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The cytokine receptor IL-2R is essential for the development of T reg cells; therefore, it has been difficult to separate this from its role in the suppressive function of T reg cells. Rudensky and colleagues use various genetic systems to show that capture of IL-2 by IL-2R is important for suppression of CD8 + T cells but not that of CD4 + T cells. Regulatory T cells (T reg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T reg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T reg cell lineage–specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T reg cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4 + T cells but was important for limiting the activation of CD8 + T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of T reg cells separable from signaling via the T cell antigen receptor.

Regulatory T cells (T cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4 T cells but was important for limiting the activation of CD8 T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of T cells separable from signaling via the T cell antigen receptor.

Th1, Th2, Th9 and Th17 cells are conventional CD4 + effector T cells identified as secretors of prototypical cytokines IFNγ, IL4, IL9, and IL-17A respectively. Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate-like phenotype have been identified in the thymus that are distinct from conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin-2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and humans. Here we show that Itk negatively regulates the development of nTh1 cells that express IFNγ in a Tbet independent manner, and whose expansion can be enhanced by IL4. Furthermore, we show that robust induction of IL4 responses during Trichinella spiralis infection enhance the presence of nTh1 cells. We conclude T cell receptor signaling via Itk controls the development of natural Th1 cells, which are expanded by the presence of IL4.

Regulatory T cells (T sub(reg) cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T sub(reg) cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T sub(reg) cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T sub(reg) cells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4 super(+) T cells but was important for limiting the activation of CD8 super(+) T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of T sub(reg) cells separable from signaling via the T cell antigen receptor.

Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg cell suppressor function separable from T cell receptor signaling.

Th1, Th2, Th9 and Th17 cells are conventional CD4+ effector T cells identified as secretors of prototypical cytokines IFNγ, IL4, IL9, and IL-17A respectively. Recently, populations of natural Th17 and Th1 cells (nTh17 and nTh1) with innate-like phenotype have been identified in the thymus that are distinct from conventional Th17 and Th1 cells. The absence of the Tec family kinase Interleukin-2 inducible T cell kinase (Itk) results in T cell immunodeficiency in mice and humans. Here we show that Itk negatively regulates the development of nTh1 cells that express IFNγ in a Tbet independent manner, and whose expansion can be enhanced by IL4. Furthermore, we show that robust induction of IL4 responses during Trichinella spiralis infection enhance the presence of nTh1 cells. We conclude T cell receptor signaling via Itk controls the development of natural Th1 cells, which are expanded by the presence of IL4.

Background An increasing incidence of colorectal cancer (CRC) is being reported in developing countries, including India. Most Indian studies on CRC are retrospective and single-centered. The present study is an attempt to understand the current clinical profile and stage of newly diagnosed CRCs across multiple centers in Tamil Nadu, India. Methods A multi-centric observational survey was conducted between September 1, 2021, and August 31, 2022, under the aegis of the Indian Society of Gastroenterology - Tamil Nadu chapter. Patients 18 years of age and older with a recent diagnosis of CRC fulfilling the inclusion criteria were prospectively recruited at the participating centers. Their demographic, clinical, biochemical, endoscopic, histopathologic, radiologic and risk factor details were systematically collected and analyzed. Results Across 23 centers in Tamil Nadu, 1208 patients were recruited. The male:female ratio was 1.49:1, while mean (SD) age was 57.7 (13.5) years. A majority (81.9%) were Tamils and 78.5% belonged to lower socioeconomic classes. The predominant symptoms were hematochezia (30.2%) and a change in bowel habits (27.5%). The most common locations were the rectum (34.3%) and rectosigmoid (15.1%). Synchronous CRCs were seen in 3.3% and synchronous colorectal polyps in 12.8%. Predisposing factors for CRC were seen in 2%. A past history of any cancer among CRC patients was obtained in 3.1% and a family history of any cancer was found in 7.6%. Patients who were either overweight or obese constituted 46.4% of the study population. At presentation, the predominant stages were stage III (44.7%) and stage IV (20.8%). Conclusions A majority of patients with newly diagnosed CRC in Tamil Nadu belonged to the lower socioeconomic classes. About 60% had CRCs located within the reach of the flexible sigmoidoscope. Two-thirds of the patients exceeded stage II disease at presentation. Trial registration Not applicable Graphical Abstract

This study focuses on building a model to predict Cumulative Grade Point Average (CGPA) categories and identify students who might struggle academically during their time at university. The study uses student-related data to classify CGPA into specific grades (O, A+, A, B+, B, C+, C and F) and tested different machine learning methods like Naive Bayes, JRIP, J48, Random Forest, and CatBoost. Since some grades, like C and A+, had fewer students, a single-point crossover technique to balance the dataset were used. The models were assessed with ten-fold cross-validation, and CatBoost performed the best after balancing the data. To determine which factors played the largest role in the predictions, SHapley Additive exPlanations (SHAP) were used. It shows that the semester grade point average (SGPA) is one of the primary factors, especially highlighting those students in their 3rd semester who need extra support to achieve a better overall CGPA. These results show how early predictions can help universities support students and improve their academic success and retention.

Chylothorax, characterised by the accumulation of chyle in the pleural space, is a rare yet clinically significant condition. This lymphatic fluid, rich in fats absorbed from the intestine, can be caused by various factors including trauma, malignancy, and tuberculosis (TB). Traumatic causes, particularly iatrogenic procedures, account for a significant proportion of cases, followed by rare etiologies like malignancies such as lymphoma, and less commonly, tuberculosis. In the first two cases, the patient was diagnosed with tuberculosis during evaluation for chylothorax; however, in the third case, the patient developed chylothorax as a complication of mantle cell lymphoma (MCL). Two male patients, aged 43 and 45, presented with respiratory symptoms and milky pleural effusions (triglycerides > 180 mg/dL). In both, bronchoalveolar lavage confirmed rifampicin‐sensitive TB. Both patients responded to anti‐tubercular therapy and dietary modification. A 69‐year‐old male with a history of non‐Hodgkin's lymphoma developed chylothorax (triglycerides 286 mg/dL) and lymphadenopathy; imaging and biopsy confirmed MCL. He responded to chemotherapy. This series underscores the importance of considering uncommon causes of chylothorax during evaluation and tailoring treatment based on specific etiologies. We present a series of three cases, which emphasises the diverse causes and treatment of chylothorax.

Background Dried blood spots (DBS) are a relatively inexpensive source of nucleic acids and are easy to collect, transport, and store in large-scale field surveys, especially in resource-limited settings. However, their performance in whole-genome sequencing (WGS) relative to that of venous blood DNA has not been analyzed for various downstream applications. Methods This study compares the WGS performance of DBS paired with venous blood samples collected from 12 subjects. Results Results of standard quality checks of coverage, base quality, and mapping quality were found to be near identical between DBS and venous blood. Concordance for single-nucleotide variants, insertions and deletions, and copy number variants was high between these two sample types. Additionally, downstream analyses typical of population-based studies were performed, such as mitochondrial heteroplasmy detection, haplotype analysis, mitochondrial copy number changes, and determination of telomere lengths. The absolute mitochondrial copy number values were higher for DBS than for venous blood, though the trend in sample-to-sample variation was similar between DBS and blood. Telomere length estimates in most DBS samples were on par with those from venous blood. Conclusion DBS samples can serve as a robust and feasible alternative to venous blood for studies requiring WGS analysis.