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Heart rate acceleration at relative workloads during treadmill and overground running for tracking exercise performance during functional overreaching
2020
AbstractMaximal rate of heart rate (HR) increase (rHRI) as a measure of HR acceleration during the transition from rest to exercise, or during an increase in workload, tracks exercise performance. rHRI assessed at relative rather than absolute workloads may track performance better, and a field test would increase applicability. This study therefore aimed to evaluate the sensitivity of rHRI assessed at individualised relative workloads during treadmill and overground running for tracking exercise performance. Treadmill running performance (5 km time trial; 5TTT) and rHRI were assessed in 11 male runners following 1 week of light training (LT), 2 weeks of heavy training (HT) and a 10-day tap…
Drosophila Full-Length Amyloid Precursor Protein is Required for Visual Working Memory and Prevents Age-Related Memory Impairment
2018
Summary The β-amyloid precursor protein (APP) plays a central role in the etiology of Alzheimer's disease (AD). However, its normal physiological functions are still unclear. APP is cleaved by various secretases whereby sequential processing by the β- and γ-secretases produces the β-amyloid peptide that is accumulating in plaques that typify AD. In addition, this produces secreted N-terminal sAPPβ fragments and the APP intracellular domain (AICD). Alternative cleavage by α-secretase results in slightly longer secreted sAPPα fragments and the identical AICD. Whereas the AICD has been connected with transcriptional regulation, sAPPα fragments have been suggested to have a neurotrophic and neu…
The emerging role of Notch pathway in ageing: Focus on the related mechanisms in age-related diseases
2016
Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until …
Precuneus Dysfunction in Parkinson's Disease With Mild Cognitive Impairment.
2018
Background: Mild cognitive impairment (MCI) frequently occurs in Parkinson's disease (PD). Neurovascular changes interact with neurodegenerative processes in PD. However, the deficits of cerebral blood flow (CBF) perfusion and the associated functional connectivity (FC) in PD patients with MCI (PD-MCI) remain unclear. Purpose: This study aimed to explore the specific neurovascular perfusion alterations in PD-MCI compared to PD with normal cognition (PD-NC) and healthy controls (HCs), and to further examine the resultant whole brain FC changes in the abnormal perfusion regions. Methods: Relative CBF (rCBF) was calculated using arterial spin labeling (ASL) in 54 patients with PD (27 patients …
Longevity-related molecular pathways are subject to midlife “switch” in humans
2019
Emerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that oppos…
Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas
2017
Abstract Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with mi…
ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice: Review
2020
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Untargeted Antifungal Treatment in Nonneutropenic Critically Ill Patients: Should Further Studies Be Performed Based on Trial Sequential Analysis Res…
2018
Peripheral artery disease, redox signaling, oxidative stress – Basic and clinical aspects
2017
Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and re…
The European regulatory environment of rna-based vaccines
2016
A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist t…