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Arrested protein states of reaction coordinates such as ATP hydrolysis can be trapped for NMR studies by using stable, non-hydrolysable ATP analogues that mimic the physiological relevant states as accurately as possible. Recent advances in solid-state NMR techniques ranging from Dynamic Nuclear Polarization (DNP), 31P-based heteronuclear correlation experiments, 1H-detected spectra at fast MAS frequencies >100 kHz to paramagnetic NMR are summarized and their applications to the bacterial DnaB helicase from Helicobacter pylori are discussed.Injectable anesthesia protocols for five-striped palm squirrels (Funambulus pennantii) are poorly described in the literature.In this study, male intact squirrels received intramuscular injections of either alfaxalone (6 mg/kg) and ketamine (40 mg/kg; AK group, n = 8); alfaxalone (6 mg/kg), ketamine (20 mg/kg), and dexmedetomidine (0.1 mg/kg; AKD group, n = 8); or alfaxalone (8 mg/kg), butorphanol (1 mg/kg), and midazolam (1 mg/kg; ABM group, n = 8). Atipamezole (0.15 mg/kg IM) and flumazenil (0.1 mg/kg IM) were administered 40 min after anesthesia induction (defined as loss of the righting reflex) with AKD and ABM, respectively. Heart rate, respiratory rate, rectal temperature, and reflexes were recorded every 5 min during anesthesia. Anesthetic induction was rapid in all groups (AK median, 49 s; range, 33 to 60 s; AKD, 60 s; 54 to 70 s; and ABM, 15 s; 5 to 58 s). The anesthetic duration (from induction to full recovery) for the AK group was 62 ± 3 min (mean ± 1 SD). Therewas no statistically significant difference between the ABM and AKD groups regarding recovery time after partial antagonist administration and was 51 ± 5 and 48 ± 5 min, respectively. All AK animals showed twitching and abnormal vocalization during recovery. The righting reflex was absent in all squirrels for 20 min in the AK treatment group and throughout the 40-min anesthetic period in the AKD and ABM groups. The frontlimb withdrawal response was absent in all squirrels for the 40-min anesthetic period in the AKD and ABM groups, with variable responses for the AK treatment. All tested protocols in this study provided safe and effective immobilization in five-striped palm squirrels, but oxygen and thermal support wereindicated. Anesthetic depth must be determined before surgical procedures are performed in palm squirrels anesthetized by using these regimens.Corynebacterium bovis is the causative agent of Corynebacterium-associated hyperkeratosis in immunocompromised mice. The resulting skin pathology can be profound and can be associated with severe wasting, making the animals unsuitable for research. Although the administration of antibiotics is effective in resolving clinical symptoms, antibiotics do not eradicate the offending bacterium. Furthermore, antibiotic use may be contraindicated as it can affect tumor growth and is associated with Clostridioides difficile enterotoxemia in highly immunocompromised murine strains. Akt chemical Lysins, which are lytic enzymes obtained from bacteriophages, are novel antimicrobial agents for treating bacterial diseases. The advantage of lysins are its target specificity, with minimal off-target complications that could affect the host or the biology of the engrafted tumor. The aim of this study was to identify lysins active against C. bovis. Chemical activation of latent prophages by using mitomycin C in 3 C. bovis isolates did not cause bacteriophage induction as determined through plaque assays and transmission electron microscopy. As an alternative approach, 8 lysins associated with other bacterial species, including those from the closely related species C. falsenii, were tested for their lytic action against C. bovis but were unsuccessful. These findings were congruentwith the previously reported genomic analysis of 21 C. bovis isolates, which failed to reveal bacteriophage sequences by usingthe PHAST and PHASTER web server tools. From these results, we suggest C. bovis is among those rare bacterial species devoid of lysogenic bacteriophages, thus making the identification of C. bovis-specific lysins more challenging. However, C. bovis may be a useful model organism for studying the effects of antiphage systems.There is growing evidence on the clinical significance of Tumor Microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactionsin tumor microenvironments have not been thoroughly studied or systematicallyanalyzed so far. In this study, 22 immune cell components in the lung adenocarcinoma(LUAD) TME were analyzed using gene expression profile from The Cancer GenomeAtlas (TCGA), Gene Expression Omnibus (GEO) . The TME based molecular subtypesof LUAD were defined to evaluate further the relationship between molecular subtypes,prognosis, and clinical characteristics. A TME risk score model was constructed byusing the differentially expressed genes (DEGs) of molecular subtypes. The relationshipbetween the TME score and clinical characteristics and genomic mutations wascompared to identify the genes that have significant associations with the TME. Thecomprehensive analysis of the TME characteristics maybe helpful in revealing theresponse of LUAD patients to immunotherapy, providing a new strategy forimmunotherapy.Background BMPR-1B is part of the transforming growth factor β super family and plays a pivotal role in ewe litter size. link2 Functional loss of exon-8 mutations in the BMPR-1B gene (namely the FecB gene) can increase both the ewe ovulation rate and litter size. Results This study constructed a eukaryotic expression system, prepared a monoclonal antibody, and characterized BMPR-1B/FecB protein-protein interactions (PPIs). Using Co-immunoprecipitation coupled to mass spectrometry (Co-IP/MS), 23 proteins were identified that specifically interact with FecB in ovary extracts of ewes. Bioinformatics analysis of selected PPIs demonstrated that FecB associated with several other BMPs, primarily via signal transduction in the ovary. FecB and its associated interaction proteins enriched the reproduction process via BMP2 and BMP4 pathways. Signal transduction was identified via Smads proteins and TGF-beta signaling pathway by analyzing the biological processes and pathways. Moreover, other target proteins (GDF5, GDF9, RhoD, and HSP 10) that interact with FecB and that are related to ovulation and litter size in ewes were identified. Conclusions In summary, this research identified a novel pathway and insight to explore the PPi network of BMPR-1B.Background Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations. Methods We conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups. We also identified the predisposition-associated two-hit events and gene expression effects in tumors. Results Genetic ancestry analysis classified the cohort of 9899 cancer cases into individuals of primarily European (N = 8184, 82.7%), African (N = 966, 9.8%), East Asian (N = 649, 6.6%), South Asian (N = 48, 0.5%), Native/Latin American (N = 41, 0.4%), and admixed (N = 11, 0.1%) ancestries. In the African ancestry, we discovered a potentially novel association of BRowed simultaneous allelic-specific expression and low gene expression of their respective affected genes, and FH splice-site variant carriers showed mis-splicing of FH. Conclusions While several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic treatment with clozapine can induce obsessive compulsive disorder (OCD)-like behavior in mice. link3 We injected mice with long-term continuous release pellets embedded with clozapine four times at 60-day intervals and then monitored the mice for signs of OCD-like behavior up to 40 wk. of age. We found clozapine increases grooming behavior as early as 30 wk. of age. We also investigated the effect clozapine on grooming behavior in Sapap3 knockout (KO) mice, which are a well-known animal model of OCD. In Sapap3 heterozygous KO mice, clozapine increases grooming behavior much earlier than in wild-type mice, suggesting a clozapine-OCD gene interaction. Fluoxetine, which is often used in the treatment of OCS and OCD, reduced the grooming behavior induced by clozapine. These data demonstrate that chronic clozapine treatment can generate OCD-like behavior in mice and support the hypothesis that clozapine produces de novo OCS regardless of schizophrenia status.Background Dysfunction of human respiratory and electro-cardiac activities could affect the ability of the heart to pump blood and the lungs to inhale oxygen. Thus, a device could simultaneously measure electro-cardiac signal and respiratory pressure could provide vital signs for predicting early warning of cardio-pulmonary function-related chronic diseases such as cardiovascular disease, and respiratory system disease. Results In this study, a flexible device integrated with piezo-resistive sensing element and voltage-sensing element was developed to simultaneously measure human respiration and electro-cardiac signal (including respiratory pressure, respiration frequency, and respiration rhythm; electro-cardio frequency, electro-cardio amplitude, and electro-cardio rhythm). When applied to the measurement of respiratory pressure, the piezo-resistive performance of the device was enhanced by nano-copper modification, which detection limitation of pressure can reduce to 100 Pa and the sensitivity of pressure can achieve to 0.053 ± 0.00079 kPa-1. In addition, the signal-to-noise ratio during bio-electrical measurement was increased to 10.7 ± 1.4, five times better than that of the non-modified device. Conclusion This paper presents a flexible device for the simultaneous detection of human respiration and cardiac electrical activity. To avoid interference between the two signals, the layout of the electrode and the strain sensor was optimized by FEA simulation analysis. To improve the piezo-resistive sensitivity and bio-electric capturing capability of the device, a feather-shaped nano-copper was modified onto the surface of carbon fiber. The operation simplicity, compact size, and portability of the device open up new possibilities for multi-parameter monitoring.Background Even though cartilage loss is a known feature of psoriatic arthritis (PsA), little is known about its role in the pathogenesis of PsA. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) as a non-invasive marker of the tissue's proteoglycan content, such early (i.e., pre-morphological) changes have been associated with inflammation in rheumatoid arthritis (RA). Yet, this association has not been studied before in PsA. Methods The metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution clinical standard morphological and dGEMRIC sequences using a 3T MRI scanner (Magnetom Skyra, Siemens) and a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), and total cartilage thickness (TCT). Kendall tau correlation coefficients (τ) were calculated. Results We found significant negative correlations between dGEMRIC indices and total PsAMRIS (τ = - 0.