Inspiratory muscle training and its effect on indices of physiological and perceived stress during incremental walking exercise in normobaric hypoxia

This study evaluated the effects of inspiratory muscle training (IMT) on inspiratory muscle fatigue (IMF) and physiological and perceptual responses during trekking-specific exercise. An 8-week IMT program was completed by 21 males (age 32.4 ± 9.61 years, VO2peak 58.8 ± 6.75 mL/kg/min) randomised within matched pairs to either the IMT group (n = 11) or the placebo group [(P), n = 9]. Twice daily, participants completed 30 (IMT) or 60 (P) inspiratory efforts using a Powerbreathe initially set at a resistance of 50% (IMT) or used at 15% (P) of maximal inspiratory pressure (MIP) throughout. A loaded (12.5 kg) 39-minute incremental walking protocol (3–5 km/hour and 1–15% gradient) was completed in normobaric hypoxia (PIO2 = 110 mmHg, 3000 m) before and after training. MIP increased from 164 to 188 cmH2O (18%) and from 161 to 171 cmH2O (6%) in the IMT and P groups (P = 0.02). The 95% CI for IMT showed a significant improvement in MIP (5.21±43.33 cmH2O), but not for P. IMF during exercise (MIP) was*5%, showing no training effect for either IMT or P (P = 0.23). Rating of perceived exertion (RPE) was consistently reduced (*1) throughout exercise following training for IMT, but not for P (P = 0.03). The mean blood lactate concentration during exercise was significantly reduced by 0.26 and 0.15 mmol/L in IMT and P (P = 0.00), with no differences between groups (P = 0.34). Rating of dyspnoea during exercise decreased (*0.4) following IMT but increased (*0.3) following P (P = 0.01). IMT may attenuate the increased physiological and perceived exercise stress experienced during normobaric hypoxia, which may benefit moderate altitude expedition

N=1 de Sitter Supersymmetry Algebra

Recalling the universal covering group of de Sitter, the transformation properties of the spinor fields $\psi(x)$ and ${\bar\psi}(x)$, in the ambient space notation, are presented in this paper. The charge conjugation symmetry of the de Sitter spinor field is then discussed in the above notation. Using this spinor field and charge conjugation, de Sitter supersymmetry algebra in the ambient space notation has been established. It is shown that a novel dS-superalgebra can be attained by the use of spinor field and charge conjugation in the ambient space notation.Comment: 8 pages, LaTeX, some details adde

Discrete Symmetries for Spinor Field in de Sitter Space

Discrete symmetries, parity, time reversal, antipodal, and charge conjugation transformations for spinor field in de Sitter space, are presented in the ambient space notation, i.e. in a coordinate independent way. The PT and PCT transformations are also discussed in this notation. The five-current density is studied and their transformation under the discrete symmetries is discussed.Comment: 13 pages, LaTeX; appendices adde

Long-term effect of neonatal inhibition of APP gamma-secretase on hippocampal development in the Ts65Dn mouse model of Down syndrome

Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed. Previous evidence showed that neonatal treatment with ELND006, an inhibitor of gamma-secretase, reinstates the Shh pathway and fully restores neurogenesis in Ts65Dn pups. In the framework of potential therapies for DS, it is extremely important to establish whether the positive effects of early intervention are retained after treatment cessation. Therefore, the goal of the current study was to establish whether early treatment with ELND006 leaves an enduring trace in the brain of Ts65Dn mice. Ts65Dn and euploid pups were treated with ELND006 in the postnatal period P3-P15 and the outcome of treatment was examined at ~ one month after treatment cessation. We found that in treated Ts65Dn mice the pool of proliferating cells in the hippocampal dentate gyrus (DG) and total number of granule neurons were still restored as was the number of pre- and postsynaptic terminals in the stratum lucidum of CA3, the site of termination of the mossy fibers from the DG. Accordingly, patch-clamp recording from field CA3 showed functional normalization of the input to CA3. Unlike in field CA3, the number of pre- and postsynaptic terminals in the DG of treated Ts65Dn mice was no longer fully restored. The finding that many of the positive effects of neonatal treatment were retained after treatment cessation provides proof of principle demonstration of the efficacy of early inhibition of gamma-secretase for the improvement of brain development in DS

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome

Study objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies

THGEM operation in Ne and Ne/CH4

The operation of Thick Gaseous Electron Multipliers (THGEM) in Ne and Ne/CH4 mixtures, features high multiplication factors at relatively low operation potentials, in both single- and double-THGEM configurations. We present some systematic data measured with UV-photons and soft x-rays, in various Ne mixtures. It includes gain dependence on hole diameter and gas purity, photoelectron extraction efficiency from CsI photocathodes into the gas, long-term gain stability and pulse rise-time. Position resolution of a 100x100 mm^2 X-rays imaging detector is presented. Possible applications are discussed.Comment: Submitted to JINST, 25 pages, 33 figure

Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure

The initial step in target cell infection by human, and the closely related simian immunodeficiency viruses (HIV and SIV, respectively) occurs with the binding of trimeric envelope glycoproteins (Env), composed of heterodimers of the viral transmembrane glycoprotein (gp41) and surface glycoprotein (gp120) to target T-cells. Knowledge of the molecular structure of trimeric Env on intact viruses is important both for understanding the molecular mechanisms underlying virus-cell interactions and for the design of effective immunogen-based vaccines to combat HIV/AIDS. Previous analyses of intact HIV-1 BaL virions have already resulted in structures of trimeric Env in unliganded and CD4-liganded states at ∼20 Å resolution. Here, we show that the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are closely comparable to that previously determined for HIV-1 BaL, with the V1 and V2 variable loops located at the apex of the spike, close to the contact zone between virus and cell. The location of the V1/V2 loops in trimeric Env was definitively confirmed by structural analysis of HIV-1 R3A virions engineered to express Env with deletion of these loops. Strikingly, in SIV CP-MAC, a CD4-independent strain, trimeric Env is in a constitutively “open” conformation with gp120 trimers splayed out in a conformation similar to that seen for HIV-1 BaL Env when it is complexed with sCD4 and the CD4i antibody 17b. Our findings suggest a structural explanation for the molecular mechanism of CD4-independent viral entry and further establish that cryo-electron tomography can be used to discover distinct, functionally relevant quaternary structures of Env displayed on intact viruses