Synthesizing Bismuth Nanoparticles

Gold nanoparticles (AuNP) have become the face of modern medicine, with promising future applications as dual-purpose diagnostic and radiation therapy (theragnostic) agents. Contrarily, bismuth nanoparticles (BiNPs) have been proposed as a cost-efficient, biodegradable alternative to AuNPs. However, BiNP research is in its infancy. This proposal aims to develop methods for the size, shape-controlled, and neutral and positively charged synthesis of BiNPs with amphiphilic ligands. Overall, this project is to provide fundamental research into BiNP synthesis with therapeutically valuable ligands and to eventually see how BiNPs interact with biomolecules, as none have been studied with proteins

Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort

Background: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short- term or long-term composition and function of the gut microbiome. Results: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence or absence of species identified in their gut microbiome. Thirty-two genera were identified as statistically different in the gut microbiome sequenced between BF and FF infants. Furthermore, the computational workflow identified 371 bacterial genes that were statistically different between the BF and FF cohorts in abundance. Only seven genes were lower in abundance (or absent) in the FF cohort compared to the BF cohort, including CRISPR/Cas9; whereas, the remaining candidates, including autotransporter adhesins, were higher in abundance in the FF cohort compared to BF cohort. Conclusions: These studies demonstrated that FF infants have, at an early age, a significantly different gut microbiome with potential implications for function of the fecal microbiota. Interactions between the fecal microbiota and host hinted at here have been linked to numerous diseases. Determining whether these non- abundant or more abundant genes have biological consequence related to infant feeding may aid in under- standing the adult gut microbiome, and the pathogenesis of obesity

A theory-based framework for understanding the establishment, persistence, and diffusion of community-based conservation

Over decades, biodiversity conservation researchers and practitioners have developed theories and conceptual frameworks to inform the planning, implementation, and evaluation of community-based conservation (CBC). While a diversity of mechanisms for understanding and supporting CBC has helped tailor approaches to local needs and conditions, the absence of a unified lens to understand CBC has limited the capacity for integrating foundational theory into practice more systemically, and for learning across different projects, stakeholders, and institutions. We introduce a theory-based framework called “the CBC framework” that draws upon three foundational theories from sociology, economics, and political science to understand the establishment, persistence, and diffusion of CBC. Experience applying aspects of the framework within different conservation organizations demonstrates how this integrative approach can provide a gateway for practitioners to engage with social science theory to understand the status and context of CBC interventions and efforts. For practitioners, scientists, evaluators, and strategists, the framework can guide the design of CBC interventions and monitoring and evaluation systems to facilitate theory-based learning and enable evidence-informed decision-making. Approaches like the CBC framework that facilitate collaborative planning, evaluation, and research can help better integrate social science theory in conservation practice while increasing the capacity for conservation scientists, practitioners, and stakeholders to learn together and adaptively manage CBC to deliver positive results for both people and nature

Effect of Duration and Amplitude of Direct Current When Lidocaine is Delivered by Iontophoresis

Dosage for the galvanic stimulation for iontophoresis varies. Clinicians manipulate the duration or the amplitude of the current, but it is not known which is more effective. We compared the anesthetic effect of lidocaine HCL (2%) by manipulating the current parameters on 21 healthy volunteers (age: 21.2 ± 4.2, height 170.7 ± 10.2 cm, mass 82.1 ± 19.2 kg). Three conditions were administered in a random order using a Phoresor II® with 2 mL, 2% lidocaine HCL in an iontophoresis electrode. (1) HASD (40 mA*min): High amplitude (4 mA), short duration (10 min); (2) LALD (40 mA.min): Low amplitude (2 mA), long duration (20 min); (3) Sham condition (0 mA, 20 min). Semmes-Weinstein monofilament (SWM) scores were taken pre and post intervention to measure sensation changes. Two-way ANOVA with repeated measures was used to compare sensation. Both iontophoresis treatments: LALD (4.2 ± 0.32 mm) and HASD (4.2 ± 0.52 mm) significantly increased SWM scores, indicating an increase in anesthesia, compared to the sham condition (3.6 ± 0.06 mm) p \u3c 0.05. Neither LALD nor HASD was more effective and there was no difference in anesthesia with the sham. Lidocaine delivered via iontophoresis reduces cutaneous sensation. However, there was no benefit in either a HASD or LALD treatment

Stigma in the health clinic and implications for PrEP access and use by adolescent girls and young women : conflicting perspectives in South Africa

DATA AVAILABILITY : Data and materials are available on request from Dr. Wendee Wechsberg at [email protected] : Globally, an urgent need exists to expand access to HIV prevention among adolescent girls and young women (AGYW), but the need is particularly acute in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) offers an effective HIV prevention method. In many countries, however, accessing PrEP necessitates that AGYW visit their local health clinic, where they may face access challenges. Some countries have implemented youth-friendly services to reduce certain challenges in local health clinics, but barriers to access persist, including clinic stigma. However, evidence of clinic stigma toward AGYW, particularly with respect to PrEP service delivery, is still limited. This mixed methods study explores stigma toward AGYW seeking clinic services, in particular PrEP, from the perspective of both clinic staff (clinical and nonclinical) and AGYW who seek services at clinic sites in Tshwane province, South Africa. METHODS : Six focus group discussions were conducted with AGYW (43 total participants) and four with clinic staff (42 total participants) and triangulated with survey data with AGYW (n = 449) and clinic staff (n = 130). Thematic analysis was applied to the qualitative data and descriptive statistics were conducted with the survey data. RESULTS : Four common themes emerged across the qualitative and quantitative data and with both AGYW and clinic staff, although with varying degrees of resonance between these two groups. These themes included (1) clinic manifestations of stigma toward AGYW, (2) concerns about providing PrEP services for AGYW, (3) healthcare providers’ identity as mothers, and (4) privacy and breaches of confidentiality. An additional theme identified mainly in the AGYW data pertained to stigma and access to healthcare. CONCLUSION : Evidence is needed to inform strategies for addressing clinic stigma toward AGYW, with the goal of removing barriers to PrEP services for this group. While awareness has increased and progress has been achieved around the provision of comprehensive, youth-friendly sexual and reproductive health services, these programs need to be adapted for the specific concerns of young people seeking PrEP services. Our findings point to the four key areas noted above where programs seeking to address stigma toward AGYW in clinics can tailor their programming.The Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health.http://www.biomedcentral.com/bmcpublichealtham2023Medical Microbiolog

The International Gene Trap Consortium Website: a portal to all publicly available gene trap cell lines in mouse

Gene trapping is a method of generating murine embryonic stem (ES) cell lines containing insertional mutations in known and novel genes. A number of international groups have used this approach to create sizeable public cell line repositories available to the scientific community for the generation of mutant mouse strains. The major gene trapping groups worldwide have recently joined together to centralize access to all publicly available gene trap lines by developing a user-oriented Website for the International Gene Trap Consortium (IGTC). This collaboration provides an impressive public informatics resource comprising ∼45 000 well-characterized ES cell lines which currently represent ∼40% of known mouse genes, all freely available for the creation of knockout mice on a non-collaborative basis. To standardize annotation and provide high confidence data for gene trap lines, a rigorous identification and annotation pipeline has been developed combining genomic localization and transcript alignment of gene trap sequence tags to identify trapped loci. This information is stored in a new bioinformatics database accessible through the IGTC Website interface. The IGTC Website () allows users to browse and search the database for trapped genes, BLAST sequences against gene trap sequence tags, and view trapped genes within biological pathways. In addition, IGTC data have been integrated into major genome browsers and bioinformatics sites to provide users with outside portals for viewing this data. The development of the IGTC Website marks a major advance by providing the research community with the data and tools necessary to effectively use public gene trap resources for the large-scale characterization of mammalian gene function

Inactivation of DltA Modulates Virulence Factor Expression in Streptococcus pyogenes

D-alanylated lipoteichoic acid is a virtually ubiquitous component of gram-positive cell walls. Mutations in the dltABCD operon of numerous species exhibit pleiotropic effects, including reduced virulence, which has been attributed to increased binding of cationic antimicrobial peptides to the more negatively charged cell surface. In this study, we have further investigated the effects that mutating dltA has on virulence factor expression in Streptococcus pyogenes.Isogenic Delta dltA mutants had previously been created in two distinct M1T1 isolates of S. pyogenes. Immunoblots, flow cytometry, and immunofluorescence were used to quantitate M protein levels in these strains, as well as to assess their ability to bind complement. Bacteria were tested for their ability to interact with human PMN and to grow in whole human blood. Message levels for emm, sic, and various regulatory elements were assessed by quantitative RT-PCR. Cell walls of Delta dltA mutants contained much less M protein than cell walls of parent strains and this correlated with reduced levels of emm transcripts, increased deposition of complement, increased association of bacteria with polymorphonuclear leukocytes, and reduced bacterial growth in whole human blood. Transcription of at least one other gene of the mga regulon, sic, which encodes a protein that inactivates antimicrobial peptides, was also dramatically reduced in Delta dltA mutants. Concomitantly, ccpA and rofA were unaffected, while rgg and arcA were up-regulated.This study has identified a novel mechanism for the reduced virulence of dltA mutants of Streptococcus pyogenes in which gene regulatory networks somehow sense and respond to the loss of DltA and lack of D-alanine esterification of lipoteichoic acid. The mechanism remains to be determined, but the data indicate that the status of D-alanine-lipoteichoic acid can significantly influence the expression of at least some streptococcal virulence factors and provide further impetus to targeting the dlt operon of gram-positive pathogens in the search for novel antimicrobial compounds

Condensation of zinc vapor in a supersonic carrier gas

A study of the condensation of a metal vapor in an inert carrier gas is made. Superheated zinc vapor is generated in a hot shot wind tunnel in a helium carrier gas and expanded in a converging-diverging nozzle. Static pressure measurements along the length of the nozzle are made to determine the location of the onset of condensation. A conical nominal Mach 5 (helium) nozzle is employed. The amount of supercooling before the onset of condensation is found to be approximately 430 K, measured along the isentrope over a range of initial zinc mass fractions of .35 to .70 for saturation partial pressures of zinc between 10 psia and 70 psia. The measurements are compared with results of an analysis based on the classical liquid drop model of nucleation. The computed results agree reasonably well with the measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41794/1/10494_2004_Article_BF00382286.pd

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes