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Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.
Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit
Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-Golgi network-proximal CTLA-4 vesicles for surface expression.
Despite playing a central role in tolerance, little is known regarding the mechanism by which intracellular CTLA-4 is shuttled from the trans-Golgi network to the surfaces of T cells. In this context, Ras-related GTPase Rab8 plays an important role in the intracellular transport, while we have previously shown that CTLA-4 binds to the immune cell adaptor TRIM in T cells. In this study, we demonstrate that CTLA-4 forms a multimeric complex comprised of TRIM and related LAX that in turn binds to GTP bound Rab8 for post-Golgi transport to the cell surface. LAX bound via its N terminus to active GTP-Rab8, as well as the cytoplasmic tail of CTLA-4. TRIM required LAX for binding to Rab8 in a complex. Wild-type LAX or its N terminus (residues 1 to 77) increased CTLA-4 surface expression, whereas small interfering RNAs of Rab8 or LAX or disruption of LAX/Rab8 binding reduced numbers of CTLA-4-containing vesicles and its coreceptor surface expression. LAX also promoted the polarization of CTLA-4 and the reorientation of the microtubule-organizing center to the site of T-cell receptor engagement. Our results identify a novel CTLA-4/TRIM/LAX/Rab8 effector complex in the transport of CTLA-4 to the surfaces of T cells
Effects of Vegetarian Nutrition–A Nutrition Ecological Perspective
Although vegetarian nutrition is a complex issue, the multidimensionality and interrelatedness of its effects are rarely explored. This article aims to demonstrate the complexity of vegetarian nutrition by means of the nutrition ecological modeling technique NutriMod. The integrative qualitative cause-effect model, which is based on scientific literature, provides a comprehensive picture of vegetarian nutrition. The nutrition ecological perspective offers a basis for the assessment of the effects of worldwide developments concerning shifts in diets and the effects of vegetarian nutrition on global problems like climate change. Furthermore, new research areas on the complexity of vegetarian nutrition can be identified
Distinct Binding and Immunogenic Properties of the Gonococcal Homologue of Meningococcal Factor H Binding Protein
Neisseria meningitidis is a leading cause of sepsis and meningitis. The bacterium recruits factor H (fH), a negative regulator of the complement system, to its surface via fH binding protein (fHbp), providing a mechanism to avoid complement-mediated killing. fHbp is an important antigen that elicits protective immunity against the meningococcus and has been divided into three different variant groups, V1, V2 and V3, or families A and B. However, immunisation with fHbp V1 does not result in cross-protection against V2 and V3 and vice versa. Furthermore, high affinity binding of fH could impair immune responses against fHbp. Here, we investigate a homologue of fHbp in Neisseria gonorrhoeae, designated as Gonococcal homologue of fHbp (Ghfp) which we show is a promising vaccine candidate for N. meningitidis. We demonstrate that Gfhp is not expressed on the surface of the gonococcus and, despite its high level of identity with fHbp, does not bind fH. Substitution of only two amino acids in Ghfp is sufficient to confer fH binding, while the corresponding residues in V3 fHbp are essential for high affinity fH binding. Furthermore, immune responses against Ghfp recognise V1, V2 and V3 fHbps expressed by a range of clinical isolates, and have serum bactericidal activity against N. meningitidis expressing fHbps from all variant groups
Detection of correlated galaxy ellipticities on CFHT data: first evidence for gravitational lensing by large-scale structures
We report the detection of a significant (5.5 sigma) excess of correlations
between galaxy ellipticities at scales ranging from 0.5 to 3.5 arc-minutes.
This detection of a gravitational lensing signal by large-scale structure was
made using a composite high quality imaging survey of 6300 arcmin^2 obtained at
the Canada France Hawaii Telescope (CFHT) with the UH8K and CFH12K panoramic
CCD cameras. The amplitude of the excess correlation is 2.2\pm 0.2 % at 1
arcmin scale, in agreement with theoretical predictions of the lensing effect
induced by large-scale structure.We provide a quantitative analysis of
systematics which could contribute to the signal and show that the net effect
is small and can be corrected for. We show that the measured ellipticity
correlations behave as expected for a gravitational shear signal. The
relatively small size of our survey precludes tight constraints on cosmological
models. However the data are in favor of cluster normalized cosmological
models, and marginally reject Cold Dark Matter models with (Omega=0.3,
sigma_8<0.6) or (Omega=1, sigma_8=1). The detection of cosmic shear
demonstrates the technical feasibility of using weak lensing surveys to measure
dark matter clustering and the potential for cosmological parameter
measurements, in particular with upcoming wide field CCD cameras.Comment: 19 pages. 19 Figures. Revised version accepted in A&
Electrode material release during high voltage breakdown Final technical report
Electrode material release during high voltage breakdow
Towards designing robust coupled networks
Natural and technological interdependent systems have been shown to be highly
vulnerable due to cascading failures and an abrupt collapse of global
connectivity under initial failure. Mitigating the risk by partial
disconnection endangers their functionality. Here we propose a systematic
strategy of selecting a minimum number of autonomous nodes that guarantee a
smooth transition in robustness. Our method which is based on betweenness is
tested on various examples including the famous 2003 electrical blackout of
Italy. We show that, with this strategy, the necessary number of autonomous
nodes can be reduced by a factor of five compared to a random choice. We also
find that the transition to abrupt collapse follows tricritical scaling
characterized by a set of exponents which is independent on the protection
strategy
Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells
Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 μg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1β, TGF-α, TGF-β1 and TGF-β2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 μg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120 μg/ml treatment. TETRA caused (i) higher expression of CASP-3, CASP-9, TGF-α, IL-1B, GPX3 and SOD3 but (ii) decreased levels of TGF-B2 and SOD2. ATP production and spare respiratory capacity declined with TETRA treatment. Cellular metabolism was reduced with CPFX 120 μg/ml in all cultures and 60 μg/ml after 72 h. The CPFX 120 μg/ml reduced MMP in all cultures and ROS levels (72 h). CPFX treatment (i) increased expression of CASP-3, CASP-9, and BCL2-L13, (ii) elevated the basal oxygen consumption rate, and (iii) lowered the mtDNA copy numbers and expression levels of TGF-B2, IL-6 and IL-1B compared to vehicle-control cells. We conclude that clinically relevant dosages of bactericidal and bacteriostatic antibiotics can have negative effects on the cellular metabolism and mitochondrial membrane potential of the retinal MIO-M1 cells in vitro. It is noteworthy to mention that apoptotic and inflammatory pathways in exposed cells were affected significantly This is the first study showing the negative impact of fluoroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells
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