Evidence for microbial iron reduction in the methanic sediments of the oligotrophic southeastern Mediterranean continental shelf

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Vigderovich, H., Liang, L., Herut, B., Wang, F., Wurgaft, E., Rubin-Blum, M., & Sivan, O. Evidence for microbial iron reduction in the methanic sediments of the oligotrophic southeastern Mediterranean continental shelf. Biogeosciences, 16(16), (2019): 3165-3181, doi: 10.5194/bg-16-3165-2019.Dissimilatory iron reduction is probably one of the oldest types of metabolisms that still participates in important biogeochemical cycles, such as those of carbon and sulfur. It is one of the more energetically favorable anaerobic microbial respiration processes and is usually coupled to the oxidation of organic matter. Traditionally this process is thought to be limited to the shallow part of the sedimentary column in most aquatic systems. However, iron reduction has also been observed in the methanic zone of many marine and freshwater sediments, well below its expected zone and occasionally accompanied by decreases in methane, suggesting a link between the iron and the methane cycles. Nevertheless, the mechanistic nature of this link (competition, redox or other) has yet to be established and has not been studied in oligotrophic shallow marine sediments. In this study we present combined geochemical and molecular evidences for microbial iron reduction in the methanic zone of the oligotrophic southeastern (SE) Mediterranean continental shelf. Geochemical porewater profiles indicate iron reduction in two zones, the uppermost part of the sediment, and the deeper zone, in the layer of high methane concentration. Results from a slurry incubation experiment indicate that the deep methanic iron reduction is microbially mediated. The sedimentary profiles of microbial abundance and quantitative PCR (qPCR) of the mcrA gene, together with Spearman correlation between the microbial data and Fe(II) concentrations in the porewater, suggest types of potential microorganisms that may be involved in the iron reduction via several potential pathways: H2 or organic matter oxidation, an active sulfur cycle, or iron-driven anaerobic oxidation of methane. We suggest that significant upward migration of methane in the sedimentary column and its oxidation by sulfate may fuel the microbial activity in the sulfate methane transition zone (SMTZ). The biomass created by this microbial activity can be used by the iron reducers below, in the methanic zone of the sediments of the SE Mediterranean.This study was supported by the joint grant of Israel Science Foundation and the National Natural Science Foundation of China (ISF-NSFC) (grant numbers 31661143022 (FW) and 2561/16 (OS)). Funding was provided to Hanni Vigderovich by the Mediterranean Sea Research Center of Israel

CEACAM1 Promotes Melanoma Cell Growth through Sox-2

AbstractThe prognostic value of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in melanoma was demonstrated more than a decade ago as superior to Breslow score. We have previously shown that intercellular homophilic CEACAM1 interactions protect melanoma cells from lymphocyte-mediated elimination. Here, we study the direct effects of CEACAM1 on melanoma cell biology. By employing tissue microarrays and low-passage primary cultures of metastatic melanoma, we show that CEACAM1 expression gradually increases from nevi to metastatic specimens, with a strong dominance of the CEACAM1-Long tail splice variant. Using experimental systems of CEACAM1 knockdown and overexpression of selective variants or truncation mutants, we prove that only the full-length long tail variant enhances melanoma cell proliferation in vitro and in vivo. This effect is not reversed with a CEACAM1-blocking antibody, suggesting that it is not mediated by intercellular homophilic interactions. Downstream, CEACAM1-Long increases the expression of Sox-2, which we show to be responsible for the CEACAM1-mediated enhanced proliferation. Furthermore, analysis of the CEACAM1 promoter reveals two single-nucleotide polymorphisms (SNPs) that significantly enhance the promoter's activity compared with the consensus nucleotides. Importantly, case-control genetic SNP analysis of 134 patients with melanoma and matched healthy donors show that patients with melanoma do not exhibit the Hardy-Weinberg balance and that homozygous SNP genotype enhances the hazard ratio to develop melanoma by 35%. These observations shed new mechanistic light on the role of CEACAM1 in melanoma, forming the basis for development of novel therapeutic and diagnostic technologies

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

The law of strangers: The form and substance of other-regarding international adjudication

The ever-intensifying trends of global interdependence have created a complex reality in which decisions of sovereign states, like those of international courts, radiate far beyond their traditional confines, affecting the interests of a range of strangers (third states, individuals, corporations, and others), without being politically accountable to them. Could and should international courts narrow these accountability gaps by insisting that states take the interests of disregarded strangers into account and by opening the courts’ own doors to the strangers affected by their judgments? In this article, we analyze the judicial commitment to bridge these accountability gaps toward globally affected others by (a) ratcheting up the substantive and procedural duties that states owe to strangers affected by their national policies and (b) by facilitating the consideration and voice of affected strangers in the adjudication process itself. In analyzing these two other-regarding judicial responses, we focus on one pivotal site of global judicial governance, the World Trade Organization dispute settlement system (WTO DSS). Based on a close analysis of the rich WTO jurisprudence, the article shows that since its inception in 1995, other-regarding considerations have played a significant role in the WTO DSS operation. This WTO’s adjudicative philosophy of regard for others, the article argues, demonstrates an evolving judicial sensitivity to the challenges of accountability and voice generated by globalization at the national and international levels

Trial of labour after caesarean (TOLAC) is associated with increased risk for instrumental delivery

We compared the rates of instrumental delivery in a cohort of nulliparous women at term (n = 19,416), to primiparous women who attempted labour after prior caesarean (TOLAC) (n = 1747). The rate of instrumental deliveries was higher in the TOLAC group compared to nulliparous gravidas (17.3 vs. 15% respectively, p = 0.001). The difference was more prominent for women who eventually had successful vaginal delivery (TOLAC: 23.9% vs. controls: 17.1%, p < 0.0001 respectively). Based on our results, previous caesarean whether urgent or elective was associated with an increased risk of instrumental delivery in the subsequent pregnancy