The cysteine protease legumain is upregulated by vitamin D and regulates vitamin D metabolism

Legumain is a lysosomal asparaginyl endopeptidase involved in different biological processes and pathogenesis of several malignant and non-malignant diseases. Although an increasing number of proteins have been identified as substrates of legumain, the upstream mechanisms regulating the expression and function of legumain are not well-understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expression and function. In turn, legumain alters VD3 bioavailability, possibly through proteolytic cleavage of vitamin D binding protein (VDBP) and thereby playing a role in the regulation of VD3 metabolism. Active VD3 (1,25(OH)2D3) increased legumain expression, activity, and secretion in osteogenic cultures of human bone marrow stromal cells. Positive regulation of legumain was also observed in vivo, evidenced by increased expression of legumain mRNA in liver and spleen, as well as increased legumain activity in the kidneys, and increased level of circulating legumain in serum from mice treated with 25(OH)D3 (50 µg/kg, subcutaneous) for 8 days, as compared to vehicle-treated mice. We further showed that legumain cleaved VDBP forming a 45 kDa VDBP fragment in vitro when purified VDBP (55 kDa) was incubated with purified active legumain. In vivo, no VDBP cleavage was found in kidneys or liver from legumain deficient mice (Lgmn-/-), whereas VDBP was cleaved in wild type control mice (Lgmn+/+). Finally, legumain deficiency resulted in increased plasma levels of 25(OH)D3 and total VD3 and altered expression of key renal enzymes involved in VD3 metabolism (CYP24A1 and CYP27B1). Taken together, our data suggest existence of a regulatory interplay between VD3 and legumain

INTEGRATION OF COMPLEMENTARY BIOMARKERS IN PATIENTS WITH FIRST EPISODE PSYCHOSIS: RESEARCH PROTOCOL OF A PROSPECTIVE FOLLOW UP STUDY

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis

MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

https://pos.sissa.it/395/815/pdfPublished versio

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies

Survey participation and response

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Acquiescence response styles: A multilevel model explaining individual-level and country-level differences

AbstractAcquiescence has been found to distort the psychometric quality of questionnaire data. Previous research has identified various determinants of acquiescence at both the individual and the country level. We aimed to synthesize the scattered body of knowledge by concurrently testing a multilevel model encompassing a set of presumed predictors of acquiescence. Based on a representative sample comprising almost 40,000 respondents from 20 European countries, we analyzed the effects of the country-level indicators economic wealth, corruption level, and collectivism and the individual-level indicators age, gender, educational attainment, and conservatism. Results revealed that 15% of the variance in acquiescence was due to country-level variations in corruption levels and collectivism. Differences among individuals within countries could be partially explained by conservatism and educational attainment

Protective and risk factors for mental distress and its impact on health-protective behaviors during the SARS-CoV-2 pandemic between march 2020 and march 2021 in Germany

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is posing a global public health burden. These consequences have been shown to increase the risk of mental distress, but the underlying protective and risk factors for mental distress and trends over different waves of the pandemic are largely unknown. Furthermore, it is largely unknown how mental distress is associated with individual protective behavior. Three quota samples, weighted to represent the population forming the German COVID-19 Snapshot Monitoring study (24 March and 26 May 2020, and 9 March 2021 with >900 subjects each), were used to describe the course of mental distress and resilience, to identify risk and protective factors during the pandemic, and to investigate their associations with individual protective behaviors. Mental distress increased slightly during the pandemic. Usage of cognitive reappraisal strategies, maintenance of a daily structure, and usage of alternative social interactions decreased. Self-reported resilience, cognitive reappraisal strategies, and maintaining a daily structure were the most important protective factors in all three samples. Adherence to individual protective behaviors (e.g., physical distancing) was negatively associated with mental distress and positively associated with frequency of information intake, maintenance of a daily structure, and cognitive reappraisal. Maintaining a daily structure, training of cognitive reappraisal strategies, and information provision may be targets to prevent mental distress while assuring a high degree of individual protective behaviors during the COVID-19 pandemic. Effects of the respective interventions have to be confirmed in further studies