Transportation of key proteins via extracellular vesicles has been recently implicated in various neurodegenerative disorders, including Parkinson’s disease, as a new mechanism of disease spreading and a new source of biomarkers. Extracellular vesicles likely to be derived from the brain can be isolated from peripheral blood and have been reported to contain higher levels of α-synuclein (α-syn) in Parkinson’s disease…
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HVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability and immunogenicity of PENNVAX®-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether PENNVAX®-GP delivered via ID/EP at 1/5th the dose could elicit equivalent immune responses to delivery via IM/EP, and if…
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Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB during disease latency and reactivation has posed a challenge. We develop an experimental system to precisely control dissolved oxygen levels…
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Humans encode proteins, called restriction factors, that inhibit replication of viruses such as HIV-1. The members of one family of antiviral proteins, apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3; shortened here to A3), act by deaminating cytidines to uridines during the reverse transcription reaction of HIV-1. The A3 locus encodes seven genes, named A3A to A3H. These genes have either one or two cytidine deaminase domains,…
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Using DEER in combination with electrophysiology, we were able to reveal a conformational change in a cyclic nucleotide-gated ion channel that we believe couples the binding of the activating ligand to the opening of the channel pore.  These results provide new insight into the structural mechanism of chemo-electrical coupling in this channel family.
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The overarching goal of our research is to develop an increasingly in- depth knowledge of autoreactive T cell responses by examining the characteristics of epitope specific cells through robust multi-parameter assays and also at the single cell level. We seek to leverage that knowledge to develop clinically meaningful biomarkers and to reveal potential new avenues for therapy.
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Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The FDA-approved drug rapamycin slows aging and extends lifespan in multiple organisms, including mice.…
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Vertebrate appendage regeneration requires precisely coordinated remodeling of the transcriptional landscape to enable the growth and differentiation of new tissue, a process executed over multiple days and across dozens of cell types. The heterogeneity of tissues and temporally-sensitive fate decisions involved has made it difficult to articulate the gene regulatory programs enabling regeneration of individual cell types. To better understand…
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Transferrin receptor (TfR) binding entities can be used as vehicles for CNS drug delivery, however pose challenges for drug development due to huge increase in drug mass. The authors identified a series of TfR-binding cystine-dense peptides that can deliver the neuropeptide neurotensin (model drug), to a mouse's brain while only adding 6 kilodaltons to its mass.
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Multidrug resistance (MDR) of pathogens is an ongoing public health crisis exacerbated by the horizontal transfer of antibiotic resistance genes via conjugative plasmids. Factors that stabilize these plasmids in bacterial communities contribute to an even higher incidence of MDR, given the increased likelihood that a host will already contain a plasmid when it acquires another through conjugation. Here, we show…
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