Protein-based imaging agents and therapeutics are superior in structural and functional diversity compared to small molecules and are much easier to design or screen. Antibodies or antibody fragments can be easily raised against virtually any target. Despite these fundamental advantages, the power and impact of protein-based agents are substantially undermined, only acting on a limited number of extracellular targets because…
Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in obesity. We find that adipose tissue versican and biglycan increase in obesity. Versican is produced mainly by adipocytes and biglycan by adipose tissue macrophages. Both proteoglycans are also present in adipose tissue from obese human subjects undergoing gastric bypass…
SS-31 is a synthetic peptide that improves mitochondrial function and is currently undergoing clinical trials for treatments of heart failure, primary mitochondrial myopathy, and other mitochondrial diseases. SS-31 interacts with cardiolipin which is abundant in the inner mitochondrial membrane, but mechanistic details of its pharmacological effects are unknown. Here we apply a chemical cross-linking/mass spectrometry method to provide direct evidence…
Growing evidence indicates a role for the gut microbiota in modulating anti-tumor treatment efficacy in human cancer. Here we study mucosa-associated invariant T (MAIT) cells to look for evidence of bacterial antigen recognition in human colon, lung, and kidney carcinomas. Using mass cytometry and single-cell mRNA sequencing, we identify a tumor-infiltrating MAIT cell subset expressing CD4 and Foxp3 and observe…
Our paper investigates differences in visual perception in people with autism versus neurotypical individuals. People with ASD often are hyper-sensitive to sensory stimuli; a loud sound or a bright light might be too intense for them, but not for other people. We also know that people with ASD can show enhanced visual perception of brief moving stimuli, but before our study we didn't know what was happening differently in the brain to cause this difference in vision in ASD.
Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject twenty-one days after the onset of clinical disease. Forty-five S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation, with limited clonal…
Over the past decade, long-read, single-molecule DNA sequencing technologies have emerged as powerful players in genomics. With the ability to generate reads tens to thousands of kilobases in length with an accuracy approaching that of short-read sequencing technologies, these platforms have proven their ability to resolve some of the most challenging regions of the human genome, detect previously inaccessible structural…
UV radiation from the sun damages DNA and generates DNA ‘lesions’ which may become genetic mutations and cause cancer. Cells respond to these deleterious lesions by activating a DNA damage response pathway called the ATR-Chk1 signaling pathway. ATR is an essential kinase that senses UV-induced DNA damage and regulates the cell cycle and cell survival. Thus, we have been addressing a long-standing, important question: How exactly is the ATR pathway activated?
Deep molecular phenotyping of individuals provides the opportunity for biological insight into host physiology. As the human microbiome is increasingly being recognized as an important determinant of host health, understanding the host–microbiome relationship in a multiomics context may pave the way forward for targeted interventions. In this study, we analyze gut microbial composition of 101 individuals over the course of…
DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59…