice and α2 Hypersensitive Mice Compared to Control Mice: Male-Female Differences and Nicotine Effects

ObjectiveNicotinic acetylcholinergic receptors (nAChRs), comprising of and {beta} subunits are present in the brain and whole body. The less abundant 2-subunit is a fast-acting receptor subtype and plays an important role in cognition and learning. To understand cellular functional consequences, this study evaluated glucose metabolism using [18F]FDG PET/CT in 2 knockout (2KO) and 2 hypersensitive (2HS) mice. MethodsControl (CN; 4M, 4F), 2 knockout (2KO; 4M, 4F) and 2 hypersensitive (2HS; 4M,4F), 12-16 month old mice were used. Mice were fasted and injected with [18F]FDG (3-5 MBq) while awake. After 40 minutes they underwent whole body PET/CT. On a separate day, nicotine challenge [18F]FDG studies were done. Reconstructed images were analyzed to obtain standard uptake values (SUV) of [18F]FDG in brain and interscapular brown adipose tissue (IBAT). Statistical analysis was performed. ResultsThe 2HS male mice exhibited the largest brain increase in [18F]FDG compared to 2KO male mice. The rank order of brain [18F]FDG uptake in the 3 groups: 2HS[male]> CN[male]> 2KO[male]> CN[female]= 2KO[female][≥] 2HS[female]. Nicotine treatment reduced brain [18F]FDG uptake in all mice. Females had lower [18F]FDG uptake compared to males and were less sensitive to 2 nAChR. In the case of IBAT, 2KO mice had significantly higher baseline [18F]FDG uptake compared to the other two groups: 2KO[male]> 2KO[female]> 2HS[female]> 2HS[male]> CN[female]> CN[male]. Nicotine decreased IBAT in 2KO mice rather than increase as observed in CN and 2HS mice. Conclusions2 nAChRs plays a significant role in brain activation as exhibited by the increase in [18F]FDG in 2HS mice. In the absence of regulatory control by the 2 nAChR, the 2KO mice IBAT exhibited higher [18F]FDG IBAT compared to controls and 2HS mice. Female mice were less affected by nicotine compared to the male mice. Overall, 2 nAChRs played a significant role in glucose metabolism in the brain and IBAT.

neuroscience↗

bioRxiv2026

Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimers disease by using IBETA autoradiography

The accumulation of tau tangles and A{beta} plaques are prominent neuropathologies that characterize Alzheimers disease (AD) and Down Syndrome (DS). Continuous developments of PET tracers as biomarkers can be supported by autoradiography to validate effectiveness and accuracy of binding properties that elucidate the pathophysiology of DSAD and AD. This in vitro comparative study evaluates [125I]IPPI binding to tau and [125I]IBETA binding to A{beta} plaques in the frontal cortex (FCX) and temporal cortex (TCX) of postmortem human brain slices of AD (n=5), DSAD (n=5), and cognitively normal (CN) (n=5) cases. With anti-tau and anti-A{beta} immunostains confirming the presence of tau and A{beta} plaques, [125I]IPPI and [125I]IBETA binding in autoradiographic images were significantly higher in DSAD and AD gray matter (GM) compared to CN. When comparing DSAD with AD, FCX and TCX GM binding was similar throughout DSAD and AD except in FCX GM where there was 48% more [125I]IPPI binding in DSAD than AD. In vitro drug inhibition studies revealed that [125I]IPPI binding was significantly inhibited with increasing harmine concentrations (IC50=115{+/-}40 nM) in DSAD FCX and TCX but KuFal194 minimally inhibited [125I]IPPI binding in the same cases. The GM/white matter ratios for DSAD ([125I]IPPI=4.1, [125I]IBETA=2.9) and AD ([125I]IPPI=4.2, [125I]IBETA=2.6) were significantly greater than CN ([125I]IPPI=1.3, [125I]IBETA=1.2). A positive correlation between [125I]IPPI and [125I]IBETA binding suggests a synergistic relationship between tau and A{beta} plaque in DSAD and AD pathology. This study demonstrates that [125I]IPPI and [125I]IBETA may serve as novel radiotracers in both DSAD and AD to continue diagnostic investigations in vivo.

neuroscience↗

bioRxiv2025

DeePhy: A Deep Learning Model to Reconstruct Phylogenetic Tree from Unaligned Nucleotide Sequences

O_LIInferring phylogenetic trees for a set of taxa is one of the primary objective in the evolutionary biology. Numerous approaches exist to reconstruct the phylogenetic trees by considering different biological data, such as DNA sequence, protein sequence, protein-protein interaction graph, etc. However, each method has its own strengths and weaknesses. Till date, no existing method guarantees to determine true phylogenetic trees all the times. Various studies identified distinct branch length configurations where the existing methods are inefficient to infer the correct tree topologies. C_LIO_LIHere, we propose a novel deep convolutional neural network (CNN)-based model, DeePhy, to reconstruct the phylogenetic trees from the unaligned sequences. The sequences are repre- sented on a two-dimensional coordinate plane by utilizing a biological semantics-based map- ping. Additionally, to assess the robustness of a method, here we also propose a novel boot- strapping technique to generate replicas from the unaligned sequences. We train the model on the triplet sequences, where the output is a triplet tree topology. C_LIO_LIWe show that the well-trained DeePhy outperforms the state-of-the-art methods in inferring triplet tree topology. We experiment DeePhy on data simulated under numerous critical conditions and various branch length configurations. We conduct the McNemar test for comparing the performance of DeePhy and the state-of-the-art methods. The results exhibit that DeePhy is significantly more accurate and remarkably robust in determining the triplet tree topologies for most of the cases than that of the conventional methods. Again, various comparison metrics show that DeePhy also outperforms the conventional methods in inferring trees. Finally, to analyze the performance of DeePhy on real biological dataset, we apply it on Gadiformes dataset. Reassuringly, DeePhy reconstructs the phylogenetic tree from real biological data with known or widely accepted topologies. C_LIO_LIAlthough various practical challenges still need to be taken care of, the outcomes of our study suggest that the deep learning approaches be a successful endeavour in inferring the accurate phylogenetic trees. C_LI

evolutionary biology↗

bioRxiv2023

Estradiol regulates local synthesis of synaptic proteome via sex-specific mechanisms.

Estrogens, specifically 17{beta}-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of synaptic proteins. However, the mechanisms underlying estradiols regulation of synaptic protein expression, and whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures and mixed-sex primary hippocampal neurons, we investigated whether local protein synthesis is required for estradiol- induced synaptic protein expression. Estradiol rapidly increased the rate of protein synthesis and the number of actively translating ribosomes along dendrites and near synapses in both male and female hippocampal neurons. Importantly, these effects occurred independently of gene transcription. Moreover, estradiol also increased the abundance of nascent proteins localised to synapses, independently of gene transcription. Specifically, estradiol increased the synaptic expression of GluN2B- containing N-methyl-D-aspartate receptors and PSD-95 in male and female hippocampus. Mechanistically, mTOR signalling was required for estradiol-induced increases in overall local protein synthesis only in male but not female hippocampus. Consistent with this, mTOR signalling mediated estradiol increases in GluN2B in male, but not female, hippocampus. Conversely, mTOR inhibition, blocked estradiol-induced increased PSD-95 expression in both male and female hippocampus. Collectively, these data suggest that the rapid modulation of local protein synthesis by estradiol is required for changes in the synaptic proteome in male and female hippocampus, and that the requirement of the mTOR signalling pathway in these effects occur in both a sex-specific and protein-dependent manner, with this signalling pathway have a greater role in male compared to female hippocampus.

neuroscience↗

bioRxiv2023

Mitochondrial genes affect the immune response against bacterial infection (Duck Pasteurellosis) through a cascade of mechanisms mediated by nuclear immune genes- a cross talk with nuclear and mitochondrial gene

Mitochondria possess 37 genes of its own, helpful for carrying out various functions including oxidative phosphorylation. But the mitochondria is neither independent in terms of its structure, nor its function, it depend upon nuclear gene for its functionality and replication. Our lab has earlier reported the role of mitochondrial genome in controlling health and reproduction in animal model. Reports also indicate that mitochondria have role in immune response against bacterial infection. In our current study, we depict the role of two polypeptide coding mitochondrial gene as cytochrome B and cytochrome C in providing host immunity against bacterial disease (Duck Pasteurellosis). We further observe that the mechanism was governed by cascade of mechanisms mediated through nuclear genes NRLP3, IL18 and Sting. In the first phase of the study, we have characterized Cytochrome B and Cytochrome C genes from Bengal duck and quantified through the assesment of the expression profiling with respect to healthy and Pasteurella infected ducks following a natural challenge with Pasteurella multocida. In the next phase of our study, we have characterized the above nuclear genes in Bengal duck and attempted to correlate the expression with mitochondrial genes. We attempted to explore the mechanism of pathway how mitochondrial DNA triggers the nuclear immune response leading to destruction of bacterial pathogen. Molecular docking revealed how IL18 directly binds with the pathogen. This is the first report in animal model.

genomics↗

bioRxiv2022

Evaluation of an image-derived input function for kinetic modeling of nicotinic acetylcholine receptor-binding PET ligands

Development of positron emission tomography (PET) radiotracers that bind with high-affinity to 4{beta}2-type nicotinic receptors (4{beta}2Rs) allows for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. One challenge associated with preclinical PET imaging involves the lack of true tissue reference regions free of specific tracer binding in the rodent brain, impeding accurate quantification of the tracer binding potential. Here, we investigate the use of an image-derived arterial input function for kinetic analysis of radiotracer binding in male and female mice. Two radiotracers were explored in this study: 2-[18F]FA85380 (2-FA), which displays similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [18F]Nifene, which displays similar pKa and binding affinity to nicotine. For both radiotracers, time-activity curves of the left ventricle of the heart displayed similar standardized uptake values (SUVs) across wild type mice, mice lacking the {beta}2 subunit for tracer binding, and acute nicotine-treated mice, whereas typical reference tissue SUVs displayed high variation between groups. Binding potential values estimated from a two-tissue compartment model (2TCM) fit of the data with the image-derived input function were significantly higher than estimates from reference tissue-based estimations. Rate constants of radiotracer dissociation were very slow for 2-FA and very fast for Nifene, similar to the in vitro dissociation rates reported for varenicline and nicotine, respectively. We conclude that use of an image-derived input function for kinetic modeling of nicotinic PET ligands improves quantification compared to reference tissue-based methods, and that the chemical properties of 2-FA and Nifene are suitable to study receptor response to nicotine addiction and smoking cessation therapies.

neuroscience↗

bioRxiv2021

Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by in vitro Cellular Studies and in vivo PET Imaging

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membranepermeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKa and high-affinity for 4{beta}2-type nicotinic receptors (4{beta}2Rs) are trapped in intracellular acidic vesicles containing 4{beta}2Rs in vitro. Nicotine, with lower pKa and 4{beta}2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in vivo in mouse brain and identifying the trapping brain organelle in vitro as Golgi satellites (GSats). Two PET 18F-labelled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKa and affinity and [18F]Nifene with nicotine-like pKa and affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in 4{beta}2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to 4{beta}2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals were eliminated in {beta}2 subunit knockout mice or by acute nicotine injections demonstrating binding to sites on {beta}2-containing receptors. Chloroquine, which dissipates GSat pH gradients, reduced [18F]2-FA distributions while having little effect on [18F]Nifene distributions in vivo consistent with only [18F]2-FA trapping in GSats. These results are further supported by in vitro findings where dissipation of GSat pH gradients blocks 2-FA trapping in GSats without affecting Nifene. By combining in vitro and in vivo imaging, we mapped both the brain-wide and subcellular distributions of weak-base nicotinic receptor ligands. We conclude that ligands, such as varenicline, are trapped in neurons in 4{beta}2R-containing GSats, which results in very slow release long after nicotine is gone after smoking. SignificanceMechanisms of nicotine addiction remain poorly understood. An earlier study using in vitro methods found that the anti-smoking nicotinic ligand, varenicline (Chantix) was trapped in 4{beta}2R-containing acidic vesicles. Using a fluorescent labeled high-affinity nicotinic ligand, this study provided evidence that these intracellular acidic vesicles were 4{beta}2R-containing Golgi satellites. In vivo PET imaging with F-18 labeled nicotinic ligands provided additional evidence that differences in PET ligand trapping in acidic vesicles were the cause of differences in PET ligand kinetics and subcellular distributions. These findings combining in vitro and in vivo imaging revealed new mechanistic insights into the kinetics of weak base PET imaging ligands and the subcellular mechanisms underlying nicotine addiction.

neuroscience↗

bioRxiv2021

A heterohexameric protein consisting of six linked single-domain antibodies is highly protective for BoNT/A, BoNT/B and BoNT/E exposures

Botulinum neurotoxin (BoNT) serotypes A, B and E cause the vast majority of human botulism cases and pose the greatest bioterrorism threats. We previously identified multiple camelid single-domain antibodies (VHHs) that each neutralize BoNT/A, BoNT/B or BoNT/E. We also demonstrated that heterodimers of linked toxin-neutralizing VHHs are much more potent than VHH monomer pools in preventing BoNT intoxication. In this study, we expressed two different heterohexamer proteins (VNA1-ABE and VNA2-ABE) of ~100 kDa secreted from mammalian host cells, each containing the same six linked anti-BoNT VHH components ordered in two different combinations. Each heterohexamer contained two VHHs that neutralize BoNT/A, BoNT/B or BoNT/E. Both heterohexameric antitoxins displayed similar strong binding properties for the three targeted BoNT serotypes by ELISA. One ug of each heterohexameric antitoxin fully protected groups of mice co-administered with 100 LD50 of BoNT/A, BoNT/B or BoNT/E, or a pool containing 100 LD50 of each of the three toxins. The results demonstrate that long chains of at least six different linked VHHs can be expressed such that all component VHHs in the multimer retain their target binding activities. These findings make more feasible the development of a BoNT antitoxin product consisting of a small pool of proteins that, in combination, neutralize all known BoNT serotypes and subtypes. Key ContributionHeteromultimeric proteins consisting of six linked, VHH antibodies, and including VHHs that neutralize BoNT/A, BoNT/B and BoNT/E, retain high potency to protect mice challenged with high doses of all three of these BoNT serotypes.

molecular biology↗

bioRxiv2020

Nicotine exposure and neuronal activity regulate Golgi membrane dispersal and distribution

How nicotine exposure produces long-lasting changes that remodel neural circuits with addiction is unknown. Here, we report that long-term nicotine exposure alters the trafficking of 4{beta}2-type nicotinic acetylcholine receptors (4{beta}2Rs) by dispersing and redistributing the Golgi apparatus. In cultured neurons, dispersed Golgi membranes were distributed throughout somata, dendrites and axons. Small, mobile vesicles in dendrites and axons lacked standard Golgi markers and were identified by other Golgi enzymes that modify glycans. Nicotine exposure increased levels of dispersed Golgi membranes, which required 4{beta}2R expression. Similar nicotine-induced changes occurred in vivo at dopaminergic neurons at mouse nucleus accumbens terminals, consistent with these events contributing to nicotines addictive effects. Characterization in vitro demonstrated that dispersal was reversible, that dispersed Golgi membranes were functional, and that membranes were heterogenous in size, with smaller vesicles emerging from larger "ministacks", similar to Golgi dispersal induced by nocadazole. Protocols that increased cultured neuronal synaptic excitability also increased Golgi dispersal, without the requirement of 4{beta}2R expression. Our findings reveal novel activity- and nicotine-dependent changes in neuronal intracellular morphology. These changes regulate levels and location of dispersed Golgi membranes at dendrites and axons, which function in local trafficking at subdomains.

neuroscience↗

bioRxiv2019

Study of human origin and migration from a novel genomic footprint derived from mitochondrial sequences

The origin of modern human and their migration across the world is one of the most debated topics for the decades. There exist two different hypotheses, recent African origin and multi-regional evolution, based on the genomic studies, haplogroups, archaeological records, cultural behaviors, palaeontology studies, etc. Various studies placed the modern humans in a phylogenetic tree to depict the relationships among them. The debate for determining those regions of Africa which witnessed the first origin of humans still exists. The conflicts between the results obtained from the molecular data and the archaeological and palaeontological reports still exist. We adopt a novel genomic feature derived from the whole mitochondrial sequence, and using a novel distance function the phylogenetic trees are constructed based on the feature which provide a new insight on human migration. We propose a new method to derive the bootstrap replica from the genome sequences by considering the genetic variance to demonstrate the robustness of the obtained trees. The results derived from the genomic feature are more consistent with the archaeological findings based on the time of origin of different communities. We find that west and central African communities are placed at the basal point with a very high bootstrap score. This study roughly estimates the existence of the archaic human at 800-900 kilo years ago and presence of human in Africa at 600-700 kilo years ago. This supports the presence of an ancestor in the west and central Africa much earlier than that of the fossils identified.

evolutionary biology↗

bioRxiv2019

Deformity Index: A semi-reference quality metric of phylogenetic trees based on their clades

Measuring the correctness of a phylogenetic tree is one of the most fundamental tasks in phylogenetic study. A large number of methods have been proposed to measure the correctness of a tree. Such methods completely depend on the reference tree and they compute the distance between reference the tree and the target tree. But it is very difficult to obtain a precise and an accurate reference tree for a selected dataset. As a result, the existing methods for comparing the phylogenetic trees can behave unexpectedly in various scenarios. In this paper, we introduce a scoring function, called the Deformity Index, to measure the correctness of a tree based on the biological knowledge of the clades. The strength of our proposed method is that it does not consider any reference tree. We have also investigated the range and the distributions of the different modules of Deformity Index. Furthermore, we perform different goodness of fit tests to understand its cumulative distribution. We have also examined in detail the robustness as well as the scalability of our measure by different statistical tests under the Yule and the uniform models. Moreover, we show that our proposed scoring function can overcome the limitations of the conventional methods of tree comparing by experimenting on different biological datasets.

bioinformatics↗

bioRxiv2018

Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

Loss of glutamatergic synapses is thought to be a key cellular pathology associated with neuropsychiatric disorders including schizophrenia (SCZ) and major depressive disorder (MDD). Genetic and cellular studies of SCZ and MDD using in vivo and in vitro systems have supported a key role for dysfunction of excitatory synapses in the pathophysiology of these disorders. Recent clinical studies have demonstrated that the estrogen, 17{beta}-estradiol can ameliorate many of the symptoms experienced by patients. Yet, to date, our understanding of how 17{beta}-estradiol exerted these beneficial effects is limited. In this study, we have tested the hypothesis that 17{beta}-estradiol can restore dendritic spine number in a cellular model that recapitulates the loss of synapses associated with SCZ and MDD. Ectopic expression of wildtype, mutant or shRNA-mediated knockdown of Disrupted in Schizophrenia (DISC1) reduced dendritic spine density in primary cortical neurons. Acute or chronic treatment with 17{beta}-estradiol increased spine density to control levels in neurons with altered DISC1 levels. In addition, 17{beta}-estradiol reduced the extent to which ectopic wildtype and mutant DISC1 aggregated. Furthermore, 17{beta}-estradiol also caused the enrichment of synaptic proteins at synapses and increased the number of dendritic spines containing PSD-95 or that overlapped with the pre-synaptic marker bassoon. Taken together, our data indicates that estrogens can restore lost excitatory synapses caused by altered DISC1 expression, potentially through the trafficking of DISC1 and its interacting partners. These data highlight the possibility that estrogens exert their beneficial effects in SCZ and MDD in part by modulating dendritic spine number.

neuroscience↗

bioRxiv2018

β-actin mRNA interactome mapping by proximity biotinylation

The molecular function and fate of mRNAs are controlled by RNA binding proteins (RBPs). However, identification of the interacting proteome of a specific mRNA in vivo is still very challenging. Based on the widely-used RNA tagging with MS2 aptamers for RNA visualization, we developed a novel RNA proximity biotinylation (RNA-BioID) method by tethering biotin ligase (BirA*) via MS2 coat protein (MCP) at the 3UTR of endogenously MS2 tagged {beta}-actin mRNA in mouse embryonic fibroblasts (MEFs). We demonstrate the dynamics of the {beta}-actin mRNA interactome by characterizing its changes upon serum-induced localization of the mRNA. Apart from the previously known interactors, we identified over 60 additional {beta}-actin associated RBPs by RNA-BioID, among them the KH-domain containing protein FUBP3/MARTA2 has shown to be required for {beta}-actin mRNA localization. This protein binds to the 3-untranslated region of {beta}-actin mRNA, is essential for {beta}-actin mRNA localization but does not interact with the characterized {beta}-actin zipcode element. RNA-BioID provides a tool to identify new mRNA interactors and to study the dynamic view of the interacting proteome of endogenous mRNAs in space and time.

cell biology↗

bioRxiv2018

GRaphical footprint based Alignment-Free method (GRAFree) for reconstructing evolutionary Traits in Large-Scale Genomic Features

In our study, we attempt to extract novel features from mitochondrial genomic sequences reflecting their evolutionary traits by our proposed method GRAFree (GRaphical footprint based Alignment-Free method). These features are used to build a phylogenetic tree given a set of species from insect, fish, bird, and mammal. A novel distance measure in the feature space is proposed for the purpose of reflecting the proximity of these species in the evolutionary processes. The distance function is found to be a metric. We have proposed a three step technique to select a feature vector from the feature space. We have carried out variations of these selected feature vectors for generating multiple hypothesis of these trees and finally we used a consensus based tree merging algorithm to obtain the phylogeny. Experimentations were carried out with 157 species covering four different classes such as, Insecta, Actinopterygii, Aves, and Mammalia. We also introduce a measure of quality of the inferred tree especially when the reference tree is not present. The performance of the output tree can be measured at each clade by considering the presence of each species at the corresponding clade. GRAFree can be applied on any graphical representation of genome to reconstruct the phylogenetic tree. We apply our proposed distance function on the selected feature vectors for three naive methods of graphical representation of genome. The inferred tree reflects some accepted evolutionary traits with a high bootstrap support. This concludes that our proposed distance function can be applied to capture the evolutionary relationships of a large number of both close and distance species using graphical methods.

evolutionary biology↗

bioRxiv2018

Data-driven analysis of biomedical literature suggests broad-spectrum benevolence of culinary herbs and spices

Spices and herbs are key dietary ingredients used across cultures worldwide. Beyond their use as flavoring and coloring agents, the popularity of these aromatic plant products in culinary preparations has been attributed to their antimicrobial properties. Last few decades have witnessed an exponential growth of biomedical literature investigating the impact of spices and herbs on health, presenting an opportunity to mine for patterns from empirical evidence. Systematic investigation of empirical evidence to enumerate the health consequences of culinary herbs and spices can provide valuable insights into their therapeutic utility. We implemented a text mining protocol to assess the health impact of spices by assimilating, both, their positive and negative effects. We conclude that spices show broad-spectrum benevolence across a range of disease categories in contrast to negative effects that are comparatively narrow-spectrum. We also implement a strategy for disease-specific culinary recommendations of spices based on their therapeutic tradeoff against adverse effects. Further by integrating spice-phytochemical-disease associations, we identify bioactive spice phytochemicals potentially involved in their therapeutic effects. Our study provides a systems perspective on health effects of culinary spices and herbs with applications for dietary recommendations as well as identification of phytochemicals potentially involved in underlying molecular mechanisms.

bioinformatics↗

bioRxiv2018

SpiceRx: an integrated resource for the health impacts of culinary spices and herbs

Spices and herbs are key dietary ingredients used in cuisines across the world. They have been reported to be of medicinal value for a wide variety of diseases through a large body of biomedical investigations. Bioactive phytochemicals in these plant products form the basis of their therapeutic potential as well as adverse effects. A systematic compilation of empirical data involving these aspects of culinary spices and herbs could help unravel molecular mechanisms underlying their effects on health.\n\nSpiceRx provides a platform for exploring the health impact of spices and herbs used in food preparations through a structured database of tripartite relationships with their phytochemicals and disease associations. Starting with an extensive dictionary of culinary spices and herbs, their disease associations were text mined from MEDLINE, the largest database of biomedical abstracts, assisted with manual curation. This information was further combined with spice-phytochemical and phytochemical-disease associations. SpiceRx is an integrated repertoire of evidence-based knowledge pertaining to the health impacts of culinary spices and herbs, and facilitates their disease-specific culinary recommendations as well as exploration of molecular mechanisms underlying their health effects.\n\nAvailability and ImplementationSpiceRx is available at http://cosylab.iiitd.edu.in/spicerx and supports all modern browsers. SpiceRx is implemented with Python web development framework Django and relational database PostgreSQL; the front-end was built using HTML, CSS, JavaScript, AJAX, jQuery, JSME Molecular Editor, Bootstrap, Jmol, DataTables and Google Charts.\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗