The Traf-linked tumor necrosis factor receptor family member CD27 is known as a T cell costimulatory molecule. We generated CD27-/- mice and found that CD27 makes essential contributions to mature ...CD4+ and CD8+ T cell function: CD27 supported antigen-specific expansion (but not effector cell maturation) of naïve T cells, independent of the cell cycle-promoting activities of CD28 and interleukin 2. Primary CD4+ and CD8+ T cell responses to influenza virus were impaired in CD27-/- mice. Effects of deleting the gene encoding CD27 were most profound on T cell memory, reflected by delayed response kinetics and reduction of CD8+ virus-specific T cell numbers to the level seen in the primary response. This demonstrates the requirement for a costimulatory receptor in the generation of T cell memory.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective Assess whether CD70 + B cells contribute to EAE. Materials and methods MOG-specific TCR transgenic mice (2D2) were crossed with mice with constitutive CD70 expression on B cells. ...The development of EAE and the phenotype of B-T lymphocytes were studied in 2D2xCD70 animals. Results Spontaneous EAE developed in 20% of 2D2xCD70 and 3% of 2D2 mice. EAE was also more severe in 2D2xCD70 versus 2D2 animals upon MOG immunization. The susceptibility of 2D2xCD70 to EAE was associated with fewer FoxP3 + T cells. Conclusions Expression of CD70 by B cells aggravates EAE possibly by reducing the number of regulatory T cells.
The development of social behavior could be affected by stressful parenting. The mineralocorticoid receptor, one of the two main receptors for the stress hormone cortisol, plays a vital role in ...adequate responses to stress. Therefore, the effects of stressful parenting on social development (i.e., empathic concern, perspective taking and prosocial behavior) may be moderated by functional genetic variation in mineralocorticoid receptor haplotypes (a combination of alleles). A group of 343 adolescents (44.3% females) was followed from the age of 13 until 24 years. Growth curve analyses showed lower levels of prosocial behaviors and a slower increase in empathic concern and perspective taking in adolescents who reported more stressful parenting. In contrast, relatively higher levels of prosocial behavior, empathic concern and perspective taking were present in combination with stress resilient mineralocorticoid receptor haplotypes. Despite sex differences in social development with earlier social development for girls, no consistent sex differences were found with regard to mineralocorticoid receptor haplotypes. The current study showed that genetic variation in mineralocorticoid receptor impacts the social development during adolescence and young adulthood.
Postoperative myocardial injury (PMI) comprises a spectrum of mechanisms resulting in troponin release. The impact of different PMI phenotypes on postoperative disability remains unknown.
This was a ...multicentre prospective cohort study including patients aged ≥50 yr undergoing elective major noncardiac surgery. Patients were stratified in five groups based on the occurrence of PMI and clinical information on postoperative adverse events: PMI classified as myocardial infarction (MI; according to fourth definition), PMI plus adverse event other than MI, clinically silent PMI (PMI without adverse events), adverse events without PMI, and neither PMI nor an adverse event (reference). The primary endpoint was 6-month self-reported disability (assessed by WHO Disability Assessment Schedule 2.0 WHODAS). Disability-free survival was defined as WHODAS ≤16%.
We included 888 patients of mean age 69 (range 53-91) yr, of which 356 (40%) were women; 151 (17%) patients experienced PMI, and 625 (71%) experienced 6-month disability-free survival. Patients with PMI, regardless of its phenotype, had higher preoperative disability scores than patients without PMI (difference in WHODAS; β: 3.3, 95% confidence interval CI: 0.5-6.2), but scores remained stable after surgery (β: 1.2, 95% CI: -3.2-5.6). Before surgery, patients with MI (n=36, 4%) were more disabled compared with patients without PMI and no adverse events (β: 5.5, 95% CI: 0.3-10.8). At 6 months, patients with MI and patients without PMI but with adverse events worsened in disability score (β: 11.2, 95% CI: 2.3-20.2; β: 8.1, 95% CI: 3.0-13.2, respectively). Patients with clinically silent PMI did not change in disability score at 6 months (β: 1.39, 95% CI: -4.50-7.29, P=0.642).
Although patients with postoperative myocardial injury had higher preoperative self-reported disability, disability scores did not change at 6 months after surgery. However, patients experiencing myocardial infarction worsened in disability score after surgery.
Phosphorus is a nutrient necessary for the development of crops and is thus
commonly applied as fertilizer to sustain agricultural production. It occurs
naturally, in indefinite quantities of ...uncertain quality in phosphate rock
formations, but also accumulates in urban and livestock wastewater wherefrom
it is often lost as a pollutant. Recovering phosphorus from wastewater,
however, is feasible through struvite crystallization technologies and has
the potential to reduce phosphorus pollution of the environment as well as
lower the agricultural demand for artificial P fertilizers. In this study, we
developed a model to assess the global potential of P fertilizer recovery
from wastewater and to visualize its trade at sub-national resolution.
Results show that humans discharge a maximum of 3.7 Mt P into wastewater,
thereby potentially satisfying 20 % of the global fertilizer demand.
Provided 2015 market dynamics, however, the model determines that only
4 % of this discharge is technologically and economically recoverable in
a market that offers cheap rock phosphate products also. The results of this
study demonstrate that in the current economic context, phosphorus recovery
from wastewater offers only a small contribution to resolving global
phosphorus issues. Nevertheless, this recovery offers many wastewater
treatment facilities the opportunity to contribute to creating sustainable
communities and protecting the environment locally, while reducing their own
operational costs.
Summary
Several assays to measure pre‐existing allospecific T cell immunity in renal transplant candidates have been developed in the past years. In 46 patients, we used flow cytometry‐based mixed ...lymphocyte culture to measure the precursor frequency and phenotype of alloreactive T cells before renal transplantation, using donor‐specific or third‐party cells for allostimulation. Allostimulation induced up‐regulation of co‐stimulatory molecules, chemokine receptors relevant for migration of T cells into the graft and effector proteins. Recipients prone for acute rejection had a higher precursor frequency of alloreactive CD8+ T cells and a lower percentage of interleukin (IL)‐7Rα expressing alloreactive CD8+ T cells than non‐rejectors. These data point to quantitative and qualitative differences between T cells of patients who will experience acute cellular rejection episodes from those who will not.
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate ...CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.
The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires ...hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700–290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620–1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions.
We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgV(H) mutation status, and ...(3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL cells displayed high constitutive expression of Bcl-2 and Flip mRNA, while Survivin, Bid and Bik were absent. Paradoxically, along with these antiapoptotic genes CLL cells had high-level expression of proapoptotic BH3-only proteins Bmf and Noxa. Treatment of CLL cells with fludarabine induced only the proapoptotic genes Bax and Puma in a p53-dependent manner. Interestingly, the degree of Puma induction was more pronounced in cells with mutated IgVH genes. Thus, disturbed apoptosis in CLL is the net result of both protective and sensitizing aberrations. This delicate balance can be tipped via induction of Puma in a p53-dependent matter, the level of which may vary between groups of patients with a different tendency for disease progression.
The soil water retention curve (SWRC) is an essential hydraulic function for the understanding and modelling of soil hydraulic processes. Its direct determination is time consuming and sometimes ...expensive because it requires extensive sampling, especially when spatial and temporal variation of soil hydraulic properties are an issue. The use of pedotransfer functions (PTFs) is a viable alternative to predict the parameters of SWRC from more easily determined soil attributes. Splintex is a physically based engineering model containing two PTFs to estimate SWRC parameters and saturated hydraulic conductivity, but its performance and functionality have not yet been fully evaluated and disseminated for soil science. We examined the functionality of the PTFs available in Splintex to estimate parameters of the Van Genuchten–Mualem (VGM) SWRC equation with a laboratory‐measured dataset containing information on particle size, bulk and particle density, saturated water content and parameters of the SWRCs. In addition, we tested the performance of both PTFs for deriving some soil physical–structural variables calculated from estimated SWRC parameters. Compared with VGM parameters fitted to the laboratory dataset, the model performed well. Its predictive performance for soil air capacity, relative field capacity and soil physical–structural quality indices was also evaluated. The performance of Splintex for estimating the VGM parameters depended on the combined effect of all input variables rather than on isolated correlations between an input variable and a model parameter.
Highlights
Splintex provides two PTFs to estimate the Van Genuchten–Mualem parameters of the SWRC.
In addition to PTF1 input, PTF2 needs an additional soil water content–retention observation.
Performance of Splintex‐PTF1 against measured data and ‐PTF2 prediction is presented.
PTF2 provided better results than PTF1 for estimating SPQ indices.
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