Manifestations of Polycystic Ovary Syndrome are Similar Regardless of the Degree of Menstrual Cycle Variation

Background: Menstrual irregularities may predict over adverse consequences in polycystic ovary syndrome (PCOS).Objective: To observe the relation of variants of menstrual cycles with clinical and biochemical features of PCOS.Methods: This cross-sectional study encompassed 200 PCOS women diagnosed by Rotterdam criteria and 120 age-matched healthy controls. Subgroups were classified according to menstrual cycle length as: polymenorrheic (<21 days), eumenorrheic (21-35 days), oligomenorrheic (36 days-3 months) and amenorrheic (>3 months). Glucose was measured by glucose oxidase, lipid by glycerol phosphate dehydrogenenase-peroxidase and all hormones by chemiluminescent immuno-assay method.Results: Around 86% of PCOS patients had menstrual irregularity, among which 75% had oligomenorrhea followed by amenorrhea (9%) and polymenorrhea (2%). All the subgroups of PCOS patients (polymenorrhea excluded from further analyses) had significantly poor metabolic manifestations than the control namely insulin resistance (IR), impaired glycaemic status, general and central obesity, metabolic syndrome and dyslipidaemia. Acanthosis nigricans (AN), hyperandrogenemia (HA) and IR had significant predictive association with PCOS patients with both irregular [OR (95% CI)- AN: 21.994 (6.427, 75.267), p<0.001; HA: 27.735 (8.672, 88.704), p<0.001; IR: 7.268 (2.647, 19.954), p<0.001] and regular cycle [AN: 16.449 (3.830, 70.643), p<0.001; HA: 24.635 (6.349, 95.590), p<0.001; IR: 6.071 (1.658, 22.234), p=0.006] in reference to control group. None of the variables had significant predictive associations with irregular cycle in reference to regular cycle in patients with PCOS.Conclusion: Oligomenorrhea was the most common variant of menstrual irregularity in PCOS patients. All menstrual variants including eumenorrhea had similar manifestations in PCOS women, but poorer than controls.International Journal of Human and Health Sciences Vol. 06 No. 01 January’22 Page: 96-103

Catalytic Prebiotic Formation of Glycerol Phosphate Esters and an Estimation of Their Steady State Abundance under Plausible Early Earth Conditions

The emergence of biological phosphate esters of glycerol could have been a crucial step in the origin and evolution of life on the early Earth as glycerol phosphates today play a central role in biochemistry. We investigate here the formation of the glycerol phosphates by employing various rock samples, salts, and minerals as potential catalysts to aid the phosphorylation process. We report the synthesis of various phosphate esters of glycerol including glycerol-1-phosphate, glycerol-2-phosphate, cyclic glycerol-monophosphate as well as various diphosphate esters. Furthermore, the decomposition rates of glycerol phosphate under mild heating were also studied while keeping the pH constant. It was observed that glycerol phosphate starts decomposing quickly under mild heating conditions into inorganic orthophosphate and pyrophosphate, and a steady state concentration of ~0.5 M of glycerol phosphate may have been reasonable in ponds with abundant glycerol, phosphate, urea, and catalytic minerals.

Biosynthetic Mechanisms and Biological Significance of Glycerol Phosphate-Containing Glycan in Mammals

Bacteria contain glycerol phosphate (GroP)-containing glycans, which are important constituents of cell-surface glycopolymers such as the teichoic acids of Gram-positive bacterial cell walls. These glycopolymers comprising GroP play crucial roles in bacterial physiology and virulence. Recently, the first identification of a GroP-containing glycan in mammals was reported as a variant form of O-mannosyl glycan on α-dystroglycan (α-DG). However, the biological significance of such GroP modification remains largely unknown. In this review, we provide an overview of this new discovery of GroP-containing glycan in mammals and then outline the recent progress in elucidating the biosynthetic mechanisms of GroP-containing glycans on α-DG. In addition, we discuss the potential biological role of GroP modification along with the challenges and prospects for further research. The progress in this newly identified glycan modification will provide insights into the phylogenetic implications of glycan.

Cancer malignancy is correlated with up-regulation of PCYT2-mediated glycerol phosphate modification of α-dystroglycan

The dystrophin-glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as CDP-Gro synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.

Unravelling the Graded Millisecond Allosteric Activation Mechanism of Imidazole Glycerol Phosphate Synthase

Deciphering the molecular mechanisms of enzymatic allosteric regulation requires the structural characterization of key functional states and also their time evolution toward the formation of the allosterically activated ternary complex. The transient nature and usually slow millisecond timescale interconversion between these functional states hamper their detailed experimental and computational characterization. Here, we design a computational strategy tailored to reconstruct millisecond timescale events to describe the graded allosteric activation of imidazole glycerol phosphate synthase (IGPS) in the ternary complex. IGPS is a heterodimeric bienzyme complex responsible for the hydrolysis of glutamine to glutamate in the HisH subunit and delivering ammonia for the cyclase activity in HisF. Despite significant advances in understanding the underlying allosteric mechanism, essential molecular details of the long-range millisecond allosteric activation pathway of wild-type IGPS remain hidden. Without using a priori information of the active state, our simulations uncover how IGPS, with the allosteric effector bound in HisF, spontaneously captures glutamine in a catalytically inactive HisH conformation, subsequently attains a closed HisF:HisH interface, and finally forms the oxyanion hole in HisH for efficient glutamine hydrolysis. We show that effector binding in HisF dramatically decreases the conformational barrier associated with the oxyanion hole formation in HisH, in line with the experimentally observed 4500-fold activity increase in glutamine production. The formation of the allosterically active state is controlled by time-evolving dynamic communication networks connecting the effector and substrate binding sites. This computational strategy can be generalized to study other unrelated enzymes undergoing millisecond timescale allosteric transitions.

Potential Probiotic Pediococcus pentosaceus M41 Modulates Its Proteome Differentially for Tolerances Against Heat, Cold, Acid, and Bile Stresses

Probiotics containing functional food confer health benefits in addition to their nutritional properties. In this study, we have evaluated the differential proteomic responses of a potential novel probiotic Pediococcus pentosaceus M41 under heat, cold, acid, and bile stress conditions. We identified stress response proteins that could provide tolerances against these stresses and could be used as probiotic markers for evaluating stress tolerance. Pediococcus pentosaceus M41 was exposed for 2 h to each condition: 50°C (heat stress), 4°C (cold stress), pH 3.0 (acid stress) and 0.05% bile (bile stress). Proteomic analysis was carried out using 2D-IEF SDS PAGE and LC-MS/MS. Out of 60 identified proteins, 14 upregulated and 6 downregulated proteins were common among all the stress conditions. These proteins were involved in different biological functions such as translation-related proteins, carbohydrate metabolism (phosphoenolpyruvate phosphotransferase), histidine biosynthesis (imidazole glycerol phosphate synthase) and cell wall synthesis (tyrosine-protein kinase CapB). Proteins such as polysaccharide deacetylase, lactate oxidase, transcription repressor NrdR, dihydroxyacetone kinase were upregulated under three out of the four stress conditions. The differential expression of these proteins might be responsible for tolerance and protection of P. pentosaceus M41 against different stress conditions.