Applying rare earth elements, Uranium, and 87Sr/86Sr to disentangle structurally forced confluence of regional groundwater resources: The case of the Lower Yarmouk Gorge

The conjoint discussion of tectonic features, correlations of element concentrations, δ18O, δD, and 87Sr/86Sr of groundwater leads to new insight into sources of groundwater, their flow patterns, and salinization in the Yarmouk Basin. The sources of groundwater are precipitation infiltrating into basaltic rock or limestone aquifers. Leaching of relic brines and dissolution of gypsum and calcite from the limestone host rocks generate enhanced salinity in groundwater in different degrees. High U(VI) suggests leaching of U from phosphorite-rich Upper Cretaceous B2 formation. Both very low U(VI) and specific rare earth element including yttrium (REY) distribution patterns indicate interaction with ferric oxyhydroxides formed during weathering of widespread alkali olivine basalts in the catchment area. REY patterns of groundwater generated in basaltic aquifers are modified by interaction with underlying limestones. Repeated sampling over 18 years revealed that the flow paths towards certain wells of groundwater varied as documented by changes in concentrations of dissolved species and REY patterns and U(VI) contents. In the Yarmouk Gorge, groundwater with basaltic REY patterns but high U(VI) and low Sr2+ and intermediate sulfate concentrations mainly ascends in artesian wells tapping a buried flower structure fault system crossing the trend of the gorge

The 49a,f haplotype 11 is a new marker of the EU19 lineage that traces migrations from northern regions of the Black Sea

Previous studies on human Y-chromosome polymorphisms in the European populations highlighted the high frequency of the 49a,f/TaqI haplotype 11 and of the Eu19 (M17) lineage in Eastern Europe. To better understand the origin and the evolution of the Eu19, and its relationship with 49a,f Ht11, this study surveyed 2,235 individuals (mainly from Europe and the Middle East) for the 49a,f Ht11 and for many biallelic markers defining the Eu19 lineage. As previously described, the highest frequency of Eu19 was found in Eastern Europe. All the Eu19 Y-chromosomes turned out to be 49a,f Ht11 or its derivatives, the distribution of which suggests that the Eu19/49a,f Ht11 emerged in Ukraine, probably in a Palaeolithic population. Thereafter, the spread of this lineage toward Europe, Asia, and India occurred at different waves over a few thousands years. At present this seems to indicate the influence of the Ukraine Palaeolithic groups in the gene pool of modern populations. For the first time it is possible to make inferences about the evolution of some haplotypes of the 49a,f system. In spite of its unknown molecular base, this is one of the first most informative polymorphisms of the Y chromosome

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The effect of Young's modulus on the neuronal differentiation of mouse embryonic stem cells

There is substantial evidence that cells produce a diverse response to changes in ECM stiffness depending on their identity. Our aim was to understand how stiffness impacts neuronal differentiation of embryonic stem cells (ESC's), and how this varies at three specific stages of the differentiation process. In this investigation, three effects of stiffness on cells were considered; attachment, expansion and phenotypic changes during differentiation. Stiffness was varied from 2 kPa to 18 kPa to finally 35 kPa. Attachment was found to decrease with increasing stiffness for both ESC's (with a 95% decrease on 35 kPa compared to 2 kPa) and neural precursors (with a 83% decrease on 35 kPa). The attachment of immature neurons was unaffected by stiffness. Expansion was independent of stiffness for all cell types, implying that the proliferation of cells during this differentiation process was independent of Young's modulus. Stiffness had no effect upon phenotypic changes during differentiation for mESC's and neural precursors. 2 kPa increased the proportion of cells that differentiated from immature into mature neurons. Taken together our findings imply that the impact of Young's modulus on attachment diminishes as neuronal cells become more mature. Conversely, the impact of Young's modulus on changes in phenotype increased as cells became more mature

Cytotoxic effects of dillapiole on MDA-MB-231 cells involve the induction of apoptosis through the mitochondrial pathway by inducing an oxidative stress while altering the cytoskeleton network

Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Here, we have demonstrated for the first time that dillapiole has broad cytotoxic effects against a variety tumor cells. For instance, we found that it can act as a pro-oxidant compound through the induction of reactive oxygen species (ROS) release in MDA-MB-231 cells. We also demonstrated that dillapiole exhibits anti-proliferative properties, arresting cells at the G0/G1 phase and its antimigration effects can be associated with the disruption of actin filaments, which in turn can prevent tumor cell proliferation. Molecular modeling studies corroborated the biological findings and suggested that dillapiole may present a good pharmacokinetic profile, mainly because its hydrophobic character, which can facilitate its diffusion through tumor cell membranes. All these findings support the fact that dillapiole is a promising anticancer agent

The effects of melatonin versus placebo on delirium in hip fracture patients: study protocol of a randomised, placebo-controlled, double blind trial

<p>Abstract</p> <p>Background</p> <p>With an ageing population, older persons become a larger part of the hospital population. The incidence of delirium is high in this group, and experiencing delirium has major short- and long-term sequelae, which makes prevention crucial. During delirium, a disruption of the sleep-wake cycle is frequently observed. Melatonin plays an important role in the regulation of the sleep-wake cycle, so this raised the hypothesis that alterations in the metabolism of melatonin might play an important role in the development of delirium. The aim of this article is to describe the design of a randomised, placebo controlled double-blind trial that is currently in progress and that investigates the effects of melatonin versus placebo on delirium in older, postoperative hip fracture patients.</p> <p>Methods/Design</p> <p>Acutely hospitalised patients aged 65 years or older admitted for surgical repair of hip fracture are randomised (n = 452) into a treatment or placebo group. Prophylactic treatment consists of orally administered melatonin (3 mg) at 21:00 h on five consecutive days. The primary outcome is the occurrence of delirium, to be diagnosed according to the Confusion Assessment Method, within eight days after start of the study medication. Secondary outcomes are delirium severity, measured by the Delirium Rating Scale; duration of delirium; differences in subtypes of delirium; differences in total length of hospital stay; total dose of antipsychotics and/or benzodiazepine use during delirium; and in-hospital complications. In the twelve-month follow up visit, cognitive function is measured by a Mini-Mental state examination and the Informant Questionnaire on Cognitive Decline in the Elderly. Functional status is assessed with the Katz ADL index score (patient and family version) and grip strength measurement. The outcomes of these assessments are compared to the outcomes that were obtained during admission.</p> <p>Discussion</p> <p>The proposed study will contribute to our knowledge because studies on the prophylactic treatment of delirium with long term follow up remain scarce. The results may lead to a prophylactic treatment for frail older persons at high risk for delirium that is safe, effective, and easily implementable in daily practice.</p> <p>Trial registration</p> <p>Dutch Clinical Trial Registry: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576">NTR1576</a></p

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes

The ACER pollen and charcoal database: A global resource to document vegetation and fire response to abrupt climate changes during the last glacial period

This is the final version of the article. Available from Copernicus Publications via the DOI in this record.Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15ka) with a temporal resolution better than 1000years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (14C, 234U/230Th, optically stimulated luminescence (OSL), 40Ar/39Ar-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access™ at https://doi.org/10.1594/PANGAEA.870867.The members of the ACER project wish to thank the QUEST-DESIRE (UK and France) bilateral project, the INQUA International Focus Group ACER and the INTIMATE-COST action for funding a suite of workshops to compile the ACER pollen and charcoal database and the workshop on ACER chronology that allow setting the basis for harmonizing the chronologies. Josué M. Polanco-Martinez was funded by a Basque Government postdoctoral fellowship (POS_2015_1_0006) and Sandy P. Harrison by the ERC Advanced Grant GC2.0: unlocking the past for a clearer future

Geographic genetic structure of Iberian columbines (gen. Aquilegia)

Southern European columbines (genus Aquilegia)are involved in active processes of diversification, and the Iberian Peninsula offers a privileged observatory to witness the process. Studies on Iberian columbines have provided significant advances on species diversification,but we still lack a complete perspective of the genetic diversification in the Iberian scenario. This work explores how genetic diversity of the genus Aquilegia is geographically structured across the Iberian Peninsula. We used Bayesian clustering methods, principal coordinates analyses, and NJ phenograms to assess the genetic relationships among 285 individuals from 62 locations and detect the main lineages. Genetic diversity of Iberian columbines consists of five geographically structured lineages, corresponding to different Iberian taxa. Differentiation among lineages shows particularly complex admixture patterns at Northeast and highly homogeneous toward Northwest and Southeast. This geographic genetic structure suggests the existence of incomplete lineage sorting and interspecific hybridization as could be expected in recent processes of diversification under the influence of quaternary postglacial migrations. This scenario is consistent with what is proposed by the most recent studies on European and Iberian columbines, which point to geographic isolation and divergent selection by habitat specialization as the main diversification drivers of the Iberian Aquilegia complex