Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Extra-gastrointestinal manifestations of inflammatory bowel disease may be less common than previously reported

Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra-intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published

Directed Evolution of Protein-Based Neurotransmitter Sensors for MRI

The production of contrast agents sensitive to neuronal signaling events is a rate-limiting step in the development of molecular-level functional magnetic resonance imaging (molecular fMRI) approaches for studying the brain. High-throughput generation and evaluation of potential probes are possible using techniques for macromolecular engineering of protein-based contrast agents. In an initial exploration of this strategy, we used the method of directed evolution to identify mutants of a bacterial heme protein that allowed detection of the neurotransmitter dopamine in vitro and in living animals. The directed evolution method involves successive cycles of mutagenesis and screening that could be generalized to produce contrast agents sensitive to a variety of molecular targets in the nervous system

R-process enrichment from a single event in an ancient dwarf galaxy

Elements heavier than zinc are synthesized through the (r)apid and (s)low neutron-capture processes. The main site of production of the r-process elements (such as europium) has been debated for nearly 60 years. Initial studies of chemical abundance trends in old Milky Way halo stars suggested continual r-process production, in sites like core-collapse supernovae. But evidence from the local Universe favors r-process production mainly during rare events, such as neutron star mergers. The appearance of a europium abundance plateau in some dwarf spheroidal galaxies has been suggested as evidence for rare r-process enrichment in the early Universe, but only under the assumption of no gas accretion into the dwarf galaxies. Cosmologically motivated gas accretion favors continual r-process enrichment in these systems. Furthermore, the universal r-process pattern has not been cleanly identified in dwarf spheroidals. The smaller, chemically simpler, and more ancient ultra-faint dwarf galaxies assembled shortly after the first stars formed, and are ideal systems with which to study nucleosynthesis events such as the r-process. Reticulum II is one such galaxy. The abundances of non-neutron-capture elements in this galaxy (and others like it) are similar to those of other old stars. Here, we report that seven of nine stars in Reticulum II observed with high-resolution spectroscopy show strong enhancements in heavy neutron-capture elements, with abundances that follow the universal r-process pattern above barium. The enhancement in this "r-process galaxy" is 2-3 orders of magnitude higher than that detected in any other ultra-faint dwarf galaxy. This implies that a single rare event produced the r-process material in Reticulum II. The r-process yield and event rate are incompatible with ordinary core-collapse supernovae, but consistent with other possible sites, such as neutron star mergers.Comment: Published in Nature, 21 Mar 2016: http://dx.doi.org/10.1038/nature1742

Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor

Current cosmological models indicate that the Milky Way's stellar halo was assembled from many smaller systems. Based on the apparent absence of the most metal-poor stars in present-day dwarf galaxies, recent studies claimed that the true Galactic building blocks must have been vastly different from the surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in the Sculptor dwarf galaxy based on a medium-resolution spectrum cast some doubt on this conclusion. However, verification of the iron-deficiency and measurements of additional elements, such as the alpha-element Mg, are mandatory for demonstrating that the same type of stars produced the metals found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars be conclusively linked to early stellar halo assembly. Here we report high-resolution spectroscopic abundances for 11 elements in S1020549, confirming the iron abundance of less than 1/4000th that of the Sun, and showing that the overall abundance pattern mirrors that seen in low-metallicity halo stars, including the alpha-elements. Such chemical similarity indicates that the systems destroyed to form the halo billions of years ago were not fundamentally different from the progenitors of present-day dwarfs, and suggests that the early chemical enrichment of all galaxies may be nearly identical.Comment: 16 pages, including 2 figures. Accepted for publication in Nature. It is embargoed for discussion in the press until formal publication in Natur

S-COL: A Copernican turn for the development of flexibly reusable collaboration scripts

Collaboration scripts are usually implemented as parts of a particular collaborative-learning platform. Therefore, scripts of demonstrated effectiveness are hardly used with learning platforms at other sites, and replication studies are rare. The approach of a platform-independent description language for scripts that allows for easy implementation of the same script on different platforms has not succeeded yet in making the transfer of scripts feasible. We present an alternative solution that treats the problem as a special case of providing support on top of diverse Web pages: In this case, the challenge is to trigger support based on the recognition of a Web page as belonging to a specific type of functionally equivalent pages such as the search query form or the results page of a search engine. The solution suggested has been implemented by means of a tool called S-COL (Scripting for Collaborative Online Learning) and allows for the sustainable development of scripts and scaffolds that can be used with a broad variety of content and platforms. The tool’s functions are described. In order to demonstrate the feasibility and ease of script reuse with S-COL, we describe the flexible re-implementation of a collaboration script for argumentation in S-COL and its adaptation to different learning platforms. To demonstrate that a collaboration script implemented in S-COL can actually foster learning, an empirical study about the effects of a specific script for collaborative online search on learning activities is presented. The further potentials and the limitations of the S-COL approach are discussed

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Numerical Algebraic Geometry: A New Perspective on String and Gauge Theories

The interplay rich between algebraic geometry and string and gauge theories has recently been immensely aided by advances in computational algebra. However, these symbolic (Gr\"{o}bner) methods are severely limited by algorithmic issues such as exponential space complexity and being highly sequential. In this paper, we introduce a novel paradigm of numerical algebraic geometry which in a plethora of situations overcomes these short-comings. Its so-called 'embarrassing parallelizability' allows us to solve many problems and extract physical information which elude the symbolic methods. We describe the method and then use it to solve various problems arising from physics which could not be otherwise solved.Comment: 36 page

Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy