julilili42/papers huggingface dataset:
Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent
2016-08-23

Background: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods: We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results: In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56–0.75, p = 3.32 × 10−10). The associations were similar for both premenopausal (OR = 0.44, 95% CI:0.31–0.62, p = 9.91 × 10−8) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46–0.71, p = 1.88 × 10−8). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60–0.84, p = 1.64 × 10−7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p &lt; 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions: BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.
Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis
2016-08-23

ABSTRACT Teixobactin represents the first member of a newly discovered class of antibiotics that act through inhibition of cell wall synthesis. Teixobactin binds multiple bactoprenol-coupled cell wall precursors, inhibiting both peptidoglycan and teichoic acid synthesis. Here, we show that the impressive bactericidal activity of teixobactin is due to the synergistic inhibition of both targets, resulting in cell wall damage, delocalization of autolysins, and subsequent cell lysis. We also find that teixobactin does not bind mature peptidoglycan, further increasing its activity at high cell densities and against vancomycin-intermediate Staphylococcus aureus (VISA) isolates with thickened peptidoglycan layers. These findings add to the attractiveness of teixobactin as a potential therapeutic agent for the treatment of infection caused by antibiotic-resistant Gram-positive pathogens.
Oxytocin Improves β-Cell Responsivity and Glucose Tolerance in Healthy Men
2016-08-23

In addition to its pivotal role in psychosocial behavior, the hypothalamic neuropeptide oxytocin contributes to metabolic control by suppressing eating behavior. Its involvement in glucose homeostasis is less clear, although pilot experiments suggest that oxytocin improves glucose homeostasis. We assessed the effect of intranasal oxytocin (24 IU) administered to 29 healthy, fasted male subjects on glucose homeostasis measured by means of an oral glucose tolerance test. Parameters of glucose metabolism were analyzed according to the oral minimal model. Oxytocin attenuated the peak excursion of plasma glucose and augmented the early increases in insulin and C-peptide concentrations in response to the glucose challenge, while slightly blunting insulin and C-peptide peaks. Oral minimal model analyses revealed that oxytocin compared with placebo induced a pronounced increase in β-cell responsivity (PHItotal) that was largely due to an enhanced dynamic response (PHId), and a more than twofold improvement in glucose tolerance (disposition index). Adrenocorticotropic hormone (ACTH), cortisol, glucagon, and nonesterified fatty acid (NEFA) concentrations were not or were only marginally affected. These results indicate that oxytocin plays a significant role in the acute regulation of glucose metabolism in healthy humans and render the oxytocin system a potential target of antidiabetic treatment.
Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer
2016-08-23

Abstract Background: The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist–hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Methods: Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. Results: The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10−17). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89–2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44–1.68, per 5 kg/m2). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10–1.39; P = 5.3 × 10−4). There was evidence of directional pleiotropy (P = 1.5 × 10−4). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P &amp;lt; 4.0 × 10−4), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. Conclusions: BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. Impact: The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503–10. ©2016 AACR.
Main fungal partners and different levels of specificity of orchid mycorrhizae in the tropical mountain forests of Ecuador
2016-08-23

Orchids are a main component of the diversity of vascular plants in Ecuador with approximately 4000 species representing about 5.3% of the orchid species described worldwide. More than a third of these species are endemics. As orchids, in contrast to other plants, depend on mycorrhizal fungi already for seed germination and early seedling establishment, availability of appropriate fungi may strongly influence distribution of orchid populations. It is currently debated if green orchids depend on specific mycobionts or may be equally promoted by a broad spectrum of mycorrhizal fungi, discussion mostly based on data from temperate regions. Here we summarize results obtained from broad scale investigations in the tropical mountain rain forest of Ecuador revealing associations with members of Serendipitaceae (Sebacinales), Tulasnellaceae, Ceratobasidiaceae (Cantharellales), and Atractiellales. Recent molecular data show that these worldwide spread fungal groups have broad ecological implications and are specifically suited as mycorrhizal fungi of green orchids. We found that main fungal partners and different levels of specificity among orchids and their mycobionts in the tropical mountain forests correspond to findings in other biomes despite the large ecological differences.
Experimental and theoretical investigations on the high-electron donor character of pyrido-annelated N-heterocyclic carbenes
2016-08-23

Rh(CO) 2 Cl(NHC) complexes of dipyrido-annelated N-heterocyclic carbenes were prepared. From the C–H coupling constant of the respective imidazolium salts and the N–C–N angle of the N-heterocyclic carbene (NHC), a weaker σ-donor character than that of typical unsaturated NHCs is expected. However, the IR stretching frequencies of their Rh(CO) 2 Cl complexes suggest an electron-donor character even stronger than that of saturated NHCs. We ascribe this to the extremely weak π-acceptor character of the dipyrido-annelated NHCs caused by the conjugated 14 πe − system that thus allows for an enhanced Rh–CO backbonding. This extremely low π-acceptor ability is also corroborated by the 77 Se NMR chemical shift of −55.8 ppm for the respective selenourea, the lowest value ever measured for imidazole derived selenoureas. DFT-calculations of the free carbene confirm the low σ-donor character by the fact that the σ-orbital of the carbene is the HOMO−1 that lies 0.58 eV below the HOMO which is located at the π-system. Natural population analysis reveals the lowest occupation of the p π -orbital for the saturated carbene carbon atom and the highest for the pyrido-annelated carbene. Going from the free carbene to the Rh(CO) 2 Cl(NHC) complexes, the increase in occupancy of the complete π-system of the carbene ligand upon coordination is lowest for the pyrido-annelated carbene and highest for the saturated carbene.
The freedom to choose neutron star magnetic field equilibria: Table 1.
2016-08-23

Our ability to interpret and glean useful information from the large body of\\nobservations of strongly magnetised neutron stars rests largely on our\\ntheoretical understanding of magnetic field equilibria. We answer the following\\nquestion: is one free to arbitrarily prescribe magnetic equilibria such that\\nfluid degrees of freedom can balance the equilibrium equations? We examine this\\nquestion for various models for neutron star matter; from the simplest\\nsingle-fluid barotrope to more realistic non-barotropic multifluid models with\\nsuperfluid/superconducting components, muons and entropy. We do this for both\\naxi- and non-axisymmetric equilibria, and in Newtonian gravity and general\\nrelativity. We show that, in axisymmetry, the most realistic model allows\\ncomplete freedom in choosing a magnetic field equilibrium whereas\\nnon-axisymmetric equilibria are never completely arbitrary.\\n
Sphenofrontal distance in euploid and aneuploid fetuses
2016-08-23

ABSTRACT Objective To examine the sphenofrontal distance ( SFD ) in a large series of aneuploid fetuses in the second and third trimesters and compare findings with those of a euploid population. Methods The database at our unit was searched to identify pregnancies with a diagnosis of trisomy 21, 18 or 13, triploidy or Turner syndrome after 15 weeks' gestation. Stored ultrasound images obtained between 19 and 22 weeks were reviewed. For the normal population, two euploid fetuses matched for gestational age were selected randomly for each aneuploid case. The SFD was measured from the anterior edge of the sphenoid bone to the lowest posterior edge of the frontal bone using on‐screen calipers. The SFD measurement was parallel to the long axis of the maxilla. If the sphenoid bone did not extend superiorly enough for direct measurement of the SFD , a tangential line was drawn at the anterior wall of the sphenoid bone and extended cranially. In these cases, the distance between the extended line and the frontal bone was measured. One operator measured the SFD twice and was blinded to the results and karyotype. Results The study population consisted of 591 pregnancies: 394 euploid fetuses, 122 fetuses with trisomy 21, 45 with trisomy 18, 16 with trisomy 13, eight with Turner syndrome and six with triploidy. For both euploid and aneuploid groups, mean gestational age at examination was 22.8 (range: euploid, 15.0–40.7; aneuploid, 15.0–40.3) weeks. For euploid fetuses, mean SFD was 1.27 cm and measurements ranged from 0.53 cm to 2.56 cm. SFD was significantly dependent on gestational age ( SFD = 0.138 + 0.005 × gestational age, P &lt; 0.001, r = 0.802). Mean SFD was significantly smaller in each aneuploid group compared with the euploid population (trisomies 21, 18 and 13: all P &lt; 0.001; triploidy: P = 0.026; Turner syndrome: P = 0.047). For 32 (26.2%), nine (20.0%) and six (37.5%) fetuses with trisomy 21, 18 and 13, respectively, SFD was &lt; 5 th percentile. Only one (12.5%) fetus with Turner syndrome and none with triploidy had SFD &lt; 5 th percentile. Conclusion In aneuploid fetuses, the SFD is smaller than in their euploid counterparts. However, for a false‐positive rate of 5%, the detection rate of trisomy 21 is only 26%. Therefore, using the method we have proposed, it is unlikely that this marker will play a major role in second‐ and third‐trimester screening for aneuploidy. Copyright © 2016 ISUOG. Published by John Wiley &amp; Sons Ltd.
Oxytocin’s inhibitory effect on food intake is stronger in obese than normal-weight men
2016-08-24

Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders.
Increased Plasma Matrix Metalloproteinase-9 Levels Contribute to Intracerebral Hemorrhage during Thrombolysis after Concomitant Stroke and Influenza Infection
2016-08-24

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Thrombolysis is the only approved therapy for acute stroke. However, life-threatening complications such as intracerebral hemorrhage (ICH) can develop after intravenous administration of tissue plasminogen activator (tPA). Both infection and thrombolysis during cerebral ischemia disrupt the blood-brain barrier (BBB). tPA can induce matrix metalloproteinase-9 (MMP-9), which is known to be involved in BBB disruption. However, it has still not been investigated whether preexisting influenza virus infection during thrombolysis after acute stroke affects systemic levels of MMP-9 and its inhibitor TIMP-1 and whether increased systemic MMP-9 levels affect ICH. This study aimed to investigate the influence of influenza virus infection on plasma levels of MMP-9 and TIMP-1 after thrombolysis in acute stroke, and to determine whether the infection correlates with intracerebral bleeding. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; C57BL/6 mice were infected by administering 1 × 10&lt;sup&gt;5&lt;/sup&gt; plaque-forming units of human influenza (H1N1) virus intranasally. After 3 days of infection the middle cerebral artery was occluded for 45 min and then reperfused. Intravenous tPA (10 mg/kg) treatment was started 10 min after stroke onset. Twenty-four hours after stroke onset, mice were deeply anesthetized with ketamine, venous blood was drawn from the caval vein and centrifuged at 2,000 rpm, and the supernatant was collected and frozen at -80°C. Plasma levels of MMP-9 and TIMP-1 were quantified by using ELISA. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; After stroke, plasma MMP-9 was significantly increased in mice with a concomitant influenza infection that were treated with tPA (9.99 ± 0.62 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA (4.74 ± 0.48 ng/ml, n = 8). Moreover, plasma levels of TIMP-1, an inhibitor of MMP-9, were also significantly increased in mice treated with tPA after concomitant infection and stroke (42.17 ± 7.02 ng/ml, n = 7) as compared to noninfected control mice that were treated with tPA after stroke (20.22 ± 2.12 ng/ml, n = 8). MMP-9 values significantly correlated with intracerebral hemoglobin levels in animals treated with tPA after stroke (p = 0.028, r = 0.76, n = 8) and after concomitant stroke and infection (p = 0.039, r = 0.78, n = 7). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Preexisting influenza A virus infection led to increased plasma MMP-9 and TIMP-1 levels in mice undergoing thrombolysis after induced stroke. MMP-9 levels closely correlated with intracerebral bleeding after thrombolysis during concomitant infection and stroke. Thus, our data indicate that thrombolysis may be dangerous during influenza infection. MMP-9 inhibitors might be considered to reduce the side effects of thrombolysis during concomitant infection and stroke.
Redox and Acid–Base Properties of Binuclear 4‐Terphenyldithiophenolate Complexes of Nickel
2016-08-24

Abstract This work reports on the redox and acid–base properties of binuclear complexes of nickel from 1,4‐terphenyldithiophenol ligands. The results provide insight into the cooperative electronic interaction between a dinickel core and its ligand. Donor/acceptor contributions flexibly adjust to stabilize different redox states at the metals, which is relevant for redox reactions like proton reduction. Proton transfer to the [S 2 Ni 2 ] core and Ni−H bond formation are kinetically favored over the thermodynamically favored yet unproductive proton transfer to ligand.
Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus
2016-08-24

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.
Narcissism and romantic relationships: The differential impact of narcissistic admiration and rivalry.
2016-08-25

Narcissism is known to be related to romantic success in short-term contexts (dating, early stage relationships) but also to problems in long-term committed relationships. We propose that these diverging romantic outcomes of narcissism can be explained by differential associations with agentic versus antagonistic dimensions of grandiose narcissism: Narcissistic Admiration and Rivalry. Both dimensions serve the central narcissistic goal of gaining and maintaining a grandiose self-view, but do so by different processes: Admiration is characterized by the tendency to promote the positivity of one's self-view by seeking social admiration (assertive self-enhancement). Rivalry is characterized by the tendency to protect oneself from a negative self-view by derogating others (antagonistic self-protection). Across 7 studies (total N = 3,560) using diverse measures and methodological approaches (self-, peer, and partner reports, as well as interpersonal perception measures in video-based studies, face-to-face laboratory encounters, and online surveys), we show that the short-term romantic appeal associated with narcissism is primarily attributable to the dimension of Admiration, whereas the long-term romantic problems associated with narcissism are primarily attributable to the dimension of Rivalry. These results highlight the utility of a 2-dimensional reconceptualization of grandiose narcissism for explaining its heterogeneous romantic outcomes. The findings further underscore the idea that different facets of personality traits might impact different aspects of romantic relationship quality, depending on the stage of the relationship. Such a more nuanced view increases the predictive validity of personality traits in social relationship research. (PsycINFO Database Record
Climate change will increase the naturalization risk from garden plants in Europe
2016-08-25

Abstract Aim Plant invasions often follow initial introduction with a considerable delay. The current non‐native flora of a region may hence contain species that are not yet naturalized but may become so in the future, especially if climate change lifts limitations on species spread. In Europe, non‐native garden plants represent a huge pool of potential future invaders. Here, we evaluate the naturalization risk from this species pool and how it may change under a warmer climate. Location Europe. Methods We selected all species naturalized anywhere in the world but not yet in Europe from the set of non‐native European garden plants. For this subset of 783 species, we used species distribution models to assess their potential European ranges under different scenarios of climate change. Moreover, we defined geographical hotspots of naturalization risk from those species by combining projections of climatic suitability with maps of the area available for ornamental plant cultivation. Results Under current climate, 165 species would already find suitable conditions in &gt; 5% of Europe. Although climate change substantially increases the potential range of many species, there are also some that are predicted to lose climatically suitable area under a changing climate, particularly species native to boreal and Mediterranean biomes. Overall, hotspots of naturalization risk defined by climatic suitability alone, or by a combination of climatic suitability and appropriate land cover, are projected to increase by up to 102% or 64%, respectively. Main conclusions Our results suggest that the risk of naturalization of European garden plants will increase with warming climate, and thus it is very likely that the risk of negative impacts from invasion by these plants will also grow. It is therefore crucial to increase awareness of the possibility of biological invasions among horticulturalists, particularly in the face of a warming climate.