Search

Abstract Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent response mechanisms which can be challenging to establish. We installed thiol-reactive derivatives of the naphthalene-based fluorophore Prodan into bacterial periplasmic glucose-binding proteins. Glucose binding elicited paired color exchanges in the excited and ground states of these conjugates. X-ray structures and mutagenesis studies established that glucose-mediated color switching arises from steric interactions that couple protein conformational changes to twisting of the Prodan carbonyl relative to its naphthalene plane. Mutations of residues contacting the carbonyl can optimize color switching by altering fluorophore conformational equilibria in the apo and glucose-bound proteins. A commonly accepted view is that Prodan derivatives report on protein conformations via solvatochromic effects due to changes in the dielectric of their local environment. Here we show that instead Prodan carbonyl twisting controls color switching. These insights enable structure-based biosensor design by coupling ligand-mediated protein conformational changes to internal chromophore twists through specific steric interactions between fluorophore and protein.

Abstract Background Mental health problems among children and adolescents are a growing public health concern. Self‐report questionnaires are pivotal for screening and early detection of mental health issues. We evaluate the psychometric properties and provide norm data of the 25‐item child and 25‐item parent‐report versions of the Revised Child Anxiety and Depression Scale (RCADS). Methods A random probability sample of 29,000 children and adolescents (ages 4–17) from the Swedish population registry was invited. Data collection occurred from September 2021 to January 2022, accompanied by one postal and four SMS reminders. Results Participants (N = 7045, 48.98% girls) demonstrate that the RCADS‐25 possesses relatively sound psychometric properties, albeit that the child‐report version assessed with children and adolescents aged 8 to 17 years rendered relatively better psychometric properties (e.g., ω = 0.87–0.92, CFI = 0.89) compared with the parent‐report version and the children 4 to 7 years old (e.g., ω = 0.72–0.82, CFI = 0.84). Conclusion The RCADS‐25 instruments may be used as an effective instrument for the initial assessment of anxiety and depression in children and adolescents in Sweden.

BackgroundThere is overwhelming evidence for the preventive effects of regular physical activity and healthy eating habits on the risk for developing a non-communicable disease (NCD). Increasing attention has been paid to community-wide approaches in the battle against NCDs. Communities can create supportive policies, modify physical environments, and foster local stakeholder engagement through intersectoral collaboration to encourage communities to support healthy lifestyles. The Pep initiative is based on intersectoral community-wide collaboration among Sweden’s municipalities. Primary targets are municipality professionals who work with children and young people as well as parents of children

Abstract Background The Lifestyle-integrated Functional Exercise (LiFE) program is an effective but resource-intensive fall prevention program delivered one-to-one in participants’ homes. A recently developed group-based LiFE (gLiFE) could enhance large-scale implementability and decrease resource intensity. The aim of this qualitative focus group study is to compare participants’ experiences regarding acceptability of gLiFE vs LiFE. Methods Programs were delivered in seven group sessions (gLiFE) or seven individual home visits (LiFE) within a multi-center, randomized non-inferiority trial. Four structured focus group discussions (90–100 min duration; one per format and study site) on content, structure, and subjective effects of gLiFE and LiFE were conducted. Qualitative content analysis using the method of inductive category formation by Mayring was applied for data analysis. Coding was managed using NVivo. Results In both formats, participants (N = 30, 22 women, ngLiFE = 15, nLiFE = 15, mean age 78.8 ± 6.6 years) were positive about content, structure, and support received by trainers. Participants reflected on advantages of both formats: the social aspects of learning the program in a peer group (gLiFE), and benefits of learning the program at home (LiFE). In gLiFE, some difficulties with the implementation of activities were reported. In both formats, the majority of participants reported positive outcomes and successful implementation of new movement habits. Conclusion This is the first study to examine participants’ views on and experiences with gLiFE and LiFE, revealing strengths and limitations of both formats that can be used for program refinement. Both formats were highly acceptable to participants, suggesting that gLiFE may have similar potential to be adopted by adults aged 70 years and older compared to LiFE. Trial registration ClinicalTrials.gov , NCT03462654 . Registered on March 12, 2018.

Abstract Background Smoking and aberrant epithelial responses are risk factors for lung cancer as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In these conditions, disease progression is associated with epithelial damage and fragility, airway remodelling and sub-epithelial fibrosis. The aim of this study was to assess the acute effects of cigarette smoke on epithelial cell phenotype and pro-fibrotic responses in vitro and in vivo. Results Apoptosis was significantly greater in unstimulated cells from COPD patients compared to control, but proliferation and CXCL8 release were not different. Cigarette smoke dose-dependently induced apoptosis, proliferation and CXCL8 release with normal epithelial cells being more responsive than COPD patient derived cells. Cigarette smoke did not induce epithelial-mesenchymal transition. In vivo, cigarette smoke exposure promoted epithelial apoptosis and proliferation. Moreover, mimicking a virus-induced exacerbation by exposing to mice to poly I:C, exaggerated the inflammatory responses, whereas expression of remodelling genes was similar in both. Conclusions Collectively, these data indicate that cigarette smoke promotes epithelial cell activation and hyperplasia, but a secondary stimulus is required for the remodelling phenotype associated with COPD.

Jakob Malin,1,2 Amol C Shetty,3 Sean Daugherty,3 Erik PH de Leeuw,1,2 1Institute of Human Virology, 2Department of Biochemistry and Molecular Biology, 3Institute for Genome Sciences, University of Maryland Baltimore School of Medicine, Baltimore, MD, USA Abstract: We have recently identified small molecule compounds that act as binders of Lipid II, an essential precursor of bacterial cell wall biosynthesis. Lipid II comprised a hydrophilic head group that includes a peptidoglycan subunit composed of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) coupled to a short pentapeptide moiety. This headgroup is coupled to a long bactoprenol chain via a pyrophosphate group. Here, we report on the cell wall activity relationship of dimethyl-3-methyl(phenyl)amino-ethenylcyclohexylidene-propenyl-3-ethyl-1,3-benzothiazolium iodide (compound 5107930) obtained by functional and genetic analyses. Our results indicate that compounds bind to Lipid II and cause specific upregulation of the vancomycin-resistance associated gene vraX. vraX is implicated in the cell wall stress stimulon that confers glycopeptide resistance. Our small molecule Lipid II inhibitor retained activity against strains of Staphylococcus aureus mutated in genes encoding the cell wall stress stimulon. This suggests the feasibility of developing this new scaffold as a therapeutic agent in view of increasing glycopeptide resistance. Keywords: defensin, Lipid II, antibiotics, bacterial membrane, vancomycin

Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF).

This is among the first longitudinal studies to report student attitudes across 4 yr of a university program. We found that the attitudes of students in biology become significantly more expert-like from the first year to the fourth year of the program, that is, there was a significant positive shift in students' overall percent favorable scores from 64.5 to 72%, as opposed to the expert response, which averaged 90%. There was a significant positive shift for the real world connection category (78-85%), the enjoyment (personal interest) category (74-82%), and the conceptual connections/memorization category (66-74%). Moreover, there was a significant correlation between students' overall percent favorable scores and performance (cumulative grade point average) at the end, but not at the beginning, of the fourth year, with high-performing students having significantly more expert-like attitudes than low-performing students. The correlation between percent favorable score and performance was the strongest for the problem solving: synthesis and application category, in which the highest-performing students finished their fourth year with 90% favorable compared with 35% favorable for the lowest-performing students. A comparison of these results with previously reported results and their implications for teaching are discussed.

Abstract: Exotic species are often planted for restoration or to enhance production. Populations that expand from plantings may undergo selection in directions that differ from those produced by artificial selection [...]

Abstract Sea ice is a key element of the global Earth system, with a major impact on global climate and regional weather. Unfortunately, accurate sea ice modeling is challenging due to the diversity and complexity of underlying physics happening there, and a relative lack of ground truth observations. This is especially true for the Marginal Ice Zone (MIZ), which is the area where sea ice is affected by incoming ocean waves. Waves contribute to making the area dynamic, and due to the low survival time of the buoys deployed there, the MIZ is challenging to monitor. In 2022-2023, we released 79 OpenMetBuoys (OMBs) around Svalbard, both in the MIZ and the ocean immediately outside of it. OMBs are affordable enough to be deployed in large number, and gather information about drift (GNSS position) and waves (1-dimensional elevation spectrum). This provides data focusing on the area around Svalbard with unprecedented spatial and temporal resolution. We expect that this will allow to perform validation and calibration of ice models and remote sensing algorithms.

The science and technology of radio receives little attention in contemporary education. This article discusses ways to explore the basic operating principles of radio. (Contains 4 figures, 3 footnotes, and 2 notes.)

Abstract Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer’s disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65–75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations. The results showed that NfL was negatively associated with working memory, and that NfL interacted with moderate-to-vigorous physical activity in its association with episodic memory. The study has thereby demonstrated the potential of neurodegenerative plasma markers for improving understanding of normative cognitive aging and encourages future research to test the hypothesis that high levels of NfL, indicative of white matter pathology, limit the beneficial effect of physical activity on episodic memory in healthy aging.