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Abstract Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.

Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate. Although IFN-γ is known to regulate T cell function and expansion during virus-specific responses, its impact on T cells with varying avidity for antigen remains unclear. Here, the authors demonstrate that IFN-γ promotes the expansion of low-avidity CD8+ T cells during the effector phase, but favours those with high avidity in the memory pool. [ABSTRACT FROM AUTHOR]

Assessment Essentials: Planning, Implementing, and Improving Assessment in Higher Education, by Catherine A. Palomba and Trudy W. Banta. San Francisco: Jossey-Bass, 1999. 405 pp. $32.95 Although assessment activities are now [...]

Perguruan tinggi sangat memperhatikan penerimaan mahasiswa baru sebagai indikator kemajuan dan pertumbuhan institusi. Namun, fluktuasi jumlah penerimaan mahasiswa baru dapat menjadi kendala dalam perencanaan dan pengambilan keputusan. Penelitian ini bertujuan untuk menerapkan metode Autoregressive Integrated Moving Average (ARIMA) dalam menghitung prediksi jumlah mahasiswa baru pada Universitas Papua. Oleh karena itu, penelitian ini menggunakan metode ARIMA untuk meramalkan jumlah mahasiswa baru tahun 2023 dengan memanfaatkan data historis dari tahun 2017 hingga 2022. Hasil analisis menggunakan R Studio menunjukkan bahwa model terbaik adalah ARIMA (11,0,12) dengan nilai error terendah. Penelitian ini memberikan manfaat bagi peneliti dalam memahami metode peramalan menggunakan ARIMA dan juga memberikan informasi yang berguna bagi Universitas Papua dalam perencanaan strategis untuk meningkatkan kualitas dan minat calon mahasiswa baru. Universities pay great attention to the acceptance of new students as an indicator of the progress and growth of the institution. However, fluctuations in the number of new student admissions can be an obstacle in planning and decision making. This study aims to apply the Autoregressive Integrated Moving Average (ARIMA) method in calculating predictions for the number of new students at the University of Papua. Therefore, this study uses the ARIMA method to predict the number of new students in 2023 by utilizing historical data from 2017 to 2022. The results of the analysis using R Studio show that the best model is ARIMA (11,0,12) with the lowest error value. This research provides benefits for researchers in understanding forecasting methods using ARIMA and also provides useful information for the University of Papua in strategic planning to improve the quality and interest of prospective new students.

Disparities persist regarding the access to pediatric and congenital cardiac catheterization procedures (PCCC). Developing capacities in French overseas territories located far away from mainland France remains essential to reducing inequalities and mortality. To describe the characteristics of patients, procedures type risk categories (PTRC) and outcomes for all PCCC performed on the French island of Martinique (Caribbean). Single center observational study. We recorded prospectively all consecutives PCCC performed in the catheter laboratory of the university Hospital of Martinique from January 2007 to December 2023. Demographics, procedures characteristics, PTRC, adverse events occurrence, as well as 24-hours mortality were documented. All results were retrospectively analysed. We performed 869 PCCC in 770 consecutives patients (31.3% < 1-year-old; 9.4% aged < 1 month) living in French territories (90%) of Martinique, Guadeloupe, French Guiana, Saint-Martin, or natives from others Caribbean islands (10%). The median age and weight (IQR) were 4 years (0.6–13) and 16 kg (6.4–4.6). There were 126 urgent and 43 (4.9%) rescue procedures. PCCC were predominantly interventional (68.7%; success rate: 95.1%) covering all types of procedures, except revalvulation. The overall median PTRC was 2 (2–3) with a 24-h mortality of 1.1%. Complications occurred in 35 cases (4%), of which 18 were major, either procedure and anaesthesia-related (40%) or likely linked (40%) to the critical condition on admission at the cathlab. Overtime, the case-mix complexity continued to increase (PTRC > 3 in 25% of patients, with a median age and weight of 2.6 years and 6.5 kg, within the past 5 years). Developing permanent PCCC capabilities in French Martinique is efficient and safe. This ongoing international program is sustainable with the inclusion of patients coming from all French territories and neighbouring Caribbean islands and the continuous support of French Health Authorities. [ABSTRACT FROM AUTHOR]

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation. [ABSTRACT FROM AUTHOR]

Abstract Alcohol dehydrogenases (ADHs) are used in reductive biotransformations for the production of valuable chiral alcohols. In this study, we used a high-throughput screening approach based on the NADPH biosensor pSenSox and fluorescence-activated cell sorting (FACS) to search for variants of the NADPH-dependent ADH of Lactobacillus brevis (LbADH) with improved activity for the reduction of 2,5-hexanedione to (2R,5R)-hexanediol. In a library of approx. 1.4 × 106 clones created by random mutagenesis we identified the variant LbADHK71E. Kinetic analysis of the purified enzyme revealed that LbADHK71E had a ~ 16% lowered KM value and a 17% higher Vmax for 2,5-hexanedione compared to the wild-type LbADH. Higher activities were also observed for the alternative substrates acetophenone, acetylpyridine, 2-hexanone, 4-hydroxy-2-butanone, and methyl acetoacetate. K71 is solvent-exposed on the surface of LbADH and not located within or close to the active site. Therefore, K71 is not an obvious target for rational protein engineering. The study demonstrates that high-throughput screening using the NADPH biosensor pSenSox represents a powerful method to find unexpected beneficial mutations in NADPH-dependent alcohol dehydrogenases that can be favorable in industrial biotransformations.