The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.
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http://dx.doi.org/10.1023/b:abme.0000017541.82498.37 | DOI Listing |
Hum Mol Genet
January 2025
Department of Human Genetics, Inselspital Bern, University of Bern, Freiburgstrasse 15, Bern 3010, Switzerland.
While de novo missense variants in the BTB domains of atypical RhoGTPase RHOBTB2 cause a severe developmental and epileptic encephalopathy, de novo missense variants in the GTPase domain or bi-allelic truncating variants are associated with more variable neurodevelopmental and seizure phenotypes. Apart from the observation of RHOBTB2 abundance resulting from BTB-domain variants and increased seizure susceptibility in Drosophila overexpressing RhoBTB, our knowledge on RHOBTB2-related pathomechanisms is limited. We now found enrichment for ion channels among the differentially expressed genes from RNA-Seq on fly heads overexpressing RhoBTB.
View Article and Find Full Text PDFFront Oncol
January 2025
Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.
Introduction: -rearrangements define a subclass of acute leukemias characterized by a distinct gene expression signature linked to the dysfunctional oncogenic fusion proteins arising from various chromosomal translocations involving the (also known as ) gene. Research on the disease pathomechanism in -rearranged acute leukemias has mainly focused on the upregulation of the stemness-related genes of the -family and their co-factor .
Results: Here we report the and fusion gene-dependent downregulation of , a TGF-β signaling axis transcription factor.
Int J Biol Macromol
January 2025
College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, 330045, PR China. Electronic address:
Due to the lack of specific antibody anti-chicken tumor necrosis factor receptor-associated factor 2 (TRAF2), it is difficult to further explore the role of TRAF2 in pulmonary artery remodeling in pulmonary hypertension(PH) in broilers. In this experiment, we prepared a polyclonal antibody to TRAF2 by constructing a TRAF2 recombinant protein prokaryotic expression vector and analyzed the expression of TRAF2 in in vivo and in vitro models of pulmonary hypertension in broiler chickens and the effect of TRAF2 on the activity and apoptosis of PASMCs. The results showed that after immunization with TRAF2 recombinant protein we obtained high titers of polyclonal antibodies, and astragalus polysaccharide as an immune adjuvant could enhance the effect of immunization.
View Article and Find Full Text PDFMamm Genome
December 2024
Experimental Medicine Centre, Medical University of Bialystok, Bialystok, Poland.
Phosphofurin acidic cluster sorting protein 2 (PACS2) plays a vital role in maintaining cellular homeostasis by regulating protein trafficking between cellular membranes. This function impacts crucial processes like apoptosis, mitochondria-endoplasmic reticulum interaction, and subsequently Ca flux, lipid biosynthesis, and autophagy. Missense mutations, particularly E209K and E211K, are linked to developmental and epileptic encephalopathy-66 (DEE66), known as PACS2 syndrome.
View Article and Find Full Text PDFEur J Pharmacol
January 2025
Postgraduation Program in Biological Sciences: Biochemistry, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, 90035-007, Brazil. Electronic address:
The biochemical hallmark of D-2-hydroxyglutaric aciduria is brain accumulation of D-2-hydroxyglutaric acid (D2HG). Patients present predominantly neurological manifestations, whose pathogenesis is still unknown. Thus, we examined the impact of elevated brain levels of D2HG, induced by intracerebral injection of this metabolite in juvenile rats, on redox and mitochondrial homeostasis and histochemical landmarks in the cerebral cortex.
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