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REST suppression mediates neural conversion of adult human fibroblasts via microRNA-dependent and -independent pathways

Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors

Johannes Magnus’ Historia de omnibus Gothorum Sueonumque regibus and Gostagus the Tyrant

The last Catholic archbishop of Sweden to hold residence in his see at Uppsala, Johannes Magnus (1488-1544), was the author of a major work about Swedish history: the Historia de omnibus Gothorum Sueonumque regibus. Johannes Magnus left Sweden in 1526, spent the rest of his life away from his home country and eventually died in Rome, where his work was published posthumously in 1554. One reason fo

The putative tumor suppressor gene EphA7 is a novel BMI-1 target

Bmi1 was originally identified as a gene that contributes to the development of mouse lymphoma by inhibiting MYC-induced apoptosis through repression of Ink4a and Arf. It codes for the Polycomb group protein BMI-1 and acts primarily as a transcriptional repressor via chromatin modifications. Although it binds to a large number of genomic regions, the direct BMI-1 target genes described so far do n

Delaying ACL reconstruction and treating with exercise therapy alone may alter prognostic factors for 5-year outcome : An exploratory analysis of the KANON trial

Aim Identify injury-related, patient-reported and treatment-related prognostic factors for 5-year outcomes in acutely ACL-ruptured individuals managed with early reconstruction plus exercise therapy, exercise therapy plus delayed reconstruction or exercise therapy alone. Methods Exploratory analysis of the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) trial (ISRCTN

Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism

Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspecte

The genomics of heart failure : design and rationale of the HERMES consortium

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and perf

“Omics” in traumatic brain injury : novel approaches to a complex disease

Background: To date, there is neither any pharmacological treatment with efficacy in traumatic brain injury (TBI) nor any method to halt the disease progress. This is due to an incomplete understanding of the vast complexity of the biological cascades and failure to appreciate the diversity of secondary injury mechanisms in TBI. In recent years, techniques for high-throughput characterization and

Proteomic data analysis for differential profiling of the autoimmune diseases SLE, RA, SS, and ANCA-associated vasculitis

Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), and

Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons

Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a ne

Prevalence of germline pathogenic variants in 22 cancer susceptibility genes in Swedish pediatric cancer patients

Up to 10% of pediatric cancer patients harbor pathogenic germline variants in one or more cancer susceptibility genes. A recent study from the US reported pathogenic variants in 22 out of 60 analyzed autosomal dominant cancer susceptibility genes, implicating 8.5% of pediatric cancer patients. Here we aimed to assess the prevalence of germline pathogenic variants in these 22 genes in a population-

Waist circumference and a body shape index and prostate cancer risk and mortality

We recently found a negative association between body mass index (BMI) and the risk of localised prostate cancer (PCa), no association with advanced PCa, and a positive association with PCa‐specific mortality. In a 15% subpopulation of that study, we here investigated the measures of abdominal adiposity including waist circumference (WC) and A Body Shape Index (ABSI) in relation to PCa risk and mo

Deep Distributional Temporal Difference Learning for Game Playing

We compare classic scalar temporal difference learning with three new distributional algorithms for playing the game of 5-in-a-row using deep neural networks: distributional temporal difference learning with constant learning rate, and two distributional temporal difference algorithms with adaptive learning rate. All these algorithms are applicable to any two-player deterministic zero sum game and

The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells

Small Cajal body-specific RNAs (scaRNAs) guide post-transcriptional modification of spliceosomal RNA and, while commonly altered in cancer, have poorly defined roles in tumorigenesis. Here, we uncover that SCARNA15 directs alternative splicing (AS) and stress adaptation in cancer cells. Specifically, we find that SCARNA15 guides critical pseudouridylation (Ψ) of U2 spliceosomal RNA to fine-tune AS

Taking sanctioning seriously : The impact of sanctions on the resilience of historical commons in Europe

In their studies of collective exploitation of common-pool resources, Ostrom and other scholars have stressed the importance of sanctioning as an essential method for preventing overuse and, eventually, the collapse of commons. However, most of the available evidence is based on data covering a relatively small period in history, and thus does not inform us about the evolution of rules, including

Vibrotactile sense might improve over time in paediatric subjects with type 1 diabetes - a mid-term follow-up using multifrequency vibrometry

AimImpaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time.MethodsA VibroSense Meter I device was used to determine the vibrotactile perception thresholds (

Defining the Emerging Blood System During Development at Single-Cell Resolution

Developmental hematopoiesis differs from adult and is far less described. In the developing embryo, waves of lineage-restricted blood precede the ultimate emergence of definitive hematopoietic stem cells (dHSCs) capable of maintaining hematopoiesis throughout life. During the last two decades, the advent of single-cell genomics has provided tools to circumvent previously impeding characteristics o

Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study.

Objective. To determine the incidence rate, predictors and outcome of severe infections in a population-based cohort of ANCA-associated vasculitis (AAV). Methods. The study included 325 cases of AAV (152 female) diagnosed from 1997 through 2016 from a defined geographic area in Sweden. All severe infection events (requiring hospitalization and treatment with intravenous antimicrobials) were identi