Basic Science and Pathogenesis.

Background: Despite the prevalence of Alzheimer's Disease in the aged human population and advancements in our understanding of the disease at the molecular level, we still lack a fundamental understanding of how cognitive dysfunction stems from alterations in cellular neuron dynamics and how it relates to the normal aging process. To address this gap in knowledge, we measured the breakdown of nervous system function with cellular resolution during normal aging and in an Alzheimer's Disease model.

Method: Employing comprehensive multi-neuron florescence microscopy in the nematode worm, C.

O-GlcNAc signaling increases neuron regeneration through one-carbon metabolism in .

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked β-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration.

Synovial Chondromatosis of Hip Joint in a Patient with Ankylosing Spondylitis: A Case Report.

Unlabelled: Synovial chondromatosis in association with ankylosing spondylitis is extremely rare and has been reported only once before and this case report is presenting a similar case. The knee is the preferential site of involvement with involvement of the hip being reported sparsely. We herein report a case of a 52-year-old male who came with complaints of the lower back pain for 5 years and left hip pain for 1.

Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.

Background: Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism.

Objective: We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771).

Design: We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array.

Maternal and Obstetric Factors Associated with Low Birth Weight.

Background: Low birth weight is a factor associated with perinatal, neonatal and post-neonatal morbidity and mortality and is associated with development of chronic diseases in adulthood. This study aimed to identify the maternal and obstetric factors associated with low birth weight in selected hospitals of Nepal.

Methods: Matched case control study was conducted in two tertiary level hospital of Nepal during May 2017 to April 2018.

Stress-responsive and metabolic gene regulation are altered in low S-adenosylmethionine.

S-adenosylmethionine (SAM) is a donor which provides the methyl groups for histone or nucleic acid modification and phosphatidylcholine production. SAM is hypothesized to link metabolism and chromatin modification, however, its role in acute gene regulation is poorly understood. We recently found that Caenorhabditis elegans with reduced SAM had deficiencies in H3K4 trimethylation (H3K4me3) at pathogen-response genes, decreasing their expression and limiting pathogen resistance.

Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism.

Background: Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course.

Methods: We review human intergenerational studies using a three-part search strategy. Search 1 investigates associations between preconceptional or pregnancy nutritional exposures, focusing on one-carbon metabolism, and offspring DNA methylation.

Identification and characterization of cis-regulatory elements 'insulator and repressor' in PPARD gene.

Aim: Identification and functional characterization of cis-regulatory elements in human PPARD gene.

Methods: We used various bioinformatic tools on the publicly available human genome and Encyclopedia of DNA Elements databases to explore potential cis-regulatory elements in PPARD gene region.

Results: We predicted an insulator and an enhancer element in intron 2 of PPARD gene.

Vitamin B supplementation influences methylation of genes associated with Type 2 diabetes and its intermediate traits.

Aim: To investigate the effect of B and/or folic acid supplementation on genome-wide DNA methylation.

Methods: We performed Infinium HumanMethylation450 BeadChip (Zymo Research, CA, USA) assay in children supplemented with B and/or folic acid (n = 12 in each group) and investigated the functional mechanism of selected differentially methylated loci.

Results: We noted significant methylation changes postsupplementation in B (589 differentially methylated CpGs and 2892 regions) and B + folic acid (169 differentially methylated CpGs and 3241 regions) groups.

Hypermethylated CpG sites in the MTR gene promoter in preterm placenta.

Aim: Altered maternal one-carbon metabolism influences placental DNA methylation patterns and 'programs' the fetus for noncommunicable diseases in adult life.

Experimental Procedures: Levels of plasma folate, vitamin B, homocysteine, mRNA and protein levels of MTHFR and MTR enzymes in placenta were compared among women delivering preterm (n = 83) and term (n = 75). MTR promoter CpG methylation was undertaken.

Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway.

PPAR signaling pathway is a key modulator of liver proteome in pups born to vitamin B(12) deficient rats.

Unlabelled: Maternal nutritional deficiency in-utero is known to predict risk of complex disorders like cardiovascular disease, diabetes and many neurological disorders in the offspring and vitamin B12 is one such critical micronutrient. Here we performed 2D-DIGE followed by MALDI TOF/TOF analysis to identify proteins that are differentially expressed in liver of pups born to mothers fed vitamin B12 deficient diet vis-à-vis control diet. To further establish causality, we analyzed the effect of B12 rehabilitation at parturition on the protein levels and the phenotype in pups.