78 research outputs found
MID2 can substitute for MID1 and control exocytosis of lytic granules in cytotoxic T cells
No full textWe have recently shown that the E3 ubiquitin ligase midline 1 (MID1) is upregulated in murine cytotoxic lymphocytes (CTL), where it controls exocytosis of lytic granules and the killing capacity. Accordingly, CTL from MID1 knock-out (MID1-/- ) mice have a 25-30% reduction in exocytosis of lytic granules and cytotoxicity compared to CTL from wild-type (WT) mice. We wondered why the MID1 gene knock-out did not affect exocytosis and cytotoxicity more severely and speculated whether MID2, a close homologue of MID1, might partially compensate for the loss of MID1 in MID1-/- CTL. Here, we showed that MID2, like MID1, is upregulated in activated murine T cells. Furthermore, MID1-/- CTL upregulated MID2 two-twenty-fold stronger than CTL from WT mice, suggesting that MID2 might compensate for MID1. In agreement, transfection of MID2 into MID1-/- CTL completely rescued exocytosis of lytic granules in MID1-/- CTL, and vice versa, knock-down of MID2 inhibited exocytosis of lytic granules in both WT and MID1-/- CTL, demonstrating that both MID1 and MID2 play a central role in the regulation of granule exocytosis and that functional redundancy exists between MID1 and MID2 in CTL
VISEM-Tracking
No full textPre-print and citation:
[Pre-print](https://arxiv.org/abs/2212.02842)
@article{thambawita2023visem,
title={VISEM-Tracking, a human spermatozoa tracking dataset},
author={Thambawita, Vajira and Hicks, Steven A and Stor{\aa}s, Andrea M and Nguyen, Thu and Andersen, Jorunn M and Witczak, Oliwia and Haugen, Trine B and Hammer, Hugo L and Halvorsen, P{\aa}l and Riegler, Michael A},
journal={Scientific Data},
volume={10},
number={1},
pages={1--8},
year={2023},
publisher={Nature Publishing Group}
}
Motivation and background
Manual evaluation of a sperm sample using a microscope is time-consuming and requires costly experts who have extensive training. In addition, the validity of manual sperm analysis becomes unreliable due to limited reproducibility and high inter-personnel variations due to the complexity of tracking, identifying, and counting sperms in fresh samples. The existing computer-aided sperm analyzer systems are not working well enough for application in a real clinical setting due to unreliability caused by the consistency of the semen sample. Therefore, we need to research new methods for automated sperm analysis.
Target group
The task is of interest to researchers in the areas of machine learning (classification and detection), visual content analysis, and multimodal fusion. Overall, this task is intended to encourage the multimedia community to help improve the health care system through the application of their knowledge and methods to reach the next level of computer and multimedia-assisted diagnosis, detection, and interpretation.
Class Label Mapping
sperm: 0
cluster: 1
small or pinhead:
The vitamin D receptor and T cell function
No full textThe vitamin D receptor (VDR) is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH)2D3, regulates the expression of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH)2D3-VDR signaling on immune function has been the focus of many recent studies as a link between 1,25(OH)2D3 and sus-ceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. It is also becoming increasingly clear that microbes slow down immune reactivity by dysregulating the VDR ultimately to increase their chance of survival. Immune modulatory therapies that enhance VDR expression and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies have been engaged investigating the impact of VDR ex-pression in T cells and found that VDR expression and activity plays an important role in both T cell development, differentiation and effector function. In this review we will analyze current know-ledge of VDR regulation and function in T cells and discuss its importance for immune activity
Leptomycin B neither inhibits nuclear export nor degradation of the VDR.
No full text<p>(A) Representative Western blot of VDR, p53 and CD3ζ (loading control) in whole cell lysates of T cells activated for 3 d in the absence of 25(OH)D<sub>3</sub> and then treated with the indicated concentrations (ng/ml) of leptomycin B (LMB) for 4 h. (B) Relative VDR and p53 protein expression obtained from Western blot analysis of whole cell lysates from T cells treated as described in A. The density of the VDR and p53 bands were normalized to the density of the VDR and p53 bands of T cells not treated with LMB, respectively. Results are presented as mean + SEM (<i>n</i> = 3; * p<0.05). (C) Representative Western blot of VDR, p53 and CD3ζ (loading control) in cytoplasmic (C) and nuclear (N) fractions of T cells treated as described in A.</p
Effect of moderate alcohol intake on blood apolipoproteins concentrations:A meta-analysis of human intervention studies
No full textAims: This study assessed the effect of alcohol intake (up to 40 g/d) on blood apolipoproteins (APOs) concentration in human intervention studies. Additionally, it evaluates whether the effect of alcohol intake on APOs differs depending on sex. Data synthesis: The literature search was performed in PubMed, Cochrane, Embase, and Web of Science databases. The Cochrane risk of bias tool was applied. A total of 5559 articles were identified, yielding 80 articles for full-text screening. Twenty-five articles were included for data extraction. Compared to no alcohol intake, alcohol intake up to a dose of 40 g/d showed an increase in Apolipoprotein A-I levels (ApoA-I) [mean difference (MD): 7.77 mg/dl, 95 % confidence interval (CI): 4.95 mg/dl, 10.59 mg/dl] and Apolipoprotein A-II levels (ApoA-II) [MD: 1.61 mg/dl, 95 % CI: 0.33 mg/dl, 2.90 mg/dl], but no significant change in Apolipoprotein B levels (ApoB) [MD: −0.06 mg/dl, 95 % CI: −3.38 mg/dl, 3.27 mg/dl]. Males showed a significant increase, while females showed a non-significant increase in ApoA-I levels [MD: 9.70 mg/dl, 95 % CI: 6.16 mg/dl, 13.28 mg/dl vs MD: 7.31 mg/dl, 95 % CI: −0.67 mg/dl, 15.30 mg/dl]. The results had less certainty as most studies were at high risk of bias. Conclusion: Alcohol consumption up to 40 g/d increases ApoA-I and ApoA-II levels. Further research is required for ApoB. Considerations should be given when applying this research to practice. High-quality clinical trials with large sample sizes and longer intervention periods are required, focusing on including female participants. PROSPERO IDCRD42021283256.</p
Human CD4+ T cells require exogenous cystine for glutathione and DNA synthesis
No full textAdaptive immune responses require activation and expansion of antigen-specific T cells. Whereas early T cell activation is independent of exogenous cystine (Cys2), T cell proliferation is dependent of Cys2. However, the exact roles of Cys2 in T cell proliferation still need to be determined. The aim of this study was to elucidate why activated human T cells require exogenous Cys2 in order to proliferate. We activated purified naïve human CD4+ T cells and found that glutathione (GSH) levels and DNA synthesis were dependent on Cys2 and increased in parallel with increasing concentrations of Cys2. Vice-versa, the GSH synthesis inhibitor L-buthionine-sulfoximine (BSO) and inhibition of Cys2 uptake with glutamate inhibited GSH and DNA synthesis in parallel. We further found that thioredoxin (Trx) can partly substitute for GSH during DNA synthesis. Finally, we show that GSH or Trx is required for the activity of ribonucleotide reductase (RNR), the enzyme responsible for generation of the deoxyribonucleotide DNA building blocks. In conclusion, we show that activated human T cells require exogenous Cys2 to proliferate and that this is partly explained by the fact that Cys2 is required for production of GSH, which in turn is required for optimal RNR-mediated deoxyribonucleotide synthesis and DNA replication.</p
Serum CD5L Responds Positively to Selenium and Coenzyme Q10 Supplementation with Relation to Thyroid Hormones, Mortality, and Health-Related Quality-of-Life—A Sub-Analysis of a Double-Blind Randomised Placebo-Controlled Trial in Elderly Low in Selenium
No full textfirst_pagesettings Order Article Reprints Open AccessArticleSerum CD5L Responds Positively to Selenium and Coenzyme Q10 Supplementation with Relation to Thyroid Hormones, Mortality, and Health-Related Quality-of-Life—A Sub-Analysis of a Double-Blind Randomised Placebo-Controlled Trial in Elderly Low in Seleniumby Urban Alehagen 1,*, Jan O. Aaseth 2,3 , Trine B. Opstad 4,5, Anders Larsson 6 , Sabrina Asaad 7, Lutz Schomburg 7 and Jan Alexander 8 1Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden2Department of Research, Innlandet Hospital Trust, 2380 Brumunddal, Norway3Faculty of Health and Social Sciences, University of Inland Norway, 2605 Lillehammer, Norway4Oslo Center for Clinical Heart Research—Laboratory, Department of Cardiology, Oslo University Hospital Ullevål, 0450 Oslo, Norway5Faculty of Medicine, University of Oslo, 0372 Oslo, Norway6Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden7Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany8Norwegian Institute of Public Health, 0213 Oslo, Norway*Author to whom correspondence should be addressed.Antioxidants 2025, 14(3), 366; https://doi.org/10.3390/antiox14030366Submission received: 8 February 2025 / Revised: 12 March 2025 / Accepted: 12 March 2025 / Published: 20 March 2025(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress) Download keyboard_arrow_down Browse Figures Versions Notes AbstractThe Cluster of Differentiation 5-like protein (CD5L) is produced by tissue-resident macrophages. It is an innate immune mediator protein with a multitude of functions, such as binding of invading microorganisms and oxidised LDL, and it is associated with clinical conditions, i.e., atherosclerosis and inflammation. The circulating CD5L level has been reported to correlate to selenium status and thyroid hormone activity. In order to test this hypothesis, we analysed CD5L in serum samples from a randomized controlled trial (RCT) with selenium and coenzyme Q10 supplementation and examined associations between CD5L and thyroid hormones, health-related quality-of-life (Hr-QoL), and mortality in an elderly population low in selenium. Circulating levels of CD5L and thyroid hormones were determined in 359 elderly community-living individuals enrolled in an RCT at inclusion and after 48 months of supplementation (179 received selenium and coenzyme Q10, and 180 placebo). Hr-QoL was recorded at both time-points using Short Form 36. Pre-intervention plasma selenium was low, mean 67 µg/L. CD5L correlated positively to free tri-iodothyronine (fT3) and showed an inverse relation with thyroid stimulating hormone (TSH). Low CD5L concentrations at inclusion in the placebo group were associated with increased cardiovascular mortality during 10 years of follow-up, and impaired Hr-QoL at 48 months. Selenium and coenzyme Q10 supplementation significantly increased CD5L and fT3 levels, in association with a better health outcome. The data indicate that circulating CD5L positively responds to selenium and coenzyme Q10 supplementation, correlates with thyroid hormone status, and associates with positive health indices. The observed effect may be due to increased selenium-dependent deiodinase isozyme expression that converts thyroxine (T4) to T3 locally and supports thyroid hormone activities. Whether the observed associations with Hr-QoL and cardiovascular mortality are a direct effect of circulating CD5L or local thyroid hormone activity is unclear and should be further investigated
Flavor physics in the quark sector
No full textIn the past decade, one of the major challenges of particle physics has been to gain an in-depth understanding of the role of quark flavor. In this time frame, measurements and the theoretical interpretation of their results have advanced tremendously. A much broader understanding of flavor particles has been achieved; apart from their masses and quantum numbers, there now exist detailed measurements of the characteristics of their interactions allowing stringent tests of Standard Model predictions. Among the most interesting phenomena of flavor physics is the violation of the CP symmetry that has been subtle and difficult to explore. In the past, observations of CP violation were confined to neutral K mesons, but since the early 1990s, a large number of CP-violating processes have been studied in detail in neutral B mesons. In parallel, measurements of the couplings of the heavy quarks and the dynamics for their decays in large samples of K, D, and B mesons have been greatly improved in accuracy and the results are being used as probes in the search for deviations from the Standard Model.
In the near future, there will be a transition from the current to a new generation of experiments; thus a review of the status of quark flavor physics is timely. This report is the result of the work of physicists attending the 5th CKM workshop, hosted by the University of Rome "La Sapienza", September 9-13, 2008. It summarizes the results of the current generation of experiments that are about to be completed and it confronts these results with the theoretical understanding of the field which has greatly improved in the past decade
Aesthetics of the beautiful: Ideologic tensions in contemporary assessment
No full textPedagogy is an uncertain art. Yet by its very nature, contemporary teaching and learning practice typically suggests that the expert teacher must come to know their student well enough to plan and predict for educational challenges that will expand and extend their thinking. In many countries, this process is underpinned by bureaucratic ideology that has persuasively developed an agenda for assessment as accountability for pedagogy. As a result assessment practice in these educational institutions is very public, highly accountable and heavily prescribed through curriculum documents that claim to encompass societal agendas. In some cases, such practices are even legislated. Assessment practice is now seen as integral to the pedagogical process since it is through assessment that the teacher purportedly comes to understand the learner; thus providing a rationale for the teaching approaches and strategies that are applied in order to progress learning. In this chronotopic location I suggest there is little room for uncertainty, since the quest to capture the "essence" of the learner and mould them towards societal goals is as much a political agenda of accountability as it is pedagogical
The VDR is spontaneously degraded by the proteasomes.
No full text<p>(A, B) Representative Western blot of VDR and CD3ζ (loading control) in (A) whole cell lysates and (B) cytoplasmic (C) and nuclear (N) fractions of T cells activated for 3 d in the absence of 25(OH)D<sub>3</sub> and then pre-treated with the indicated concentrations of lactacystin (µM) for 1 h before treatment with cycloheximide (10 µg/ml) as indicated for one additional h. (C) Relative VDR protein expression obtained from Western blot analysis of whole cell lysates (W), cytoplasmic (C) and nuclear (N) fractions from T cells treated as described in A and B. The density of the VDR bands were normalized to the density of the VDR bands of T cells not treated with lactacystin and cycloheximide. Results are presented as mean + SEM (<i>n</i> = 3).</p
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