Purpose: 2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood.
Methods: Healthy wild-type mice of both sexes (2-21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons.
Importance: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide.
Objective: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery.
Evidence Acquisition: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery.
The matrix metalloprotease ADAMTS7 has been identified by multiple genome-wide association studies as being involved in the development of coronary artery disease. Subsequent research revealed the proteolytic function of the enzyme to be relevant for atherogenesis and restenosis after vessel injury. Based on a publicly known dual ADAMTS4/ADAMTS5 inhibitor, we have in silico designed an ADAMTS7 inhibitor of the catalytic domain, which served as a starting point for an optimization campaign.
View Article and Find Full Text PDFJ Craniomaxillofac Surg
January 2024
The aim of this study was to investigate the impact of orthognathic therapy on patients' quality of life. Therefore, a systematic review was conducted including all prospective studies that compared pretherapeutic and posttherapeutic Oral Health Impact Profile (OHIP) or Overall Quality of Life (OQOL) questionnaire scores. Studies in patients with congenital deformities, clefts, or posttraumatic or cancer-associated deformities were excluded.
View Article and Find Full Text PDFBackground: COVID-19 is a worldwide pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various pathological conditions.
View Article and Find Full Text PDFThe actin cytoskeleton is of fundamental importance for cellular structure and plasticity. However, abundance and function of filamentous actin in the nucleus are still controversial. Here we show that the actin-based molecular motor myosin VI contributes to the stabilization of stalled or reversed replication forks.
View Article and Find Full Text PDFBackground: The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity.
View Article and Find Full Text PDFFTSJ1 is a conserved human 2'-O-methyltransferase (Nm-MTase) that modifies several tRNAs at position 32 and the wobble position 34 in the anticodon loop. Its loss of function has been linked to X-linked intellectual disability (XLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear.
View Article and Find Full Text PDFSeveral collagen subtypes are involved in pancreatic ductal adenocarcinoma (PDAC) desmoplasia, which constrains therapeutic efficacy. We evaluated collagen type VIII alpha 1 chain (COL8A1), whose function in PDAC is currently unknown. We identified COL8A1 expression in 7 examined PDAC cell lines by microarray analysis, western blotting, and RT‒qPCR.
View Article and Find Full Text PDFBi-allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the "AP4 deficiency syndrome." Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936).
View Article and Find Full Text PDFThe transient receptor potential cation channel, subfamily M, members 6 and 7 (TRPM6 and TRPM7) are homologous membrane proteins encompassing cation channel units fused to cytosolic serine/threonine-protein kinase domains. Clinical studies and experiments with animal disease models suggested that selective inhibition of TRPM6 and TRPM7 currents might be beneficial for subjects with immune and cardiovascular disorders, tumours and other pathologies, but the suitable pharmacological toolkit remains underdeveloped. The present study identified small synthetic molecules acting specifically on the channel moieties of TRPM6 and TRPM7.
View Article and Find Full Text PDFBackground: Prostaglandin E (PGE) increases pulmonary vascular permeability by activation of the PGE receptor 3 (EP), which may explain adverse pulmonary effects of the EP/EP receptor agonist sulprostone in patients. In addition, PGE contributes to pulmonary oedema in response to platelet-activating factor (PAF). PAF increases endothelial permeability by recruiting the cation channel transient receptor potential canonical 6 (TRPC6) to endothelial caveolae acid sphingomyelinase (ASMase).
View Article and Find Full Text PDFZn, Mg and Ca are essential divalent cations implicated in many metabolic processes and signalling pathways. An emerging new paradigm is that the organismal balance of these cations predominantly depends on a common gatekeeper, the channel-kinase TRPM7. Despite extensive electrophysiological studies and recent cryo-EM analysis, an open question is how the channel activity of TRPM7 is activated.
View Article and Find Full Text PDFBackground: Interorgan cross-talk describes the phenomenon in which a primarily injured organ causes secondary damage to a distant organ. This cross-talk is well known between the lung and brain. One theory suggests that the release and systemic distribution of cytokines the bloodstream from the primarily affected organ sets in motion proinflammatory cascades in distant organs.
View Article and Find Full Text PDFObjectives: There are disparities in the adherence to guideline-recommended therapies after coronary artery bypass graft (CABG). We therefore sought to evaluate the effect of guideline-adherent medical secondary prevention on 1-year outcome after CABG.
Methods: Data were taken from the randomized 'Ticagrelor in CABG' trial.
Purpose: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype-phenotype correlations.
Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases.
Proc Natl Acad Sci U S A
September 2021
Sex strongly impacts genome evolution via recombination and segregation. In the absence of these processes, haplotypes within lineages of diploid organisms are predicted to accumulate mutations independently of each other and diverge over time. This so-called "Meselson effect" is regarded as a strong indicator of the long-term evolution under obligate asexuality.
View Article and Find Full Text PDFFar too often, one meets patients who went for years or even decades from doctor to doctor without obtaining a valid diagnosis. This brings pain to millions of patients and their families, not to speak of the enormous costs. Often patients cannot tell precisely enough which factors (or combinations thereof) trigger their problems.
View Article and Find Full Text PDFDespite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance.
View Article and Find Full Text PDFInteractome maps are valuable resources to elucidate protein function and disease mechanisms. Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions. This network reveals interconnectivity across diseases and links many known ND-causing proteins, such as α-synuclein, TDP-43, and ATXN1, to a host of proteins previously unrelated to NDs.
View Article and Find Full Text PDFThe first measurement at the LHC of charge-dependent directed flow (v_{1}) relative to the spectator plane is presented for Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV. Results are reported for charged hadrons and D^{0} mesons for the transverse momentum intervals p_{T}>0.
View Article and Find Full Text PDFThe first evidence of spin alignment of vector mesons (K^{*0} and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element ρ_{00} is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at a center-of-mass energy (sqrt[s_{NN}]) of 2.
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