Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.

High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function.

A case of rapidly progressive unilateral non-nephrogenic hemorrhagic bullous calciphylaxis responding to systemic sodium thiosulfate therapy.

Background: Calciphylaxis is a rare and life-threatening condition characterized by cutaneous necrosis resulting from vessel calcification and thrombosis. Commonly associated with end-stage renal disease and hyperparathyroidism, calciphylaxis presents as retiform purpura evolving into necrotic eschars.

Case Report: This report details an atypical case of non-nephrogenic unilateral bullous calciphylaxis in a 71-year-old female, emphasizing the importance of considering calciphylaxis in the differential diagnosis of bullous disorders.

The ester-containing prodrug NT-0796 enhances delivery of the NLRP3 inflammasome inhibitor NDT-19795 to monocytic cells expressing carboxylesterase-1.

NT-0796 is an ester prodrug which is metabolized by carboxylesterase-1 (CES1) to yield the carboxylic acid NDT-19795, an inhibitor of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome. When applied to human monocytes/macrophages which express CES1, however, NT-0796 is much more potent at inhibiting NLRP3 inflammasome activation than is NDT-19795. Comparison of the binding of NDT-19795 and NT-0796 in a cell-based NLRP3 target engagement assay confirms that NDT-19795 is the active species.

EventLFM: event camera integrated Fourier light field microscopy for ultrafast 3D imaging.

Ultrafast 3D imaging is indispensable for visualizing complex and dynamic biological processes. Conventional scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product (SBP). Emerging single-shot 3D wide-field techniques offer a promising alternative but are bottlenecked by the synchronous readout constraints of conventional CMOS systems, thus restricting data throughput to maintain high SBP at limited frame rates.

Pharmacological Analysis of NLRP3 Inflammasome Inhibitor Sodium [(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1-pyrazol-4-yl)({[(2)-oxolan-2-yl]methyl})sulfamoyl]azanide in Cellular and Mouse Models of Inflammation Provides a Translational Framework.

Interleukin (IL)-1β is an apex proinflammatory cytokine produced in response to tissue injury and infection. The output of IL-1β from monocytes and macrophages is regulated not only by transcription and translation but also post-translationally. Release of the active cytokine requires activation of inflammasomes, which couple IL-1β post-translational proteolysis with pyroptosis.

Translation, Cross-Cultural Adaptation, and Validation of the Persian Version of the Harris Hip Score.

Background: The Harris hip score (HHS), a self-administered questionnaire, is widely used to evaluate hip pathology affecting health-related quality of life and physical function. This study's purpose was HHS translation to Persian (HHS-Pr) and validation in patients with different hip pathologies.

Methods: Translation and cultural adaptation followed existing guidelines.

Translation, cross-cultural adaptation, and validation of the 10-item spine functional index (SFI-10) in the Brazilians with musculoskeletal spine disorders.

Purpose: To translate and cross-culturally adapt the Spine Functional Index (SFI) into Brazilian Portuguese (SFI-Br) in individuals with musculoskeletal spine disorders.

Methods: Participants (n=194) answered the Numerical Pain Rating Scale (NPRS), 36-item Short-Form Health Survey (SF-36), Roland-Morris Disability Questionnaire for General Pain (RMDQ-g), and SFI-25 incorporating the SFI-10. Structural validity, from confirmatory factor analysis (CFA), used comparative fit index (CFI), Tucker-Lewis index (TLI), root mean square error of approximation (RMSEA), and chi-square/degrees of freedom (DF).

Developing a shortened spine functional index (SFI-10) for patients with sub-acute/chronic spinal disorders: a cross-sectional study.

Background: Brief whole-spine patient-reported outcome measures (PROMs) provide regional solutions and future directions for quantifying functional status, evidence, and effective interventions. The whole-spine regional Spine Functional Index (SFI-25) is used internationally in clinical and scientific contexts to assess general sub-acute/chronic spine populations. However, to improve structural validity and practicality a shortened version is recommended.

Species-specific NLRP3 regulation and its role in CNS autoinflammatory diseases.

The NLRP3 inflammasome is essential for caspase-1 activation and the release of interleukin (IL)-1β, IL-18, and gasdermin-D in myeloid cells. However, research on species-specific NLRP3's physiological impact is limited. We engineer mice with the human NLRP3 gene, driven by either the human or mouse promoter, via syntenic replacement at the mouse Nlrp3 locus.

O-GlcNAc signaling increases neuron regeneration through one-carbon metabolism in .

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked β-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration.

Translation, cultural adaptation and assessment of psychometrics properties of the Extended Version of the Nordic Musculoskeletal Questionnaire (NMQ-E) in Persian language speaking people.

Background: To translate and cross-culturally adapt the Extended Version of the Nordic Musculoskeletal Questionnaire (NMQ-E) into Persian (NMQ-E-P) and evaluate the psychometric properties in a general population with different occupational tasks across nine body regions.

Methods: This cross-sectional study was designed according to the standard guidelines and the COSMIN checklist. The NMQ-E-P was achieved through forward and backward translation methods and consensus to produce the final draft.

Smartphone addiction prevalence, patterns of use, and experienced musculoskeletal discomfort during the COVID-19 pandemic in a general Iranian population.

Background: Smartphone usage is an essential everyday tool in Iran, however problematic use has escalated and become a concern for the Iranian health policy system, particularly during and following the COVID-19 Pandemic. This study's aim was investigation of the prevalence of smartphone addiction, patterns of use, and the relationship to specific demographic characteristics and associated musculoskeletal disorders during the COVID-19 pandemic.

Methods: A descriptive-analytical correlational study recruited participants from a population of convenience (n = 2344) who were smartphone owners with > 1 year of use.

Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders.

The NLRP3 inflammasome is a component of the innate immune system involved in the production of proinflammatory cytokines. Neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, have been shown to have a component driven by NLRP3 inflammasome activation. Diseases such as these with large unmet medical needs have resulted in an interest in inhibiting the NLRP3 inflammasome as a potential pharmacological treatment, but to date, no marketed drugs specifically targeting NLRP3 have been approved.

Structured Multidisciplinary work Evaluation Tool (SMET) questionnaire: Translation, cultural adaptation and psychometric evaluation of the Persian version.

Background: To assess relevant environmental conditions in any work-setting requires a multidisciplinary perspective that is practical, valid, and reliable. This includes the physical, environmental, and psychosocial risk-factors. The Structured Multidisciplinary work Evaluation Tool (SMET) questionnaire simultaneously considers multiple work-related demands.

Molecular mechanism for Tn7-like transposon recruitment by a type I-B CRISPR effector.

Tn7-like transposons have co-opted CRISPR-Cas systems to facilitate the movement of their own DNA. These CRISPR-associated transposons (CASTs) are promising tools for programmable gene knockin. A key feature of CASTs is their ability to recruit Tn7-like transposons to nuclease-deficient CRISPR effectors.

The HOME-Health (HOusing, environMEnt, and Health) Study; Description of a Danish natural experiment, designed as a longitudinal study with repeated measurements, providing internal- and external validity of the study.

Background: The ambient and indoor environment are pivotal to our health. We spend most of our time indoors within our home, why our home is where we are most exposed to indoor pollutants and indoor air quality (IAQ). Populations within social housing areas are more vulnerable due to advanced age, co-morbidity and social economic status.

Laptop use and muscle activity in adult females: Ground sitting has lower muscular demand than using a chair.

Background: With progressing technology in the portable computing field, laptops are now integral for work, home and social settings. Different working postures adopted by laptop users impose different loads on the relevant muscles, which can be associated with musculoskeletal discomfort in the various body regions. Some Arabic and Asian cultures adopted postures are not well investigated, particularly for the 20-30 years age-group.

Cross Cultural Adaptation and Psychometric Evaluation of the Short Version of Smart Phone Addiction Scale in the Persian Language.

The addiction pattern of smartphone usage has increased concerns about potential complications. The Smartphone Addiction Scale (SAS), a self-administered questionnaire, evaluates smartphone usage and dependency. The study's purpose was to translate and culturally adapt the SAS short-version into the Persian language (SAS-SV-Pr), and evaluate its psychometric properties.

Measures of Information Content during Anesthesia and Emergence in the Caenorhabditis elegans Nervous System.

Background: Suppression of behavioral and physical responses defines the anesthetized state. This is accompanied, in humans, by characteristic changes in electroencephalogram patterns. However, these measures reveal little about the neuron or circuit-level physiologic action of anesthetics nor how information is trafficked between neurons.