Use of antibodies against Epstein-Barr virus nuclear antigen 1 for detection of cellular proteins with monomethylated arginine residues that are potentially involved in viral transformation.

Epstein-Barr virus nuclear antigen 1 (EBNA1) contains two arginine-glycine (RG) repeats that contain symmetric/asymmetric dimethylarginine (SDMA/ADMA) and monomethylarginine (MMA) residues. We generated mouse monoclonal antibodies directed against a monomethylated GRGRGG-containing repeat located between amino acids 328 and 377 of EBNA1. In addition to detecting MMA-modified EBNA1, we also had the goal of identifying cellular proteins that bind to MMA-modified EBNA1 in EBV-positive Raji cells.

Acceptance of a digital therapy recommender system for psoriasis.

Background: About 2% of the German population are affected by psoriasis. A growing number of cost-intensive systemic treatments are available. Surveys have shown high proportions of patients with moderate to severe psoriasis are not adequately treated despite a high disease burden.

Feline leishmaniosis with focus on ocular manifestation: a case report.

Background: In Europe, feline leishmaniosis is commonly caused by Leishmania infantum. There is little knowledge regarding pathogenesis, ocular manifestations and long-term follow-ups in cats with leishmaniosis.

Findings: A 6-year-old female, spayed European Shorthair cat was imported from Spain to Germany 2 years prior to its first clinical presentation.

A drug recommender system for the treatment of hypertension.

Background: One third (20% to 30%) of patients suffering from hypertension show increased blood pressure resistant to treatment. This resistance often has multifactorial causes, like therapeutic inertia and inappropriate medication but also poor patient adherence. Evidence-based guidelines aim to support appropriate health care decisions.

Protein Kinase CK2 and Epstein-Barr Virus.

Protein kinase CK2 is a pleiotropic protein kinase, which phosphorylates a number of cellular and viral proteins. Thereby, this kinase is implicated in the regulation of cellular signaling, controlling of cell proliferation, apoptosis, angiogenesis, immune response, migration and invasion. In general, viruses use host signaling mechanisms for the replication of their genome as well as for cell transformation leading to cancer.

Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma.

Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines.

Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL.

Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4.

HLA-DRB1*15:01 is a co-receptor for Epstein-Barr virus, linking genetic and environmental risk factors for multiple sclerosis.

The strongest genetic and environmental risk factors for MS, an inflammatory CNS disease, are HLA-DRB1*15:01 and EBV. This work shows that HLA-DRB1*15:01 acts as a co-receptor for EBV infection of a B cell line, suggesting a mechanistic link between both risk factors for MS.

Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch.

Neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes , , and .

Integrative functional genomics decodes herpes simplex virus 1.

The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs.

Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program.

Herpesvirus infection initiates a range of perturbations in the host cell, which remain poorly understood at the level of individual cells. Here, we quantify the transcriptome of single human primary fibroblasts during the first hours of lytic infection with HSV-1. By applying a generalizable analysis scheme, we define a precise temporal order of early viral gene expression and propose a set-wise emergence of viral genes.

Predicting sepsis with a recurrent neural network using the MIMIC III database.

Objective: Predicting sepsis onset with a recurrent neural network and performance comparison with InSight - a previously proposed algorithm for the prediction of sepsis onset.

Methodology: A retrospective analysis of adult patients admitted to the intensive care unit (from the MIMIC III database) who did not fall under the definition of sepsis at the time of admission. The area under the receiver operating characteristic (AUROC) measures the performance of the prediction task.

Exploring the MIR143-UPAR Axis for the Inhibition of Human Prostate Cancer Cells In Vitro and In Vivo.

MIR143 is pathologically downregulated and may function as a tumor suppressor in prostate cancer. Likewise, the urokinase plasminogen activator receptor (UPAR) is overexpressed in prostate carcinoma, representing a negative prognostic marker and putative therapeutic target gene. In this paper, we establish UPAR as a new direct target of MIR143.

An estimate of the total number of true human miRNAs.

While the number of human miRNA candidates continuously increases, only a few of them are completely characterized and experimentally validated. Toward determining the total number of true miRNAs, we employed a combined in silico high- and experimental low-throughput validation strategy. We collected 28 866 human small RNA sequencing data sets containing 363.

Amplified Host Defense by Toll-Like Receptor-Mediated Downregulation of the Glucocorticoid-Induced Leucine Zipper (GILZ) in Macrophages.

Activation of toll-like receptors (TLRs) plays a pivotal role in the host defense against bacteria and results in the activation of NF-κB-mediated transcription of proinflammatory mediators. Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory mediator, which inhibits NF-κB activity in macrophages. Thus, we aimed to investigate the regulation and role of GILZ expression in primary human and murine macrophages upon TLR activation.

Epstein-Barr Virus Infection of Cell Lines Derived from Diffuse Large B-Cell Lymphomas Alters MicroRNA Loading of the Ago2 Complex.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoid tumor which is occasionally Epstein-Barr virus (EBV) positive and is further subtyped as activated B-cell DLBCL (ABC-DLBCL) and germinal center B-cell DLBCL (GCB-DLBCL), which has implications for prognosis and treatment. We performed Ago2 RNA immunoprecipitation followed by high-throughput RNA sequencing (Ago2-RIP-seq) to capture functionally active microRNAs (miRNAs) in EBV-negative ABC-DLBCL and GCB-DLBCL cell lines and their EBV-infected counterparts. In parallel, total miRNA profiles of these cells were determined to capture the cellular miRNA profile for comparison with the functionally active profile.

Modulation of intracellular calcium signaling by microRNA-34a-5p.

Adjusting intracellular calcium signaling is an important feature in the regulation of immune cell function and survival. Here we show that miR-34a-5p, a small non-coding RNA that is deregulated in many common diseases, is a regulator of store-operated Ca entry (SOCE) and calcineurin signaling. Upon miR-34a-5p overexpression, we observed both a decreased depletion of ER calcium content and a decreased Ca influx through Ca release-activated Ca channels.

Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring.

Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection.

Background: Herpesviruses can infect a wide range of animal species. Herpes simplex virus 1 (HSV-1) is one of the eight herpesviruses that can infect humans and is prevalent worldwide. Herpesviruses have evolved multiple ways to adapt the infected cells to their needs, but knowledge about these transcriptional and post-transcriptional modifications is sparse.

Therapy Decision Support Based on Recommender System Methods.

We present a system for data-driven therapy decision support based on techniques from the field of recommender systems. Two methods for therapy recommendation, namely, and , are proposed. Both algorithms aim to predict the individual response to different therapy options using diverse patient data and recommend the therapy which is assumed to provide the best outcome for a specific patient and time, that is, consultation.

Quinalizarin inhibits adipogenesis through down-regulation of transcription factors and microRNA modulation.

Background: Protein kinase CK2 is induced early in adipogenesis whereas later on, this kinase seems to be dispensable. Here, we have analysed how CK2 might be involved in early steps of differentiation of 3T3-L1 cells.

Methods: 3T3-L1 cells were differentiated to adipocytes in the absence or presence of quinalizarin.

MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins.

Although microRNAs have been recognized as central cellular regulators, there is an evident lack of knowledge about their targets. Here, we analyzed potential target genes for miR-148a functioning in Ras signaling in B cells, including SOS1 and SOS2. A dual-luciferase reporter assay showed significantly decreased luciferase activity upon ectopic overexpression of miR-148a in HEK-293T cells that were co-transfected with the 3'UTR of either SOS1 or SOS2.

Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation.

The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues.

Identification of C/EBPα as a novel target of the HPV8 E6 protein regulating miR-203 in human keratinocytes.

Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet.

Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration.

An intronic GGGGCC expansion in C9orf72 is the most common known cause of both frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat expansion leads to the generation of sense and antisense repeat RNA aggregates and dipeptide repeat (DPR) proteins, generated by repeat-associated non-ATG translation. The arginine-rich DPR proteins poly(glycine-arginine or GR) and poly(proline-arginine or PR) are potently neurotoxic and can localise to the nucleolus when expressed in cells, resulting in enlarged nucleoli with disrupted functionality.