Risk and Protective Factors for Depression and Anxiety in PCOS

Polycystic Ovary Syndrome, PCOS, is an endocrine condition among individuals born with ovaries. Though the condition name refers to the underdeveloped follicles as multiple cysts on the ovary, individuals living with PCOS frequently encounter menstrual irregularity, hirsutism (male-patterned body/facial hair), acne, and obesity. Prior research has noted that PCOS also is associated with psychological outcomes, most notably increased risk for depression and anxiety. However, relative to large amount of medical research on PCOS, few studies have examined these psychological outcomes and their etiology. Work is needed that uncovers the connection between the risks (e. g., stigma, weight bias, and quality of life), the protective (e.g., self-compassion, social support) factors that explain these psychological outcomes (e.g., depression, anxiety). The present study examined potential risks and protective factors that might explain the increased risk for depressive and anxiety symptoms in individuals living with PCOS. Specifically, we examined risk and protective factors reported by a gender (48% cisgender women, 52% gender diverse) and ethnically diverse (46% white non-Hispanic, 54% ethnically diverse) sample of individuals living with PCOS. Ages ranged from 19-46, with an average age of 29 (SD = 6.49). Individuals initially completed a qualitative interview by phone and were subsequently invited to participate in an online survey. Of the original 50 individuals living with PCOS, 46 completed the online survey through Redcap, answering questions about risk (perceived stigma, body image) and protective (self-compassion, social support) factors, and mental health (depression and anxiety). Results of bivariate correlations revealed that perceived stigma (r = .37, p = .02; r = .34, p = .03) and body image (r = .53, p = .00; r = .38, p = .02) were significantly related to more depressive and anxiety symptoms, respectively. In addition, self-compassion (r = -.72, p = .00; r = -.61, p = .00) and social support (r = -.42, p = .01; r = -.37, p = .02) were significantly related to fewer depressive and anxiety symptoms. Thus, this study found evidence that the more perceived stigma and negative body image, the more depressive and anxiety symptoms, whereas the more self-compassion and social support, the less depressive and anxiety symptoms in individuals living with PCOS. Importantly, the study had a small sample size, and the design was a self-report cross-sectional study. Thus, future research is needed that is longitudinal in design with large samples of diverse individuals with PCOS. Still, the present study is among the small literature attempting to understand the psychosocial risk and protective factors that may explain depressive and anxiety symptoms in this vulnerable population

NOA1, a Novel ClpXP Substrate, Takes an Unexpected Nuclear Detour Prior to Mitochondrial Import

The mitochondrial matrix GTPase NOA1 is a nuclear encoded protein, essential for mitochondrial protein synthesis, oxidative phosphorylation and ATP production. Here, we demonstrate that newly translated NOA1 protein is imported into the nucleus, where it localizes to the nucleolus and interacts with UBF1 before nuclear export and import into mitochondria. Mutation of the nuclear localization signal (NLS) prevented both nuclear and mitochondrial import while deletion of the N-terminal mitochondrial targeting sequence (MTS) or the C-terminal RNA binding domain of NOA1 impaired mitochondrial import. Absence of the MTS resulted in accumulation of NOA1 in the nucleus and increased caspase-dependent apoptosis. We also found that export of NOA1 from the nucleus requires a leptomycin-B sensitive, Crm1-dependent nuclear export signal (NES). Finally, we show that NOA1 is a new substrate of the mitochondrial matrix protease complex ClpXP. Our results uncovered an unexpected, mandatory detour of NOA1 through the nucleolus before uptake into mitochondria. We propose that nucleo-mitochondrial translocation of proteins is more widespread than previously anticipated providing additional means to control protein bioavailability as well as cellular communication between both compartments.Max Planck Society for the Advancement of Scienc

A Comprehensive Characterization of the 70 Virgins Planetary System

An on-going effort in the characterization of exoplanetary systems is the accurate determination of host star properties. This effort extends to the relatively bright host stars of planets discovered with the radial velocity method. The Transit Ephemeris Refinement and Monitoring Survey (TERMS) is aiding in these efforts as part of its observational campaign for exoplanet host stars. One of the first known systems is that of 70 Virginis, which harbors a jovian planet in an eccentric orbit. Here we present a complete characterization of this system with a compilation of TERMS photometry, spectroscopy, and interferometry. We provide fundamental properties of the host star through direct interferometric measurements of the radius (1.5% uncertainty) and through spectroscopic analysis. We combined 59 new Keck HIRES radial velocity measurements with the 169 previously published from the ELODIE, Hamilton, and HIRES spectrographs, to calculate a refined orbital solution and construct a transit ephemeris for the planet. These newly determined system characteristics are used to describe the Habitable Zone of the system with a discussion of possible additional planets and related stability simulations. Finally, we present 19 years of precision robotic photometry that constrain stellar activity and rule out central planetary transits for a Jupiter-radius planet at the 5σ level, with reduced significance down to an impact parameter of b = 0.95

Skeletal Muscle-Specific Methyltransferase METTL21C Trimethylates p97 and Regulates Autophagy-Associated Protein Breakdown

Summary: Protein aggregates and cytoplasmic vacuolization are major hallmarks of multisystem proteinopathies (MSPs) that lead to muscle weakness. Here, we identify METTL21C as a skeletal muscle-specific lysine methyltransferase. Insertion of a β-galactosidase cassette into the Mettl21c mouse locus revealed that METTL21C is specifically expressed in MYH7-positive skeletal muscle fibers. Ablation of the Mettl21c gene reduced endurance capacity and led to age-dependent accumulation of autophagic vacuoles in skeletal muscle. Denervation-induced muscle atrophy highlighted further impairments of autophagy-related proteins, including LC3, p62, and cathepsins, in Mettl21c−/− muscles. In addition, we demonstrate that METTL21C interacts with the ATPase p97 (VCP), which is mutated in various human MSP conditions. We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo. We conclude that the methyltransferase METTL21C is an important modulator of protein degradation in skeletal muscle under both normal and enhanced protein breakdown conditions. : Wiederstein et al. describe the skeletal muscle methyltransferase Mettl21c. They found that ablation of Mettl21c in mice results in muscle weakness and disturbance of the protein degradation machinery. Those changes are hallmarks of multisystem proteinopathies. They demonstrate that Mettl21c modulates p97 activity, which is frequently mutated in human patients with muscle weakness. Keywords: methyltransferases, skeletal muscle, p97, atrophy, autophag

The cerebellum ages slowly according to the epigenetic clock

Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2x10-9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8x10-3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases

Clinical and Cost-Effectiveness of PSYCHOnlineTHERAPY: Study Protocol of a Multicenter Blended Outpatient Psychotherapy Cluster Randomized Controlled Trial for Patients With Depressive and Anxiety Disorders

Introduction: Internet- and mobile-based interventions (IMIs) and their integration into routine psychotherapy (i.e., blended therapy) can offer a means of complementing psychotherapy in a flexible and resource optimized way. Objective: The present study will evaluate the non-inferiority, cost-effectiveness, and safety of two versions of integrated blended psychotherapy for depression and anxiety compared to standard cognitive behavioral therapy (CBT). Methods: A three-armed multicenter cluster-randomized controlled non-inferiority trial will be conducted comparing two implementations of blended psychotherapy (PSYCHOnlineTHERAPYfix/flex) compared to CBT. Seventy-five outpatient psychotherapists with a CBT-license will be randomized in a 1:1:1 ratio. Each of them is asked to include 12 patients on average with depressive or anxiety disorders resulting in a total sample size of N = 900. All patients receive up to a maximum of 16 psychotherapy sessions, either as routine CBT or alternating with Online self-help sessions (fix: 8/8; flex: 0–16). Assessments will be conducted at patient study inclusion (pre-treatment) and 6, 12, 18, and 24 weeks and 12 months post-inclusion. The primary outcome is depression and anxiety severity at 18 weeks post-inclusion (post-treatment) using the Patient Health Questionnaire Anxiety and Depression Scale. Secondary outcomes are depression and anxiety remission, treatment response, health-related quality of life, patient satisfaction, working alliance, psychotherapy adherence, and patient safety. Additionally, several potential moderators and mediators including patient characteristics and attitudes toward the interventions will be examined, complemented by ecological day-to-day digital behavior variables via passive smartphone sensing as part of an integrated smart-sensing sub-study. Data-analysis will be performed on an intention-to-treat basis with additional per-protocol analyses. In addition, cost-effectiveness and cost-utility analyses will be conducted from a societal and a public health care perspective. Additionally, qualitative interviews on acceptance, feasibility, and optimization potential will be conducted and analyzed. Discussion: PSYCHOnlineTHERAPY will provide evidence on blended psychotherapy in one of the largest ever conducted psychotherapy trials. If shown to be non-inferior and cost-effective, PSYCHOnlineTHERAPY has the potential to innovate psychotherapy in the near future by extending the ways of conducting psychotherapy. The rigorous health care services approach will facilitate a timely implementation of blended psychotherapy into standard care

Dispersion, solvent and metal effects in the binding of gold cations to alkynyl ligands: implications for Au(i) catalysis.

The coordination modes of the [Au(PPh3)](+) cation to metal alkynyl complexes have been investigated. On addition to ruthenium, a vinylidene complex, [Ru(η(5)-C5H5)(PPh3)2([double bond, length as m-dash]C[double bond, length as m-dash]CPh{AuPPh3})](+), is obtained while addition to a gold(iii) compound gives di- and trinuclear gold complexes depending on the conditions employed. In the trinuclear species, a gold(i) cation is sandwiched between two gold(iii) alkynyl complexes, suggesting that coordination of multiple C-C triple bonds to gold is facile