Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): Cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein

Searching for hormone-regulated genes in testicular Sertoli cells, we cloned and sequenced a cDNA of 3108 base pairs, named LRPR1 (signifying leucine-rich primary response gene 1). This cDNA sequence has an open reading frame of 2238 base pairs encoding a leucine-rich protein of 746 amino acid residues with a relative molecular mass of 85.6 kDa. As much as 16% of the amino acid residues is leucine. Database analysis revealed significant similarity of LRPR1 to the human brain cDNA sequence EST00443, but not to any other sequences present in databases. The expression of LRPR1 mRNA in Sertoli cells is strongly and rapidly up-regulated by follicle-stimulating hormone (FSH). The level of LRPR1 mRNA was very low in Sertoli cells isolated from 21-day-old rats and cultured for 3 days in the absence of FSH, but LRPR1 mRNA expression was markedly increased within 2 h after addition of FSH to these cultures. A maximal response was reached within 4 h. Dibutyryl-cyclic AMP [(Bu)2cAMP] and forskolin had similar effects compared to FSH, indicating that cAMP acts as a second messenger in the regulation of LRPR1 expression. The up-regulation of LRPR1 mRNA expression by FSH was also observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that FSH regulates LRPR1 mRNA expression through a direct mechanism which does not require de novo protein synthesis. Thus, LRPR1 represents a primary response gene in FSH action on Sertoli cells. The presently available data indicate that LRPR1 mRNA expression is regulated specifically by FSH, since several other hormones and growth factors did not affect LRPR1 mRNA expression in the cultured Sertoli cells. LRPR1 mRNA expression is relatively high in testis, ovary and spleen. A much lower mRNA level was found in brain and lung, and no expression was detected in liver, kidney, heart, muscle, pituitary gland, prostate, epididymis and seminal vesicle. The basal level of testicular LRPR1 expression in intact 21-day-old rats was markedly increased within several hours after a single i.p. injection of FSH, indicating that in vivo LRPR1 mRNA expression may appear to be a useful parameter to evaluate testicular FSH action

Survivorship care planning in gynecologic oncology perspectives from patients, caregivers, and health care providers

Purpose This qualitative study sought to describe the challenges following treatment and the preferences regarding survivorship care among patients treated for gynecological cancer, their caregivers, and health care providers. Methods Between July and August 2017, in-depth semi-structured interviews regarding survivorship were conducted at a large academic hospital in the USA among patients who recently completed treatment (< 12 months) for a gynecological cancer (ovarian, endometrial, cervical, and vulvar) and their primary caregivers. A focus group was conducted among health care providers (oncologists, nurses, and fellows). Main themes were identified using descriptive content analysis. Results A total of 30 individuals participated in this study (13 patients, 9 caregivers, 8 health care providers). Almost all participants reported a desire for more information on how to address survivorship needs, specifically as they related to side effects, follow-up schedule, and psychological assistance. Despite this uniformly identified need for more information, preferences for survivorship care planning differed across cancer types and individuals, with respect to content, timing, and mode of delivery. Health care providers expressed challenges in communicating with patients about survivorship, a desire to shift post-treatment conversations to the goal of improving quality of life as opposed to focusing on disease recurrence, and an unmet need for disease specific and individualized survivorship care planning. Conclusions Patients, caregivers, and health care providers each expressed a need for gynecologic cancer-tailored survivorship care resources

Full Counting Statistics of Multiple Andreev Reflections in incoherent diffusive superconducting junctions

We present a theory for the full distribution of current fluctuations in incoherent diffusive superconducting junctions, subjected to a voltage bias. This theory of full counting statistics of incoherent multiple Andreev reflections is valid for arbitrary applied voltage. We present a detailed discussion of the properties of the first four cumulants as well as the low and high voltage regimes of the full counting statistics. The work is an extension of the results of Pilgram and the author, Phys. Rev. Lett. 94, 086806 (2005).Comment: Included in special issue Spin Physics of Superconducting heterostructures of Applied Physics A: Materials Science & Processin

The Amundsen Sea Polynya International Research Expedition (ASPIRE)

In search of an explanation for some of the greenest waters ever seen in coastal Antarctica and their possible link to some of the fastest melting glaciers and declining summer sea ice, the Amundsen Sea Polynya International Research Expedition (ASPIRE) challenged the capabilities of the US Antarctic Program and RVIB Nathaniel B. Palmer during Austral summer 2010–2011. We were well rewarded by both an extraordinary research platform and a truly remarkable oceanic setting. Here we provide further insights into the key questions that motivated our sampling approach during ASPIRE and present some preliminary findings, while highlighting the value of the Palmer for accomplishing complex, multifaceted oceanographic research in such a challenging environment

Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development

The fragile X syndrome is the most frequent hereditary form of mental retardation. This X-linked disorder is, in most cases, caused by an unstable and expanding trinucleotide CGG repeat located in the 5'-untranslated region of the gene involved, the fragile X mental retardation 1 (FMR1) gene. Expansion of the CGG repeat to a length of more than 200 trinucleotides results in silencing of the FMR1 gene promoter and, thus, in an inactive gene. The clinical features of male fragile X patients include mental retardat

Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT)

Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term

Induction versus expectant monitoring for intrauterine growth restriction at term: Randomised equivalence trial (DIGITAT)

Objective: To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design: Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting: Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008. Participants: Pregnant women who had a singleton pregnancy beyond 36+0 weeks' g

Multi-ethnic genome-wide association study of decomposed cardioelectric phenotypes illustrates strategies to identify and characterize evidence of shared genetic effects for complex traits

Background: We examined how expanding electrocardiographic trait genome-wide association studies to include ancestrally diverse populations, prioritize more precise phenotypic measures, and evaluate evidence for shared genetic effects enabled the detection and characterization of loci. Methods: We decomposed 10 seconds, 12-lead electrocardiograms from 34 668 multi-ethnic participants (15% Black; 30% Hispanic/Latino) into 6 contiguous, physiologically distinct (P wave, PR segment, QRS interval, ST segment, T wave, and TP segment) and 2 composite, conventional (PR interval and QT interval) interval scale traits and conducted multivariable-adjusted, trait-specific univariate genome-wide association studies using 1000-G imputed single-nucleotide polymorphisms. Evidence of shared genetic effects was evaluated by aggregating meta-analyzed univariate results across the 6 continuous electrocardiographic traits using the combined phenotype adaptive sum of powered scores test. Results: We identified 6 novels (CD36, PITX2, EMB, ZNF592, YPEL2, and BC043580) and 87 known loci (adaptive sum of powered score test P&lt;5×10-9). Lead single-nucleotide polymorphism rs3211938 at CD36 was common in Blacks (minor allele frequency=10%), near monomorphic in European Americans, and had effects on the QT interval and TP segment that ranked among the largest reported to date for common variants. The other 5 novel loci were observed when evaluating the contiguous but not the composite electrocardiographic traits. Combined phenotype testing did not identify novel electrocardiographic loci unapparent using traditional univariate approaches, although this approach did assist with the characterization of known loci. Conclusions: Despite including one-third as many participants as published electrocardiographic trait genome-wide association studies, our study identified 6 novel loci, emphasizing the importance of ancestral diversity and phenotype resolution in this era of ever-growing genome-wide association studies

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society