Osteoarthritis and Neurological Disorder Diagnoses in Adults: A Meta-Analysis Examining Associations With Parkinson's Disease, Multiple Sclerosis, and Alzheimer's Disease.

Osteoarthritis (OA) is a highly prevalent joint disorder that is emerging as a global threat to health. OA is associated with low-grade chronic systemic inflammation that can affect overall health, leading to a sedentary lifestyle and potentially increased risk of neurological disorders (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). A meta-analysis was conducted following the Preferred Reporting Items for 2020 Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Functional lower extremity strength influences stepping strategy in community-dwelling older adults during single and dual-task walking.

As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies.

Functional Lower Extremity Strength Influences Stepping Strategy in Community-Dwelling Older Adults During Single and Dual-Task Walking.

As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies.

Effects of Stroboscopic Vision on Depth Jump Motor Control: A Biomechanical Analysis.

Researchers commonly use the 'free-fall' paradigm to investigate motor control during landing impacts, particularly in drop landings and depth jumps (DJ). While recent studies have focused on the impact of vision on landing motor control, previous research fully removed continuous visual input, limiting ecological validity. The aim of this investigation was to evaluate the effects of stroboscopic vision on depth jump (DJ) motor control.

Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry.

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets.

Building a life sciences innovation ecosystem.

Universities should support research with commercial potential, provide a supportive environment for start-ups, and partner enthusiastically with the private sector.

Nogo-B receptor is necessary for cellular dolichol biosynthesis and protein N-glycosylation.

Dolichol monophosphate (Dol-P) functions as an obligate glycosyl carrier lipid in protein glycosylation reactions. Dol-P is synthesized by the successive condensation of isopentenyl diphosphate (IPP), with farnesyl diphosphate catalysed by a cis-isoprenyltransferase (cis-IPTase) activity. Despite the recognition of cis-IPTase activity 40 years ago and the molecular cloning of the human cDNA encoding the mammalian enzyme, the molecular machinery responsible for regulating this activity remains incompletely understood.

Eph-B4 prevents venous adaptive remodeling in the adult arterial environment.

Eph-B4 determines mammalian venous differentiation in the embryo but is thought to be a quiescent marker of adult veins. We have previously shown that surgical transposition of a vein into the arterial environment is characterized by loss of venous identity, as indicated by the loss of Eph-B4, and intimal thickening. We used a mouse model of vein graft implantation to test the hypothesis that Eph-B4 is a critical determinant of venous wall thickness during postsurgical adaptation to the arterial environment.

Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking.

The Nogo-B receptor (NgBR) is a recently identified receptor for the N terminus of reticulon 4B/Nogo-B. Other than its role in binding Nogo-B, little is known about the biology of NgBR. To elucidate a basic cellular role for NgBR, we performed a yeast two-hybrid screen for interacting proteins, using the C-terminal domain as bait, and identified Niemann-Pick type C2 protein (NPC2) as an NgBR-interacting protein.

The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo.

Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant.

Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis.

Posttranscriptional gene regulation by microRNAs (miRNAs) is important for many aspects of development, homeostasis, and disease. Here, we show that reduction of endothelial miRNAs by cell-specific inactivation of Dicer, the terminal endonuclease responsible for the generation of miRNAs, reduces postnatal angiogenic response to a variety of stimuli, including exogenous VEGF, tumors, limb ischemia, and wound healing. Furthermore, VEGF regulated the expression of several miRNAs, including the up-regulation of components of the c-Myc oncogenic cluster miR-17-92.

Approaches for studying angiogenesis-related signal transduction.

Understanding how extracellular growth factors activate intracellular pathways that promote angiogenesis is a broad area of research. In this chapter, we outline the systematic dissection of vascular endothelial growth factor (VEGF)-mediated activation of endothelial nitric oxide synthase and other downstream targets that are relevant to the angiogenic response. These approaches may also be applied to most other angiogenic-factor signaling cascades.

Dominant-negative Hsp90 reduces VEGF-stimulated nitric oxide release and migration in endothelial cells.

Objective: Heat-shock protein 90 (Hsp90) coordinates the regulation of diverse signaling proteins. We try to develop a new tool to explore the regulatory functions of Hsp90 in endothelial cells (ECs) instead of the existing chemical approaches.

Methods And Results: We designed a dominant-negative Hsp90 construct by site-direct mutagenesis of residue Asp-88 to Asn (D88N-Hsp90) based on the structure of the ATP/ADP-binding site.

Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells.

Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates vascular function is unknown. Here, we identify a previously uncharacterized Nogo-B receptor specific for the amino terminus of Nogo-B and show that Nogo-B receptor localizes with the ligand Nogo-B during VEGF and wound healing angiogenesis in vivo, mediates chemotaxis in a heterologous expression system and chemotaxis, and 3D tube formation in native endothelial cells.

Functional coupling of chromogranin with the inositol 1,4,5-trisphosphate receptor shapes calcium signaling.

Chromogranins A and B are high capacity, low affinity calcium (Ca(2+)) storage proteins that bind to the inositol 1,4,5-trisphosphate-gated receptor (InsP(3) R). Although most commonly associated with secretory granules of neuroendocrine cells, chromogranins have also been found in the lumen of the endoplasmic reticulum (ER) of many cell types. To investigate the functional consequences of the interaction between the InsP(3) R and the chromogranins, we disrupted the interaction between the two proteins by adding a chromogranin fragment, which competed with chromogranin for its binding site on the InsP(3)R.