Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology

The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern

How can latent trajectories of back pain be translated into defined subgroups?

Background: Similar types of trajectory patterns have been identified by Latent Class Analyses (LCA) across multiple low back pain (LBP) cohorts, but these patterns are impractical to apply to new cohorts or individual patients. It would be useful to be able to identify trajectory subgroups from descriptive definitions, as a way to apply the same definitions of mutually exclusive subgroups across populations. In this study, we investigated if the course trajectories of two LBP cohorts fitted with previously suggested trajectory subgroup definitions, how distinctly different these subgroups were, and if the subgroup definitions matched with LCA-derived patterns. Methods: Weekly measures of LBP intensity and frequency during 1 year were available from two clinical cohorts. We applied definitions of 16 possible trajectory subgroups to these observations and calculated the prevalence of the subgroups. The probability of belonging to each of eight LCA-derived patterns was determined within each subgroup. LBP intensity and frequency were described within subgroups and the subgroups of 'fluctuating' and 'episodic' LBP were compared on clinical characteristics. Results: All of 1077 observed trajectories fitted with the defined subgroups. 'Severe episodic LBP' was the most frequent pattern in both cohorts and 'ongoing LBP' was almost non-existing. There was a clear relationship between the defined trajectory subgroups and LCA-derived trajectory patterns, as in most subgroups, all patients had high probabilities of belonging to only one or two of the LCA patterns. The characteristics of the six defined subgroups with minor LBP were very similar. 'Fluctuating LBP' subgroups were significantly more distressed, had more intense leg pain, higher levels of activity limitation, and more negative expectations about future LBP than 'episodic LBP' subgroups. Conclusion: Previously suggested definitions of LBP trajectory subgroups could be readily applied to patients' observed data resulting in subgroups that matched well with LCA-derived trajectory patterns. We suggest that the number of trajectory subgroups can be reduced by merging some subgroups with minor LBP. Stable levels of LBP were almost not observed and we suggest that minor fluctuations in pain intensity might be conceptualised as 'ongoing LBP'. Lastly, we found clear support for distinguishing between fluctuating and episodic LBP

Wind speed variability over the Canary Islands, 1948-2014: focusing on trend differences at the land-ocean interface and below-above the trade-wind inversion layer

This study simultaneously examines wind speed trends at the land?ocean interface, and below?above the trade-wind inversion layer in the Canary Islands and the surrounding Eastern North Atlantic Ocean: a key region for quantifying the variability of trade-winds and its response to large-scale atmospheric circulation changes. Two homogenized data sources are used: (1) observed wind speed from nine land-based stations (1981?2014), including one mountain weather station (Izaña) located above the trade-wind inversion layer; and (2) simulated wind speed from two atmospheric hindcasts over ocean (i.e., SeaWind I at 30 km for 1948?2014; and SeaWind II at 15 km for 1989?2014). The results revealed a widespread significant negative trend of trade-winds over ocean for 1948?2014, whereas no significant trends were detected for 1989?2014. For this recent period wind speed over land and ocean displayed the same multi-decadal variability and a distinct seasonal trend pattern with a strengthening (late spring and summer; significant in May and August) and weakening (winter?spring?autumn; significant in April and September) of trade-winds. Above the inversion layer at Izaña, we found a predominance of significant positive trends, indicating a decoupled variability and opposite wind speed trends when compared to those reported in boundary layer. The analysis of the Trade Wind Index (TWI), the North Atlantic Oscillation Index (NAOI) and the Eastern Atlantic Index (EAI) demonstrated significant correlations with the wind speed variability, revealing that the correlation patterns of the three indices showed a spatio-temporal complementarity in shaping wind speed trends across the Eastern North Atlantic.C. A. -M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 703733 (STILLING project). This research was also supported by the Research Projects: Swedish BECC, MERGE, VR (2014–5320), PCIN-2015-220, CGL2014-52135-C03-01 and Red de variabilidad y cambio climático RECLIM (CGL2014-517221-REDT). M.M is indebted to the Spanish Government for funding through the “Ramón y Cajal” program and supported by Grant PORTIO (BIA2015-70644-R

Regulation of Apoptotic Pathways by Stylophora pistillata (Anthozoa, Pocilloporidae) to Survive Thermal Stress and Bleaching

Elevated seawater temperatures are associated with coral bleaching events and related mortality. Nevertheless, some coral species are able to survive bleaching and recover. The apoptotic responses associated to this ability were studied over 3 years in the coral Stylophora pistillata from the Gulf of Eilat subjected to long term thermal stress. These include caspase activity and the expression profiles of the S. pistillata caspase and Bcl-2 genes (StyCasp and StyBcl-2-like) cloned in this study. In corals exposed to thermal stress (32 or 34°C), caspase activity and the expression levels of the StyBcl-2-like gene increased over time (6–48 h) and declined to basal levels within 72 h of thermal stress. Distinct transcript levels were obtained for the StyCasp gene, with stimulated expression from 6 to 48 h of 34°C thermal stress, coinciding with the onset of bleaching. Increased cell death was detected in situ only between 6 to 48 h of stress and was limited to the gastroderm. The bleached corals survived up to one month at 32°C, and recovered back symbionts when placed at 24°C. These results point to a two-stage response in corals that withstand thermal stress: (i) the onset of apoptosis, accompanied by rapid activation of anti-oxidant/anti-apoptotic mediators that block the progression of apoptosis to other cells and (ii) acclimatization of the coral to the chronic thermal stress alongside the completion of symbiosis breakdown. Accordingly, the coral's ability to rapidly curb apoptosis appears to be the most important trait affecting the coral's thermotolerance and survival

Response to ‘Re: Kakkos et al. Efficacy and Safety of the New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban in the Treatment and Secondary Prevention of Venous Thromboembolism: A Systematic Review and Meta-analysis of Phase III Trials’

We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl. Cohort study based on routinely collected data from the HIV-CAUSAL collaboration. For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2). Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation

Alternative way to test the efficacy of swine FMD vaccines: measurement of pigs median infected dose (PID50) and regulation of live virus challenge dose

Foot-and -mouth disease to pigs is serious recently around the world. "Vaccination prevention" is still an important policy. OIE specifies 10,000 TCID50(0.2 ml) of virulent virus for challenge test in pigs to test the potency of FMD vaccine by intradermal route inoculating the virus in the heel bulbs of one foot or by intramuscular route administering into one site of the neck behind the ear. Convenience and speediness are available in the process of potency test of commercial FMD vaccine. We selected the route of "administering into one site of the muscular part of the neck behind the ear" because of convenience and speediness. However, it was difficult to infect control pigs even up to 100,000TCID50, so we changed the challenged virus from cell-passaged strain to suckling mice-passaged one, measured its PID50 (pigs median infected dose) and defined the virus challenge dose as 1000PID50. Meanwhile, we arranged the number of control pigs from two to three for easy evaluation