Projecting coral responses to intensifying marine heatwaves under ocean acidification

Over this century, coral reefs will run the gauntlet of climate change, as marine heatwaves (MHWs) become more intense and frequent, and ocean acidification (OA) progresses. However, we still lack a quantitative assessment of how, and to what degree, OA will moderate the responses of corals to MHWs as they intensify throughout this century. Here, we first projected future MHW intensities for tropical regions under three future greenhouse gas emissions scenario (representative concentration pathways, RCP2.6, RCP4.5 and RCP8.5) for the near-term (2021-2040), mid-century (2041-2060) and late-century (2081-2100). We then combined these MHW intensity projections with a global data set of 1,788 experiments to assess coral attribute performance and survival under the three emissions scenarios for the near-term, mid-century and late-century in the presence and absence of OA. Although warming and OA had predominately additive impacts on the coral responses, the contribution of OA in affecting most coral attributes was minor relative to the dominant role of intensifying MHWs. However, the addition of OA led to greater decreases in photosynthesis and survival under intermediate and unrestricted emissions scenario for the mid- and late-century than if intensifying MHWs were considered as the only driver. These results show that role of OA in modulating coral responses to intensifying MHWs depended on the focal coral attribute and extremity of the scenario examined. Specifically, intensifying MHWs and OA will cause increasing instances of coral bleaching and substantial declines in coral productivity, calcification and survival within the next two decades under the low and intermediate emissions scenario. These projections suggest that corals must rapidly adapt or acclimatize to projected ocean conditions to persist, which is far more likely under a low emissions scenario and with increasing efforts to manage reefs to enhance resilience

Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were Present in the First Bilaterians

Homeodomain transcription factors are involved in many developmental processes across animals and have been linked to body plan evolution. Detailed classifications of these proteins identified 11 distinct classes of homeodomain proteins in animal genomes, each harboring specific sequence composition and protein domains. Although humans contain the full set of classes, Drosophila melanogaster and Caenorhabditis elegans each lack one specific class. Furthermore, representative previous analyses in sponges, ctenophores, and cnidarians could not identify several classes in those nonbilaterian metazoan taxa. Consequently, it is currently unknown when certain homeodomain protein classes first evolved during animal evolution. Here, we investigate representatives of the sister group to all remaining bilaterians, the Xenacoelomorpha. We analyzed three acoel, one nemertodermatid, and one Xenoturbella transcriptomes and identified their expressed homeodomain protein content. We report the identification of representatives of all 11 classes of animal homeodomain transcription factors in Xenacoelomorpha and we describe and classify their homeobox genes relative to the established animal homeodomain protein families. Our findings suggest that the genome of the last common ancestor of bilateria contained the full set of these gene classes, supporting the subsequent diversification of bilaterians

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Visualization of postoperative anterior cruciate ligament reconstruction bone tunnels: Reliability of standard radiographs, CT scans, and 3D virtual reality images

Background and purpose: Non-anatomic bone tunnel placement is the most common cause of a failed ACL reconstruction. Accurate and reproducible methods to visualize and document bone tunnel placement are therefore important. We evaluated the reliability of standard radiographs, CT scans, and a 3-dimensional (3D) virtual reality (VR) approach in visualizing and measuring ACL reconstruction bone tunnel placement. Methods: 50 consecutive patients who underwent single-bundle ACL reconstructions were evaluated postoperatively by standard radiographs, CT scans, and 3D VR images. Tibial and femoral tunnel positions were measured by 2 observers using the traditional methods of Amis, Aglietti, Hoser, Stubli, and the method of Benereau for the VR approach. Results: The tunnel was visualized in 50-82% of the standard radiographs and in 100% of the CT scans and 3D VR images. Using the intraclass correlation coefficient (ICC), the inter- and intraobserver agreement was between 0.39 and 0.83 for the standard femoral and tibial radiographs. CT scans showed an ICC range of 0.49-0.76 for the inter- and intraobserver agreement. The agreement in 3D VR was almost perfect, with an ICC of 0.83 for the femur and 0.95 for the tibia. Interpretation: CT scans and 3D VR images are more reliable in assessing postoperative bone tunnel placement following ACL reconstruction than standard radiographs. Copyright

Understanding fear of opportunism in global prize-based science contests: Evidence for gender and age differences

Global prize-based science contests have great potential for tapping into diverse knowledge on a global scale and overcoming important scientific challenges. A necessary step for knowledge to be utilized in these contests is for that knowledge to be disclosed. Knowledge disclosure, however, is paradoxical in nature: in order for the value of knowledge to be assessed, inventors must disclose their knowledge, but then the person who receives that knowledge does so at no cost and may use it opportunistically. This risk of potential opportunistic behavior in turn makes the inventor fearful of disclosing knowledge, and this is a major psychological barrier to knowledge disclosure. In this project, we investigated this fear of opportunism in global prize-based science contests by surveying 630 contest participants in the InnoCentive online platform for science contests. We found that participants in these science contests experience fear of opportunism to varying degrees, and that women and older participants have significantly less fear of disclosing their scientific knowledge. Our findings highlight the importance of taking differences in such fears into account when designing global prize-based contests so that the potential of the contests for reaching solutions to important and challenging problems can be used more effectively

Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1) in young and elderly breast cancer patients.</p> <p>Methods</p> <p>The study population (N = 574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5). Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment.</p> <p>Results</p> <p>Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (<it>P </it>< .001). In patients aged > 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged < 65 years, ALDH1 positivity was an independent risk factor of worse outcome for relapse free period (hazard ratio = 1.71 (95% CI, 1.09 to 2.68); <it>P </it>= .021) and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68); <it>P </it>= .016). Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients.</p> <p>Conclusion</p> <p>ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.</p

Primary care utilisation patterns among an urban immigrant population in the Spanish National Health System

<p>Abstract</p> <p>Background</p> <p>There is evidence suggesting that the use of health services is lower among immigrants after adjusting for age and sex. This study takes a step forward to compare primary care (PC) utilisation patterns between immigrants and the native population with regard to their morbidity burden.</p> <p>Methods</p> <p>This retrospective, observational study looked at 69,067 individuals representing the entire population assigned to three urban PC centres in the city of Zaragoza (Aragon, Spain). Poisson models were applied to determine the number of annual PC consultations per individual based on immigration status. All models were first adjusted for age and sex and then for age, sex and case mix (ACG System^®).</p> <p>Results</p> <p>The age and sex adjusted mean number of total annual consultations was lower among the immigrant population (children: IRR = 0.79, p < 0.05; adults: IRR = 0.73, p < 0.05). After adjusting for morbidity burden, this difference decreased among children (IRR = 0.94, p < 0.05) and disappeared among adults (IRR = 1.00). Further analysis considering the PC health service and type of visit revealed higher usage of routine diagnostic tests among immigrant children (IRR = 1.77, p < 0.05) and a higher usage of emergency services among the immigrant adult population (IRR = 1.2, p < 0.05) after adjusting for age, sex and case mix.</p> <p>Conclusions</p> <p>Although immigrants make lower use of PC services than the native population after adjusting the consultation rate for age and sex, these differences decrease significantly when considering their morbidity burden. These results reinforce the 'healthy migration effect' and discount the existence of differences in PC utilisation patterns between the immigrant and native populations in Spain.</p

Loss of Pluripotency in Human Embryonic Stem Cells Directly Correlates with an Increase in Nuclear Zinc

The pluripotency of human embryonic stem cells (hESCs) is important to investigations of early development and to cell replacement therapy, but the mechanism behind pluripotency is incompletely understood. Zinc has been shown to play a key role in differentiation of non-pluripotent cell types, but here its role in hESCs is directly examined. By mapping the distribution of metals in hESCs at high resolution by x-ray fluorescence microprobe (XFM) and by analyzing subcellular metal content, we have found evidence that loss of pluripotency is directly correlated with an increase in nuclear zinc. Zinc elevation not only redefines our understanding of the mechanisms that support pluripotency, but also may act as a biomarker and an intervention point for stem cell differentiation

Modeling the Instantaneous Pressure–Volume Relation of the Left Ventricle: A Comparison of Six Models

Simulations are useful to study the heart’s ability to generate flow and the interaction between contractility and loading conditions. The left ventricular pressure–volume (PV) relation has been shown to be nonlinear, but it is unknown whether a linear model is accurate enough for simulations. Six models were fitted to the PV-data measured in five sheep and the estimated parameters were used to simulate PV-loops. Simulated and measured PV-loops were compared with the Akaike information criterion (AIC) and the Hamming distance, a measure for geometric shape similarity. The compared models were: a time-varying elastance model with fixed volume intercept (LinFix); a time-varying elastance model with varying volume intercept (LinFree); a Langewouter’s pressure-dependent elasticity model (Langew); a sigmoidal model (Sigm); a time-varying elastance model with a systolic flow-dependent resistance (Shroff) and a model with a linear systolic and an exponential diastolic relation (Burkh). Overall, the best model is LinFree (lowest AIC), closely followed by Langew. The remaining models rank: Sigm, Shroff, LinFix and Burkh. If only the shape of the PV-loops is important, all models perform nearly identically (Hamming distance between 20 and 23%). For realistic simulation of the instantaneous PV-relation a linear model suffices