Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib.

Background: Acute respiratory distress syndrome (ARDS) in corona virus disease 19 (COVID-19) is triggered by hyperinflammation, thus providing a rationale for immunosuppressive treatments. The Janus kinase inhibitor Ruxolitinib (Ruxo) has shown efficacy in severe and critical COVID-19. In this study, we hypothesized that Ruxo's mode of action in this condition is reflected by changes in the peripheral blood proteome.

Further Extension of Lifespan by and Mutations in Germline-Deficient .

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode , ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators (calcium/calmodulin-dependent kinase type II) and (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor for lifespan extension, but how they functionally interact is unknown.

Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board.

Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept.

Methods: We retrospectively analyzed all patients referred to our center's Molecular Tumor Board (MTB) from 2018 to 2021.

Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans.

Background: In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1's physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C.

Expression of β-1,4-galactosyltransferases during Aging in Caenorhabditis elegans.

Background: Altered plasma activity of β-1,4-galac-tosyl-transferases (B4GALTs) is a novel candidate biomarker of human aging. B4GALT1 is assumed to be largely responsible for this activity increase, but how it modulates the aging process is unclear at present.

Objectives: To determine how expression of B4GALT1 and other B4GALT enzymes changes during aging of an experimentally tractable model organism, Caenorhabditis elegans.

Modulation of serotonin signaling by the putative oxaloacetate decarboxylase FAHD-1 in Caenorhabditis elegans.

Human fumarylacetoacetate hydrolase (FAH) domain containing protein 1 (FAHD1) is a mitochondrial oxalocatate decarboxylase, the first of its kind identified in eukaryotes. The physiological role of FAHD1 in other eukaryotes is still poorly understood. In C.

Comprehensive genetic diagnosis of acute myeloid leukemia by next-generation sequencing.

Differential induction therapy of all subtypes of acute myeloid leukemia other than acute promyelocytic leukemia is impeded by the long time required to complete complex and diverse cytogenetic and molecular genetic analyses for risk stratification or targeted treatment decisions. Here, we describe a reliable, rapid and sensitive diagnostic approach that combines karyotyping and mutational screening in a single, integrated, next-generation sequencing assay. Numerical karyotyping was performed by low coverage whole genome sequencing followed by copy number variation analysis using a novel algorithm based on -generated reference karyotypes.

Emerging topics in C. elegans aging research: Transcriptional regulation, stress response and epigenetics.

Key discoveries in aging research have been made possible with the use of model organisms. Caenorhabditis elegans is a short-lived nematode that has become a well-established system to study aging. The practicality and powerful genetic manipulations associated with this metazoan have revolutionized our ability to understand how organisms age.

The protein kinase MBK-1 contributes to lifespan extension in mutant and germline-deficient .

In , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of and mutant animals while decreasing wild-type lifespan to a lesser extent.

The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines.

Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown.

AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization.

Autophagy is activated in response to a variety of cellular stresses including metabolic stress. While elegant genetic studies in yeast have identified the core autophagy machinery, the signaling pathways that regulate this process are less understood. AMPK is an energy sensing kinase and several studies have suggested that AMPK is required for autophagy.

Autophagy prolongs survival after NFκB inhibition in B-cell lymphomas.

Autophagy allows cells to survive under conditions of nutrient deprivation. We have demonstrated that autophagy inhibitors are synthetically lethal with NFκB inhibitors in B-cell lymphomas because the NFκB pathway promotes survival by increasing glucose import. When NFκB is inhibited in B-cell lymphoma, glucose import decreases and cells become sensitive to perturbations in mitochondrial metabolism and autophagy.

Modulation of autophagy-like processes by tumor viruses.

Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection.