Dissociable Roles of the Nucleus Accumbens Core and Shell Subregions in the Expression and Extinction of Conditioned Fear

The nucleus accumbens (NAc), consisting of core (NAcC) and shell (NAcS) sub-regions, has primarily been studied as a locus mediating the effects of drug reward and addiction. However, there is ample evidence that this region is also involved in regulating aversive responses, but the exact role of the NAc and its subregions in regulating associative fear processing remains unclear. Here, we investigated the specific contribution of the NAcC and NAcS in regulating both fear expression and fear extinction in C57BL/6J mice. Using Arc expression as an indicator of neuronal activity, we first show that the NAcC is specifically active only in response to an associative fear cue during an expression test. In contrast, the NAcS is specifically active during fear extinction. We next inactivated each subregion using lidocaine and demonstrated that the NAcC is necessary for fear expression, but not for extinction learning or consolidation of extinction. In contrast, we demonstrate that the NAcS is necessary for the consolidation of extinction, but not fear expression or extinction learning. Further, inactivation of mGluR1 or ERK signaling specifically in the NAcS disrupted the consolidation of extinction but had no effect on fear expression or extinction learning itself. Our data provide the first evidence for the importance of the ERK/MAPK pathway as the underlying neural mechanism facilitating extinction consolidation within the NAcS. These findings suggest that the NAc subregions play dissociable roles in regulating fear recall and the consolidation of fear extinction, and potentially implicate them as critical regions within the canonical fear circuit

NRP2 transcriptionally regulates its downstream effector WDFY1.

Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, essential for promotion of oncogenic activation and cancer cell survival. Here, we have delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our results indicated that NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells. Thus, inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce cell death in metastatic cancer

Interpreting the HI 21-cm cosmology maps through Largest Cluster Statistics -- I: Impact of the synthetic SKA1-Low observations

We analyse the evolution of the largest ionized region using the topological and morphological evolution of the redshifted 21-cm signal coming from the neutral hydrogen distribution during the different stages of reionization. For this analysis, we use the "Largest Cluster Statistics" - LCS. We mainly study the impact of the array synthesized beam on the LCS analysis of the 21-cm signal considering the upcoming low-frequency Square Kilometer Array (SKA1-Low) observations using a realistic simulation for such observation based on the 21cmE2E-pipeline using OSKAR. We find that bias in LCS estimation is introduced in synthetic observations due to the array beam. This in turn shifts the apparent percolation transition point towards the later stages of reionization. The biased estimates of LCS, occurring due to the effect of the lower resolution (lack of longer baselines) and the telescope synthesized beam will lead to a biased interpretation of the reionization history. This is important to note while interpreting any future 21-cm signal images from upcoming or future telescopes like the SKA, HERA, etc. We conclude that one may need denser $uv$-coverage at longer baselines for a better deconvolution of the array synthesized beam from the 21-cm images and a relatively unbiased estimate of LCS from such images.Comment: 37 pages, 14 figures, text revised, Comments are welcom

A study to assess the level of knowledge regarding prevention and management of acute respiratory infection among mothers of children 0-5 years in selected hospital in Siliguri

Background: In developing countries like India acute respiratory infection (ARI) contributes in child mortality upto 75% and out of 10, 7 deaths are due to ARI. The knowledge of the mothers towards the disease is a significant determinant of child’s health.Methods: A descriptive cross-sectional study included 100 mothers of children 0-5 years admitted in pediatric ward and postnatal ward in selected hospital Siliguri during the year 2022 in the month of March. Data was collected using structured interview method.Results: 20% of mothers have good knowledge in prevention and 33% had good knowledge in management of ARI.Conclusions: As the leading cause of death among children, knowledge assessment about ARI among the mothers is very important, which helps for better understanding of the intensity of the problem

Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy-resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer

Mergers and acquisitions: A comparative review of literature

The paper aims to review scholastic research on the effect of M&As on firm performance and present a comparative analysis of Indian M&As vis­a-vis those occurring in other nations. 108 articles in referred journals published between 2005 and 2015 have been surveyed with a focus on comparing firm performance parameters prior and post the M&A. Firm performance has been inspected via three measures i.e. accounting measures, stock market performance measures and qualitative measures. On the basis of these three measures, literature on mergers in India with those occurring in another 23 countries was compared. The review has shown that irrespective of the nation, M&As may impact the accounting and stock market performance measures of the acquirer and target firms in a positive, negative or mixed manner. M&As in nations other than India have received more academic attention with respect to the effect on qualitative issues like cultural compatibility, downsizing and innovation. Cultural incompatibility and downsizing are problems of M&As in India as well as other nations. Indian domestic M&As have resulted in greater market share whereas majority of the M&As in other nations have lost customer base. Although literature studying the outcomes of M&As on firm performance from a pre-post perspective are multifarious, a comparative assessment of the studies on M&As occurring in India with those carried out in other nations of the world is a novel attempt

Two Dosages of Dexamethasone (2 mg and 4 mg) as Analgesic Adjuvant to Levobupivacaine in Ultrasound-guided Brachial Plexus Block in Upper Limb Surgery- A Randomised Clinical Trial

Introduction: Perineural dexamethasone gives promising results in prolonging duration of analgesia in brachial plexus block. Doses between 1 to 10 mg have been used but the optimum dose is not yet settled. Aim: To compare the analgesic efficacy of two low doses of dexamethasone in Ultrasonography (USG)-guided brachial plexus block for planned upper limb surgery. Materials and Methods: A double-blind randomised clinical trial was conducted with 126 adult patients of either sex, randomised in equal numbers to 2 mg and 4 mg dexamethasone groups, the steroid being administered in conjunction with 0.5% levobupivacaine. Time to onset of sensory and motor blocks, duration of analgesia, duration of motor block, total consumption of analgesics in the first 24 hours postoperative period, haemodynamic parameters and features of neurotoxicity were compared. Tramadol 50mg intravenous was permitted as rescue analgesic. Results: No significant differences in onset of sensory and motor blocks were encountered. Duration of sensory block with 4 mg {median (Interquartile range); 1080 (900-1140) min} clearly exceeded that with 2 mg {840 (720-960) min} (p-value<0.001) dexamethasone. Duration of motor block was also greater with 4 mg dexamethasone {1080 (1020-1170) versus 870 (810-990)min} (p-value<0.001). Total analgesic consumption in first 24 hours was 225 (175-250) mg versus 100 (75-200) mg in 2 mg and 4 mg groups respectively (p-value<0.001). No features of neurotoxicity were encountered in either group. Conclusion: Perineural dexamethasone 4 mg gives better results as analgesic adjuvant to bupivacaine compared to 2mg in brachial plexus block for upper limb surgery without increasing adverse effects

Geochemical cycling during subduction initiation: Evidence from serpentinized mantle wedge peridotite in the south Andaman ophiolite suite

The ophiolite suite from south Andaman Islands forms part of the Tethyan Ophiolite Belt and preserves the remnants of an ideal ophiolite sequence comprising a basal serpentinized and tectonised mantle peridotite followed by ultramafic and mafic cumulate units, basaltic dykes and spilitic pillow basalts interlayered with arkosic wacke. Here, we present new major, trace, rare earth (REE) and platinum group (PGE) element data for serpentinized and metasomatized peridotites (dunites) exposed in south Andaman representing the tectonized mantle section of the ophiolite suite. Geochemical features of the studied rocks, marked by Al2O3/TiO2 > 23, LILE-LREE enrichment, HFSE depletion, and U-shaped chondrite-normalized REE patterns with (La/Sm)N > 1 and (Gd/Yb)N < 1, suggest contributions from boninitic mantle melts. These observations substantiate a subduction initiation process ensued by rapid slab roll-back with extension and seafloor spreading in an intraoceanic fore-arc regime. The boninitic composition of the serpentinized peridotites corroborate fluid and melt interaction with mantle manifested in terms of (i) hydration, metasomatism and serpentinization of depleted, MORB-type, sub-arc wedge mantle residual after repeated melt extraction; and (ii) refertilization of refractory mantle peridotite by boninitic melts derived at the initial stage of intraoceanic subduction. Serpentinized and metasomatized mantle dunites in this study record both MOR and intraoceanic arc signatures collectively suggesting suprasubduction zone affinity. The elevated abundances of Pd (4.4–12.2 ppb) with high ΣPPGE/ΣIPGE (2–3) and Pd/Ir (2–5.5) ratios are in accordance with extensive melt-rock interaction through percolation of boninitic melts enriched in fluid-fluxed LILE-LREE into the depleted mantle after multiple episodes of melt extraction. The high Pd contents with relatively lower Ir concentrations of the samples are analogous to characteristic PGE signatures of boninitic magmas and might have resulted by the infiltration of boninitic melts into the depleted and residual mantle wedge peridotite during fore-arc extension at the initial stage of intraoceanic subduction. The PGE patterns with high Os + Ir (2–8.6 ppb) and Ru (2.8–8.4 ppb) also suggest mantle rejuvenation by infiltration of melts derived by high degree of mantle melting. The trace, REE and PGE data presented in our study collectively reflect heterogeneous mantle compositions and provide insights into ocean-crust-mantle interaction and associated geochemical cycling within a suprasubduction zone regime. Keywords: South Andaman Ophiolite, Mantle peridotite, Metasomatism, Geochemical cycling, Subduction initiatio

Assessing vegetation fragmentation and plantation efficiency in an intertidal mudflat of Eastern India using Radar Forest Degradation Index and spatial metrics

Potentiality of Synthetic Aperture Radar (SAR) based Radar Forest Degradation Index (RFDI) combined with field observations for monitoring spatio-temporal dynamics of intertidal mudflat vegetation was assessed in this study. Five vegetation zones were delineated in the Junput mudflat of eastern India with very high classification accuracy (Kappa coefficient ≥ 0.79). Fragmentation and coalescence patterns of different vegetation zones under two plantation initiatives were also analysed by different spatial metrics. Results reveal gradual degradation of tree dominated vegetation zones and growth of shrub dominated and herbaceous ones from 2007 to 2019. Plantation of exotic species like Eucalyptus globulus and Casuarina equisetifolia along the shoreline had been found to be less effective against storms and sea surges. Conversely, native mangrove plantations and associated herbs had demonstrated remarkable growth in the intertidal areas. Based on the findings, the study pointed out that a zone-wise cum site-specific plantation strategy is needed towards developing effective bio-shields

Dnmt3a Is a Haploinsufficient Tumor Suppressor in CD8+ Peripheral T Cell Lymphoma

<div><p>DNA methyltransferase 3A (DNMT3A) is an enzyme involved in DNA methylation that is frequently mutated in human hematologic malignancies. We have previously shown that inactivation of Dnmt3a in hematopoietic cells results in chronic lymphocytic leukemia in mice. Here we show that 12% of Dnmt3a-deficient mice develop CD8+ mature peripheral T cell lymphomas (PTCL) and 29% of mice are affected by both diseases. 10% of <i>Dnmt3a</i>^<i>+/-</i> mice develop lymphomas, suggesting that Dnmt3a is a haploinsufficient tumor suppressor in PTCL. DNA methylation was deregulated genome-wide with 10-fold more hypo- than hypermethylated promoters and enhancers, demonstrating that hypomethylation is a major event in the development of PTCL. Hypomethylated promoters were enriched for binding sites of transcription factors AML1, NF-κB and OCT1, implying the transcription factors potential involvement in Dnmt3a-associated methylation. Whereas 71 hypomethylated genes showed an increased expression in PTCL, only 3 hypermethylated genes were silenced, suggesting that cancer-specific hypomethylation has broader effects on the transcriptome of cancer cells than hypermethylation. Interestingly, transcriptomes of <i>Dnmt3a</i>^<i>+/-</i> and <i>Dnmt3a</i>^<i>Δ/Δ</i> lymphomas were largely conserved and significantly overlapped with those of human tumors. Importantly, we observed downregulation of tumor suppressor p53 in <i>Dnmt3a</i>^<i>+/-</i> and <i>Dnmt3a</i>^<i>Δ/Δ</i> lymphomas as well as in pre-tumor thymocytes from 9 months old but not 6 weeks old <i>Dnmt3a</i>^<i>+/-</i> tumor-free mice, suggesting that p53 downregulation is chronologically an intermediate event in tumorigenesis. Decrease in p53 is likely an important event in tumorigenesis because its overexpression inhibited proliferation in mouse PTCL cell lines, suggesting that low levels of p53 are important for tumor maintenance. Altogether, our data link the haploinsufficient tumor suppressor function of Dnmt3a in the prevention of mouse mature CD8+ PTCL indirectly to a <i>bona fide</i> tumor suppressor of T cell malignancies p53.</p></div