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Empirical research on international student migrants has sometimes homogenised this group, framing it as predominantly made up of privileged members of the global middle- class. This has led to calls to acknowledge and address the precarity faced by international students in their respective host countries more comprehensively. This study aims to explore how levels of financial precarity vary among international students in Australia, and how this in turn contributes to varying levels of precariousness in the personal spheres of students' lives. In doing so, we centre and refine the concept of precarity for use in studies of internationally mobile students, arguing for its use as a 'relational nexus', bridging financial precarity and broader lived experiences. Drawing on a large-scale survey and semi-structured interviews with 48 students, we emphasise the linkages between financial precarity and precariousness as a socio-ontological experience, explored through the examples of time poverty, physical and mental wellbeing, and relationships. [Author abstract]

Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing. When fed a high fat, high cholesterol diet LXRα mutant mice rapidly develop pathologies associated with Metabolic Dysfunction-Associated Steatohepatitis (MASH) including ballooning hepatocytes, liver inflammation, and fibrosis. Strikingly LXRα mutant mice have decreased liver triglycerides but increased liver cholesterol. Therefore, elevated cholesterol in the liver may play a critical role in the development of MASH. Reengaging LXR signaling by treatment with synthetic agonist reverses MASH in LXRα mutant mice suggesting that LXRα normally functions to impede the development of liver disease. Liver x receptors (LXRs) regulate lipid metabolism in response to changing cholesterol levels. Here, the authors show that inactivation of LXR signaling leads to the rapid development of metabolic dysfunction-associated steatohepatitis (MASH).

BackgroundTo assist neurologists with effectively planning multiple sclerosis (MS) services in the NHS, this study quantified the administration and monitoring time burden associated with selected high-efficacy disease-modifying therapies (DMTs; alemtuzumab, cladribine tablets [CladT], fingolimod, natalizumab, and ocrelizumab) for highly-active relapsing MS in the UK.MethodsA time and motion study was conducted across four MS centres over 3–4 months per-site (Aug 2019–Feb 2021). Time dedicated by healthcare professionals (HCPs) to pre-specified drug administration and monitoring activities was assessed for each of the selected DMTs. Data were extrapolated over 4 years per-patient, based on the relevant Summaries of Product Characteristics, and analysed descriptively.ResultsFor oral DMTs, projected total active HCP time (monitoring only) per-patient over 4 years was 12.3 hours for CladT and 15.9 hours for fingolimod. For infusion DMTs, total time (administration and monitoring) was 35.5 hours for alemtuzumab (6.1 and 29.4 hours), 46.5 hours for natalizumab (17.2 and 29.3 hours), and 21.6 hours for ocrelizumab (6.2 and 15.4 hours).ConclusionsWhile active HCP time varies across sites, infusion DMTs are projected to require the greatest amount of HCP time associated with administration and monitoring over 4 years versus oral DMTs.

Liver x receptor alpha (LXRα, Nr1h3) functions as an important intracellular cholesterol sensor that regulates fat and cholesterol metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing. When fed a high fat, high cholesterol diet LXRα mutant mice rapidly develop pathologies associated with Metabolic Dysfunction-Associated Steatohepatitis (MASH) including ballooning hepatocytes, liver inflammation, and fibrosis. Strikingly LXRα mutant mice have decreased liver triglycerides but increased liver cholesterol. Therefore, MASH-like phenotypes can arise in the absence of large increases in triglycerides. Reengaging LXR signaling by treatment with synthetic agonist reverses MASH suggesting that LXRα normally functions to impede the development of liver disease.

Background Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. Methods In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. Results A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. Conclusion These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer.

Student Last week, an article titled \"Don't Spend Your Vote on Gary Johnson\" was published, encouraging readers not to vote for Libertarian Presidential Candidate Gary Johnson. [...]the reason I want Gary Johnson out there is because people are begging for a third alternative.

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.