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Abstract Background In light of several recent studies, there is evidence that the coronavirus disease 2019 (COVID-19) pandemic has caused various mental health concerns in the general population, as well as among healthcare workers (HCWs). The main aim of this study was to assess the psychological distress, burnout and structural empowerment status of HCWs during the COVID-19 outbreak, and to evaluate its predictors. Methods This multi-center, cross-sectional web-based questionnaire survey was conducted on HCWs during the outbreak of COVID-19 from August 2020 to January 2021. HCWs working in hospitals from 48 different countries were invited to participate in an online anonymous survey that investigated sociodemographic data, psychological distress, burnout and structural empowerment (SE) based on Depression Anxiety and Stress Scale 21 (DASS-21), Maslach Burnout Inventory (MBI) and Conditions for work effectiveness questionnaire (CWEQ_II), respectively. Predictors of the total scores of DASS-21, MBI and CWEQ-II were assessed using unadjusted and adjusted binary logistic regression analysis. Results Out of the 1030 HCWs enrolled in this survey, all completed the sociodemographic section (response rate 100%) A total of 730 (70.9%) HCWs completed the DASS-21 questionnaire, 852 (82.6%) completed the MBI questionnaire, and 712 (69.1%) completed the CWEQ-II questionnaire. The results indicate that 360 out of 730 responders (49.3%) reported severe or extremely severe levels of stress, anxiety, and depression. Additionally, 422 out of 851 responders (49.6%) reported a high level of burnout, while 268 out of 712 responders (37.6%) reported a high level of structural empowerment based on the DASS-21, MBI, and CWEQ-II scales, respectively. In addition, the analysis showed that HCWs working in the COVID-19 areas experienced significantly higher symptoms of severe stress, anxiety, depression and higher levels of burnout compared to those working in other areas. The results also revealed that direct work with COVID-19 patients, lower work experience, and high workload during the outbreak of COVID-19 increase the risks of negative psychological consequences. Conclusion Health professionals had high levels of burnout and psychological symptoms during the COVID-19 emergency. Monitoring and timely treatment of these conditions is needed.

Abstract Transforming growth factor β (TGFβ) pathway is a master regulator of cell proliferation, differentiation, and death. Deregulation of TGFβ signalling is well established in several human diseases including autoimmune disorders and cancer. Thus, understanding molecular pathways governing TGFβ signalling may help better understand the underlying causes of some of those conditions. Here, we show that a HECT domain E3 ubiquitin ligase TRIP12 controls TGFβ signalling in multiple models. Interestingly, TRIP12 control of TGFβ signalling is completely independent of its E3 ubiquitin ligase activity. Instead, TRIP12 recruits SMURF2 to SMAD4, which is most likely responsible for inhibitory monoubiquitination of SMAD4, since SMAD4 monoubiquitination and its interaction with SMURF2 were dramatically downregulated in TRIP12 -/- cells. Additionally, genetic inhibition of TRIP12 in human and murine cells leads to robust activation of TGFβ signalling which was rescued by re-introducing wildtype TRIP12 or a catalytically inactive C1959A mutant. Importantly, TRIP12 control of TGFβ signalling is evolutionary conserved. Indeed, genetic inhibition of Drosophila TRIP12 orthologue, ctrip, in gut leads to a reduced number of intestinal stem cells which was compensated by the increase in differentiated enteroendocrine cells. These effects were completely normalised in Drosophila strain where ctrip was co-inhibited together with Drosophila SMAD4 orthologue, Medea. Similarly, in murine 3D intestinal organoids, CRISPR/Cas9 mediated genetic targeting of Trip12 enhances TGFβ mediated proliferation arrest and cell death. Finally, CRISPR/Cas9 mediated genetic targeting of TRIP12 in MDA-MB-231 breast cancer cells enhances the TGFβ induced migratory capacity of these cells which was rescued to the wildtype level by re-introducing wildtype TRIP12. Our work establishes TRIP12 as an evolutionary conserved modulator of TGFβ signalling in health and disease.

Background: Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. Aim: of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved in neuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further explored in humans through clinical trials.Key Scientific Concepts of Review: Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neuropsychiatric disorders that frequently co-occur. Previous evidence suggests a shared genetic diathesis underlying the comorbidity of TS and OCD. This review aims to comprehensively summarize the current literature on the genetic factors linked with TS and its comorbidities, with a focus on OCD. Family studies, linkage analysis, cytogenetic studies, and genome-wide association studies (GWAS) have played a pivotal role in identifying common and rare genetic variants connected with TS and OCD. Although the genetic framework of TS and OCD is complex and multifactorial, several susceptibility loci and candidate genes have been identified that might play a crucial role in the pathogenesis of both disorders. Additionally, post-infectious environmental elements have also been proposed to contribute to the development of TS-OCD, although the dynamics between genetic and environmental factors is not yet fully understood. International collaborations and studies with well-defined phenotypes will be crucial in the future to further elucidate the genetic basis of TS and OCD and to develop targeted therapeutic strategies for individuals suffering from these debilitating conditions.

Abstract Background Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons’ blood, organs, or other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches. Methods The glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine immunodominant T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus. Results After rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans. Conclusions Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%–100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the in silico cloning of the vaccine into the pET28+(a) cloning vector. In conclusion, the vaccine candidate developed in this study is anticipated to augment the immune response in humans and effectively combat the virus. Nevertheless, it is imperative to conduct in vitro and in vivo assays to evaluate the efficacy of these vaccine candidates thoroughly. These evaluations will provide critical insights into the vaccine’s effectiveness and potential for further development.

Let Γ be a finite group with identity element e and let S ⊆ Γ − {e} which is inverse-closed, i.e., S = S−1 := {s−1 : s ∈ S}. An undirected Cayley graph on a group Γ with connection set S, denoted by Cay(Γ, S), is a graph with vertex set Γ and edges xy for all pairs x,y ∈ Γ such that xy−1 ∈ S. The dihedral group of order 2n, denoted by D2n, is a group generated by two elements a and b subject to the three relations: an = e, b2 = e, and bab−1 = a−1. In this paper, we investigate the Cayley graphs of the dihedral group for some connection sets S satisfying |S| = 1, 2, 3 by doing simulations using Wolfram Mathematica.

Mitochondrial dysfunction remains a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria, the power-generating organelle of the cell, have a dominant role in several processes associated with genomic integrity and cellular equilibrium. They are involved in maintaining optimal cell functioning and ensuring guidance against possible DNA damage, which could lead to mutations and the onset of diseases. Conversely, system perturbations, which could be due to environmental factors or senescence, induce changes in the physiological balance and result in mitochondrial function impairment.As a result, we present a general overview of the pathological pathways involved in Alzheimer's and Parkinson's diseases caused by changes in mitochondrial homeostasis. The focal point of this review is on mitochondrial dysfunction being a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria, which are common among the most recurring neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Are mitochondrial dysfunctions an early event in the progression of neuropathological processes? We discovered that mtDNA mutation is a major contributor to the metabolic pathology of most neurological disorders, causing changes in genes important for physiological homeostasis. As a result, genetic changes in presenilin, Amyloid-, ABAD, DJ-1, PINK-1, PARKIN, alpha-synuclein, and other important controlling genes occur. Therefore, we suggest possible therapeutic solutions.

To survive, animals maintain energy homeostasis by seeking out food. Compared to freely feeding animals, food-deprived animals may choose different strategies to balance both energy and nutrition demands, per the metabolic state of the animal. Serotonin mediates internal states, modifies existing neural circuits, and regulates animal feeding behavior, including in humans and fruit flies. However, an in-depth study on the neuromodulatory effects of serotonin on feeding microstructure has been held back for several technical reasons. Firstly, most feeding assays lack the precision of manipulating neuronal activity only when animals start feeding, which does not separate neuronal effects on feeding from foraging and locomotion. Secondly, despite the availability of optogenetic tools, feeding in adult fruit flies has primarily been studied using thermogenetic systems, which are confounded with heat. Thirdly, most feeding assays have used food intake as a measurement, which has a low temporal resolution to dissect feeding at the microstructure level. To circumvent these problems, we utilized OptoPAD assay, which provides the precision of optogenetics to control neural activity contingent on the ongoing feeding behavior. We show that manipulating the serotonin circuit optogenetically affects multiple feeding parameters state-dependently. Food-deprived flies with optogenetically activated and suppressed serotonin systems feed with shorter and longer sip durations and longer and shorter inter-sip intervals, respectively. We further show that serotonin suppresses and enhances feeding via 5-HT1B and 5-HT7 receptors, respectively.

Summary: When trapped in a physical restraint, animals must select an escape strategy to increase their chances of survival. After falling into an inescapable trap, they react with stereotypical behaviors that differ from those displayed in escapable situations. Such behaviors involve either a wriggling response to unlock the trap or feigning death to fend off a predator attack. The neural mechanisms that regulate animal behaviors have been well characterized for escapable situations but not for inescapable traps. We report that restrained vinegar flies exhibit alternating flailing and immobility to free themselves from the trap. We used optogenetics and intersectional genetic approaches to show that, while broader serotonin activation promotes immobility, serotonergic cells in the ventral nerve cord (VNC) regulate immobility states majorly via 5-HT7 receptors. Restrained and freely moving locomotor states are controlled by distinct mechanisms. Taken together, our study has identified serotonergic switches of the VNC that promote environment-specific adaptive behaviors.

Abstract The idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

The BRAF gene is responsible for transferring signals from outside of the cell to inside of the nucleus by converting a protein namely B-Raf through the RAS/MAPK pathway. This pathway contribute to cell division, proliferation, migration, and apoptotic cell death of human and animal. Mutation in this gene may cause the development of several cancers, including lung, skin, colon, and neuroblastoma. Currently, a few available drugs are being used that has developed by targeting the BRAF mutated protein, and due to the toxic side effects, patients suffer a lot during their treatment. Therefore this study aimed to identify potentially lead compounds that can target and block the expression of BRAF and subsequently inhibit the cancer. The hits were generated through the pharmacophore model-based virtual screening, molecular docking, pharmacohore model validation, ADME (absorption, distribution, metabolism, and excretion) analysis molecular dynamics (MD) simulation to find more suitable candidate against the overexpress BRAF gene. The pharmacophore based screening initially identified 14 k possible hits from online database which were further screened by ligand scout advance software to get hit compound. Based on molecular docking score of ZINC70454679 (-10.6 kcal/mol), ZINC253500968 (-9.4 kcal/mol), ZINC106887736 (-8.6 kcal/mol), and ZINC107434492 (-8.1 kcal/mol), pharmacophore feature and toxicity evaluation, we selected four possible lead compounds. The dynamic simulation with Schrodinger Maestro software was used to determine the stability of the potential lead candidates with target protein (PDB ID: 5VAM). The results showed that the newly obtained four compounds were more stable than the control ligand (Pub Chem ID: 90408826). The current results showed that the ZINC70454679, ZINC253500968, ZINC106887736, and ZINC107434492 compounds may be able to work against several cancers through targeting the BRAF overexpressed gene. To develop a novel drug candidate, however the evaluation of the web lab based experimental work are necessary to evaluate the efficiency of the each compound against the BRAF target gene.

There is a new public health catastrophe forbidding the world. With the advent and spread of 2019 novel coronavirus (2019-nCoV). Learning from the experiences of various countries and the World Health Organization (WHO) guidelines, social distancing, use of sanitizers, thermal screening, quarantining, and provision of lockdown in the cities being the effective measure that can contain the spread of the pandemic. Though complete lockdown helps in containing the spread, it generates complexity by breaking the economic activity chain. Besides, laborers, farmers, and workers may lose their daily earnings. Owing to these detrimental effects, the government has to open the lockdown strategically. Prediction of the COVID-19 spread and analyzing when the cases would stop increasing helps in developing a strategy. An attempt is made in this paper to predict the time after which the number of new cases stops rising, considering the strong implementation of lockdown conditions using three different techniques such as Decision Tree, Support Vector Machine, and Gaussian Process Regression algorithm are used to project the number of cases. Thus, the projections are used in identifying inflection points, which would help in planning the easing of lockdown in a few of the areas strategically. The criticality in a region is evaluated using the criticality index (CI), which is proposed by authors in one of the past of research works. This research work is made available in a dashboard to enable the decision-makers to combat the pandemic.

In this paper, we have applied the univariate time series model to predict the number of COVID-19 infected cases that can be expected in upcoming days in India. We adopted an Auto-Regressive Integrated Moving Average (ARIMA) model on the data collected from 31st January 2020 to 25th March 2020 and verified it using the data collected from 26th March 2020 to 04th April 2020. A nonlinear autoregressive (NAR) neural network was developed to compare the accuracy of predicted models. The model has been used for daily prediction of COVID-19 cases for next 50 days without any additional intervention. Statistics from various sources, including the Ministry of Health and Family Welfare (MoHFW) and http://covid19india.org/ are used for the study. The results showed an increasing trend in the actual and forecasted numbers of COVID-19 cases with approximately 1500 cases per day, based on available data as on 04th April 2020. The appropriate ARIMA (1,1,0) model was selected based on the Bayesian Information Criteria (BIC) values and the overall highest R2 values of 0.95. The NAR model architecture constitutes ten neurons, which was optimized using the Levenberg-Marquardt optimization training algorithm (LM) with the overall highest R2 values of 0.97.

Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of −10.4, −10.1, and −9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.

Psychedelic compounds that target the 5-HT2A receptor are reported to evoke psychoplastogenic effects, including enhanced dendritic arborization and synaptogenesis. Transcriptional regulation of neuronal plasticity-associated genes is implicated in the cytoarchitectural effects of serotonergic psychedelics, however, the transcription factors that drive this regulation are poorly elucidated. Here, we addressed the contribution of the transcription factor cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) in the regulation of neuronal plasticity-associated genes by the hallucinogenic 5-HT2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI). In vitro studies with rat cortical neurons indicated that DOI enhances the phosphorylation of CREB (pCREB) through mitogen-activated protein (MAP) kinase and calcium/calmodulin dependent kinase II (CaMKII) pathways, with both cascades contributing to the DOI-evoked upregulation of Arc, Bdnf1, Cebpb, and Egr2 expression, whilst the upregulation of Egr1 and cFos mRNA involved the MAP kinase and CaMKII pathway respectively. We observed a robust DOI-evoked increase in the expression of several neuronal plasticity-associated genes in the rat neocortex in vivo. This DOI-evoked upregulation of neuronal plasticity-associated genes was completely blocked by the 5-HT2A receptor antagonist MDL100,907 in vitro and was also abrogated in the neocortex of 5-HT2A receptor deficient mice. Further, 5-HT2A receptor stimulation enhanced pCREB enrichment at putative cAMP response element (CRE) binding sites in the Arc, Bdnf1, Cebpb, cFos, but not Egr1 and Egr2, promoters in the rodent neocortex. The DOI-mediated transcriptional induction of Arc, cFos and Cebpb was significantly attenuated in the neocortex of CREB deficient/knockout (CREBαδ KO) mice. Collectively, these results indicate that the hallucinogenic 5-HT2A receptor agonist DOI leads to a rapid transcriptional upregulation of several neuronal plasticity-associated genes, with a subset of them exhibiting a CREB-dependent regulation. Our findings raise the intriguing possibility that similar to slow-acting classical antidepressants, rapid-action serotonergic psychedelics that target the 5-HT2A receptor may also recruit the transcription factor CREB to enhance the expression of neuronal plasticity-associated genes in the neocortex, which could in turn contribute to the rapid psychoplastogenic changes evoked by these compounds.

Abstract The analysis of behavior requires that the underlying neuronal circuits are identified and genetically isolated. In several major model species—most notably Drosophila—neurogeneticists identify and isolate neural circuits with a binary heterologous expression-control system: Gal4–UASG. One limitation of Gal4–UASG is that expression patterns are often too broad to map circuits precisely. To help refine the range of Gal4 lines, we developed an intersectional genetic AND operator. Interoperable with Gal4, the new system’s key component is a fusion protein in which the DNA-binding domain of Gal4 has been replaced with a zinc finger domain with a different DNA-binding specificity. In combination with its cognate binding site (UASZ) the zinc-finger-replaced Gal4 (‘Zal1’) was functional as a standalone transcription factor. Zal1 transgenes also refined Gal4 expression ranges when combined with UASGZ, a hybrid upstream activation sequence. In this way, combining Gal4 and Zal1 drivers captured restricted cell sets compared with single drivers and improved genetic fidelity. This intersectional genetic AND operation presumably derives from the action of a heterodimeric transcription factor: Gal4-Zal1. Configurations of Zal1–UASZ and Zal1-Gal4-UASGZ are versatile tools for defining, refining, and manipulating targeted neural expression patterns with precision.

Abstract Background Optical silencing of activity provides a way to test the necessity of neurons in behaviour. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown to potently inhibit activity in cultured mammalian neurons and in Drosophila. Here, we test the usefulness of these channels in larval zebrafish, using spontaneous coiling behaviour as the assay. Results When the GtACRs were expressed in spinal neurons of embryonic zebrafish and actuated with blue or green light, spontaneous movement was inhibited. In GtACR1-expressing fish, only 3 μW/mm2 of light was sufficient to have an effect; GtACR2, which is poorly trafficked, required slightly stronger illumination. No inhibition was seen in non-expressing siblings. After light offset, the movement of GtACR-expressing fish increased, which suggested that termination of light-induced neural inhibition may lead to activation. Consistent with this, two-photon imaging of spinal neurons showed that blue light inhibited spontaneous activity in spinal neurons of GtACR1-expressing fish, and that the level of intracellular calcium increased following light offset. Conclusions These results show that GtACR1 and GtACR2 can be used to optically inhibit neurons in larval zebrafish with high efficiency. The activity elicited at light offset needs to be taken into consideration in experimental design, although this property can provide insight into the effects of transiently stimulating a circuit.

The control of movements is a fundamental feature shared by all animals. At the most basic level, simple movements are generated by coordinated neural activity and muscle contraction patterns that are controlled by the central nervous system. How behavioral responses to various sensory inputs are processed and integrated by the downstream neural network to produce flexible and adaptive behaviors remains an intense area of investigation in many laboratories. Due to recent advances in experimental techniques, many fundamental neural pathways underlying animal movements have now been elucidated. For example, while the role of motor neurons in locomotion has been studied in great detail, the roles of interneurons in animal movements in both basic and noxious environments have only recently been realized. However, the genetic and transmitter identities of many of these interneurons remains unclear. In this review, we provide an overview of the underlying circuitry and neural pathways required by Drosophila larvae to produce successful movements. By improving our understanding of locomotor circuitry in model systems such as Drosophila, we will have a better understanding of how neural circuits in organisms with different bodies and brains lead to distinct locomotion types at the organism level. The understanding of genetic and physiological components of these movements types also provides directions to understand movements in higher organisms.

Cardiac sarcomas are extremely rare primary malignant tumors of the heart. In this article, we present the case of a 70-year-old female, who was found to have a left atrial mass during a routine outpatient transthoracic echocardiography. Further investigation with cardiac magnetic resonance imaging confirmed the presence of a bilobulated mass with heterogeneous enhancement. Left atrial myxoma was the first diagnostic consideration, followed by other primary cardiac tumors, and thrombus. The patient subsequently underwent resection of the mass, utilizing cardiopulmonary bypass. Upon pathological examination, the mass was found to be an intimal sarcoma. The objective of this report is to describe a case of this rare disease entity, and to discuss its presentation, pathological findings and management.

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.

Primary effusion lymphoma (PEL) or body cavity lymphoma is a rare type of extra nodal lymphoma of B-cell origin that presents as lymphomatous effusion(s) without any nodal enlargement or tumor masses. It belongs to the group of AIDS related non-Hodgkin’s lymphomas. First described in 1996 in HIV infected individuals who were coinfected with Kaposi’s sarcoma-associated herpesvirus (KSHV) or HHV-8 virus, it was included as a separate entity in WHO classification of tumors of hematopoietic and lymphoid tissue in the year 2001. The definition included association with HHV-8 virus as a mandatory diagnostic criterion. However, cases were later reported where PEL-like disease process was diagnosed in HHV-8 negative patients. This was eventually recognized as a rare but distinct entity termed as “HHV-8-unrelated PEL-like lymphoma”. Herein, we are reporting a case of an elderly patient who presented with a large pleuropericardial effusion and was eventually diagnosed with this entity. Till date, only around 50 cases of HHV-8-unrelated PEL-like lymphoma have been reported and our case being EBV, HIV, and Hepatitis C negative makes it very unique and rare occurrence. We are also presenting a review of relevant literature focused mainly on comparing outcomes in patients treated with and without chemotherapy.

A male Drosophila model of locomotor deficit induced by chronic pentylenetetrazole (PTZ), a proconvulsant used to model epileptogenesis in rodents, has recently been described. Antiepileptic drugs (AEDs) ameliorate development of this behavioral abnormality. Time-series of microarray profiling of heads of male flies treated with PTZ has shown epileptogenesis-like transcriptomic perturbation in the fly model. Gender differences are known to exist in neurological and psychiatric conditions including epileptogenesis. We describe here the effects of chronic PTZ in Drosophila females, and compare the results with the male model. As in males, chronic PTZ was found to cause a decreased climbing speed in females. In males, overrepresentation of Wnt, MAPK, TGF-beta, JAK-STAT, Cell communication, and Dorso-Ventral axis formation pathways in downregulated genes was previously described. Of these, female genes showed enrichment only for Dorso-Ventral axis formation. Surprisingly, the ribosomal pathway was uniquely overrepresented in genes downregulated in females. Gender differences thus exist in the Drosophila model. Gender neutral, the developmental pathway Dorso-Ventral axis formation may be considered as the candidate causal pathway in chronic pentylenetetrazole induced behavioral deficit. Prior evidence of developmental mechanisms in epileptogenesis may support potential usefulness of the fly model. Given this, gender specific pathways identified here may provide a lead for further understanding brain dimorphism in neuropsychiatric disorders.

ANJUM HASAN History's Angel London. Bloomsbury. 2023. 288 pages. INDIAN NOVELIST Anjum Hasan dexterously weaves together the history of communal fault lines in History's Angel, her evocative new novel. The [...]

SUKRITA Salt and Pepper: Selected Poems Mumbai. Poetrywala. 2023.196 pages. INDIAN ACADEMIC AND POET Sukrita Paul Kumar's recent collection of selected poems, Salt and Pepper, traces the trajectory of the [...]