Vikas Pareek

A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome.

Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological features are in favor of our hypothesis, additional studies including animal models are warranted to validate our proposition. Such studies are likely to unfold ZIKV-microcephaly association and may help in devising methods to combat it.

Regulatory role of NGFs in neurocognitive functions

Abstract Nerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain. They have also been associated extensively with brain disorders characterized by neurocognitive dysfunction. In the present article, we aimed to make an exhaustive review of literature to get a comprehensive view on the role of NGFs in neurocognitive functions in health and disease. Starting with historical perspective, distribution in adult brain, implied molecular mechanisms, and developmental basis, this article further provides a detailed account of NGFs’ role in specified neurocognitive functions. Furthermore, it discusses plausible NGF-based homeostatic and adaptation mechanisms operating in the pathogenesis of neurocognitive disorders and has presents a survey of such disorders. Finally, it elaborates on current evidence and future possibilities in therapeutic applications of NGFs with an emphasis on recent research updates in drug delivery mechanisms. Conclusive remarks of the article make a strong case for plausible role of NGFs in comprehensive regulation of the neurocognitive functions and pathogenesis of related disorders and advocate that future research should be directed to explore use of NGF-based mechanisms in the prevention of implicated diseases as well as to target these molecules pharmacologically.

Establishing Identity from the Skeletal Remains: In Reference of Alum Bheg a Martyr from 1857 Indian Freedom Struggle

Introduction: We undertook the present study to analyze morphological features of a skull supposed to be that of Alum Bheg, a martyr from 1857 Indian Freedom Struggle (also called Sepoy Mutiny), using established methods to validate identity with regards to age and height as available in the note found with the skull (about 32 year and 5 feet 71⁄2 inch). Methods: Identification of sex of the skull was done based on established criteria. Analysis for closure of skull sutures (cranial and facial) and measurement of orbitomedial (OM) & maxillomedial (MM) facial anthropometric lines were undertaken to provide an estimated age against each examined suture as well as group of sutures through established scoring systems. Further, approximate height of individual was estimated from skull length using regression equations from a reference adult Indian male population. Results: Established criteria confirmed that the skull was of a male individual and skull sutures and age related morphological changes in bones indicate that it belonged to an individual in age range 20 -50 years with an average of 30 years and approximate height between 5 feet 8.2 inch to 6 feet 1.3 inch. Discussion: Based on our observations we suggest that the skull belonged to a male individual around 30 years of age and height 5 feet 8.2 inch to 6 feet 1 inch. The observed values are in approximation with that mentioned in the historical note and slight differences may be attributed either to gross reporting of original values or limitations of anthropometric analysis.

Commentary: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome

Citation: Faiq MA, Kumar A, Singh HN, Pareek V and Kumar P (2018) Commentary: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome. Front. Microbiol. 9:190. doi: 10.3389/fmicb.2018.00190 Commentary: A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome

Altered Expression Of A Unique Set Of Genes Reveals Complex Etiology Of Schizophrenia

Purpose The etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality. Materials and Methods GSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor-affy-package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The analysis of the derived genes performed using PANTHER Classification System and NCBI database. Results A set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions. The analyses unraveled genes implicated in biological processes and events, and molecular pathways relating basic neuronal functions. Conclusions The deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing in SCZ. Abbreviations Schizophrenia (SCZ), Hippocampus (HIP), Associative striatum (STR), Prefrontal cortex (PFC)