let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following injury.

Neuronal injury often leads to devastating consequences such as loss of senses or locomotion. Restoration of function after injury relies on whether the injured axons can find their target cells. Although fusion between injured proximal axon and distal fragment has been observed in many organisms, its functional significance is not clear. Here, using Caenorhabditis elegans mechanosensory neurons, we address this question. Using two femtosecond lasers simultaneously, we could scan and sever posterior lateral microtubule neurons [posterior lateral microtubules (PLMs)] on both sides of the worm. We showed that axotomy of both PLMs leads to a dramatic loss of posterior touch sensation. During the regenerative phase, only axons that fuse to their distal counterparts contribute to functional recovery. Loss of let-7 miRNA promotes functional restoration in both larval and adult stages. In the L4 stage, loss of let-7 increases fusion events by increasing the mRNA level of one of the cell-recognition molecules, CED-7. The ability to establish cytoplasmic continuity between the proximal and distal ends declines with age. Loss of let-7 overcomes this barrier by promoting axonal transport and enrichment of the EFF-1 fusogen at the growing tip of cut processes. Our data reveal the functional property of a regenerating neuron.

Expression profile of diagnostic genes in oral submucous fibrosis.

Oral Submucous Fibrosis (OSMF) is a chronic precancerous disorder of the oral mucosa caused by chewing of areca nut and its other variants. Chewing of areca nuts leads to dysregulated expression of specific genes, leading to various premalignant or malignant disorders. This study aimed to determine the differential expression of the diagnostic genes (MYH6, TNNT3, MYL1, and TPM2) in healthy controls and OSMF patients using saliva and tissue samples, determining the histopathological grade of the clinical samples. A total of 20 patients were included in the study and were divided into two groups: Group I consisted of 10 healthy patients (control group) and Group II consisted of 10 OSMF patients. Unstimulated whole saliva samples were collected from both groups, and the tissue samples were divided into two parts: one for RT-qPCR analysis and the other for histopathological assay. The expression profile of genes concerning OSMF saliva and tissue samples was significantly upregulated compared to the healthy control, and all the clinical samples of the study were categorized into histopathological grade 1. The findings of this study concluded that these genes can be referred to as diagnostic genes for OSMF in early and very early clinical samples, and saliva can be used as a promising diagnostic tool for early OSMF studies.

Empathic Accuracy Task: Indian Adaptation and Validation.

Background: The Empathic Accuracy Task (EAT) is an objective measure to assess empathic accuracy. Due to the variability in the number and linked emotions of the narrated events, we adapted EAT for the Indian sociocultural setting as Indian EAT (I-EAT). Methods: Eight videos were adapted in three languages (English, Hindi, and Kannada), narrating emotional events with a uniform representation of age groups, different emotions, and sex. The adapted I-EAT was then validated by cross-sectional comparison with different tests similar to EAT and those that assessed concepts different from or similar to empathy, in 29 healthy young adults, 23 healthy older adults (aged ≥60 years) along with clinical groups of 15 young people with depression, 15 older people with depression, and 15 young people with schizophrenia. Results: We selected eight videos with good content validity and internal consistency (Cronbach's alpha = 0.73. We obtained satisfactory concurrent validity of the EAT scores with the self-reported empathic assessments using the Questionnaire of Cognitive and Affective Empathy (Cognitive empathy score = 0.29, p = .034; Total score = 0.29, p = .035) and Interpersonal Reactivity Index (Empathic concern score = 0.45, p = .001). Good divergent validity was revealed in the high inverse correlation recorded with the Apathy Evaluation Scale ( = -0.67, p < .001). I-EAT did not correlate significantly with measures of social cognition. Known-groups validity was adequate in young adults with the significantly lower EAT scores (Cohen's d: 0.77 to 1.15) in the Schizophrenia group and higher EAT-N scores (Cohen's d: 0.51) in the Depression group, compared to the Healthy group. The Healthy group of the geriatric population also achieved significantly higher EAT scores (Cohen's d: 0.71 to 0.85) than the Depression group. Conclusion: With a good validity and internal consistency, I-EAT can be used in the Indian population to assess empathic accuracy without compromising performance of the original EAT.

Bacteriophages Can Make a Difference in Water Quality: Evidence From a Community-Based Study From North India.

Background and objectives Diarrhoea is a preventable and treatable faecal-oral disease. Despite significant inputs from the health and non-health sector in the treatment and prevention of diarrhoea, it remains a significant contributor to under-five-years children mortality and exerts profound effects on their growth and development. Bacteriophage has the potential to prevent diarrhoea. Bacteriophage status may influence the extent of diarrhoea. The objectives of the study were a) to assess the bacteriophage status and quality of water based on the Most Probable Number (MPN) count in the drinking water of under-five years children, and b) to find the association of the extent of diarrhoea with the bacteriophage status and quality of drinking water of under-five-years children in rural areas of Varanasi. Methods This is a community-based cross-sectional study done in the Chiraigaon community development block in a rural area of Varanasi. Water samples were collected and analysed in the Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi. Results The result of the study was that bacteriophage is present in 118 samples of water, whereas bacteriophage for Escherichia coli (E. coli), Klebsiella, and Vibrio were present in the drinking water of 81.1%, 53.8%, and 25.8% of under-five-years children, respectively. The water quality was highly satisfactory in 41.7% of samples and unsatisfactory in 15.2% of samples (p<0.004). All samples with highly satisfactory water quality had bacteriophages. Diarrhoea was present in 57.14% of samples without bacteriophage and 24.5% in samples with bacteriophage (p<0.01). The unadjusted odds ratio is 4.09. Interpretation and conclusions The odds of diarrhoea are four times higher in the water sample without bacteriophage than in the water sample in which bacteriophage is present. Bacteriophage study in preventing diarrhoea in children under five and health risk assessment call for focus.

Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells.

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal 'starburst' amacrine cells is one of the several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ~3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Taken together, these results provide direct support for the 'space-time wiring' model for direction selectivity.

Everything is not on track in management of diarrhoea in under-five children: Evidence from rural area of India.

CONTEXT: Diarrhea is one of the leading causes of death and morbidity in under-five children. Effective management can significantly influence survival of children with diarrhea. OBJECTIVES: This study was carried out to assess extent of diarrhea, its source of treatment, and type of therapy. SETTINGS AND DESIGN: This snapshot study was conducted in rural setting of India. METHODS AND MATERIAL: This study was conducted on 217 under-five children selected through multistage sampling procedure. STATISTICAL ANALYSIS USED: Statistical association of diarrhea with age and gender of children was established by computing Chi-square. RESULTS: Period prevalence (Recall period 2 weeks of visit) of diarrhea in rural under-five children was 35.9% (95%C.I. 29.3-42.2%). Highest prevalence in age group 0-12 months (47.8%) and lowest in 49-59 months (18.2%). Number of episode per child is 1.08. Diarrhea was watery in 69.4%. Quacks were treatment provider for 36.4% cases. In 17.6% episodes, no treatment was taken. Only 9.4% episodes were treated in government facilities. For the treatment of diarrhea, antibiotic was used in 71.8% cases, ORS use was 33.3% cases, and zinc was used 21.8% of diarrhea episodes. CONCLUSIONS: Diarrhea is a significant problem in under-five children from a rural area of India. In spite of existence of National Program for Control of Diarrheal Diseases (NPCDD) since four decades, management of diarrhea is not on track. Focusing on primary care provision to under-five children can help in bringing the management of diarrhea on track.

Network neurobiology of electroconvulsive therapy in patients with depression.

Graph theory, a popular analytic tool for resting state fMRI (rsfMRI) has provided important insights in the neurobiology of depression. We aimed to analyze the changes in the network measures of segregation and integration associated with the administration of ECT in patients with depression and to correlate with both clinical response and cognitive deficits. Changes in normalised clustering coefficient (γ), path length (λ) and small-world (σ) index were explored in 17 patients with depressive episode before 1st and after 6th brief-pulse bifrontal ECT (BFECT) sessions. Significant brain regions were then correlated with differences in clinical and cognitive scales. There was significantly increased γ and σ despite significant increase in λ in several brain regions after ECT in patients with depression. The brain areas revealing significant differences in γ before and after ECT were medial left superior frontal gyrus, left paracentral lobule, right pallidum and left inferior frontal operculum; correlating with changes in verbal fluency, HAM-D scores and delayed verbal memory (last two regions) respectively. BFECT reorganized the brain network topology in patients with depression and made it more segregated and less integrated; these correlated with clinical improvement and associated cognitive deficits.

MPDB: Molecular Pathways Brain Database.

Molecular Pathways Brain Database (MPDB), is a novel database for molecular information of the brain pathways and is an initiative to provide an organized platform for researchers in the field of neuro-informatics. The database currently has information from 1850 molecules for three different sensory pathways namely olfactory transduction, photo transduction and long-term potentiation. The usefulness of the database is demonstrated by an analysis of the olfactory transduction pathway which helps understand their olfactory specifity and further indicates that some of the molecules have evolved independently among these organisms as per the need of time and function. The database is available for free at http://pranag.physics.iisc.ernet.in/mpdb/.

Differential alterations in the expression of neurotransmitter receptors in inner retina following loss of photoreceptors in rd1 mouse.

Loss of photoreceptors leads to significant remodeling in inner retina of rd1 mouse, a widely used model of retinal degeneration. Several morphological and physiological alterations occur in the second- and third-order retinal neurons. Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced. Retinal ganglion cells (RGCs) exhibit hyperactivity and aberrant spiking pattern, which adversely affects the quality of signals they can carry to the brain. To further understand the pathophysiology of retinal degeneration, and how it may lead to aberrant spiking in RGCs, we asked how loss of photoreceptors affects some of the neurotransmitter receptors in rd1 mouse. Using Western blotting, we measured the levels of several neurotransmitter receptors in adult rd1 mouse retina. We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type. Since GABAa receptor is expressed in several retinal layers, we employed quantitative immunohistochemistry to measure GABAa receptor levels in specific retinal layers. We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse. Specifically, we found that the number of GABAa-immunoreactive somas in the inner nuclear layer of rd1 mouse retina was significantly higher than in wild-type. These findings provide further insights into neurochemical remodeling in the inner retina of rd1 mouse, and how it might lead to oscillatory activity in RGCs.