Publications by authors named "Joseph P Salisbury"

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment.

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Numerous virtual reality (VR) systems have received regulatory clearance as therapeutic medical devices for in-clinic and at-home use. These systems enable remote patient monitoring of clinician-prescribed rehabilitation exercises, although most of these systems are nonimmersive. With the expanding availability of affordable and easy-to-use head-mounted display (HMD)-based VR, there is growing interest in immersive VR therapies.

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0.5-1% of ALS (Amyotrophic Lateral Sclerosis) and Parkinson's disease (PD) are associated with mutations in the angiogenin (ANG). These mutations are thought to cause disease through a loss of ANG function, but this hypothesis has not been evaluated statistically.

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There is a growing interest in the use of augmented reality (AR) to assist children and adults with autism spectrum disorders (ASD); however, little investigation has been conducted into the safety of AR devices, such as smartglasses. The objective of this report was to assess the safety and potential negative effects of the , a novel AR smartglasses-based social communication aid for people with ASD. The version of the Empowered Brain in this report utilized Google Glass (Google, Mountain View, CA, USA) as its hardware platform.

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This work addresses the need for chemical tools that can selectively form cross-links. Contemporary thiol-selective cross-linkers, for example, modify all accessible thiols, but only form cross-links between a subset. The resulting terminal "dead-end" modifications of lone thiols are toxic, confound cross-linking-based studies of macromolecular structure, and are an undesired, and currently unavoidable, byproduct in polymer synthesis.

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Background: People with autism spectrum disorder (ASD) commonly experience symptoms related to attention-deficit/hyperactivity disorder (ADHD), including hyperactivity, inattention, and impulsivity. One-third of ASD cases may be complicated by the presence of ADHD. Individuals with dual diagnoses face greater barriers to accessing treatment for ADHD and respond less positively to primary pharmacologic interventions.

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Background: Lightweight and portable devices that objectively measure concussion-related impairments could improve injury detection and critical decision-making in contact sports and the military, where brain injuries commonly occur but remain underreported. Current standard assessments often rely heavily on subjective methods such as symptom self-reporting. Head-mounted wearables, such as smartglasses, provide an emerging platform for consideration that could deliver the range of assessments necessary to develop a rapid and objective screen for brain injury.

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Background: Computerized smartglasses are being developed as an assistive technology for daily activities in children and adults with autism spectrum disorder (ASD). While smartglasses may be able to help with educational and behavioral needs, their usability and acceptability in children with ASD is largely unknown. There have been reports of negative social perceptions surrounding smartglasses use in mainstream populations, a concern given that assistive technologies may already carry their own stigma.

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With the advent of biosimilars to the U.S. market, it is important to have better analytical tools to ensure product quality from batch to batch.

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Background: Augmented reality (AR) smartglasses are an emerging technology that is under investigation as a social communication aid for children and adults with autism spectrum disorder (ASD) and as a research tool to aid with digital phenotyping. Tolerability of this wearable technology in people with ASD is an important area for research, especially as these individuals may experience sensory, cognitive, and attentional challenges.

Objective: The aim of this study was to assess the tolerability and usability of a novel smartglasses system that has been designed as a social communication aid for children and adults with autism (the Brain Power Autism System [BPAS]).

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Background: Autism spectrum disorder (ASD) is a childhood-onset neurodevelopmental disorder with a rapidly rising prevalence, currently affecting 1 in 68 children, and over 3.5 million people in the United States. Current ASD interventions are primarily based on in-person behavioral therapies that are both costly and difficult to access.

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Stable isotope labeling techniques for quantitative top-down proteomics face unique challenges. These include unpredictable mass shifts following isotope labeling, which impedes analysis of unknown proteins and complex mixtures and exponentially greater susceptibility to incomplete isotope incorporation, manifesting as broadening of labeled intact protein peaks. Like popular bottom-up isotope labeling techniques, most top-down labeling methods are restricted to defined media/feed as well as amino acid auxotrophic organisms.

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For nearly a century, histopathology involved the laborious morphological analyses of tissues stained with broad-spectrum dyes (i.e., eosin to label proteins).

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Background: The brown ghost knifefish (Apteronotus leptorhynchus) is a weakly electric teleost fish of particular interest as a versatile model system for a variety of research areas in neuroscience and biology. The comprehensive information available on the neurophysiology and neuroanatomy of this organism has enabled significant advances in such areas as the study of the neural basis of behavior, the development of adult-born neurons in the central nervous system and their involvement in the regeneration of nervous tissue, as well as brain aging and senescence. Despite substantial scientific interest in this species, no genomic resources are currently available.

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Background: Hydrogen/deuterium exchange (HDX) coupled to mass spectrometry permits analysis of structure, dynamics, and molecular interactions of proteins. HDX mass spectrometry is confounded by deuterium exchange-associated peaks overlapping with peaks of heavy, natural abundance isotopes, such as carbon-13. Recent studies demonstrated that high-performance mass spectrometers could resolve isotopic fine structure and eliminate this peak overlap, allowing direct detection and quantification of deuterium incorporation.

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Pilot Project #1--the identification and characterization of human histone H4 proteoforms by top-down MS--is the first project launched by the Consortium for Top-Down Proteomics (CTDP) to refine and validate top-down MS. Within the initial results from seven participating laboratories, all reported the probability-based identification of human histone H4 (UniProt accession P62805) with expectation values ranging from 10(-13) to 10(-105). Regarding characterization, a total of 74 proteoforms were reported, with 21 done so unambiguously; one new PTM, K79ac, was identified.

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Bottom-up MS studies typically employ a reduction and alkylation step that eliminates a class of PTM, S-thiolation. Given that molecular oxygen can mediate S-thiolation from reduced thiols, which are abundant in the reducing intracellular milieu, we investigated the possibility that some S-thiolation modifications are artifacts of protein preparation. Cu/Zn-superoxide dismutase (SOD1) was chosen for this case study as it has a reactive surface cysteine residue, which is readily cysteinylated in vitro.

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Background: Neuropeptides are a diverse category of signaling molecules in the nervous system regulating a variety of processes including food intake, social behavior, circadian rhythms, learning, and memory. Both the identification and functional characterization of specific neuropeptides are ongoing fields of research. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of nervous tissues from a variety of organisms allows direct detection and identification of neuropeptides.

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Reactive oxygen species (ROS) are cytotoxic. To remove ROS, cells have developed ROS-specific defense mechanisms, including the enzyme Cu/Zn superoxide dismutase (SOD1), which catalyzes the disproportionation of superoxide anions into molecular oxygen and hydrogen peroxide. Although hydrogen peroxide is less reactive than superoxide, it is still capable of oxidizing, unfolding, and inactivating SOD1, at least in vitro.

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Virtual high throughput screening (VHTS) was performed to assess possible interactions which might occur between commercially available triphenylphosphonium (TPP) cations and estrogen receptor alpha (ERalpha) that could be exploited to design novel ERalpha modulators. One application of TPP cations is for delivering bioactive molecules to targets in mitochondria as the large membrane potential of mitochondria leads cations to accumulate inside them. The estrogen receptors (ERs) alpha and beta, normally activated by the endogenous hormone 17beta-estradiol, are responsible for controlling transcription of nuclear DNA necessary for human development and reproduction.

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