Leukocyte telomere length predicts subsequent infectious morbidity among Colombian schoolchildren

Abstract

Objective

Telomere length (TL) attrition is related to chronic disease risk. However, less is known on whether TL predicts infectious outcomes, especially in childhood. We examined whether leukocyte TL (LTL) was associated with subsequent infectious morbidity in schoolchildren.

Methods

We assessed LTL in 717 Colombian children 5–12 years-old at the beginning of a school year and followed them through the year for daily occurrence of common infection symptoms and doctor visits. We estimated adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI) of gastrointestinal and respiratory syndromes for quartiles of standardized LTL Z score and per unit LTL Z score.

Results

A longer LTL was associated with increased incidence of all infectious morbidity syndromes considered. Adjusted IRR (95% CI) per unit LTL Z score were 1.55 (1.20, 2.00) for diarrhea with vomiting, 1.34 (1.13, 1.60) for cough with fever, 1.70 (1.28, 2.28) for ear infection, and 1.66 (1.36, 2.02) for doctor visits with symptoms.

Conclusions

Longer LTL is related to increased incidence of common infectious morbidities in middle childhood.

Nutrient‐dependent signaling pathways that control autophagy in yeast

Nutrient-dependent signaling pathways that control autophagy in yeast

Living organisms experience diverse external environments throughout life; one common situation is nutrient limitation. To survive nutrient stress, eukaryotic cells utilize macroautophagy/autophagy. During autophagy, cells remove unwanted material by packaging them within double-membraned autophagosomes and delivering the cargo to vacuoles for degradation. Here, we summarize different nutrient contexts and signaling pathways that regulate autophagy, specifically in Saccharomyces cerevisiae.


Macroautophagy/autophagy is a highly conserved catabolic process vital for cellular stress responses and maintaining equilibrium within the cell. Malfunctioning autophagy has been implicated in the pathogenesis of various diseases, including certain neurodegenerative disorders, diabetes, metabolic diseases, and cancer. Cells face diverse metabolic challenges, such as limitations in nitrogen, carbon, and minerals such as phosphate and iron, necessitating the integration of complex metabolic information. Cells utilize a signal transduction network of sensors, transducers, and effectors to coordinate the execution of the autophagic response, concomitant with the severity of the nutrient-starvation condition. This review presents the current mechanistic understanding of how cells regulate the initiation of autophagy through various nutrient-dependent signaling pathways. Emphasizing findings from studies in yeast, we explore the emerging principles that underlie the nutrient-dependent regulation of autophagy, significantly shaping stress-induced autophagy responses under various metabolic stress conditions.

Structural and functional diversity of type IV secretion systems

Nature Reviews Microbiology, Published online: 09 October 2023; doi:10.1038/s41579-023-00974-3

In this Review, Costa and colleagues summarize the current knowledge of type IV secretion system functioning in Gram-negative bacteria, with a focus on their architectures and adaptations for specialized functions. They also explore the biogenesis pathways and spatial localization of type IV secretion systems.

ERMAP activates phagocytosis in Kupffer cells to restrict liver metastases

Nature Immunology, Published online: 09 October 2023; doi:10.1038/s41590-023-01647-2

Kupffer cells, hepatic resident macrophages, are the first line of defense against liver metastases by engulfing disseminated malignant cells. We found that ERMAP expressed on tumor cells binds to galectin-9 and dectin-2 on Kupffer cells to deliver pro-phagocytosis ‘eat me’ signals to Kupffer cells to restrict liver metastases.

A logical model of Ewing sarcoma cell epithelial‐to‐mesenchymal transition supports the existence of hybrid cellular phenotypes

A logical model of Ewing sarcoma cell epithelial-to-mesenchymal transition supports the existence of hybrid cellular phenotypes

Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the EWS/FLi1 transcription factor, influencing epithelial–mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying this ES phenotype remain elusive. Through a computational model, we predicted ZEB2, miR-200, and miR-145 circuits responsible for maintaining hybrid states in ES.


Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA-binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial–mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive. Our study proposes a logical EMT model for ES, highlighting zinc finger E-box-binding homeobox 2 (ZEB2), miR-145, and miR-200 circuits that maintain hybrid states. The model aligns with experimental findings and reveals a previously unknown circuit supporting the mesenchymal phenotype. These insights emphasize the role of ZEB2 in the maintenance of the hybrid state in ES.