Males do not reduce the fitness of their female co-twins in contemporary samples.

Lummaa et al. (2007) presented historical data collected from twins born in Finland between 1734 and 1888 which suggested that females (N = 31) born as part of an opposite sex (OS) twin pair were 25% less likely to reproduce than female twins (N = 35) born as part of a same sex (SS) pair. They hypothesized that this reduction in fitness was due to masculinization of the female fetus via prenatal effects of the hormones of a male fetus. Because such masculinization would presumably take place in modern populations as well, it would seem important to establish to what degree it does so, and if so, whether reproduction is affected. We therefore address the question of reproduction differences in individual female twins from same-sex (N = 1979) and opposite-sex (N = 913) dizygotic pairs in studies carried out in Australia, the Netherlands, and the United States. In all three samples, there were no differences in the number of children or age of first pregnancies in women from same sex pairs compared to those from opposite sex pairs. Similarly, there were no differences in psychological femininity between women from pairs of the same or opposite sex

Stray-light contamination and spatial deconvolution of slit-spectrograph observations

Stray light caused by scattering on optical surfaces and in the Earth's atmosphere degrades the spatial resolution of observations. We study the contribution of stray light to the two channels of POLIS. We test the performance of different methods of stray-light correction and spatial deconvolution to improve the spatial resolution post-facto. We model the stray light as having two components: a spectrally dispersed component and a component of parasitic light caused by scattering inside the spectrograph. We use several measurements to estimate the two contributions: observations with a (partly) blocked FOV, a convolution of the FTS spectral atlas, imaging in the pupil plane, umbral profiles, and spurious polarization signal in telluric lines. The measurements allow us to estimate the spatial PSF of POLIS and the main spectrograph of the German VTT. We use the PSF for a deconvolution of both spectropolarimetric data and investigate the effect on the spectra. The parasitic contribution can be directly and accurately determined for POLIS, amounting to about 5%. We estimate a lower limit of about 10% across the full FOV for the dispersed stray light. In quiet Sun regions, the stray-light level from the close surroundings (d< 2") of a given spatial point is about 20%. The stray light reduces to below 2% at a distance of 20" from a lit area for both POLIS and the main spectrograph. A two-component model of the stray-light contributions seems to be sufficient for a basic correction of observed spectra. The instrumental PSF obtained can be used to model the off-limb stray light, to determine the stray-light contamination accurately for observation targets with large spatial intensity gradients such as sunspots, and also allows one to improve the spatial resolution of observations post-facto.Comment: 14 pages, 16 figures, accepted by A&A. Version V2 revised for language editin

Amine Containing Analogs of Sulindac for Cancer Prevention

Background: Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity. Objective: Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities. Method: A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted sulindac amine sub-libraries. All analogs were screened against three cancer cell lines (prostate, colon and breast). Results: Several active compounds were identified viain vitro cancer cell line screening with the most potent compound (26) in the nanomolar range. Conclusion: Compound 26 and analogs showing the most potent inhibitory activity may be considered for further design and optimization efforts as anticancer hit scaffolds

Global impact of COVID-19 restrictions on the surface concentrations of nitrogen dioxide and ozone

Social distancing to combat the COVID-19 pandemic has led to widespread reductions in air pollutant emissions. Quantifying these changes requires a business-as-usual counterfactual that accounts for the synoptic and seasonal variability of air pollutants. We use a machine learning algorithm driven by information from the NASA GEOS-CF model to assess changes in nitrogen dioxide (NO2) and ozone (O3) at 5756 observation sites in 46 countries from January through June 2020. Reductions in NO2 coincide with the timing and intensity of COVID-19 restrictions, ranging from 60 % in severely affected cities (e.g., Wuhan, Milan) to little change (e.g., Rio de Janeiro, Taipei). On average, NO2 concentrations were 18 (13-23) % lower than business as usual from February 2020 onward. China experienced the earliest and steepest decline, but concentrations since April have mostly recovered and remained within 5 % of the business-as-usual estimate. NO2 reductions in Europe and the US have been more gradual, with a halting recovery starting in late March. We estimate that the global NOx (NO + NO2) emission reduction during the first 6 months of 2020 amounted to 3.1 (2.6-3.6) TgN, equivalent to 5.5 (4.7-6.4) % of the annual anthropogenic total. The response of surface O3 is complicated by competing influences of nonlinear atmospheric chemistry. While surface O3 increased by up to 50 % in some locations, we find the overall net impact on daily average O3 between February-June 2020 to be small. However, our analysis indicates a flattening of the O3 diurnal cycle with an increase in nighttime ozone due to reduced titration and a decrease in daytime ozone, reflecting a reduction in photochemical production. The O3 response is dependent on season, timescale, and environment, with declines in surface O3 forecasted if NOx emission reductions continue

Therapeutic Implications of GIPC1 Silencing in Cancer

GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppression of GIPC1 in human pancreatic cancer cells inhibits in vivo tumor growth in immunodeficient mice. To better understand GIPC1 function, we suppressed its expression in human breast and colorectal cancer cell lines and human mammary epithelial cells (HMECs) and assayed both gene expression and cellular phenotype. Suppression of GIPC1 promotes apoptosis in MCF-7, MDA-MD231, SKBR-3, SW480, and SW620 cells and impairs anchorage-independent colony formation of HMECs. These observations indicate GIPC1 plays an essential role in oncogenic transformation, and its expression is necessary for the survival of human breast and colorectal cancer cells. Additionally, a GIPC1 knock-down gene signature was used to interrogate publically available breast and ovarian cancer microarray datasets. This GIPC1 signature statistically correlates with a number of breast and ovarian cancer phenotypes and clinical outcomes, including patient survival. Taken together, these data indicate that GIPC1 inhibition may represent a new target for therapeutic development for the treatment of human cancers

The prevalence of anxiety and depression in people with age-related macular degeneration: a systematic review of observational study data

Background Comorbid mental health problems have been shown to have an adverse effect on the quality of life of people with common eye disorders. This study aims to assess whether symptoms of anxiety and/or depression are more prevalent in people with age-related macular degeneration (AMD) than in people without this condition. Methods A systematic search of electronic databases (Medline, CINAHL, EMBASE, PsycINFO) from inception to February 2012 was conducted to identify studies of AMD populations which measured symptoms of anxiety and/or depression. Reference checking of relevant articles was also performed. Data on the study setting, prevalence and how anxiety and depression were measured were extracted from the papers. Critical appraisal was performed using the Critical Appraisal Skills Programme (CASP) tools. Results A total of 16 papers were included in the review, from an original search result of 597. The prevalence estimates, taken from nine cross-sectional and cohort studies, ranged from 15.7%-44% for depressive symptoms and 9.6%-30.1% for anxiety symptoms in people with AMD. The seven case–control studies found that people with AMD were more likely to experience symptoms of depression compared with those without AMD, but not more likely to experience symptoms of anxiety. Conclusions Overall, the evidence suggests that symptoms of depression are more prevalent amongst AMD populations than anxiety symptoms. The heterogeneity of the studies included in this review means that it is difficult to draw strong conclusions as to the true estimates of depression and anxiety symptoms in AMD populations and prevented formal meta-analysis. Further research which specifies clinical anxiety and gives clear definitions as to the type of AMD being investigated is required

Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia

A better description of the extent and structure of genetic diversity in dengue virus (DENV) in endemic settings is central to its eventual control. To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 and 2009. Strikingly, an episode of genotype replacement was observed, with Asian 1 lineage viruses entirely displacing the previously dominant Asian/American lineage viruses. This genotype replacement event also seems to have occurred within DENV-2 in Thailand and Cambodia, suggestive of a major difference in viral fitness. To determine the cause of this major evolutionary event we compared both the infectivity of the Asian 1 and Asian/American genotypes in mosquitoes and their viraemia levels in humans. Although there was little difference in infectivity in mosquitoes, we observed significantly higher plasma viraemia levels in paediatric patients infected with Asian 1 lineage viruses relative to Asian/American viruses, a phenotype that is predicted to result in a higher probability of human-to-mosquito transmission. These results provide a mechanistic basis to a marked change in the genetic structure of DENV-2 and more broadly underscore that an understanding of DENV evolutionary dynamics can inform the development of vaccines and anti-viral drugs

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version