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Enhancing social functioning using multi-user, immersive virtual reality
Association of domain-specific physical activity with nocturia: a population-based study
Comprehensive RNA-seq analysis of benign prostatic hyperplasia (BPH) in rats exposed to testosterone and estradiol
Hydrogenotrophic methanogenesis at 7–12 mbar by Methanosarcina barkeri under simulated martian atmospheric conditions
Analysis of retinal sublayers in patients with systemic COVID-19 illness with varying degrees of severity
Growth-rate distributions of gut microbiota time series
Abstract Logarithmic growth-rates are fundamental observables for describing ecological systems and the characterization of their distributions with analytical techniques can greatly improve their comprehension. Here a neutral model based on a stochastic differential equation with demographic noise, which presents a closed form for these distributions, is used to describe the population dynamics of microbiota. Results show that this model can successfully reproduce the log-growth rate distribution of the considered abundance time-series. More significantly, it predicts its temporal dependence, by reproducing its kurtosis evolution when the time lag $$\tau$$ is increased. Furthermore, its typical shape for large $$\tau$$ is assessed, verifying that the distribution variance does not diverge with $$\tau$$ . The simulated processes generated by the calibrated stochastic equation and the analysis of each time-series, taken one by one, provided additional support for our approach. Alternatively, we tried to describe our dataset by using a logistic neutral model with an environmental stochastic term. Analytical and numerical results show that this model is not suited for describing the leptokurtic log-growth rates distribution found in our data. These results support an effective neutral model with demographic stochasticity for describing the considered microbiota.
Author Correction: Effectiveness of physical activity interventions on reducing perceived fatigue among adults with chronic conditions: a systematic review and meta-analysis of randomised controlled trials
When did recombination suppression events occur in bird ZW sex chromosomes?
Development and validation of a machine learning-based prediction model for hepatorenal syndrome in liver cirrhosis patients using MIMIC-IV and eICU databases
Chemical tools to define and manipulate interferon-inducible Ubl protease USP18
Abstract Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating the interferon-inducible ubiquitin-like modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) that incorporate unnatural amino acids into the C-terminal tail of ISG15, enabling the selective detection of USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) such as USP5 and USP14. Combined with a ubiquitin-based DUB ABP, the USP18 ABP is employed in a chemoproteomics screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.
SLC1A5 is a key regulator of glutamine metabolism and a prognostic marker for aggressive luminal breast cancer
Abstract Cancer cells exhibit altered metabolism, often relying on glutamine (Gln) for growth. Breast cancer (BC) is a heterogeneous disease with varying clinical outcomes. We investigated the role of the amino acid transporter SLC1A5 (ASCT2) and its association with BC subtypes and patient outcomes. In large BC cohorts, SLC1A5 mRNA (n = 9488) and SLC1A5 protein (n = 1274) levels were assessed and correlated their expression with clinicopathological features, molecular subtypes, and patient outcomes. In vitro SLC1A5 knockdown and inhibition studies in luminal BC cell lines (ZR-75-1 and HCC1500) were used to further explore the role of SLC1A5 in Gln metabolism. Statistical analysis was performed using chi-squared tests, ANOVA, Spearman’s correlation, Kaplan–Meier analysis, and Cox regression. SLC1A5 mRNA and SLC1A5 protein expression were strongly correlated in luminal B, HER2 + and triple-negative BC (TNBC). Both high SLC1A5 mRNA and SLC1A5 protein expression were associated with larger tumour size, higher grade, and positive axillary lymph node metastases (P < 0.01). Importantly, high SLC1A5 expression correlated with poor BC-specific survival specifically in the highly proliferative luminal subtype (P < 0.001). Furthermore, SLC1A5 knockdown by siRNA or GPNA inhibition significantly reduced cell proliferation and glutamine uptake in ZR-75-1 cells. Our findings suggest SLC1A5 plays a key role in the aggressive luminal BC subtype and represents a potential therapeutic target. Further research is needed to explore SLC1A5 function in luminal BC and its association with Gln metabolism pathways.
Fast updating feedback from piriform cortex to the olfactory bulb relays multimodal identity and reward contingency signals during rule-reversal
Identification of hub biomarkers and immune cell infiltrations participating in the pathogenesis of endometriosis
Myosin-based nucleation of actin filaments contributes to stereocilia development critical for hearing
Abstract Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism. Here, we show that MYO15A is itself an actin nucleation-promoting factor. Moreover, a deafness-causing mutation in the MYO15A actin-binding interface inhibits nucleation activity but still preserves some movement on filaments in vitro and partial trafficking on stereocilia in vivo. Stereocilia fail to elongate correctly in this mutant mouse, providing evidence that MYO15A-driven actin nucleation contributes to hair bundle biogenesis. Our work shows that in addition to generating force and motility, the ATPase domain of MYO15A can directly regulate actin polymerization and that disrupting this activity can promote cytoskeletal disease, such as hearing loss.
Evaluation of feasibility accuracy and safety after 79 O-ARM based stereotactic brain biopsies
Mechanism of sensor kinase CitA transmembrane signaling
Abstract Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA. Citrate binding in the sensory extracytoplasmic PAS domain (PASp) causes the linker to transmembrane helix 2 (TM2) to adopt a helical conformation. This triggers a piston-like pulling of TM2 and a quaternary structure rearrangement in the cytosolic PAS domain (PASc). Crystal structures of PASc reveal both anti-parallel and parallel dimer conformations. An anti-parallel to parallel transition upon citrate binding agrees with interdimer distances measured in the lipid embedded protein using a site-specific 19 F label in PASc. These data show how Angstrom scale structural changes in the sensor domain are transmitted across the membrane to be converted and amplified into a nm scale shift in the linker to the phosphorylation subdomain of the kinase.
Association of the triglyceride glucose index with all cause and CVD mortality in the adults with diabetes aged < 65 years without cardiovascular disease
Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice
Abstract Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c + DCs and CD4 + T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2 + cDC2s and CCR7 + DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2 + cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.