The traditional external standard calibration method (EC) is automated and simplified using a four-port switching valve (SV4) and a multi-signal approach that enables the generation of several calibration points from a single calibration solution. The SV4-EC method is applied to inductively coupled plasma optical emission spectrometry (ICP-OES) and is based on gradient dilution taking place within the instrument's sample introduction tubing. Both the calibration solution and the samples are diluted by a blank solution containing an internal standard species.
View Article and Find Full Text PDFIn an animal model of compulsive drug use, a subset of rats continues to self-administer cocaine despite footshock consequences and is considered punishment resistant. We recently found that punishment resistance is associated with habits that persist under conditions that typically encourage a transition to goal-directed control. Given that random ratio (RR) and random interval (RI) schedules of reinforcement influence whether responding is goal-directed or habitual, we investigated the influence of these schedules on punishment resistance for cocaine or food.
View Article and Find Full Text PDFUnlabelled: Phagosomal lysis is a key aspect of mycobacterial infection of host macrophages. Acetylation is a protein modification mediated enzymatically by N-acetyltransferases (NATs) that impacts bacterial pathogenesis and physiology. To identify NATs required for lytic activity, we leveraged a nontubercular pathogen and an established model for hemolysis is a proxy for phagolytic activity.
View Article and Find Full Text PDFCalibration by Proxy (CbPx) is a matrix-matched calibration method that utilizes multiple internal standard species to build a calibration curve. The technique requires only two solutions: solution 1 containing a sample solution and a suite of internal standards at known concentrations, and solution 2 identical to solution 1, plus an aliquot of a standard containing all analytes and the internal standards at the same concentration. The calibration curve is prepared by plotting the signal measured for each internal standard in solution 1 divided by the signal arising due to the aliquot of internal standard added to solution 2 on the -axis.
View Article and Find Full Text PDFHypermutated proviruses, which arise in a single HIV replication cycle when host antiviral APOBEC3 proteins introduce extensive G-to-A mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). But, the within-host evolutionary origins of hypermutated sequences are incompletely understood because phylogenetic inference algorithms, which assume that mutations gradually accumulate over generations, incorrectly reconstruct their ancestor-descendant relationships. Using > 1400 longitudinal single-genome-amplified HIV sequences isolated from six women over a median 18 years of follow-up - including plasma HIV RNA sequences collected over a median 9 years between seroconversion and ART initiation, and > 500 proviruses isolated over a median 9 years on ART - we evaluated three approaches for removing hypermutation from nucleotide alignments.
View Article and Find Full Text PDFAddiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking.
View Article and Find Full Text PDFThe mycobacterial cell envelope is a major virulence determinant in pathogenic mycobacteria. Specific outer lipids play roles in pathogenesis, modulating the immune system and promoting the secretion of virulence factors. ESX-1 (ESAT-6 system-1) is a conserved protein secretion system required for mycobacterial pathogenesis.
View Article and Find Full Text PDFIntroduction: Coronavirus disease 2019 (COVID-19) and the resulting societal reaction presented new challenges to the medical community by limiting patient access to care in 2020 and 2021. The Navy Postgraduate Dental School (NPDS) oral and maxillofacial pathology biopsy service is dependent on in-office physician or dentist appointments and patient biopsies. The purpose of this study was to understand the regulatory and societal impacts of COVID-19 restrictions on biopsy service submissions by assessing NPDS biopsy submission quantities and disease distribution.
View Article and Find Full Text PDFThe mycobacterial cell envelope is a major virulence determinant in pathogenic mycobacteria. Specific outer lipids play roles in pathogenesis, modulating the immune system and promoting the secretion of virulence factors. ESX-1 (ESAT-6 system-1) is a conserved protein secretion system required for mycobacterial pathogenesis (1, 2).
View Article and Find Full Text PDFTo address the history of unethical research and community distrust in research among Native Hawaiian and Pacific Islander communities, we developed the "Community 101 for Researchers" training program, which was launched in 2014 to enhance the capacity of researchers to engage in ethical community-engaged research. The purpose of this paper is to describe the development of this training program as well as its reach and feedback from participants. The Community 101 training program is a self-paced, 2-h online training program featuring community-engaged researchers from the University of Hawai'i and their longstanding community partners.
View Article and Find Full Text PDFWithin-host HIV populations continually diversify during untreated infection, and this diversity persists within infected cell reservoirs during antiretroviral therapy (ART). Achieving a better understanding of on-ART proviral evolutionary dynamics, and a better appreciation of how the overall persisting pool of (largely genetically defective) proviruses differs from the much smaller replication-competent HIV reservoir, is critical to HIV cure efforts. We reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study who experienced HIV seroconversion, and used these data to characterize the diversity, lineage origins, and ages of proviral sequences sampled longitudinally up to 12 years on ART.
View Article and Find Full Text PDFShoulder sores predominantly arise in breeding sows and often result in untimely culling. Reported prevalence rates vary significantly, spanning between 5% and 50% depending upon the type of crate flooring inside a farm, the animal's body condition, or an existing injury that causes lameness. These lesions represent not only a welfare concern but also have an economic impact due to the labor needed for treatment and medication.
View Article and Find Full Text PDFCharacterizing the human immunodeficiency virus (HIV) reservoir that endures despite antiretroviral therapy (ART) is critical to cure efforts. We observed that the oldest proviruses persisting during ART were exclusively defective, while intact proviruses (and rebound HIV) dated to nearer ART initiation. This helps explain why studies that sampled sub-genomic proviruses on-ART (which are largely defective) routinely found sequences dating to early infection, whereas those that sampled replication-competent HIV found almost none.
View Article and Find Full Text PDFN-terminal acetylation is a protein modification that broadly impacts basic cellular function and disease in higher organisms. Although bacterial proteins are N-terminally acetylated, little is understood how N-terminal acetylation impacts bacterial physiology and pathogenesis. Mycobacterial pathogens cause acute and chronic disease in humans and in animals.
View Article and Find Full Text PDFWithin-host HIV populations continually diversify during untreated infection, and members of these diverse forms persist within infected cell reservoirs, even during antiretroviral therapy (ART). Characterizing the diverse viral sequences that persist during ART is critical to HIV cure efforts, but our knowledge of on-ART proviral evolutionary dynamics remains incomplete, as does our understanding of the differences between the overall pool of persisting proviral DNA (which is largely genetically defective) and the subset of intact HIV sequences capable of reactivating. Here, we reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study (WIHS) who experienced HIV seroconversion.
View Article and Find Full Text PDFHuman immunodeficiency virus 1 (HIV) proviruses archived in the persistent reservoir currently pose the greatest obstacle to HIV cure due to their evasion of combined antiretroviral therapy and ability to reseed HIV infection. Understanding the dynamics of the HIV persistent reservoir is imperative for discovering a durable HIV cure. Here, we explore Bayesian methods using the software BEAST2 to estimate HIV proviral integration dates.
View Article and Find Full Text PDFAddiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking.
View Article and Find Full Text PDFObjectives: We aimed to investigate the effects of directly manipulating response style to simulated voice hearing on emotional and cognitive outcomes in a non-clinical population.
Design: A between-subjects design with one independent variable, response style (with two levels: mindful acceptance vs attentional avoidance). The dependent variables were subjective distress and anxiety (primary outcomes) and performance on a sustained attention task (secondary outcomes).
In order to cure HIV, we need to better understand the within-host evolutionary origins of the small reservoir of genome-intact proviruses that persists within infected cells during antiretroviral therapy (ART). Most prior studies on reservoir evolutionary dynamics however did not discriminate genome-intact proviruses from the vast background of defective ones. We reconstructed within-host pre-ART HIV evolutionary histories in six individuals and leveraged this information to infer the ages of intact and defective proviruses sampled after an average >9 years on ART, along with the ages of rebound and low-level/isolated viremia occurring during this time.
View Article and Find Full Text PDFN-terminal protein acetylation is a ubiquitous post-translational modification that broadly impacts diverse cellular processes in higher organisms. Bacterial proteins are also N-terminally acetylated, but the mechanisms and consequences of this modification in bacteria are poorly understood. We previously quantified widespread N-terminal protein acetylation in pathogenic mycobacteria (C.
View Article and Find Full Text PDFHabits are theorized to play a key role in compulsive cocaine seeking, yet there is limited methodology for assessing habitual responding for intravenous (IV) cocaine. We developed a novel outcome devaluation procedure to discriminate goal-directed from habitual responding in cocaine-seeking rats. This procedure elicits devaluation temporarily and requires no additional training, allowing repeated testing at different time points.
View Article and Find Full Text PDFThe lung is an understudied site of HIV persistence. We isolated 898 subgenomic proviral sequences (nef) by single-genome approaches from blood and lung from nine individuals on long-term suppressive antiretroviral therapy (ART), and characterized genetic diversity and compartmentalization using formal tests. Consistent with clonal expansion as a driver of HIV persistence, identical sequences comprised between 8% to 86% of within-host datasets, though their location (blood vs.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
December 2022
Raman spectroscopy (RS) was used to identify and quantify different nitrogen species in fertilizers. This is a fast and inexpensive method that requires no extensive sample preparation. Urea and nitrate were determined at 1000 and 1045 cm, respectively.
View Article and Find Full Text PDFACS Appl Bio Mater
February 2021
Due to its attractive mechanical properties and biocompatibility, poly(dimethyl)siloxane (PDMS) is widely used in the fabrication of biomedical materials. On the other hand, PDMS is also prone to adsorption of both proteins and bacteria, making PDMS implants susceptible to infection. Herein, we examine the use of durably cross-linked zwitterionic coatings for PDMS surfaces to mitigate bacterial adhesion.
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