Animal models for aberrations of gonadotropin action

During the last two decades a large number of genetically modified mouse lines with altered gonadotropin action have been generated. These mouse lines fall into three categories: the lack-of-function mice, gain-of-function mice, and the mice generated by breeding the abovementioned lines with other disease model lines. The mouse strains lacking gonadotropin action have elucidated the necessity of the pituitary hormones in pubertal development and function of gonads, and revealed the processes from the original genetic defect to the pathological phenotype such as hypo- or hypergonadotropic hypogonadism. Conversely, the strains of the second group depict consequences of chronic gonadotropin action. The lines vary from those expressing constitutively active receptors and those secreting follicle-stimulating hormone (FSH) with slowly increasing amounts to those producing human choriogonadotropin (hCG), amount of which corresponds to 2000-fold luteinizing hormone (LH)/hCG biological activity. Accordingly, the phenotypes diverge from mild anomalies and enhanced fertility to disrupted gametogenesis, but eventually chronic, enhanced and non-pulsatile action of both FSH and LH leads to female and male infertility and/or hyper- and neoplasias in most of the gonadotropin gain-of-function mice. Elevated gonadotropin levels also alter the function of several extra-gonadal tissues either directly or indirectly via increased sex steroid production. These effects include promotion of tumorigenesis in tissues such as the pituitary, mammary and adrenal glands. Finally, the crossbreedings of the current mouse strains with other disease models are likely to uncover the contribution of gonadotropins in novel biological systems, as exemplified by the recent crossbreed of LHCG receptor deficient mice with Alzheimer disease mice

Climate Variability and Hemorrhagic Fever with Renal Syndrome Transmission in Northeastern China

Background: The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by climatic variables. However, few studies have examined the quantitative relationship between climate variation and HFRS transmission. ---------- Objective: We examined the potential impact of climate variability on HFRS transmission and developed climate-based forecasting models for HFRS in northeastern China. ---------- Methods: We obtained data on monthly counts of reported HFRS cases in Elunchun and Molidawahaner counties for 1997–2007 from the Inner Mongolia Center for Disease Control and Prevention and climate data from the Chinese Bureau of Meteorology. Cross-correlations assessed crude associations between climate variables, including rainfall, land surface temperature (LST), relative humidity (RH), and the multivariate El Niño Southern Oscillation (ENSO) index (MEI) and monthly HFRS cases over a range of lags. We used time-series Poisson regression models to examine the independent contribution of climatic variables to HFRS transmission. ----------- Results: Cross-correlation analyses showed that rainfall, LST, RH, and MEI were significantly associated with monthly HFRS cases with lags of 3–5 months in both study areas. The results of Poisson regression indicated that after controlling for the autocorrelation, seasonality, and long-term trend, rainfall, LST, RH, and MEI with lags of 3–5 months were associated with HFRS in both study areas. The final model had good accuracy in forecasting the occurrence of HFRS. ---------- Conclusions: Climate variability plays a significant role in HFRS transmission in northeastern China. The model developed in this study has implications for HFRS control and prevention

All-cause mortality and risk factors in a cohort of retired military male veterans, Xi'an, China: an 18-year follow up study

<p>Abstract</p> <p>Background</p> <p>Risk factors of all-cause mortality have not been reported in Chinese retired military veterans. The objective of the study was to examine the risk factors and proportional mortality in a Chinese retired military male cohort.</p> <p>Methods</p> <p>A total of 1268 retired military men aged 55 or older were examined physically and interviewed using a standard questionnaire in 1987. The cohort was followed up every two years and the study censored date was June30, 2005 with a follow-up of up to 18 years. Death certificates were obtained from hospitals and verified by two senior doctors. Data were entered (double entry) by Foxbase, and analysis was carried out by SAS for Windows 8.2. Multivariate Cox proportional hazard regression model was used to compute hazard ratio (HR) and 95% confidence interval (CI).</p> <p>Results</p> <p>The total person-years of follow-up was 18766.28. Of the initial cohort of 1268 men, 491 had died, 748 were alive and 29 were lost to follow up. Adjusted mortality (adjusted for age, blood pressure, body mass index, cholesterol, triglycerides, alcohol, exercise, and existing disease) was 2,616 per 100,000 person years. The proportional mortality of cancer, vascular disease and Chronic Obstructive Pulmonary Disease (COPD) were 39.71%, 28.10% and 16.90% respectively. Multivariate analysis showed that age, cigarettes per day, systolic blood pressure, triglyceride, family history of diseases (hypertension, stroke and cancer), existing diseases (stroke, diabetes and cancer), body mass index, and age of starting smoking were associated with all-cause mortality, HR (95%CI) was1.083(1.062–1.104), 1.026(1.013–1.039), 1.009(1.003–1.015), 1.002(1.001–1.003), 1.330(1.005–1.759), 1.330(1.005–1.759), 1.444(1.103–1.890), 2.237(1.244–4.022), 1.462(1.042–2.051), 2.079(1.051–4.115), 0.963(0.931–0.996)and 0.988(0.978–0.999)respectively. Compared with never-smokers, current smokers had increased risks of total mortality [HR 1.369(1.083–1.731)], CHD [HR 1.805 (1.022–3.188)], and lung cancer [HR 2.939 (1.311–6.585)].</p> <p>Conclusion</p> <p>The three leading causes of diseases were cancer, CHD and stroke, and COPD. Aging, cigarette smoking, high systolic blood pressure, high triglyceride, family history of cancer, hypertension and stroke, existing cases recovering from stroke, diabetes and cancer, underweight, younger age of smoking were risk factors for all-cause mortality. Quitting cigarette smoking, maintaining normal blood pressure, triglyceride and weight are effect control strategies to prevent premature mortality in this military cohort.</p

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Junctional Adhesion Molecule 2 Mediates the Interaction between Hatched Blastocyst and Luminal Epithelium: Induction by Progesterone and LIF

National Basic Research Program of China [2011CB944402]; National Natural Science Foundation of China [30930013, 31071276]Background: Junctional adhesion molecule 2 (Jam2) is a member of the JAM superfamily. JAMs are localized at intercellular contacts and participated in the assembly and maintenance of junctions, and control of cell permeability. Because Jam2 is highly expressed in the luminal epithelium on day 4 of pregnancy, this study was to determine whether Jam2 plays a role in uterine receptivity and blastocyst attachment in mouse uterus. Methodology/Principal Findings: Jam2 is highly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy. Progesterone induces Jam2 expression in ovariectomized mice, which is blocked by progesterone antagonist RU486. Jam2 expression on day 4 of pregnancy is also inhibited by RU486 treatment. Leukemia inhibitory factor (LIF) up-regulates Jam2 protein in isolated luminal epithelium from day 4 uterus, which is blocked by S3I-201, a cell-permeable inhibitor for Stat3 phosphorylation. Under adhesion assay, recombinant Jam2 protein increases the rate of blastocyst adhesion. Both soluble recombinant Jam2 and Jam3 can reverse this process. Conclusion: Jam2 is highly expressed in the luminal epithelium of receptive uterus and up-regulated by progesterone and LIF via tyrosine phosphorylation of Stat3. Jam2 may play a role in the interaction between hatched blastocyst and receptive uterus

Ethnic Differences in Body Composition and Obesity Related Risk Factors: Study in Chinese and White Males Living in China

The purpose of this cross-sectional observational study was to identify ethnic differences in body composition and obesity-related risk factors between Chinese and white males living in China. 115 Chinese and 114 white male pilots aged 28–63 years were recruited. Fasting body weight, height and blood pressure were measured following standard procedures. Whole-body and segmental body composition were measured using an 8-contact electrode bioimpedance analysis (BIA) system. Fasting serum glucose, fasting plasma total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed using automatic biochemistry analyzer. After adjusting for age and body mass index (BMI), Chinese males had significantly higher percentage of body fat (PBF) both with respect to whole body (Chinese: 23.7%±0.2% vs. Whites: 22.4%±0.2%) and the trunk area (Chinese: 25.0%±0.3% vs. Whites: 23.2%±0.3%) compared to their white counterparts. At all BMIs, Chinese males had significantly higher fasting glucose levels (Chinese: 5.7±1.0 mmol/L vs. Whites: 5.2±1.0 mmol/L) but lower high-density lipoprotein levels (Chinese: 0.8±1.0 mmol/L vs. Whites: 1.0±1.0 mmol/L) than white males. In addition, a marginally significantly higher diastolic blood pressure was found among Chinese men than that among white men (Chinese: 80±1.0 mmHg vs. Whites: 77±1.0 mmHg). Chinese males had more body fat and a greater degree of central fat deposition pattern than that seen in white males in the present study. Furthermore, data on blood pressure, fasting glucose and blood lipids suggest that Chinese men may be more prone to obesity-related risk factors than white men

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials

Novel hybrid organic/inorganic 2D quasiperiodic PC: from diffraction pattern to vertical light extraction

Recently, important efforts have been dedicated to the realization of a fascinating class of new photonic materials or metamaterials, known as photonic quasicrystals (PQCs), in which the lack of the translational symmetry is compensated by rotational symmetries not achievable by the conventional periodic crystals. As ever, more advanced functionality is demanded and one strategy is the introduction of non-linear and/or active functionality in photonic materials. In this view, core/shell nanorods (NRs) are a promising active material for light-emitting applications. In this article a two-dimensional (2D) hybrid a 2D octagonal PQC which consists of air rods in an organic/inorganic nanocomposite is proposed and experimentally demonstrated. The nanocomposite was prepared by incorporating CdSe/CdS core/shell NRs into a polymer matrix. The PQC was realized by electron beam lithography (EBL) technique. Scanning electron microscopy, far field diffraction and spectra measurements are used to characterize the experimental structure. The vertical extraction of the light, by the coupling of the modes guided by the PQC slab to the free radiation via Bragg scattering, consists of a narrow red emissions band at 690 nm with a full width at half-maximum (FWHM) of 21.5 nm. The original characteristics of hybrid materials based on polymers and colloidal NRs, able to combine the unique optical properties of the inorganic moiety with the processability of the host matrix, are extremely appealing in view of their technological impact on the development of new high performing optical devices such as organic light-emitting diodes, ultra-low threshold lasers, and non-linear devices

An Intronic Variant in the GRP78, a Stress-Associated Gene, Improves Prediction for Liver Cirrhosis in Persistent HBV Carriers

Background: Our previous study indicated that a common variant (rs430397 G>A) in the intron 5 of glucose-regulated protein 78 (GRP78) gene was associated with risk and prognosis of primary hepatocellular carcinoma (HCC), including HBV- and cirrhosis-related HCC. rs430397 polymorphism may be a contributing factor or biomarker of HBV infection or HBV-related cirrhosis. Methodology/Principal Findings: 539 non-HBV-infected individuals, 205 self-limited infection and 496 persistent HBV infection were recruited between January 2001 and April 2005 from the hospitals in Southern China. Genomic DNA was genotyped for rs430397. The associations between the variation and susceptibility to liver cirrhosis (LC) in persistent HBV infection were examined. We observed that individuals carrying allele rs430397A were more likely to become HBV-related LC. When persistently infected patients were divided into four subgroups, patients with phase IV had an increased allele A and genotype AG compared with phase I and/or phase III. Decreased serum albumin and prolonged plasma prothrombin time (PT) were showed in LC patients carrying genotype AA. Furthermore, rs430397 genotype had an increased susceptibility to LC with dose-dependent manners (P-trend = 0.005), and the genotype did constitute a risk factor for the development of advanced LC (Child-Pugh classification C and B, P-trend = 0.021). Conclusions/Significance: rs430397 polymorphism may be a contributing factor to LC in persistent HBV carriers. © 2011 Zhu et al.published_or_final_versio