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

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 ß-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here, we define the specific metabolic pathway by which O-GlcNAc transferase (ogt-1) loss of function mediates increased regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans, we find that glycolysis, serine synthesis pathway (SSP), one-carbon metabolism (OCM), and the downstream transsulfuration metabolic pathway (TSP) are all essential in this process. The regenerative effects of ogt-1 mutation are abrogated by genetic and/or pharmacological disruption of OCM and the SSP linking OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 independent shunt pathway. These results are further supported by RNA sequencing that reveals dramatic transcriptional changes by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP, and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury.

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

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 1.5 years who was diagnosed with synovial chondromatosis of the hip joint with axial ankylosing spondylitis and was managed operatively. We here review briefly the clinical manifestations, pathogenesis, diagnosis, previously reported cases as well as treatment of synovial chondromatosis in patients with immune-mediated inflammatory arthritides. There should be a high index of suspicion to diagnose synovial chondromatosis in association with inflammatory arthritides. We also believe that surgical management is an effective method of treatment of an established synovial chondromatosis of the hip joint. Keywords: ankylosing spondylitis; case reports; hip joint; synovial chondromatosis.

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. There were 368 mothers with single full term live low birth weight babies (cases) and 736 mothers with single full term live normal birth weight babies (controls) matched on babies' gender and place of delivery included in the study. Multivariable conditional logistic regression analysis was used to eliminate the effects of potential confounders and to identify the independent effect of various risk factors associated with low birth weight. RESULTS: A total of 1104 respondents (1 case : 2 controls) were included in the study. Multivariable conditional logistic regression analysis revealed that maternal height <146 cm [AOR 5.14, (95%CI:2.03-13.01),(p=0.001)], maternal weight ?50 kg [AOR 3.75,(95%CI:2.15-6.56), (p<0.001)], primi-parity [AOR 4.58, (95%CI:1.71-12.25),(p=0.002)], multi-parity [AOR 3.01,(95%CI: 1.11-8.12),(p=0.030)], rest in day time ?2 hours [AOR 3.68, (95%CI: 2.01-6.75),(p<0.001)], rest in night time for <8 hours [AOR 5.76, (95%CI: 2.32-14.33), (p<0.001)], Iron and folic acid consumption for ?60 days [AOR 5.47, (95%CI: 2.73-10.95),(p<0.001)], Iron and folic acid consumption for 61-120 days [AOR 3.04, (95%CI: 1.90-4.87),(p<0.001), no calcium consumption [AOR 3.00, (95%CI: 1.78-5.04),(p<0.001)] were the significant risk factors associated with Low birth weight Conclusions: Height and weight of women, parity, duration of rest in day time and night time, consumption of Iron and folic acid and calcium were the maternal and obstetric determinants for the occurrence of low birth weight.

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. Search 2 considers associations between offspring DNA methylation at genes found in the first search and growth-related, cardiometabolic and cognitive outcomes. Search 3 isolates those studies explicitly linking maternal nutritional exposure to offspring phenotype via DNA methylation. Finally, we compile all candidate genes and regions of interest identified in the searches and describe their genomic locations, annotations and coverage on the Illumina Infinium Methylation beadchip arrays. Results: We summarize findings from the 34 studies found in the first search, the 31 studies found in the second search and the eight studies found in the third search. We provide details of all regions of interest within 45 genes captured by this review. Conclusions: Many studies have investigated imprinted genes as priority loci, but with the adoption of microarray-based platforms other candidate genes and gene classes are now emerging. Despite a wealth of information, the current literature is characterized by heterogeneous exposures and outcomes, and mostly comprise observational associations that are frequently underpowered. The synthesis of current knowledge provided by this review identifies research needs on the pathway to developing possible early life interventions to optimize lifelong health.