Regulation of autoimmunity and donor cell engraftment by recipient Lyt-2+ cells during the graft-versus-host reaction.

When lymphocytes from DBA/2 mice are transferred to (C57BL X DBA/2)F1 (BDF1) mice, the ensuing graft-vs.-host reaction (GVHR) causes an autoimmune illness resembling human SLE. To examine the role of recipient T cells in this process, BDF1 mice were depleted of L3T4+ or Lyt-2+ cells by thymectomy followed by treatment with mAbs to L3T4 or Lyt-2. This produced sustained depletion of these T cell subsets. Subsequent grafting with parental DBA/2 lymphocytes produced autoimmune disease in mice depleted of L3T4+ cells and controls but not in mice depleted of Lyt-2+ cells. Analysis of blood lymphocytes 4 wk after donor cell transfer demonstrated that BDF1 recipients depleted of Lyt-2+ cells were virtually repopulated with donor T lymphocytes, compared with less than or equal to 35% donor cell engraftment in all other groups. Thus, recipient Lyt-2+ cells influence both host cell engraftment and autoimmunity during the parent-into-F1 GVHR

Simulating increased permafrost peatland plant productivity in response to belowground fertilisation using the JULES land surface model

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: Abisko meteorological data and snow depth data are available on request from the Abisko Scientific Research Station (https://polar.se/en/research-in-abisko) (last access: 17 April 2022), and the soil temperature data are archived in the GTN-P database (https: //gtnp.arcticportal.org/) (last access: 17 April 2022). Soil carbon profiles are available from the following Zenodo repository: https://zenodo.org/record/5818180#.YmmBftrMKUk (last access: 17 April 2022).Several experimental studies have shown that climate-warming-induced permafrost thaw releases previously unavailable nitrogen which can lower nitrogen limitation, increase plant productivity, and counteract some of the carbon released from thawing permafrost. The net effect of this belowground fertilisation effect remains debated and is yet to be included in Earth System models. Here, we included the impact of thaw-related nitrogen fertilisation on vegetation in the Joint UK Land Environment Simulator (JULES) land surface model for the first time. We evaluated its ability to replicate a three-year belowground fertilisation experiment in which JULES was generally able to simulate belowground fertilisation in accordance with the observations. We also ran simulations under future climate to investigate how belowground nitrogen fertilisation affects the carbon cycle. These simulations indicate an increase in plant-available inorganic nitrogen at the thaw front by the end of the century with only the productivity of deep-rooting plants increasing in response. This suggests that deep-rooting species will have a competitive advantage under future climate warming. Our results also illustrate the capacity to simulate belowground nitrogen fertilisation at the thaw front in a global land surface model, leading towards a more complete representation of coupled carbon and nitrogen dynamics in the northern high latitudes.European Union’s Horizon 2020e Joint UK BEIS/Defra Met Office Hadley Centre Climate ProgrammeNatural Environment Research Council (NERC

Molecular diagnosis of Huntington disease in Portugal : implications for genetic counselling and clinical practice

Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenatal testing (four were done for family studies). Most referring physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were confirmed, while 83.1% of those sent for exclusion were in fact excluded. In presymptomatic testing, an excess of female subjects (59.4%) was again verified; 37.5% of the consultands were found to be carriers. None of the foetuses, in four prenatal tests, were mutation carriers. One juvenile case was inherited from her mother. Our patient population is very similar to others described so far, namely in terms of mean age at onset and (CAG)n distribution, except perhaps for a higher frequency of large normal (class 2) alleles (3.7%). We also identify cases posing particular problems for genetic counselling, such as, ‘homozygosity’ that can pose a serious ethical dilemma, carriers of large normal alleles, and ‘homoallelism’ for a normal gene, which will demand further procedures and may delay results in presymptomatic and prenatal testing

Development of IR-based short-range communication techniques for swarm robot applications

This paper proposes several designs for a reliable infra-red based communication techniques for swarm robotic applications. The communication system was deployed on an autonomous miniature mobile robot (AMiR), a swarm robotic platform developed earlier. In swarm applications, all participating robots must be able to communicate and share data. Hence a suitable communication medium and a reliable technique are required. This work uses infrared radiation for transmission of swarm robots messages. Infrared transmission methods such as amplitude and frequency modulations will be presented along with experimental results. Finally the effects of the modulation techniques and other parameters on collective behavior of swarm robots will be analyzed

Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington's Disease patients

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Environmental DNA is effective in detecting the federally threatened Louisiana Pinesnake ( Pituophis ruthveni)

Successful conservation of rare, threatened, or endangered (RTE) species is dependent upon rapid and accurate assessment of their distribution and abundance. However, assessments are challenging as RTE species typically exist as numerically small populations in often fragmented habitats and can possess complex natural histories. Environmental DNA (eDNA) analysis may provide a rapid, cost‐effective means of assessing RTE species presence/absence in viable habitat patches. We evaluated the efficacy of eDNA surveillance for the Louisiana Pinesnake (Pituophis ruthveni), an elusive, semi‐fossorial, nonvenomous colubroid snake endemic to Louisiana and Texas, USA, that has dramatically declined in both distribution and abundance. We developed two quantitative polymerase chain reaction (qPCR) assays that target the mitochondrial cytochrome c oxidase subunit I (COI) and mitochondrially encoded ATP synthase membrane subunit 6 (ATP6) genes. We validated each assay in silico, in vitro, and in situ, and investigated the influence of eDNA extraction method and genetic marker on assay performance. Both assays were highly sensitive and successfully detected the Louisiana Pinesnake under artificial and field conditions, including bedding samples collected from captive snake enclosures (100%), soil samples from Louisiana Pinesnake release sites (100%), and soil samples from sites where Louisiana Pinesnakes were documented via radio telemetry (45%). Although differences between genetic markers were negligible, assay performance was strongly influenced by eDNA extraction method. Informed by our results, we discuss methodological and environmental factors influencing Louisiana Pinesnake eDNA detection and quantification, broader implications for management and conservation of the Louisiana Pinesnake and other terrestrial reptiles and provide recommendations for future research. We suggest that eDNA surveys can more effectively assess Louisiana Pinesnake occupancy than conventional sampling, highlighting the need for comprehensive eDNA monitoring initiatives to better identify suitable habitat that will promote persistence of this imperiled species going forward

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.Peer reviewedFinal Published versio

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

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