Ocean Acidification-Induced Food Quality Deterioration Constrains Trophic Transfer

Our present understanding of ocean acidification (OA) impacts on marine organisms caused by rapidly rising atmospheric carbon dioxide (CO2) concentration is almost entirely limited to single species responses. OA consequences for food web interactions are, however, still unknown. Indirect OA effects can be expected for consumers by changing the nutritional quality of their prey. We used a laboratory experiment to test potential OA effects on algal fatty acid (FA) composition and resulting copepod growth. We show that elevated CO2 significantly changed the FA concentration and composition of the diatom Thalassiosira pseudonana, which constrained growth and reproduction of the copepod Acartia tonsa. A significant decline in both total FAs (28.1 to 17.4 fg cell−1) and the ratio of long-chain polyunsaturated to saturated fatty acids (PUFA:SFA) of food algae cultured under elevated (750 µatm) compared to present day (380 µatm) pCO2 was directly translated to copepods. The proportion of total essential FAs declined almost tenfold in copepods and the contribution of saturated fatty acids (SFAs) tripled at high CO2. This rapid and reversible CO2-dependent shift in FA concentration and composition caused a decrease in both copepod somatic growth and egg production from 34 to 5 eggs female−1 day−1. Because the diatom-copepod link supports some of the most productive ecosystems in the world, our study demonstrates that OA can have far-reaching consequences for ocean food webs by changing the nutritional quality of essential macromolecules in primary producers that cascade up the food web

Net1 and Myeov: computationally identified mediators of gastric cancer

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells

Structural Basis of Cytotoxicity Mediated by the Type III Secretion Toxin ExoU from Pseudomonas aeruginosa

The type III secretion system (T3SS) is a complex macromolecular machinery employed by a number of Gram-negative pathogens to inject effectors directly into the cytoplasm of eukaryotic cells. ExoU from the opportunistic pathogen Pseudomonas aeruginosa is one of the most aggressive toxins injected by a T3SS, leading to rapid cell necrosis. Here we report the crystal structure of ExoU in complex with its chaperone, SpcU. ExoU folds into membrane-binding, bridging, and phospholipase domains. SpcU maintains the N-terminus of ExoU in an unfolded state, required for secretion. The phospholipase domain carries an embedded catalytic site whose position within ExoU does not permit direct interaction with the bilayer, which suggests that ExoU must undergo a conformational rearrangement in order to access lipids within the target membrane. The bridging domain connects catalytic domain and membrane-binding domains, the latter of which displays specificity to PI(4,5)P2. Both transfection experiments and infection of eukaryotic cells with ExoU-secreting bacteria show that ExoU ubiquitination results in its co-localization with endosomal markers. This could reflect an attempt of the infected cell to target ExoU for degradation in order to protect itself from its aggressive cytotoxic action

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Experimental investigations of plasma dynamics in the hysteresis regime of reactive RF sputter processes

Reactive radio frequency (RF) sputter processes are highly relevant for thin film deposition, but there is no complete understanding of the fundamentals of their operation. While the Berg model describes the hysteresis regime considering the oxygen coverage of the boundary surfaces, a complete fundamental understanding of the plasma–surface interactions and their effects on the discharge is still missing. In this work, we provide such fundamental insights based on an extensive experimental analysis of the physics in the hysteresis regime of magnetized reactive sputter processes, where the same reactive gas admixture can lead to different discharge characteristics depending on the previous state of the plasma. A variety of plasma and surface diagnostics is used to reveal these insights. A low pressure capacitively coupled RF discharge (CCP, 13.56 MHz) with a magnetron-like magnetic field topology adjacent to the target is operated in argon gas with a variable admixture of O$_2$. The applied RF power, the gas flows/pumping speed, as well as the neutral gas pressure are changed systematically to understand the effects of these external control parameters on the hysteresis regime. The magnetic asymmetry effect is found to play an important role, since an axially non-uniform magnetic field is used to realize a local electron confinement at the target. Similar to process control in applications, the DC self-bias is measured to stabilize the surface composition using a feedback controller with the oxygen gas flow as the manipulated variable

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

10.1016/j.ajhg.2021.05.013American Journal of Human Genetics10871190-120

Epstein–Barr virus and Hodgkin’s lymphoma in Cairo, Egypt

Fifty-five consecutive cases of Hodgkin’s lymphoma (HL), collected between 1996 and 1998 from Cairo, Egypt, were histologically subtyped, phenotyped, and then studied for the presence of Epstein–Barr virus (EBV). We used immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) and in situ hybridization stains for EBV-encoded small RNA (EBER-1) transcripts. Forty-five cases (82%) had classic HL (cHL), and ten cases (18%) had nodular lymphocyte predominant HL (NLPHL), with each group expressing its typical phenotype. LMP-1 stains were positive in 63% and 0% of cHL and NLPHL cases, respectively. EBER-positive Reed–Sternberg cells and variants were also present in 62% and 0% of each group, respectively. The cHL cases showed variable EBER positivity: nodular sclerosis, 58%; mixed cellularity, 100%; lymphocyte depletion, 100%; and unclassifiable, 67%. Our findings are similar to those from other developing countries and point towards a pathogenic role of EBV in cHL

Ecosystem services from smallholder forestry and agroforestry in the tropics

Smallholder forestry and agroforestry systems in the tropics provide essential products and services for millions of producers, their surrounding communities, national and international consumers, and global society. The diversity of products provided by these systems meet the needs of smallholder producers for fuelwood, food, animal fodder, and other household and farm needs; they provide additional income to supplement major commodity crops; and they offer flexibility in production and income to buffer against falling commodity prices, crop failure, or other sources of financial or economic difficulty. The sustainability of these systems is increasingly dependent upon sources of income beyond the sale of conventional products, such as price premiums from sustainability certification and agro- and ecotourism. Payments for ecosystem services (PES) programs have been developed at multiple levels to provide incentives for smallholders to conserve and enhance tree cover and management practices to provide ecosystem services such as watershed protection and carbon sequestration. Ecotourism provides an enterprise-based strategy to engage producers in conservation and enhancement of these services. This review evaluates the ability of smallholder systems to support the provision of ecosystem services (ES) and the capacity of smallholders to participate in support programs and take advantage of other emerging opportunities to support smallholder enterprises