Intracellular uptake of chitosan nanoparticle-based vaccines

Particle-based delivery systems are a promising approach to enhance antigen-specific immunity for use in vaccines. Chitosan, a natural polysaccharide derived from the exoskeletons of crustaceans, shows great potential as a vaccine carrier due to its favorable properties as a biomaterial, including biocompatibility and biodegradability. In this study, the intracellular uptake of chitosan nanoparticles is explored and compared to that of other commonly used particle-based delivery vehicles, such as poly (lactic-co-glycolic acid) (PLGA). Fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) was used as a model protein antigen and encapsulated in both chitosan particles via precipitation-coacervation and PLGA particles via double emulsion solvent evaporation. Fluorescence microscopy images showed that, when co-incubated with dendritic cells, all cells were found to internalize FITC-BSA-chitosan nanoparticles. Additionally, punctate fluorescence in the cytoplasm indicated that at least some of the particles were within endosomes at early (less than 24 hour) time points. Furthermore, flow cytometry results showed chitosan particles to have a greater uptake (74%) by dendritic cells compared to PLGA particles (32%) or soluble protein (43%) at early time points (1 hour)

Altered Emotional Interference Processing in the Amygdala and Insula in Women with Post-Traumatic Stress Disorder

Background: Post-Traumatic Stress Disorder (PTSD) is characterized by distinct behavioral and physiological changes. Given the significant impairments related to PTSD, examination of the biological underpinnings is crucial to the development of theoretical models and improved treatments of PTSD. Methods: We used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 32 women with PTSD (based on an interpersonal trauma) and 21 matched controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli. Results: Compared to controls, patients with PTSD showed hyperactivity in several brain regions, including the amygdala, insula, as well as dorsal lateral and ventral PFC regions. Conclusions: These results are consistent with previous studies that have higher amygdala and insular activation in PTSD subjects. However, inhibition of suppression of PFC regions is inconsistent with the fear circuitry model hypothesized by prior research. We suggest that the specific emotional conflict task used appears to target implicit or automatic emotional regulation instead of explicit or effortful emotional regulation. This is particularly relevant as it posited that emotional regulatory difficulties in anxiety disorders such as PTSD appear to occur in implicit forms of emotion regulation

Variable responses of human and non-human primate gut microbiomes to a Western diet

BACKGROUND: The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. RESULTS: Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. CONCLUSIONS: These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.P40 OD010965 - NIH HHS; P40 RR019963 - NCRR NIH HHS; P51 OD011132 - NIH HHS; R01 RR016300 - NCRR NIH HHS; 5R01RR016300 - NCRR NIH HH

Discovery and genotyping of structural variation from long-read haploid genome sequence data

In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that &gt;89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF &gt; 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.</jats:p

A Structural Atlas of the Developing Zebrafish Telencephalon Based on Spatially-Restricted Transgene Expression

Zebrafish telencephalon acquires an everted morphology by a two-step process that occurs from 1 to 5 days post-fertilization (dpf). Little is known about how this process affects the positioning of discrete telencephalic cell populations, hindering our understanding of how eversion impacts telencephalic structural organization. In this study, we characterize the neurochemistry, cycle state and morphology of an EGFP positive (+) cell population in the telencephalon of Et(gata2:EGFP)bi105 transgenic fish during eversion and up to 20dpf. We map the transgene insertion to the early-growth-response-gene-3 (egr3) locus and show that EGFP expression recapitulates endogenous egr3 expression throughout much of the pallial telencephalon. Using the gata2:EGFP bi105 transgene, in combination with other well-characterized transgenes and structural markers, we track the development of various cell populations in the zebrafish telencephalon as it undergoes the morphological changes underlying eversion. These datasets were registered to reference brains to form an atlas of telencephalic development at key stages of the eversion process (1dpf, 2dpf, and 5dpf) and compared to expression in adulthood. Finally, we registered gata2:EGFPbi105 expression to the Zebrafish Brain Browser 6dpf reference brain (ZBB, see Marquart et al., 2015, 2017; Tabor et al., 2019), to allow comparison of this expression pattern with anatomical data already in ZBB

Children's perspectives on neighbourhood barriers and enablers to active school travel: A participatory mapping study: Children's perspectives on active school travel

Children today are spending more sedentary time indoors than time playing and being active outdoors. The daily journey to and from school represents a valuable opportunity for children to be physically active through active school travel. The majority of research on children's active school travel omits children from the research process even though children interpret their environments in fundamentally different ways than adults. Our research uses innovative participatory mapping and qualitative GIS methods to examine how children's perceptions of their environments influence their school journey experiences. Through our thematic analysis of 25 map‐based focus groups, we identified three main themes characterizing barriers and enablers to active school travel: safety‐related, material, and affective features. By positioning children as experts of their environments in our participatory methodology, our findings provide an important counterpoint to the adultist privilege characterizing the majority of research on children's active school travel. Environmental features that mattered for children's school journeys took on multiple meanings in their eyes, demonstrating that children's perspectives must be engaged to inform interventions to promote active school travel. We thus argue that identifying barriers and enablers to active school travel for children requires engaging children's views

Every Day a New Discovery: Share History

This project aims to strengthen the sense of community and shared identity within VCU through a historical understanding of the interconnectedness of the formerly standalone institutions (i.e., the Medical College of Virginia and the Richmond Professional Institute). Additionally, it will seek to cultivate a sense of pride and greater esteem for our community by facilitating knowledge of the significant contributions to innovation that were developed at VCU

Socioeconomic position and use of health care in the last year of life: a systematic review and meta-analysis

BACKGROUND: Low socioeconomic position (SEP) is recognized as a risk factor for worse health outcomes. How socioeconomic factors influence end-of-life care, and the magnitude of their effect, is not understood. This review aimed to synthesise and quantify the associations between measures of SEP and use of healthcare in the last year of life. METHODS AND FINDINGS: MEDLINE, EMBASE, PsycINFO, CINAHL, and ASSIA databases were searched without language restrictions from inception to 1 February 2019. We included empirical observational studies from high-income countries reporting an association between SEP (e.g., income, education, occupation, private medical insurance status, housing tenure, housing quality, or area-based deprivation) and place of death, plus use of acute care, specialist and nonspecialist end-of-life care, advance care planning, and quality of care in the last year of life. Methodological quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). The overall strength and direction of associations was summarised, and where sufficient comparable data were available, adjusted odds ratios (ORs) were pooled and dose-response meta-regression performed. A total of 209 studies were included (mean NOS quality score of 4.8); 112 high- to medium-quality observational studies were used in the meta-synthesis and meta-analysis (53.5% from North America, 31.0% from Europe, 8.5% from Australia, and 7.0% from Asia). Compared to people living in the least deprived neighbourhoods, people living in the most deprived neighbourhoods were more likely to die in hospital versus home (OR 1.30, 95% CI 1.23-1.38, p < 0.001), to receive acute hospital-based care in the last 3 months of life (OR 1.16, 95% CI 1.08-1.25, p < 0.001), and to not receive specialist palliative care (OR 1.13, 95% CI 1.07-1.19, p < 0.001). For every quintile increase in area deprivation, hospital versus home death was more likely (OR 1.07, 95% CI 1.05-1.08, p < 0.001), and not receiving specialist palliative care was more likely (OR 1.03, 95% CI 1.02-1.05, p < 0.001). Compared to the most educated (qualifications or years of education completed), the least educated people were more likely to not receive specialist palliative care (OR 1.26, 95% CI 1.07-1.49, p = 0.005). The observational nature of the studies included and the focus on high-income countries limit the conclusions of this review. CONCLUSIONS: In high-income countries, low SEP is a risk factor for hospital death as well as other indicators of potentially poor-quality end-of-life care, with evidence of a dose response indicating that inequality persists across the social stratum. These findings should stimulate widespread efforts to reduce socioeconomic inequality towards the end of life

The Concussion Challenge Assessment: Development and reliability of a novel gross motor assessment tool for paediatric concussion

AimsThe aim of this study was to develop a gross motor performance clinical assessment tool, the Concussion Challenge Assessment (CCA), for paediatric concussion populations.MethodsAn expert panel evaluated tasks from the Acquired Brain Injury Challenge Assessment to determine relevant tasks for a paediatric concussion population. These tasks were administered to a convenience sample of 854 healthy youth. An analysis of the response options for each task, considering task difficulty, was performed. The test–retest reliability of each task was considered to finalise the tool.ResultsThe Acquired Brain Injury Challenge Assessment was reduced to six tasks (three coordination, two speed and agility, and one strength) to create the CCA. Population-specific 4-point response options were generated, which, upon examination of task difficulty, were revised as 5-point response sets to better capture performance differences. The test–retest reliability results led to acceptance of all six: three performance tasks and three exertion tasks.ConclusionThis development of the CCA is an important step in creating a gross motor performance assessment tool that can assist in the determination of when youth are able to safely return to activity following a concussion

The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch

SummaryAtopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the “atopic march.” Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways