Biology subjects

Mukherjee, N.

Publications and source records attributed to Mukherjee, N..

44 records · Page 3Linked to original sources

bioRxiv2019

Azadirachta indica (A. Juss.) reduces circulating Dirofilaria immitis microfilariae in vivo

The present study enumerates the effectiveness of ethanolic leaf extract of A. indica against circulating microfilariae (mf) of D. immitis in vivo of Canis familiaris. An ethanolic extract was prepared from the leaves of A. indica (EEA) and treated on dogs infected with the filarial nematode Dirofilaria immitis, the causative agent of canine cardiopulmonary dirofilariasis. Before treatment, all the infected dogs were vigilantly supervised for any natural fluctuation of mf count. Two doses; 25 and 50 mg/kg body weight/twice a day; both for 15 days were selected for in vivo tests along with a control group which received an empty capsule during the study period. The highest reduction of circulating mf was counted on day 60, showing mf reduction of 77.9% and 86.7% respectively for the two doses. Thereafter mf density increased with a minor change and maintained reduction of 49.5% and 64.1% on day 180 respectively. Additionally, no appreciable side effects in the treated dogs were recorded as evident from serum toxicity parameter analyses. In conclusion, the ethanolic formulation of A. indica leaves possesses considerable effectiveness against D. immitis in vivo with no toxic modification in the host after exposure. Thus, EEA appears to be a good alternative remedy against heartworm infection in infected dogs.

zoology↗

bioRxiv2019

Single and population coding of taste in the gustatory cortex of awake mice

Electrophysiological analysis has reveals much about the broad coding and neural ensemble dynamics that characterize gustatory cortical (GC) taste processing in awake rats, and about how these dynamics relate to behavior. With regard to mice, meanwhile, data concerning cortical taste coding have largely been restricted to imaging--a technique that reveals average levels of neural responsiveness, but that (currently) lacks the temporal sensitivity necessary for evaluation of fast response dynamics; furthermore, the few extant studies have thus far failed to provide consensus on basic features of coding. We have recorded the spiking activity of ensembles of GC neurons while presenting representatives of the basic taste modalities (sweet, salty, sour and bitter) to awake mice. Our first central result is the identification of similarities between rat and mouse taste processing: most mouse GC neurons (~66%) responded distinctly to multiple (3-4) tastes; temporal coding analyses further reveal, for the first time, that single mouse GC neurons sequentially code taste identity and palatability--the latter responses emerging ~0.5s after the former--with whole GC ensembles transitioning suddenly and coherently from coding taste identity to coding taste palatability. The second finding is that spatial location plays very little role in any aspect of taste responses--neither between- (anterior-posterior) nor within-mouse (dorsal-ventral) mapping revealed anatomical regions with narrow or temporally simple taste responses. These data confirm recent results showing that mouse cortical taste responses are not \"gustatopic,\" but also go beyond these imaging results to show that mice process tastes through time.

neuroscience↗

bioRxiv2018

Dynamical structure of cortical taste responses revealed by precisely-timed optogenetic perturbation

The purpose of perception is driving action. During tasting, for instance, every stimulus must be either swallowed or rejected (the latter via a behavior known as "gaping"). Taste responses in the rodent primary gustatory cortex (GC) span this sensorimotor divide, progressing through a series of firing epochs that culminate in the emergence of action-related firing. Population analyses reveal this emergence to be a sudden, coherent ensemble transition that, despite varying in latency between trials, precedes gaping onset by 0.2-0.3s. Here, we tested whether this transition drives gaping, delivering 0.5s GC perturbations at various time-points in tasting trials. Perturbations significantly delayed gaping, but only when they preceded the action-related transition - thus, the same perturbation might have an impact or not, depending on the transition latency in that particular trial. Our results suggest a distributed attractor network model of taste processing, and a dynamical role for cortex in driving motor behavior.

neuroscience↗

bioRxiv2018

A triterpenoid saponin, Spergulin-A from Glinus oppositifolius is a potent immunostimulator and antileishmanial agent

Present chemotherapeutics are inadequate against visceral leishmaniasis (VL) an immunosuppressive ailment caused by Leishmania donovani. Despite the interest in plant-based drug development, an antileishmanial drug from plant source is unavailable. Glinus oppositifolius had been reported in favor of being immunomodulators along with other traditional uses. Novel anti-VL therapies can rely on host immune-modulation with associated leishmanicidal action. With this rationale, an n-BuOH fraction of the methanolic extract of the plant and isolated triterpenoid saponin Spergulin-A were evaluated against acellular and intracellular L. donovani. Immunostimulatory activity of them was confirmed by elevated TNF-a and extracellular NO production from treated M{Phi}s and was found nontoxic to the host cells. Identification and structure confirmation for isolated Spergulin-A was performed by ESI-MS,13C, and 1H NMR. Spergulin-A was found ineffective against the acellular forms while, against the intracellular parasites at 30g/ml, the reduction was 92.6% after 72h. Spergulin-A enhanced ROS and nitric oxide (NO) release and changes in Gp91-phox, i-NOS, and pro and anti-inflammatory cytokines elaborated its intracellular anti-leishmanial activity. The results supported that G. oppositifolius and Spergulin-A can potentiate new lead molecules for the development of alternative drugs against VL.\n\nAuthor summaryVisceral Leishmaniasis (VL) is prevalent in tropical and temperate regions and is endemic in 88 countries with an estimated yearly incidence of 1-1.5 million cases of cutaneous leishmaniasis and 500,000 cases of VL, of which 70,000 people die every year. More than 90% of cases occur in India, Bangladesh, Nepal, Sudan, Ethiopia, and Brazil with an estimated incidence of at least 500,000 new cases and 50,000 deaths each year.\n\nThis work highlights the anti-leishmanial effect of a triterpenoid saponin that was extracted from a tropical plant, Glinus oppositifolius, commonly found in Asian and parts of African countries. The drug showed potent Leishmanicidal activity against Leishmania donovani at very low concentration. As the application of the conventional drugs (pentavalent antimoniates, amphotericin B, and pentamidine) is limited due to low efficacy, life-threatening side effects, high toxicity, induction of parasite resistance, length of treatment and high cost and anti-leishmanial vaccines may not become available in the near future, so plant extracts or plant compounds, represent a valuable source of new medicinal agents and alternative, effective and less toxic treatments, leading to a search for natural products with a potential leishmanicidal action. Being an immunosuppressive disease efficacy against VL can be demonstrated against intracellular parasites in the lights of emphasizing host M{Phi} immunostimulation as elaborated precisely in the present study.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC=\"FIGDIR/small/458653_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (30K):\norg.highwire.dtl.DTLVardef@f93fa1org.highwire.dtl.DTLVardef@1c073f0org.highwire.dtl.DTLVardef@1fbb86aorg.highwire.dtl.DTLVardef@1085c11_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2018

Global identification of functional microRNA::mRNA interactions in Drosophila

MicroRNAs (miRNAs) are key mediators of post-transcriptional gene expression silencing. Although Drosophila has been of critical importance for miRNA discovery, biogenesis and function, there has been no comprehensive experimental annotation of functional miRNA target sites. To close this gap, we generated the first in vivo map of miRNA::mRNA interactions in Drosophila melanogaster, making use of crosslinked nucleotides in Argonaute (AGO) crosslinking and immunoprecipitation (CLIP) experiments that enable an unambiguous assignment of miRNAs to AGO binding sites at much higher signal-to-noise ratio than computational predictions alone.\n\nAbsolute quantification of cellular miRNA levels showed the miRNA pool in Drosophila cell lines to be more diverse than previously reported. Benchmarking two different CLIP approaches, we identified a similar predictive potential to unambiguously assign thousands of miRNA::mRNA pairs from AGO1 interaction data at unprecedented depth. Quantitative RNA-Seq and subcodon-resolution ribosomal footprinting data upon AGO1 depletion enabled the determination of miRNA-mediated effects on target expression and translation. We thus provide the first comprehensive resource of miRNA target sites as well as their quantitative functional impact in Drosophila.

systems biology↗

bioRxiv2018

The role of the gustatory cortex in incidental experience-evoked enhancement of later taste learning

The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with incidental stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste pre-exposure, TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (cFos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change cFos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA related cFos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

neuroscience↗

bioRxiv2018

Deciphering human ribonucleoprotein regulatory networks

RNA-binding proteins (RBPs) control and coordinate each stage in the life cycle of RNAs. Although in vivo binding sites of RBPs can now be determined genome-wide, most studies typically focused on individual RBPs. Here, we examined a large compendium of 114 high-quality transcriptome-wide in vivo RBP-RNA cross-linking interaction datasets generated by the same protocol in the same cell line and representing 64 distinct RBPs. Comparative analysis of categories of target RNA binding preference, sequence preference, and transcript region specificity was performed, and identified potential posttranscriptional regulatory modules, i.e. specific combinations of RBPs that bind to specific sets of RNAs and targeted regions. These regulatory modules encoded functionally related proteins and exhibited distinct differences in RNA metabolism, expression variance, as well as subcellular localization. This integrative investigation of experimental RBP-RNA interaction evidence and RBP regulatory function in a human cell line will be a valuable resource for understanding the complexity of post-transcriptional regulation.

genomics↗

bioRxiv2018

SSMART: Sequence-structure motif identification for RNA-binding proteins

MotivationRNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized.\n\nResultsWe developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3 UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP.\n\nAvailabilitySSMART is freely available at https://ohlerlab.mdc-berlin.de/software/SSMART_137/\n\nContactuwe.ohler@mdc-berlin.de

bioinformatics↗