Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils.

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration.

Imaging the Architecture of Granulomas Induced by Mycobacterium tuberculosis Infection with Single-molecule Fluorescence In Situ Hybridization.

Granulomas are an important hallmark of Mycobacterium tuberculosis infection. They are organized and dynamic structures created when immune cells assemble around the sites of infection in the lungs that locally restrict M. tuberculosis growth and the host's inflammatory responses.

A genetic cross reveals the contributions of and to piperaquine drug resistance.

Piperaquine (PPQ) is widely used in combination with dihydroartemisinin as a first-line treatment against malaria. Multiple genetic drivers of PPQ resistance have been reported, including mutations in the () and increased copies of (). We generated a cross between a Cambodia-derived multidrug-resistant KEL1/PLA1 lineage isolate (KH004) and a drug-susceptible Malawian parasite (Mal31).

Circulating Sphingolipids and All-Cause Mortality: The Strong Heart Family Study.

Background: A growing body of research indicates that associations of ceramides and sphingomyelins with mortality depend on the chain length of the fatty acid acylated to the backbone sphingoid base. We examined associations of 8 ceramide and sphingomyelin species with mortality among an American Indian population.

Methods And Results: The analysis comprised 2688 participants from the SHFS (Strong Heart Family Study).

B cells in perivascular and peribronchiolar granuloma-associated lymphoid tissue and B-cell signatures identify asymptomatic lung infection in Diversity Outbred mice.

Because most humans resist infection, there is a paucity of lung samples to study. To address this gap, we infected Diversity Outbred mice with and studied the lungs of mice in different disease states. After a low-dose aerosol infection, progressors succumbed to acute, inflammatory lung disease within 60 days, while controllers maintained asymptomatic infection for at least 60 days, and then developed chronic pulmonary tuberculosis (TB) lasting months to more than 1 year.

Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Mycobacterium tuberculosis infects two billion people across the globe, and results in 8-9 million new tuberculosis (TB) cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease.

SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity.

SARS-CoV-2 uses the double-membrane vesicles as replication organelles. However, how virion assembly occurs has not been fully understood. Here we identified a SARS-CoV-2-driven membrane structure named the 3a dense body (3DB).

Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.

Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging.

Inhibition of mRNA nuclear export promotes SARS-CoV-2 pathogenesis.

The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of the various Nsp1-mediated functions and their contributions to SARS-CoV-2 virulence remain unclear. Among the targets of Nsp1 is the mRNA (messenger ribonucleic acid) export receptor NXF1-NXT1, which mediates nuclear export of mRNAs from the nucleus to the cytoplasm.

SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

Background: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial.

Methods: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 μg or 50 μg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181.

Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring.

We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically.

High all-cause mortality and increasing proportion of older adults with tuberculosis in Texas, 2008-2020.

Pulmonary tuberculosis (PTB) elimination efforts must consider the global growth of the ageing population. Here we used TB surveillance data from Texas, United States (2008-2020; total  = 10656) to identify unique characteristics and outcomes in older adults (OA, ≥65 years) with PTB, compared to young adults (YA, 18-39 years) or middle-aged adults (40-64 years). We found that the proportion of OA with PTB increased from 15% in 2008 to 24% in 2020 (trend  < 0.

Protocol to develop human alveolar macrophage-like cells from mononuclear cells or purified monocytes for use in respiratory biology research.

Human alveolar macrophages are a unique myeloid subset critical for understanding pulmonary diseases and are difficult to access. Here, we present a protocol to generate human alveolar macrophage-like (AML) cells from fresh peripheral blood mononuclear cells or purified monocytes. We describe steps for cell isolation, incubation in a defined cocktail of pulmonary surfactant and lung-associated cytokines, phenotype analysis, and validation with human alveolar macrophages.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized.

Contribution of parasite and host genotype to immunopathology of schistosome infections.

Background: The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host.

Fostering the unleashing potential of nanocarriers-mediated delivery of ocular therapeutics.

Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye.

Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat.

Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study.

Background: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205.

Genetic characterization of a captive marmoset (Callithrix jacchus) colony using genotype-by-sequencing.

The marmoset is a fundamental nonhuman primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost-effective, genome-wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype-by-sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC).

Drug resistant strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages.

, the causative agent of tuberculosis (TB), is considered one of the top infectious killers in the world. In recent decades, drug resistant (DR) strains of have emerged that make TB even more difficult to treat and pose a threat to public health. has a complex cell envelope that provides protection to the bacterium from chemotherapeutic agents.

Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons.

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level.

Label-free and amplification-free viral RNA quantification from primate biofluids using a trapping-assisted optofluidic nanopore platform.

Viral outbreaks can cause widespread disruption, creating the need for diagnostic tools that provide high performance and sample versatility at the point of use with moderate complexity. Current gold standards such as PCR and rapid antigen tests fall short in one or more of these aspects. Here, we report a label-free and amplification-free nanopore sensor platform that overcomes these challenges via direct detection and quantification of viral RNA in clinical samples from a variety of biological fluids.