Identification of novel non-myelin biomarkers in multiple sclerosis using an improved phage-display approach

Although the etiology of multiple sclerosis is not yet understood, it is accepted that its pathogenesis involves both autoimmune and neurodegenerative processes, in which the role of autoreactive T-cells has been elucidated. Instead, the contribution of humoral response is still unclear, even if the presence of intrathecal antibodies and B-cells follicle-like structures in meninges of patients has been demonstrated. Several myelin and non-myelin antigens have been identified, but none has been validated as humoral biomarker. In particular autoantibodies against myelin proteins have been found also in healthy individuals, whereas non-myelin antigens have been implicated in neurodegenerative phase of the disease. To provide further putative autoantigens of multiple sclerosis, we investigated the antigen specificity of immunoglobulins present both in sera and in cerebrospinal fluid of patients using phage display technology in a new improved format. A human brain cDNA phage display library was constructed and enriched for open-read-frame fragments. This library was selected against pooled and purified immunoglobulins from cerebrospinal fluid and sera of multiple sclerosis patients. The antigen library was also screened against an antibody scFv library obtained from RNA of B cells purified from the cerebrospinal fluid of two relapsing remitting patients. From all biopanning a complex of 14 antigens were identified; in particular, one of these antigens, corresponding to DDX24 protein, was present in all selections. The ability of more frequently isolated antigens to discriminate between sera from patients with multiple sclerosis or other neurological diseases was investigated. The more promising novel candidate autoantigens were DDX24 and TCERG1. Both are implicated in RNA modification and regulation which can be altered in neurodegenerative processes. Therefore, we propose that they could be a marker of a particular disease activity state

The supernova impostor PSN J09132750+7627410 and its progenitor

We report the results of our follow-up campaign of the supernova impostor PSN J09132750+7627410, based on optical data covering $\sim250\,\rm{d}$. From the beginning, the transient shows prominent narrow Balmer lines with P-Cygni profiles, with a blue-shifted absorption component becoming more prominent with time. Along the $\sim3\,\rm{months}$ of the spectroscopic monitoring, broad components are never detected in the hydrogen lines, suggesting that these features are produced in slowly expanding material. The transient reaches an absolute magnitude $M_r=-13.60\pm0.19\,\rm{mag}$ at maximum, a typical luminosity for supernova impostors. Amateur astronomers provided $\sim4\,\rm{years}$ of archival observations of the host galaxy, NGC 2748. The detection of the quiescent progenitor star in archival images obtained with the Hubble Space Telescope suggests it to be an $18-20$\msun white-yellow supergiant.Comment: 7 pages, 4 figures, supplemental material available in the source file. Accepted for publication on Astrophysical Journal Letter

Endogenous extracellular matrix regulates the response of osteosarcoma 3D spheroids to doxorubicin

The extracellular matrix (ECM) modulates cell behavior, shape, and viability as well as mechanical properties. In recent years, ECM disregulation and aberrant remodeling has gained considerable attention in cancer targeting and prevention since it may stimulate tumorigenesis and metastasis. Here, we developed an in vitro model that aims at mimicking the in vivo tumor microenvironment by recapitulating the interactions between osteosarcoma (OS) cells and ECM with respect to cancer progression. We long-term cultured 3D OS spheroids made of metastatic or non-metastatic OS cells mixed with mesenchymal stromal cells (MSCs); confirmed the deposition of ECM proteins such as Type I collagen, Type III collagen, and fibronectin by the stromal component at the interface between tumor cells and MSCs; and found that ECM secretion is inhibited by a neutralizing anti-IL-6 antibody, suggesting a new role of this cytokine in OS ECM deposition. Most importantly, we showed that the cytotoxic effect of doxorubicin is reduced by the presence of Type I collagen. We thus conclude that ECM protein deposition is crucial for modelling and studying drug response. Our results also suggest that targeting ECM proteins might improve the outcome of a subset of chemoresistant tumors

A New COL3A1 Mutation in Ehlers-Danlos Syndrome Vascular Type with Different Phenotypes in the Same Family

Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe connective tissue disorder caused by mutations in the collagen type III alpha I chain (COL3A1) gene. We describe a pathogenetic heterozygous COL3A1 mutation c.3140 G>A, p. Gly1047Asp, identified using next-generation sequencing, in a 40-year-old Italian female. The genetic test performed on her relatives, which present different clinical phenotypes, confirmed that they carry the same mutation in heterozygous state. This finding confirms that mutations causing vEDS have an incomplete penetrance

A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context

The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study (N = 1481). Reliability and content, construct, and nomological validity were supported, as well as measurement invariance across work role (researchers, associate professors, and full professors) and gender. Evidence from the present study shows that the AQ@workT represents a useful and reliable tool to assist university management to enhance quality of life, to manage work-related stress, and to mitigate the potential for harm to academics, particularly during a pandemic. Future studies, such as longitudinal tests of the AQ@workT, should test predictive validity among the variables in the tool

Violent behavior of patients living in psychiatric residential facilities: A comparison of male patients with different violence histories

People with severe mental disorders and a history of violence are often seen as a difficult-to-manage segment of the population. In addition, this group is usually characterized by a high risk of crime recidivism, and poor compliance with community and aftercare programs. To investigate a sample of male patients living in Residential Facilities (RFs) with a history of violent behavior against people and to compare their characteristics with those of never-violent residents; to analyze the associations between aggressive behaviors in the last two years and a history of previous violence; and, to assess the predictors of aggressive behaviors. This study is part of a prospective observational cohort study which involved 23 RFs in Northern Italy. A comprehensive set of sociodemographic, clinical, and treatment-related information was gathered, and standardized assessments were administered to each participant. Also a detailed assessment of aggressive behaviors in the past two years was carried out. The study involved 268 males: 81 violent and 187 never-violent. Compared to never-violent patients, violent patients were younger, with a higher proportion of personality disorders, and have displayed an increased number of aggressive behaviors in the last two years. The presence of a history of violent behavior in the past significantly increases the probability of committing aggressive acts in the future

The effect of service satisfaction and spiritual well-being on the quality of life of patients with schizophrenia.

Quality of life (QOL) has been considered an important outcome measure in psychiatric research and determinants of QOL have been widely investigated. We aimed at detecting predictors of QOL at baseline and at testing the longitudinal interrelations of the baseline predictors with QOL scores at a 1-year follow-up in a sample of patients living in Residential Facilities (RFs). Logistic regression models were adopted to evaluate the association between WHOQoL-Bref scores and potential determinants of QOL. In addition, all variables significantly associated with QOL domains in the final logistic regression model were included by using the Structural Equation Modeling (SEM). We included 139 patients with a diagnosis of schizophrenia spectrum. In the final logistic regression model level of activity, social support, age, service satisfaction, spiritual well-being and symptoms' severity were identified as predictors of QOL scores at baseline. Longitudinal analyses carried out by SEM showed that 40% of QOL follow-up variability was explained by QOL at baseline, and significant indirect effects toward QOL at follow-up were found for satisfaction with services and for social support. Rehabilitation plans for people with schizophrenia living in RFs should also consider mediators of change in subjective QOL such as satisfaction with mental health services

Massive star mergers and the recent transient in NGC 4490: A more massive cousin of V838 Mon and V1309 Sco

The Galactic transient V1309 Sco was the result of a merger in a low-mass star system, while V838 Mon was thought to be a similar merger event from a more massive B-type progenitor. In this paper, we study a recent optical and infrared (IR) transient discovered in the nearby galaxy NGC4490 named NGC4490-OT2011 (NGC 4490-OT hereafter), which appeared similar to these merger events (unobscured progenitor, irregular multi-peaked light curve, increasingly red colour, similar optical spectrum, IR excess at late times), but which had a higher peak luminosity and longer duration in outburst. NGC4490-OT has less in common with the class of SN 2008S-like transients. A progenitor detected in pre-eruption Hubble Space Telescope (HST) images, combined with upper limits in the IR, requires a luminous and blue progenitor that has faded in late-time HST images. The same source was detected by Spitzer and groundbased data as a luminous IR (2-5 μm) transient, indicating a transition to a self-obscured state qualitatively similar to the evolution seen in other stellar mergers and in luminous blue variables. The post-outburst dust-obscured source is too luminous and too warm at late times to be explained with an IR echo, suggesting that the object survived the event. The luminosity of the enshrouded IR source is similar to that of the progenitor. Compared to proposed merger events, the more massive progenitor of NGC4490-OT seems to extend a correlation between stellar mass and peak luminosity, and may suggest that both of these correlate with duration. We show that spectra of NGC4490-OT and V838 Mon also resemble light-echo spectra of η Car, prompting us to speculate that η Car may be an extreme extension of this phenomenon