232 research outputs found
Investigating the effectiveness and feasibility of exercise on microvascular reactivity and quality of life in systemic sclerosis patients: study protocol for a feasibility study
Background: Raynaudâs phenomenon is one of the first clinical manifestations observed in systemic sclerosis (SSc).
This microvasculature disorder affects mostly the digits in over 95% of SSc patients, significantly affecting their healthrelated
quality of life (HRQoL) and incurring higher hospital admissions and other healthcare costs. Exercise is known to
improve both micro- and macrovascular function â aerobic exercise and resistance training, separately or combined,
have been demonstrated to lead to significant vasculo-physiological improvements in conditions that present
vasculopathy. However, the effects of a combined exercise programme on microcirculation in SSc patients has yet to
be investigated. Therefore, the purpose of this study is to assess the effects of high-intensity interval training (HIIT)
combined with circuit resistance training on the microvascular function in the digital area of SSc patients.
Methods: This will be a randomised controlled, feasibility trial with two arms, wherein 30 patients with SSc in receipt
of medical treatment will be randomly assigned to usual care (medical treatment) or to a 12-week supervised exercise
programme. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30 min HIIT (30
s 100% peak power output/30 s passive recovery) on the arm crank ergometer and 15 min of upper body circuit
resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary
outcomes of the study will be recruitment and retention rate, intervention acceptability and adherence to the exercise
programme. Secondary outcomes include the digital area cutaneous microvascular function (laser Doppler fluximetry
combined with iontophoresis), physical fitness, functional ability, upper back transcutaneous oxygen tension, body
composition and quality of life (EQ-5D-5L). Selected interviews with a subsample of patients will be undertaken to
explore their experiences of having Raynaudâs phenomenon and the acceptability of the exercise intervention and
study procedures.
Discussion: Data from this study will be used to identify the feasibility of a combined exercise programme to be
implemented in SSc patients, the acceptability of the intervention and the study design, and to determine the effects
of exercise on the microvasculature. Overall, this study will provide sufficient data to inform and support a full
multicentre clinical trial
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1\u3b2-induced autophagy article
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily "ancient", and three "modern". The MTBC strains belonging to "modern" lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1\u3b2, IL-6, and TNF-\u3b1) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL-1\u3b2, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1\u3b2-induced autophagy is not disadvantageous for the survival of modern Mtb strains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages
The Lysosome and Intracellular Signalling.
In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed
Scaled momentum distributions for K-S(0) and Î /Ì Î in DIS at HERA
Scaled momentum distributions for the strange hadrons K0S and Î/ÎÂŻ were measured in deep inelastic ep scattering with the ZEUS detector at HERA using an integrated luminosity of 330 pbâ1. The evolution of these distributions with the photon virtuality, Q 2, was studied in the kinematic region 10â<âQ 2â <â40000 GeV2 and 0.001â<âxâ<â0.75, where x is the Bjorken scaling variable. Clear scaling violations are observed. Predictions based on different approaches to fragmentation were compared to the measurements. Leading-logarithm parton-shower Monte Carlo calculations interfaced to the Lund string fragmentation model describe the data reasonably well in the whole range measured. Next-to-leading-order QCD calculations based on fragmentation functions, FFs, extracted from e + e â data alone, fail to describe the measurements. The calculations based on FFs extracted from a global analysis including e + e â, ep and pp data give an improved description. The measurements presented in this paper have the potential to further constrain the FFs of quarks, anti-quarks and gluons yielding K0S and Î/ÎÂŻ strange hadrons
Purinergic signalling and immune cells
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells
Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
First measurement of the |t|-dependence of coherent J/Ï photonuclear production
The first measurement of the cross section for coherent J/Ï photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral PbâPb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/Ï produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3â1.4)Ă10â3.
The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent BalitskyâKovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio
First measurement of coherent Ï0 photoproduction in ultra-peripheral XeâXe collisions at âsNN = 5.44 TeV
The first measurement of the coherent photoproduction of Ï0 vector mesons in ultra-peripheral XeâXe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA Îłp data and ÎłâPb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+XeâÏ0+Xe+Xe process, measured at midrapidity through the decay channel Ï0âÏ+Ïâ, is found to be dÏ/dy=131.5±5.6(stat.)â16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent Ï0 photoproduction at a centre-of-mass energy per nucleon of the ÎłA system of WÎłA,n=65 GeV is found to be consistent with a power-law behaviour Ï(ÎłAâÏ0A)âAα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio
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