Limited sex-biased neural gene expression patterns across strains in zebrafish (Danio rerio)

Background: Male and female vertebrates typically differ in a range of characteristics, from morphology to physiology to behavior, which are influenced by factors such as the social environment and the internal hormonal and genetic milieu. However, sex differences in gene expression profiles in the brains of vertebrates are only beginning to be understood. Fishes provide a unique complement to studies of sex differences in mammals and birds given that fish show extreme plasticity and lability of sexually dimorphic characters and behaviors during development and even adulthood. Hence, teleost models can give additional insight into sexual differentiation. The goal of this study is to identify neurotranscriptomic mechanisms for sex differences in the brain. Results: In this study we examined whole-brain sex-biased gene expression through RNA-sequencing across four strains of zebrafish. We subsequently conducted systems level analyses by examining gene network dynamics between the sexes using weighted gene coexpression network analysis. Surprisingly, only 61 genes (approximately 0.4% of genes analyzed) showed a significant sex effect across all four strains, and 48 of these differences were male-biased. Several of these genes are associated with steroid hormone biosynthesis. Despite sex differences in a display of stress-related behaviors, basal transcript levels did not predict the intensity of the behavioral display. WGCNA revealed only one module that was significantly associated with sex. Intriguingly, comparing intermodule dynamics between the sexes revealed only moderate preservation. Further we identify sex-specific gene modules. Conclusions: Despite differences in morphology, physiology, and behavior, there is limited sex-biased neural gene expression in zebrafish. Further, genes found to be sex-biased are associated with hormone biosynthesis, suggesting that sex steroid hormones may be key contributors to sexual behavioral plasticity seen in teleosts. A possible mechanism is through regulating specific brain gene networks

Effects of High-Volume Versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations

We evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (−0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV \u3c HL at POST and POSTPR, p \u3c 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development

The TESS Grand Unified Hot Jupiter Survey. I. Ten TESS Planets

We report the discovery of ten short-period giant planets (TOI-2193A b, TOI-2207 b, TOI-2236 b, TOI-2421 b, TOI-2567 b, TOI-2570 b, TOI-3331 b, TOI-3540A b, TOI-3693 b, TOI-4137 b). All of the planets were identified as planet candidates based on periodic flux dips observed by NASA's Transiting Exoplanet Survey Satellite (TESS). The signals were confirmed to be from transiting planets using ground-based time-series photometry, high angular resolution imaging, and high-resolution spectroscopy coordinated with the TESS Follow-up Observing Program. The ten newly discovered planets orbit relatively bright F and G stars ($G < 12.5$,~$T_\mathrm{eff}$ between 4800 and 6200 K). The planets' orbital periods range from 2 to 10~days, and their masses range from 0.2 to 2.2 Jupiter masses. TOI-2421 b is notable for being a Saturn-mass planet and TOI-2567 b for being a ``sub-Saturn'', with masses of $0.322\pm 0.073$ and $0.195\pm 0.030$ Jupiter masses, respectively. In most cases, we have little information about the orbital eccentricities. Two exceptions are TOI-2207 b, which has an 8-day period and a detectably eccentric orbit ($e = 0.17\pm0.05$), and TOI-3693 b, a 9-day planet for which we can set an upper limit of $e < 0.052$. The ten planets described here are the first new planets resulting from an effort to use TESS data to unify and expand on the work of previous ground-based transit surveys in order to create a large and statistically useful sample of hot Jupiters.Comment: 44 pages, 15 tables, 21 figures; revised version submitted to A

Changes in conceptions in women younger than 18 years and the circumstances of young mothers in England in 2000–12: an observational study

BACKGROUND: In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals. METHODS: In this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994-98 to 2009-13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990-91), Natsal-2 (1999-2001), and Natsal-3 (2010-12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18-24 years; and the prevalence of participation in education, work, and training in young mothers. FINDINGS: Conception rates in women younger than 18 years declined steadily from their peak in 1996-98 and more rapidly from 2007 onwards. More deprived areas and those receiving greater Teenage Pregnancy Strategy-related investment had higher rates of conception in 1994-98 and had greater declines to 2009-13. Regression analyses assessing the association between Teenage Pregnancy Strategy funding and decline in conception rates in women younger than 18 years showed an estimated reduction in the conception rate of 11.4 conceptions (95% CI 9.6-13.2; p<0.0001) per 1000 women aged 15-17 years for every £100 Teenage Pregnancy Strategy spend per head and a reduction of 8.2 conceptions (5.8-10.5; p<0.0001) after adjustment for socioeconomic deprivation and region. The association between conception in women younger than 18 years and lower socioeconomic status weakened slightly between Natsal-2 and Natsal-3. The prevalence of participation in education, work, or training among young women with a child conceived before age 18 years was low, but the odds of them doing so doubled between Natsal-2 and Natsal-3 (odds ratio 1.99, 95% CI 0.99-4.00). INTERPRETATION: A sustained, multifaceted policy intervention involving health and education agencies, alongside other social and educational changes, has probably contributed to a substantial and accelerating decline in conceptions in women younger than 18 years in England since the late 1990s. FUNDING: Medical Research Council, Wellcome Trust, Economic and Social Research Council, and Department of Health

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Another Shipment of Six Short-Period Giant Planets from TESS

We present the discovery and characterization of six short-period, transiting giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) -- TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642), TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467). All six planets orbit bright host stars (8.9 <G< 11.8, 7.7 <K< 10.1). Using a combination of time-series photometric and spectroscopic follow-up observations from the TESS Follow-up Observing Program (TFOP) Working Group, we have determined that the planets are Jovian-sized (R$_{P}$ = 1.00-1.45 R$_{J}$), have masses ranging from 0.92 to 5.35 M$_{J}$, and orbit F, G, and K stars (4753 $<$ T$_{eff}$ $<$ 7360 K). We detect a significant orbital eccentricity for the three longest-period systems in our sample: TOI-2025 b (P = 8.872 days, $e$ = $0.220\pm0.053$), TOI-2145 b (P = 10.261 days, $e$ = $0.182^{+0.039}_{-0.049}$), and TOI-2497 b (P = 10.656 days, $e$ = $0.196^{+0.059}_{-0.053}$). TOI-2145 b and TOI-2497 b both orbit subgiant host stars (3.8 $<$ $\log$ g $<$4.0), but these planets show no sign of inflation despite very high levels of irradiation. The lack of inflation may be explained by the high mass of the planets; $5.35^{+0.32}_{-0.35}$ M$_{\rm J}$ (TOI-2145 b) and $5.21\pm0.52$ M$_{\rm J}$ (TOI-2497 b). These six new discoveries contribute to the larger community effort to use {\it TESS} to create a magnitude-complete, self-consistent sample of giant planets with well-determined parameters for future detailed studies.Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRA