T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells

Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al

Survival and morbidity in very preterm infants in Shenzhen: a multi-center study

ObjectiveTo analyze survival and morbidity among very preterm infants (VPIs) in Shenzhen and explore factors associated with survival without major morbidity.MethodsBetween January 2022 and December 2022, 797 infants were admitted to 25 neonatal intensive care units in Shenzhen with gestational age (GA) < 32 weeks, excluded discharged against medical advice, insufficient information, and congenital malformation, 742 VPIs were included. Comparison of maternal and neonate characteristics, morbidities, survival, and survival without major morbidities between groups used Mann Whitney U test and X2 test, multivariate logistic regression was used to analyze of risk factors of survival without major morbidities.ResultsThe median GA was 29.86 weeks (interquartile range [IQR], 28.0–31.04), and the median birth weight was 1,250 g (IQR, 900–1,500). Of the 797 VPIs, 721 (90.46%) survived, 53.52% (38 of 71) at 25 weeks’ or less GA, 86.78% (105 of 121) at 26 to 27 weeks' GA, 91.34% (211 of 230) at 28 to 29 weeks' GA, 97.86% (367 of 375) at 30 to 31 weeks' GA. The incidences of the major morbidities were moderate-to-severe bronchopulmonary dysplasia,16.52% (113 of 671); severe intraventricular hemorrhage and/or periventricular leukomalacia, 2.49% (17 of 671); severe necrotizing enterocolitis, 2.63% (18 of 671); sepsis, 2.34% (16 of 671); and severe retinopathy of prematurity, 4.55% (27 of 593), 65.79% (450 of 671) survived without major morbidities. After adjustment for GA, birth weight, and 5-min Apgar score, antenatal steroid administration (OR = 2.397), antenatal magnesium sulfate administration (OR =  1.554) were the positivity factors to survival without major morbidity of VPIs, however, surfactant therapy (OR = 0.684,), and delivery room resuscitation (OR = 0.626) that were the negativity factors.ConclusionsThe present results indicate that survival and the incidence of survival without major morbidities increased with GA. Further, antenatal administration of steroids and magnesium sulfate, surfactant therapy, and delivery room resuscitation were pronounced determinants of survival without morbidities

The 2006 NESCent Phyloinformatics Hackathon: A Field Report

In December, 2006, a group of 26 software developers from some of the most widely used life science programming toolkits and phylogenetic software projects converged on Durham, North Carolina, for a Phyloinformatics Hackathon, an intense five-day collaborative software coding event sponsored by the National Evolutionary Synthesis Center (NESCent). The goal was to help researchers to integrate multiple phylogenetic software tools into automated workflows. Participants addressed deficiencies in interoperability between programs by implementing “glue code” and improving support for phylogenetic data exchange standards (particularly NEXUS) across the toolkits. The work was guided by use-cases compiled in advance by both developers and users, and the code was documented as it was developed. The resulting software is freely available for both users and developers through incorporation into the distributions of several widely-used open-source toolkits. We explain the motivation for the hackathon, how it was organized, and discuss some of the outcomes and lessons learned. We conclude that hackathons are an effective mode of solving problems in software interoperability and usability, and are underutilized in scientific software development

S100A1 gene therapy for heart failure: a novel strategy on the verge of clinical trials

Representing the common endpoint of various cardiovascular disorders, heart failure (HF) shows a dramatically growing prevalence. As currently available therapeutic strategies are not capable of terminating the progress of the disease, HF is still associated with a poor clinical prognosis. Among the underlying molecular mechanisms, the loss of cardiomyocyte Ca(2+) cycling integrity plays a key role in the pathophysiological development and progression of the disease. The cardiomyocyte EF-hand Ca(2+) sensor protein S100A1 emerged as a regulator both of sarcoplasmic reticulum (SR), sarcomere and mitochondrial function implicating a significant role in cardiac physiology and dysfunction. In this review, we aim to recapitulate the translation of S100A1-based investigation from first clinical observations over basic research experiments back to a near-clinical setting on the verge of clinical trials today. We also address needs for further developments towards "second-generation" gene therapy and discuss the therapeutic potential of S100A1 gene therapy for HF as a promising novel strategy for future cardiologists. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy"