Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

Initial investigations into the MOS interface of freestanding 3C-SiC layers for device applications

This letter reports on initial investigation results on the material quality and device suitability of a homo-epitaxial 3C-SiC growth process. Atomic force microscopy surface investigations revealed root-mean square surface roughness levels of 163.21 nm, which was shown to be caused by pits (35 μm width and 450 nm depth) with a density of 1.09 × 105 cm−2 which had formed during material growth. On wider scan areas, the formation of these were seen to be caused by step bunching, revealing the need for further epitaxial process improvement. X-ray diffraction showed good average crystalline qualities with a full width of half-maximum of 160 arcseconds for the 3C-SiC (002) being lower than for the 3C-on-Si material (210 arcseconds). The analysis of C–V curves then revealed similar interface-trapped charge levels for freestanding 3C-SiC, 3C-SiC on Si and 4H-SiC, with forming gas post-deposition annealed freestanding 3C-SiC devices showing DIT levels of 3.3 × 1011 cm−2 eV−1 at EC−ET = 0.2 eV. The homo-epitaxially grown 3C-SiC material's suitability for MOS applications could also be confirmed by leakage current measurements

Differential penetration of raltegravir throughout gastrointestinal tissue: implications for eradication and cure

To investigate the concentration of the integrase strand inhibitor raltegravir (RAL) throughout gastrointestinal (GI) tissue, especially gutassociated lymphoid tissue (GALT), as an adjunct to current prevention and cure strategies

Therapeutic Targeting of ATP7B in Ovarian Carcinoma.

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models. EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). RESULTS: ATP7A and ATP7B genes were expressed at higher levels in platinum-resistant cells compared with sensitive cells; however, only differences in ATP7B reached statistical significance. ATP7A gene silencing had no significant effect on the sensitivity of resistant cells to cisplatin, but ATP7B silencing resulted in 2.5-fold reduction of cisplatin IC(50) levels and increased DNA adduct formation in cisplatin-resistant cells (A2780-CP20 and RMG2). Cisplatin was found to bind to the NH(2)-terminal copper-binding domain of ATP7B, which might be a contributing factor to cisplatin resistance. For in vivo therapy experiments, ATP7B siRNA was incorporated into DOPC and was highly effective in reducing tumor growth in combination with cisplatin (70-88% reduction in both models compared with controls). This reduction in tumor growth was accompanied by reduced proliferation, increased tumor cell apoptosis, and reduced angiogenesis. CONCLUSION: These data provide a new understanding of cisplatin resistance in cancer cells and may have implications for therapeutic reversal of drug resistance

Focal Adhesion Kinase Silencing Augments Docetaxel-Mediated Apoptosis in Ovarian Cancer Cells

Docetaxel causes cell death through induction of apoptosis; however, cell death characteristics for docetaxel have not yet been fully elucidated. We examined the role of focal adhesion kinase (FAK) cleavage in docetaxel-mediated apoptosis

Single- and Multiple-Dose Pharmacokinetics of Darunavir Plus Ritonavir and Etravirine in Semen and Rectal Tissue of HIV-Negative Men

Antiretroviral therapy (ART) has become a central component of combination HIV prevention efforts. Defining the individual exposure of commercially available ART in genital secretions and vulnerable mucosal tissues is paramount to designing future prevention interventions

Hyptiogastrites electrinus Cockerell, 1917, from Myanmar (Burmese) amber: Redescription and its placement within the Evanioidea (Insecta: Hymenoptera)

© The Natural History MuseumThe wasp Hyptiogastrites electrinus Cockerell, 1917, from the Lower Cretaceous (Upper Albian) Myanmar (Burmese) amber is redescribed from the well-preserved holotype and its relationship with extant Aulacidae and Gasteruptiidae (Hymenoptera: Evanioidea) evaluated. Although the wing venation is identical to the majority of extant Hyptiogastrinae (Gasteruptiidae), phylogenetic analysis places H. electrinus as sister taxon to the Aulacidae s.str., (i.e. Aulacus + Pristaulacus). Thus, Hyptiogastrinae is confirmed as having a restricted Southern Hemisphere distribution (i.e. Australasia and South America). Consistent with this result, H. electrinus is included within a slightly more broadly defined Aulacidae rather than being placed in a new monotypic family. Characters that align this species with the Aulacidae include: having small circular eyes, percurrent Y-shaped notauli, pyramidal shape of the propodeum and the presence of a groove or ovipositor guide on the hind coxae.John T. Jennings, Andrew D. Austin and Nicholas B. Steven

The Future of Fundamental Science Led by Generative Closed-Loop Artificial Intelligence

Recent advances in machine learning and AI, including Generative AI and LLMs, are disrupting technological innovation, product development, and society as a whole. AI's contribution to technology can come from multiple approaches that require access to large training data sets and clear performance evaluation criteria, ranging from pattern recognition and classification to generative models. Yet, AI has contributed less to fundamental science in part because large data sets of high-quality data for scientific practice and model discovery are more difficult to access. Generative AI, in general, and Large Language Models in particular, may represent an opportunity to augment and accelerate the scientific discovery of fundamental deep science with quantitative models. Here we explore and investigate aspects of an AI-driven, automated, closed-loop approach to scientific discovery, including self-driven hypothesis generation and open-ended autonomous exploration of the hypothesis space. Integrating AI-driven automation into the practice of science would mitigate current problems, including the replication of findings, systematic production of data, and ultimately democratisation of the scientific process. Realising these possibilities requires a vision for augmented AI coupled with a diversity of AI approaches able to deal with fundamental aspects of causality analysis and model discovery while enabling unbiased search across the space of putative explanations. These advances hold the promise to unleash AI's potential for searching and discovering the fundamental structure of our world beyond what human scientists have been able to achieve. Such a vision would push the boundaries of new fundamental science rather than automatize current workflows and instead open doors for technological innovation to tackle some of the greatest challenges facing humanity today.Comment: 35 pages, first draft of the final report from the Alan Turing Institute on AI for Scientific Discover

Macrophages Facilitate Resistance to Anti-VEGF Therapy by Altered VEGFR Expression

Abstract Purpose: VEGF-targeted therapies have modest efficacy in cancerpatients, butacquiredresistance iscommon. Themechanisms underlying such resistance are poorly understood. Experimental Design: To evaluate the potential role of immune cells in the development of resistance to VEGF blockade, we first established a preclinical model of adaptive resistance to anti-VEGF therapy. Additional in vitro and in vivo studies were carried out to characterize the role of macrophages in such resistance. Results: Using murine cancer models of adaptive resistance to anti-VEGF antibody (AVA), we found a previously unrecognized roleofmacrophagesinsuchresistance.Macrophageswereactively recruited to the tumor microenvironment and were responsible for the emergence of AVA resistance. Depletion of macrophages following emergence of resistance halted tumor growth and prolonged survival of tumor-bearing mice. In a macrophagedeficient mouse model, resistance to AVA failed to develop, but could be induced by injection of macrophages. Downregulation of macrophage VEGFR-1 and VEGFR-3 expression accompanied upregulation of alternative angiogenic pathways, facilitating escape from anti-VEGF therapy. Conclusions: These findings provide a new understanding of the mechanisms underlying the modest efficacy of current antiangiogenesis therapies and identify new opportunities for combinationapproachesforovarianandothercancers. ClinCancerRes; 23(22); 7034–46. �2017 AACR

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin