Metal-macrofauna interactions determine microbial community structure and function in copper contaminated sediments

Peer reviewedPublisher PD

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. METHODS: UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017. RESULTS: After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell-depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell-replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003). CONCLUSION: This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available

The role of planetary formation and evolution in shaping the composition of exoplanetary atmospheres

Over the last twenty years, the search for extrasolar planets revealed us the rich diversity of the outcomes of the formation and evolution of planetary systems. In order to fully understand how these extrasolar planets came to be, however, the orbital and physical data we possess are not enough, and they need to be complemented with information on the composition of the exoplanets. Ground-based and space-based observations provided the first data on the atmospheric composition of a few extrasolar planets, but a larger and more detailed sample is required before we can fully take advantage of it. The primary goal of the Exoplanet Characterization Observatory (EChO) is to fill this gap, expanding the limited data we possess by performing a systematic survey of hundreds of extrasolar planets. The full exploitation of the data that EChO and other space-based and ground-based facilities will provide in the near future, however, requires the knowledge of what are the sources and sinks of the chemical species and molecules that will be observed. Luckily, the study of the past history of the Solar System provides several indications on the effects of processes like migration, late accretion and secular impacts, and on the time they occur in the life of planetary systems. In this work we will review what is already known about the factors influencing the composition of planetary atmospheres, focusing on the case of gaseous giant planets, and what instead still need to be investigated.Comment: 26 pages, 9 figures, 1 table. Accepted for publication on Experimental Astronomy, special issue on the M3 EChO mission candidat

Carbon budgets of Scotia Sea mesopelagic zooplankton and micronekton communities during austral spring

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: Macrozooplankton and nekton vertical distribution and abundance at the sustained observation location P3 in the northern Scotia Sea (Southern Ocean) during November and December 2017 https://doi.org/10.5285/e184e81a-e43c-424e-abec-122036ee2cfd. Micronekton and zooplankton respiration rates on COMICS Cruises DY086 and DY090 https://doi.org/10.5285/b9f5c5ec-100a-7ff0-e053-6c86abc0f494. All other data is available on request.Zooplankton form an integral component of epi- and mesopelagic ecosystems, and there is a need to better understand their role in ocean biogeochemistry. The export and remineralisation of particulate organic matter at depth plays an important role in controlling atmospheric CO2 concentrations. Pelagic mesozooplankton and micronekton communities may influence the fate of organic matter in a number of ways, including: the consumption of primary producers and export of this material as fast-sinking faecal pellets, and the active flux of carbon by animals undertaking diel vertical migration (DVM) into the mesopelagic. We present day and night vertical biomass profiles of mesozooplankton and micronekton communities in the upper 500 m during three visits to an ocean observatory station (P3) to the NW of South Georgia (Scotia Sea, South Atlantic) in austral spring, alongside estimates of their daily rates of ingestion and respiration throughout the water column. Day and night community biomass estimates were dominated by copepods >330 μm, including the lipid-rich species, Calanoides acutus and Rhincalanus gigas. We found little evidence of synchronised DVM, with only Metridia spp. and Salpa thompsoni showing patterns consistent with migratory behaviour. At depths below 250 m, estimated community carbon ingestion rates exceeded those of metabolic costs, supporting the understanding that food quality in the mesopelagic is relatively poor, and organisms have to consume a large amount of food in order to fulfil their nutritional requirements. By contrast, estimated community rates of ingestion and metabolic costs at shallower depths were approximately balanced, but only when we assumed that the animals were predominantly catabolising lipids (i.e. respiratory quotient = 0.7) and had relatively high absorption efficiencies. Our work demonstrates that it is possible to balance the metabolic budgets of mesopelagic animals to within observational uncertainties, but highlights the need for a better understanding of the physiology of lipid-storing animals and how it influences carbon budgeting in the pelagic.Natural Environment Research Council (NERC

Pressure during decision making of continuous sedation in end-of-life situations in Dutch general practice

<p>Abstract</p> <p>Background</p> <p>Little is known about pressure from patients or relatives on physician’s decision making of continuous palliative sedation. We aim to describe experienced pressure by general practitioners (GPs) in cases of continuous sedation after the introduction of the Dutch practice guideline, using a questionnaire survey.</p> <p>Methods</p> <p>A sample of 918 Dutch GPs were invited to fill out a questionnaire about their last patient under continuous sedation. Cases in which GPs experienced pressure from the patient, relatives or other persons were compared to those without pressure.</p> <p>Results</p> <p>399 of 918 invite GPs (43%) returned the questionnaire and 250 provided detailed information about their most recent case of continuous sedation. Forty-one GPs (16%) indicated to have experienced pressure from the patient, relatives or colleagues. In GPs younger than 50, guideline knowledge was not related to experienced pressure, whereas in older GPs, 15% with and 36% without guideline knowledge reported pressure. GPs experienced pressure more often when patients had psychological symptoms (compared to physical symptoms only) and when patients had a longer estimated life expectancy. A euthanasia request of the patient coincided with a higher prevalence of pressure for GPs without, but not for GPs with previous experience with euthanasia. GPs who experienced pressure had consulted a palliative consultation team more often than GPs who did not experience pressure.</p> <p>Conclusion</p> <p>One in six GPs felt pressure from patients or relatives to start sedation. This pressure was related to guideline knowledge, especially in older GPs, longer life expectancy and the presence of a euthanasia request, especially for GPs without previous experience of euthanasia.</p

SPECULOOS exoplanet search and its prototype on TRAPPIST

One of the most significant goals of modern science is establishing whether life exists around other suns. The most direct path towards its achievement is the detection and atmospheric characterization of terrestrial exoplanets with potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs), i.e. very-low-mass stars and brown dwarfs with effective temperatures lower than 2700 K, represent a unique opportunity to reach this goal within the next decade. The potential of the transit method for detecting potentially habitable Earth-sized planets around these objects is drastically increased compared to Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby UCD would be amenable for a thorough atmospheric characterization, including the search for possible biosignatures, with near-future facilities such as the James Webb Space Telescope. In this chapter, we first describe the physical properties of UCDs as well as the unique potential they offer for the detection of potentially habitable Earth-sized planets suitable for atmospheric characterization. Then, we present the SPECULOOS ground-based transit survey, that will search for Earth-sized planets transiting the nearest UCDs, as well as its prototype survey on the TRAPPIST telescopes. We conclude by discussing the prospects offered by the recent detection by this prototype survey of a system of seven temperate Earth-sized planets transiting a nearby UCD, TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H. Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

Background:Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets(ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of theircombined use.Methods:1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC)visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess thesafety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.Findings:Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence atdelivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection(p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinicalmalaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p,0.001), and ofactively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderlinestatistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was morethan 90% in both groups.Conclusions:Two-dose SP was associated with a reduction in some indicators, but these were not translated to significantimprovement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administerIPTp. ITNs should be part of the ANC package in sub-Saharan Afric

An update of malaria infection and anaemia in adults in Buea, Cameroon

<p>Abstract</p> <p>Background</p> <p>Anaemia is caused by many factors in developing countries including malaria. We compared anaemia rates in patients with malaria parasitaemia to that of patients without malaria parasitaemia.</p> <p>Findings</p> <p>A cross-sectional study was carried out from November 2007 to July 2008 in health units in Buea, Cameroon. Adult patients with fever or history of fever were included in the study. Information on socio-demographic variables and other variables was collected using a questionnaire. Malaria parasitaemia status was determined by microscopy using Giemsa stained thick blood smears. Haemoglobin levels were determined by the microhaematocrit technique.</p> <p>The study population consisted of 250 adult patients with a mean age of 29.31 years (SD = 10.63) and 59.44% were females. 25.60% of the patients had malaria parasitaemia while 14.80% had anaemia (haemoglobin < 11 g/dl). Logistic regression revealed that those with malaria parasitaemia had more anaemia compared to those without malaria parasitaemia(OR = 4.33, 95%CI = 1.21-15.43, p = 0.02) after adjusting for age, sex, rural residence, socioeconomic status, use of antimalarials, use of insecticide treated nets(ITN) and white blood cell count.</p> <p>Conclusions</p> <p>In adult patients with fever in this setting, malaria parasitaemia contributes to anaemia and is of public health impact. Our results also provide a baseline prevalence for malaria parasitaemia in febrile adults in health units in this setting.</p