Individual cell types in C. elegans age differently and activate distinct cell-protective responses.

Aging is characterized by a global decline in physiological function. However, by constructing a complete single-cell gene expression atlas, we find that Caenorhabditis elegans aging is not random in nature but instead is characterized by coordinated changes in functionally related metabolic, proteostasis, and stress-response genes in a cell-type-specific fashion, with downregulation of energy metabolism being the only nearly universal change. Similarly, the rates at which cells age differ significantly between cell types.

LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice.

Chaperone-mediated autophagy (CMA) selectively degrades proteins that are crucial for glycolysis, fatty acid metabolism, and the progression of several age-associated diseases. Several previous studies, each of which evaluated males of a single inbred mouse or rat strain, have reported that CMA declines with age in many tissues, attributed to an age-related loss of LAMP2A, the primary and indispensable component of the CMA translocation complex. This has led to a paradigm in the field of CMA research, stating that the age-associated decline in LAMP2A in turn decreases CMA, contributing to the pathogenesis of late-life disease.

The Observatory: High-throughput exploration of behavioral aging.

Organisms undergo a variety of characteristic changes as they age, suggesting a substantial commonality in the mechanistic basis of aging. Experiments in model organisms have revealed a variety of cellular systems that impact lifespan, but technical challenges have prevented a comprehensive evaluation of how these components impact the trajectory of aging, and many components likely remain undiscovered. To facilitate the deeper exploration of aging trajectories at a sufficient scale to enable primary screening, we have created the Observatory, an automated system for monitoring the behavior of group-housed throughout their lifespans.

Diverse partial reprogramming strategies restore youthful gene expression and transiently suppress cell identity.

Partial pluripotent reprogramming can reverse features of aging in mammalian cells, but the impact on somatic identity and the necessity of individual reprogramming factors remain unknown. Here, we used single-cell genomics to map the identity trajectory induced by partial reprogramming in multiple murine cell types and dissected the influence of each factor by screening all Yamanaka Factor subsets with pooled single-cell screens. We found that partial reprogramming restored youthful expression in adipogenic and mesenchymal stem cells but also temporarily suppressed somatic identity programs.

Novel insights from a multiomics dissection of the Hayflick limit.

The process wherein dividing cells exhaust proliferative capacity and enter into replicative senescence has become a prominent model for cellular aging in vitro. Despite decades of study, this cellular state is not fully understood in culture and even much less so during aging. Here, we revisit Leonard Hayflick's original observation of replicative senescence in WI-38 human lung fibroblasts equipped with a battery of modern techniques including RNA-seq, single-cell RNA-seq, proteomics, metabolomics, and ATAC-seq.

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g.

Impact of a multifaceted intervention to improve emergency care on newborn and child health outcomes in Rwanda.

Implementing context-appropriate neonatal and paediatric advanced life support management interventions has increasingly been recommended as one of the approaches to reduce under-five mortality in resource-constrained settings like Rwanda. One such intervention is ETAT+, which stands for Emergency Triage, Assessment and Treatment plus Admission care for severely ill newborns and children. In 2013, ETAT+ was implemented in Rwandan district hospitals.

Developing and implementing a model of equitable distribution of mentorship in districts with spatial inequities and maldistribution of human resources for maternal and newborn care in Rwanda.

Background: The shortage of health care providers (HCPs) and inequity in their distribution along with the lack of sufficient and equal professional development opportunities in low-income countries contribute to the high mortality and morbidity of women and newborns. Strengthening skills and building the capacity of all HCPs involved in Maternal and Newborn Health (MNH) is essential to ensuring that mothers and newborns receive the required care in the period around birth. The Training, Support, and Access Model (TSAM) project identified onsite mentorship at primary care Health Centers (HCs) as an approach that could help reduce mortality and morbidity through capacity building of HCPs in Rwanda.

A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage.

Somatic cells age and die, but the germ-cell lineage is immortal. In , germline immortality involves proteostasis renewal at the beginning of each new generation, when oocyte maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen.

Mentors' perspectives on strengths and weaknesses of a novel clinical mentorship programme in Rwanda: a qualitative study.

Objectives: To identify mentors' perspectives on strengths and weaknesses of the Training, Support and Access Model for Maternal, Newborn and Child Health (TSAM-MNCH) clinical mentorship programme in Rwandan district hospitals. Understanding the perspectives of mentors involved in this programme can aid in the improvement of its implementation.

Design: The study used a qualitative approach with in-depth interviews.

Split-wrmScarlet and split-sfGFP: tools for faster, easier fluorescent labeling of endogenous proteins in Caenorhabditis elegans.

We create and share a new red fluorophore, along with a set of strains, reagents and protocols, to make it faster and easier to label endogenous Caenorhabditis elegans proteins with fluorescent tags. CRISPR-mediated fluorescent labeling of C. elegans proteins is an invaluable tool, but it is much more difficult to insert fluorophore-size DNA segments than it is to make small gene edits.

Developing and implementing a novel mentorship model (4) for maternal, newborn and child health in Rwanda.

Background: There are a number of factors that may contribute to high mortality and morbidity of women and newborns in low-income countries. These include a shortage of competent health care providers (HCP) and a lack of sufficient continuous professional development (CPD) opportunities. Strengthening the skills and building the capacity of HCP involved in the provision of maternal, newborn and child health (MNCH) is essential to ensure quality care for mothers, newborns and children.

Parental attitudes and decisions regarding MMR vaccination during an outbreak of measles among an undervaccinated Somali community in Minnesota.

Incidence of measles is increasing in the US, largely due to transmission among growing unvaccinated communities. To elucidate predictors of parental decision to obtain measles, mumps, and rubella (MMR) vaccine for unvaccinated children during a measles outbreak, we surveyed families among a vaccine-hesitant Somali community in Minnesota. The survey assessed attitudes and beliefs about MMR vaccine, motivators for vaccinating, and intention to vaccinate future children on time.

Pertussis Infections Among Pregnant Women in the United States, 2012-2017.

Background: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used the Centers for Disease Control and Prevention's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and nonpregnant women of childbearing age.

Methods: Pertussis cases in women aged 18-44 years with cough onset between 1 January 2012 and 31 December 2017 were identified in 7 EPS states.

Application of Transcriptional Gene Modules to Analysis of ' Gene Expression Data.

Identification of co-expressed sets of genes (gene modules) is used widely for grouping functionally related genes during transcriptomic data analysis. An organism-wide atlas of high-quality gene modules would provide a powerful tool for unbiased detection of biological signals from gene expression data. Here, using a method based on independent component analysis we call DEXICA, we have defined and optimized 209 modules that broadly represent transcriptional wiring of the key experimental organism These modules represent responses to changes in the environment (, starvation, exposure to xenobiotics), genes regulated by transcriptions factors (, ATFS-1, DAF-16), genes specific to tissues (, neurons, muscle), genes that change during development, and other complex transcriptional responses to genetic, environmental and temporal perturbations.

Identifying Vaccine-associated Rash Illness Amidst a Large Measles Outbreak: Minnesota, 2017.

Characteristics of vaccine-associated rash illness (VARI) and confirmed measles cases were compared during a measles outbreak. Although some clinical differences were noted, measles exposure and identification of the vaccine strain were helpful for public health decision-making. Rapid, vaccine strain-specific diagnostic assays will more efficiently distinguish VARI from measles.

Stress Resistance Screen in a Human Primary Cell Line Identifies Small Molecules That Affect Aging Pathways and Extend ' Lifespan.

Increased resistance to environmental stress at the cellular level is correlated with the longevity of long-lived mutants and wild-animal species. Moreover, in experimental organisms, screens for increased stress resistance have yielded mutants that are long-lived. To find entry points for small molecules that might extend healthy longevity in humans, we screened ∼100,000 small molecules in a human primary-fibroblast cell line and identified a set that increased oxidative-stress resistance.

X Chromosome Domain Architecture Regulates Caenorhabditis elegans Lifespan but Not Dosage Compensation.

Mechanisms establishing higher-order chromosome structures and their roles in gene regulation are elusive. We analyzed chromosome architecture during nematode X chromosome dosage compensation, which represses transcription via a dosage-compensation condensin complex (DCC) that binds hermaphrodite Xs and establishes megabase-sized topologically associating domains (TADs). We show that DCC binding at high-occupancy sites (rex sites) defines eight TAD boundaries.

Imported Toxin-Producing Cutaneous Diphtheria - Minnesota, Washington, and New Mexico, 2015-2018.

From September 2015 to March 2018, CDC confirmed four cases of cutaneous diphtheria caused by toxin-producing Corynebacterium diphtheriae in patients from Minnesota (two), Washington (one), and New Mexico (one). All patients had recently returned to the United States after travel to countries where diphtheria is endemic. C.

The mTOR Target S6 Kinase Arrests Development in When the Heat-Shock Transcription Factor Is Impaired.

The widely conserved heat-shock response, regulated by heat-shock transcription factors, is not only essential for cellular stress resistance and adult longevity, but also for proper development. However, the genetic mechanisms by which heat-shock transcription factors regulate development are not well understood. In , we conducted an unbiased genetic screen to identify mutations that could ameliorate the developmental-arrest phenotype of a heat-shock factor mutant.