The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

Illegal Substance Use among Italian High School Students: Trends over 11 Years (1999–2009)

Purpose: To monitor changes in habits in drug use among Italian high school students. Methods: Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out in Italy annually for 11 years (1999-2009) with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT), use in the last year (LY), use in the last 30 days (LM), frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. Results: When the time-averaged value was considered, cannabis (30% LT) was the most, and heroin the least (2%) frequently used, with cocaine (5%), hallucinogens (2%) and stimulants (2%) in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7-2.4, p,0.05), less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2-1.5, p,0.05). Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. Conclusions: Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.-

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Complete Multiwavelength Characterization of Faint Chandra X-ray Sources Seen in the Spitzer Wide-Area IR Extragalactic (SWIRE) Survey

We exploit deep combined observations with Spitzer and Chandra of the SWIRE survey in the ELAIS-N1 region, to investigate the nature of the faint X-ray and IR sources in common, to identify AGN/starburst diagnostics, and to study the sources of the X-ray and IR cosmic backgrounds. In the 17'x17' area of the Chandra ACIS-I image there are 3400 SWIRE near-IR sources with 4 sigma detections in at least 2 IRAC bands and 988 sources detected at 24micron with MIPS brighter than 0.1 mJy. Of these, 102 IRAC and 59 MIPS sources have Chandra counterparts, out of a total of 122 X-ray sources present in the area with S(0.5-8 kev)>10^(-15) erg/cm^2/s. We have constructed SEDs for each source using data from the 4 IRAC wavebands, Chandra fluxes, and optical follow-up data in the wavebands U, g', r', i', Z, and H. We fit a number of spectral templates to the SEDs at optical and infrared wavelengths to determine photometric redshifts and spectral categories, and also make use of diagnostics based on the X-ray luminosities, hardness ratios, X-ray to infrared spectral slopes and optical morphologies. Although we have spectroscopic redshifts for only a minority of the Chandra sources, the available SEDs constrain the redshifts for most of the sample sources, which turn out to be typically at 0.5<z<2. We find that 39% of the Chandra sources are dominated by type-1 AGN emission, 23% display optical/IR spectra typical of type-2 AGNs, while the remaining 38% fraction show starburst-like or even normal galaxy spectra. Since we prove that all these galaxies are dominated by AGN emission in X-rays this brings the fraction of type-1 AGNs to be 80% of the type-2: even assuming that all the Chandra sources undetected by Spitzer are type-2 AGNs, the type-1 fraction would exceed 1/3 of the total population (abridged).Comment: Accepted for publication in AJ, March 2005 issu

The N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD

The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri, providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is comprised of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g. deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. While the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study due to the hydrophobic nature of the IpaB and IpaC translocator proteins. Here we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11–27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Immunoprotectivity of HLA-A2 CTL Peptides Derived from Respiratory Syncytial Virus Fusion Protein in HLA-A2 Transgenic Mouse

Identification of HLA-restricted CD8+ T cell epitopes is important to study RSV-induced immunity and illness. We algorithmically analyzed the sequence of the fusion protein (F) of respiratory syncytial virus (RSV) and generated synthetic peptides that can potentially bind to HLA-A*0201. Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33–41), 13 (F214–222), 14 (F273–281), and 23 (F559–567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F. HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall. Effector responses induced by these peptides were observed to confer differential protection against live RSV challenge. These peptides also caused better recovery of body weight loss induced by RSV. A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs. Whereas, significant reduction of infiltrated eosinophils induced by RSV infection was found in mice pre-immunized with peptide 13. Our results suggest that HLA-A2-restricted epitopes of RSV F protein could be useful for the development of epitope-based RSV vaccine

Dairying, diseases and the evolution of lactase persistence in Europe

Update notice Author Correction: Dairying, diseases and the evolution of lactase persistence in Europe (Nature, (2022), 608, 7922, (336-345), 10.1038/s41586-022-05010-7) Nature, Volume 609, Issue 7927, Pages E9, 15 September 2022In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years(1). Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions(2,3). Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectoriesthan uniform selection since the Neolithic period. In the UK Biobank(4,5) cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.Peer reviewe