Search results for "OLD"
showing 10 items of 6469 documents
NMR Investigation of Structures of G-Protein Coupled Receptor Folding Intermediates
2016
Folding of G-protein coupled receptors (GPCRs) according to the two-stage model (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031-4037) is postulated to proceed in 2 steps: partitioning of the polypeptide into the membrane followed by diffusion until native contacts are formed. Herein we investigate conformational preferences of fragments of the yeast Ste2p receptor using NMR. Constructs comprising the first, the first two, and the first three transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently linked to TM7 were examined. We observed that the isolated TM1 does not form a stable helix nor does it integrate well into the micelle. TM1 is significant…
Thermosensory mapping of skin wetness sensitivity across the body of young males and females at rest and following maximal incremental running
2019
Key points: Humans lack skin receptors for wetness (i.e. hygroreceptors), yet we present a remarkable wetness sensitivity. Afferent inputs from skin cold-sensitive thermoreceptors are key for sensing wetness; yet, it is unknown whether males and females differ in their wetness sensitivity across their body and whether high intensity exercise modulates this sensitivity. We mapped sensitivity to cold, neutral and warm wetness across five body regions and show that females are more sensitive to skin wetness than males, and that this difference is greater for cold than warm wetness sensitivity. We also show that a single bout of maximal exercise reduced the sensitivity to skin wetness (i.e. hyg…
Analysis of cold activation of the contact system in hereditary angioedema with normal C1 inhibitor.
2021
Hereditary angioedema (HAE) attacks are caused by excessive activation of the contact system. Understanding how the contact system is activated in HAE, especially in patients with normal C1 inhibitor (HAEnCI), is essential to effectively treat this disease. Contact system activation involves the cleavage of several proteins including Factor XII (FXII), high molecular weight kininogen (HK), prekallikrein, sgp120 (ITIH4) and C1 inhibitor (C1-INH) before the subsequent generation of bradykinin that mediates HAE. In this study, we evaluated the fragmentation and enzymatic activity of contact system proteins in HAEnCI plasma samples before and after contact system activation induced by incubatio…
IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss
2021
This article belongs to the Collection Insulin-Like Growth Factors in Development, Cancers and Aging.
Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress
2017
Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspa…
Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis.
2019
Frailty syndrome is prevalent among hospitalized older adults as are the occurrence of adverse outcomes. This systematic review and meta-analysis investigated whether frailty in older adults at hospital admission predicts adverse outcomes. Manual (ProQuest, conferences annals and references) and electronic searches (PUBMED, EMBASE, Web of Science, Lilacs, CINAHL, PsycINFO and Google Scholar) were performed. We included prospective studies of hospitalized older adults. Primary outcomes were functional decline at hospital discharge and mortality after discharge. Other data were considered secondary outcomes. Methodological quality was evaluated by the Quality Assessment Tool for Observational…
Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction
2017
In endothelial cells, the tight control of the redox environment is essential for the maintenance of vascular homeostasis. The imbalance between ROS production and antioxidant response can induce endothelial dysfunction, the initial event of many cardiovascular diseases. Recent studies have revealed that the endoplasmic reticulum could be a new player in the promotion of the pro- or antioxidative pathways and that in such a modulation, the unfolded protein response (UPR) pathways play an essential role. The UPR consists of a set of conserved signalling pathways evolved to restore the proteostasis during protein misfolding within the endoplasmic reticulum. Although the first outcome of the U…
THE EFFICACY AND SAFETY OF INFLUENZA VACCINATION IN OLDER PEOPLE: AN UMBRELLA REVIEW OF EVIDENCE FROM META-ANALYSES OF BOTH OBSERVATIONAL AND RANDOMI…
2020
Vaccination is the main public health intervention to prevent influenza. We aimed to evaluate the efficacy and safety of influenza vaccination including systematic reviews and meta-analyses of observational studies and randomized controlled trials (RCTs). Peer-reviewed systematic reviews with meta-analyses of prospective studies that investigated the association of influenza vaccination with any health-related outcome, as well as RCTs that investigated the efficacy and safety of influenza vaccination, were included. Among 1240 references, 6 meta-analyses were included. In cohort studies of community-dwelling older people influenza vaccination was associated with a lower risk of hospitalizat…
The Early Indicators of Functional Decrease in Mild Cognitive Impairment
2016
OBJECTIVES: Motor deficiency is associated with cognitive frailty in patients with Mild Cognitive Impairments (MCI). In this study we aimed to test the integrity of the muscle synergy involved in an arm-pointing movement in MCI patients, non-impaired functionally. Thus, we were able to test the hypothesis that early motor indicators exist in this population at a preclinical level. METHODS: The electromyographic signals were collected for 11 muscles in 3 groups: Young Adults (YA), Aged Adults (AA), and MCI patients. The AA and MCI groups presented the same functional status. Each subject performed twenty arm-pointing movements from a standing position. RESULTS: The main differences were (1) …
MiRNome of epileptic children suggests the involvement of antioxidant pathways in the neuroprotective role of ketogenic diet
2018
Ketogenic diet (KD) has been used as treatment for refractory epilepsy in children since the 1920s. However, the neuroprotective mechanism of this diet is still unknown. Recent evidence points to a multifactorial effect of KD that involves a decrease of oxidative stress. Mononuclear cells from 14 children with refractory epilepsy, from the Paediatric Hospital “Nino Jesus” in Madrid, were obtained before and after treatment with a ketogenic diet for 6 months. A global analysis of miRNA expression (miRNome) indicates that there are 230 miRNAs which are expressed differently before and after the treatment with KD. If additionally, we restrict the miRNAs with a fold change > |1.3|we obtain 11 r…