Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors

Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin's favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities

A catena between psychiatric disorders and non-scarring alopecias-A systematic review

For many years, clinical observations have suggested that there is an intrinsic connection between psychological state and skin diseases. Stress responses are typically mediated by several hormones, which are modulated via the hypothalamic-pituitary-adrenal axis. This typical stress response is not only one theory for psychiatry disorder pathophysiology, but it also modifies hair growth by altering the skin's inflammatory environment. Given that different forms of hair loss, such as androgenetic alopecia, alopecia areata, or telogen effluvium, and hair follicle cycling can be altered by immune cells within the follicle milieu, we hypothesized that specific forms of hair loss are correlated to psychiatric illnesses. To address this, we conducted a systematic review by searches in April and May 2021 through Ovid MEDLINE and PUBMED (ranging from 1951 to the present day), identifying 179 reports. A further 24 reports were identified through website and citation searches giving a total of 201 reports. After applying exclusion criteria, 21 papers were reviewed, and 17 were included for data analysis. It is undeniable that hair loss greatly affects Health-related Quality of Life (HrQol) and it is heavily associated with major depressive disorder and anxiety. The correlation between hair loss and mental health disorders was significant, however, due to the low number of publications with quantitative data we were not able to identify correlations between each hair loss type with each psychiatric disorder. Further studies to better connect specific hair loss diseases to specific disorders are therefore critical in bettering the way both psychiatric disease, and hair loss, are managed

The State of Women Veterans' Health Research: Results of a Systematic Literature Review

OBJECTIVE: Assess the state of women veterans' health research. DESIGN: Systematic review of studies that pertained specifically to or included explicit information about women veterans. A narrative synthesis of studies in 4 domains/topics was conducted: Stress of military life; Health and performance of military/VA women; Health services research/quality of care; and Psychiatric conditions. MEASUREMENTS AND MAIN RESULTS: We identified 182 studies. Of these, 2 were randomized-controlled trials (RCTs) and the remainder used observational designs. Forty-five percent of studies were VA funded. We identified 77 studies pertaining to the stress of military life, of which 21 reported on sexual harassment or assault. Rates of harassment ranged from 55% to 79% and rates of sexual assault from 4.2% to 7.3% in active duty military women and 11% to 48% among women veterans. Forty-two studies concerned the health and performance of military/VA women, with 21 studies evaluating sexual assault and posttraumatic stress disorder (PTSD) and their effect on health. Fifty-nine studies assessed various aspects of health services research. Eight studies assessed quality of care and 5, patient satisfaction. Twenty-five studies assessed utilization and health care organization, and findings include that women veterans use the VA less than men, that gender-specific reasons for seeking care were common among female military and veteran personnel, that provision of gender-specific care increased women veterans' use of VA, and that virtually all VAs have available on-site basic women's health services. Fifty studies were classified as psychiatric; 31 of these were about the risk, prevalence, and treatment of PTSD. CONCLUSIONS: Most research on VA women's health is descriptive in nature and has concerned PTSD, sexual harassment and assault, the utilization and organization of care, and various psychiatric conditions. Experimental studies and studies of the quality of care are rare