Mitochondrial and sex steroid hormone crosstalk during aging

Decline in circulating sex steroid hormones accompanies several age-associated pathologies which may influence human healthspan. Mitochondria play important roles in biosynthesis of sex steroid hormones, and these hormones can also regulate mitochondrial function. Understanding the cross talk between mitochondria and sex steroid hormones may provide insights into the pathologies associated with aging. The aim of this review is to summarize the current knowledge regarding the interplay between mitochondria and sex steroid hormones during the aging process. The review describes the effect of mitochondria on sex steroid hormone production in the gonads, and then enumerates the contribution of sex steroid hormones on mitochondrial function in hormone responsive cells. Decline in sex steroid hormones and accumulation of mitochondrial damage may create a positive feedback loop that contributes to the progressive degeneration in tissue function during aging. The review further speculates whether regulation between mitochondrial function and sex steroid hormone action can potentially influence healthspan

Well Water Screening in Suffolk, VA, for Contaminants Affecting Human Health

Purpose: Despite regulations, one area that remains outside the scope of the clean water policies is well water. With the lack of oversight, the millions of home that rely on well water remain susceptible to numerous pollutants and contaminants. To ensure the safety of well water, development of screening and testing protocols is imperative. Many households in Suffolk, VA still use well water making it an apt location to conduct a preliminary study screening for potential water contaminants. Methods: Water samples from kitchen and garden sources were collected from households in Suffolk, VA. These samples assessed for TDS via Milwaukee EC59 pen, pH via Sper Scientific test tube pen, arsenic via Quick Rapid Arsenic Test Kit, E. coli and coliform, and lead via Simpletek Micro Tester Pro self-filling test ampoules. Findings: Four of the thirty kitchen-sourced samples tested positive for coliform contamination. The positive findings may represent hazards for health thus warranting further investigation. Conclusion: Many Suffolk homes rely on well water but lack of regulations can bring risk for contamination. This study indicated a potential coliform problem in Suffolk and more work must be done to evaluate for coliform contamination and its resultant health consequences

Endometriosis as a highly relevant yet neglected gynecologic condition in Asian women

Endometriosis is a chronic, debilitating disease characterized by the growth of endometrial tissues outside the endometrium. Its prevalence seems to differ across ethnicities, with the disease affecting and presenting with advanced stages in Asians more than any other race. Despite this, data on endometriosis in Asians is limited, and there seems to be a lack of support for endometriosis research in Asia. Hence, this review aims to consolidate the available literature on endometriosis in Asians to identify the gaps in knowledge regarding its occurrence in this population and emphasize the need to address the disease in this part of the world. Certain genetic, dietary, and environmental factors that predominate in Asians compared to other ethnicities may potentially impact end ometriosis. Understanding these differences is essential in providing innovative strategies for reducing health disparities in endometriosis incidence and presentation across ethnic groups, thus improving disease management and health outcomes

Proliferative Activities of Benguet Legume Cultivars on a Breast Epithelial Cell Line

Legumes are extensively cultivated around the globe for human consumption and may contain potential estrogenic activities that interfere with normal physiology and pathophysiology. However, different cultivars grown in different regions of the world have different activities that may provide different nutritional value. Hence, in this study, legume cultivars from Benguet, a major source of legumes and other highland vegetables in Northern Philippines, were evaluated for their proliferative effects in the breast epithelial cancer cell line MCF7. Ethyl acetate extracts from Phaseolus vulgaris L. and Vigna unguiculata (L.) Walp., but not from Tamarindus indica L. and Pisum sativum L., induced slight proliferative effects on MCF7 cells at a low dose but reduced cell number at a higher dose. The proliferative effect of the extracts is likely estrogen receptor (ER)-dependent, as the same legume extracts only displayed inhibitory effects in the ER-negative MDA-MB-231 cells. Similar proliferative effects of P. vulgaris and V. unguiculata ethyl acetate extracts were reflected in their similar HPLC profiles, which is distinct from the HPLC profile of the T. indica ethyl acetate extract. Overall, our findings show that certain legumes from Benguet have slight proliferative activities in MCF7 cells, implying their potential estrogenic activities

A novel rapamycin analog is highly selective for mTORC1 in vivo.

Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. Our results demonstrate that highly selective pharmacological inhibition of mTORC1 can be achieved in vivo, and that selective inhibition of mTORC1 significantly reduces the side effects associated with conventional rapalogs

Observation of bi-directional global Alfvén eigenmodes in the MAST-U tokamak

The first observations and classification of deuterium beam-driven sub-cyclotron frequency range Alfvén eigenmodes (AEs) are presented for the MAST-Upgrade tokamak. Sets of observed eigenmodes are separated in frequency by approximately 200 kHz. We observe a lower frequency separation of ∼10 kHz within each set, and the toroidal mode number n increases with frequency sequentially. The ∼200 kHz step between the sets coincides with the interval between successive curves of the Shear Alfvén continuum according to linear ideal MHD modeling. The sub-cyclotron frequency AEs can be identified as the global AEs (GAEs) localized at the continuum extrema regions. Each set contains the same range of n. These observations are consistent with our GAE modeling. In low plasma current (Ip) discharges, we observe only GAEs propagating counter to the plasma current and the beam direction. These GAEs are located near the magnetic axis. We observe counter and co-propagating GAEs simultaneously in higher Ip discharges. The co-propagating GAEs occur because of the formation of second continuum minima. Very flat safety factor profiles in higher Ip MAST-U discharges give rise to these minima. They are located at around half of the plasma radius. The GAEs have properties that are very different to those of compressional AEs previously reported for the MAST tokamak with low magnetic fields (Sharapov et al 2014 Phys. Plasmas 21 082501) before the upgrade

Long Astral Microtubules and RACK-1 Stabilize Polarity Domains during Maintenance Phase in Caenorhabditis elegans Embryos

Cell polarity is a very well conserved process important for cell differentiation, cell migration, and embryonic development. After the establishment of distinct cortical domains, polarity cues have to be stabilized and maintained within a fluid and dynamic membrane to achieve proper cell asymmetry. Microtubules have long been thought to deliver the signals required to polarize a cell. While previous studies suggest that microtubules play a key role in the establishment of polarity, the requirement of microtubules during maintenance phase remains unclear. In this study, we show that depletion of Caenorhabditis elegans RACK-1, which leads to short astral microtubules during prometaphase, specifically affects maintenance of cortical PAR domains and Dynamin localization. We then investigated the consequence of knocking down other factors that also abolish astral microtubule elongation during polarity maintenance phase. We found a correlation between short astral microtubules and the instability of PAR-6 and PAR-2 domains during maintenance phase. Our data support a necessary role for astral microtubules in the maintenance phase of cell polarity

A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research