This study describes the process of designing and developing the user interface of a digital solution aiming to promote physical and cognitive training (DanceMove) and testing for its usability by community-dwelling older adults. This study is subdivided into four phases: (i) concept and ideation, (ii) design and development of the prototype, (iii) testing of the functional mock-ups, and (iv) testing of the prototype in the laboratory and in the real context of use. Through the different phases of the study technological and healthcare professionals and users were involved.
View Article and Find Full Text PDFResearch suggests that nursing facility structural characteristics are important contributors toward residents' quality of care. We use 2021 data from 220 Maryland nursing facilities to examine associations between two different quality-of-care metrics: family satisfaction and Care Compare five-star quality ratings. We used descriptive statistics to explore differences in quality metrics across facility ownership (for-profit vs.
View Article and Find Full Text PDFB cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.
View Article and Find Full Text PDFRecent advances in tissue engineering have been remarkable, yet the precise control of cellular behavior in 2D and 3D cultures remains challenging. One approach to address this limitation is to genomically engineer optogenetic control of cellular processes into tissues using gene switches that can operate with only a few genomic copies. Here, we implement blue and red light-responsive gene switches to engineer genomically stable two- and three-dimensional mammalian tissue models.
View Article and Find Full Text PDFmetabolic systems allow the reconstitution of natural and new-to-nature pathways outside of their cellular context and are of increasing interest in bottom-up synthetic biology, cell-free manufacturing, and metabolic engineering. Yet, the analysis of the activity of such networks is very often restricted by time- and cost-intensive methods. To overcome these limitations, we sought to develop an transcription (IVT)-based biosensing workflow that is compatible with the complex conditions of metabolism, such as the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle, a 27-component metabolic system that converts CO into glycolate.
View Article and Find Full Text PDFSchizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals.
View Article and Find Full Text PDFOne of the hallmarks of living organisms is their capacity for self-organization and regeneration, which requires a tight integration of metabolic and genetic networks. We sought to construct a linked metabolic and genetic network in vitro that shows such lifelike behavior outside of a cellular context and generates its own building blocks from nonliving matter. We integrated the metabolism of the crotonyl-CoA/ethyl-malonyl-CoA/hydroxybutyryl-CoA cycle with cell-free protein synthesis using recombinant elements.
View Article and Find Full Text PDFUnlabelled: is the primary etiological agent of aspergillosis. Here, we show that the host defense peptide mimetic brilacidin (BRI) can potentiate ibrexafungerp (IBX) against clinical isolates of . BRI + IBX can inhibit the growth of voriconazole- and caspofungin-resistant clinical isolates.
View Article and Find Full Text PDFIndividuals diagnosed with schizophrenia (SZ) demonstrate difficulty distinguishing between internally and externally generated stimuli. These aberrations in "source monitoring" have been theorized as contributing to symptoms of the disorder, including hallucinations and delusions. Altered connectivity within the default mode network (DMN) of the brain has been proposed as a mechanism through which discrimination between self-generated and externally generated events is disrupted.
View Article and Find Full Text PDFUnlabelled: causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against .
View Article and Find Full Text PDFIntroduction: Surgical oncology patients have a high symptom burden and increased risk of morbidity. The aim of palliative care is to evaluate and treat the patient in a holistic manner focusing on the unique attributes of each patient. This goal-concordant approach could help surgical patients cope with the stress and uncertainty that often accompany serious illness and surgery, improving overall outcomes.
View Article and Find Full Text PDFHypothesis: Nonionic surfactants can counter the deleterious effect that anionic surfactants have on proteins, where the folded states are retrieved from a previously unfolded state. However, further studies are required to refine our understanding of the underlying mechanism of the refolding process. While interactions between nonionic surfactants and tightly folded proteins are not anticipated, we hypothesized that intermediate stages of surfactant-induced unfolding could define new interaction mechanisms by which nonionic surfactants can further alter protein conformation.
View Article and Find Full Text PDFWe have previously described a new series of selective and orally available galectin-1 inhibitors resulting in the thiazole-containing glycomimetic GB1490. Here, we show that the introduction of polar substituents to the thiazole ring results in galectin-1-specific compounds with low nM affinities. X-ray structural analysis of a new ligand-galectin-1 complex shows changes in the binding mode and ligand-protein hydrogen bond interactions compared to the GB1490-galectin-1 complex.
View Article and Find Full Text PDFBackground: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects.
Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition.
is the primary etiological agent of aspergillosis. Here, we show that the host defense peptide mimetic, brilacidin (BRI) can potentiate ibrexafungerp (IBX) against clinical isolates of . CAS-resistant strains with mutations in that encodes the 1,3-β-D-glucan synthase are not IBX-resistant and BRI+IBX can inhibit their growth.
View Article and Find Full Text PDFObjective: Borderline and antisocial personality disorders are characterized by pervasive psychosocial impairment, disproportionate criminal justice involvement, and high mental health care utilization. Although some evidence suggests that systemic bias may contribute to demographic inequities in criminal justice and mental health care among persons experiencing these mental health conditions, no research to date has explicitly examined such differences.
Hypotheses: Women and White persons would be more likely to endorse internalizing symptoms and have a more extensive history of mental health service utilization, whereas men, persons from minoritized racial groups, and persons identifying as Hispanic/Latino would be more likely to endorse externalizing symptoms and have more extensive histories of involvement with the criminal justice system.
Oscillations serve a critical role in organizing biological systems. In the brain, oscillatory coupling is a fundamental mechanism of communication. The possibility that neural oscillations interact directly with slower physiological rhythms (e.
View Article and Find Full Text PDFProtein-ligand complex formation is fundamental to biological function. A central question is whether proteins spontaneously adopt binding-competent conformations to which ligands bind conformational selection (CS) or whether ligands induce the binding-competent conformation induced fit (IF). Here, we resolve the CS and IF binding pathways by characterizing protein conformational dynamics over a wide range of ligand concentrations using NMR relaxation dispersion.
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