Dynamics of Alfvén waves in the night-side ionospheric Alfvén resonator at mid-latitudes

International audienceA numerical solution of the problem on dynamics of shear-mode Alfvén waves in the ionospheric Alfvén resonator (IAR) region at middle latitudes at nighttime is presented for a case when a source emits a single pulse of duration ? into the resonator region. It is obtained that a part of the pulse energy is trapped by the IAR. As a result, there occur Alfvén waves trapped by the resonator which are being damped. It is established that the amplitude of the trapped waves depends essentially on the emitted pulse duration ? and it is maximum at ?=(3/4)T, where T is the IAR fundamental period. The maximum amplitude of these waves does not exceed 30% of the initial pulse even under optimum conditions. Relatively low efficiency of trapping the shear-mode Alfvén waves is caused by a difference between the optimum duration of the pulse and the fundamental period of the resonator. The period of oscillations of the trapped waves is approximately equal to T, irrespective of the pulse duration ?. The characteristic time of damping of the trapped waves ?dec is proportional to T, therefore the resonator Q-factor for such waves is independent of T. For a periodic source the amplitude-frequency characteristic of the IAR has a local minimum at the frequency ?/?=(3/4)T, and the waves of such frequency do not accumulate energy in the resonator region. At the fundamental frequency ?=2?/T the amplitude of the waves coming from the periodic source can be amplified in the resonator region by more than 50%. This alone is a basic difference between efficiencies of pulse and periodic sources of Alfvén waves. Explicit dependences of the IAR characteristics (T, ?dec, Q-factor and eigenfrequencies) on the altitudinal distribution of Alfvén velocity are presented which are analytical approximations of numerical results

Biochemical indicators of sports achievements in highly qualified wrestlers

Objective: to conduct comparative analysis of blood biochemical parameters (urea, ALT, AST, creatinkinase, cortisol, testosterone and testosterone / cortisol ratio) in groups of high­class wrestlers with different levels of sports achievements.Materials and methods: male athletes (n = 78), members of the Russian national team in one of the types of wrestling (the average age is 25.2 (21.5–28.9) years, the average weight is 76.9 (68.4–83.4) kg) were recruited to this study. The examined athletes were divided into two groups according to their sporting achievements. The first one — SHA group (super­high achievements) which included athletes (n = 19) who had victories and prizes at the largest international competitions (European, World, Olympic Games), and the second group — MNT group (members of the national team) which included athletes that did not have similar achievements (n = 59). The following biochemical parameters were studied: urea, creatine kinase, ALT, AST, testosterone, cortisol, anabolic index (AI).Results: the absolute values of all metabolites in the examined athletes were within the reference intervals. Statistically significant differences in most of the biochemical parameters were revealed between the compared groups in terms of the level of sports achievements. The SHA group showed a statistically significant shift in relation to MNT group, in direction of increasing the level of metabolites that characterize the predominance of anabolic processes — ALT, testosterone, AI. Metabolite levels, increase which reflects catabolic processes activity and inadequate or insufficient adaptation processes, in the SHA group were significantly lower than in the MNT group. The above changes of the absolute values of biochemical parameters were confirmed by correlation analysis.Conclusions: the obtained results allow us to state the optimal adaptation of this sport, the adequacy of metabolic processes in the group of highly qualified athletes

The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis

DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.This research was supported by USPHS grant NS073976 (TKH) and P30 ES 06676 that support the NIEHS Center Cell Biology Core and Molecular Genomics Core of UTMB’s NIEHS Center for DNA sequencing. TKP is supported by CA129537 and CA154320. This work was also supported by Fundação para a Ciência e Tecnologia through the project [PTDC/SAU-GMG/101572/2008] and through fellowships [SFRH/BPD/91562/2012 to ASF, SFRH/BD/51059/2010 to ANC]. IB is supported by NIEHS R01 ES018948 and NIAID/AI06288

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.This study was funded by NIH grant NS073976 to TKH and a John Sealy Grant to PSS

Observation of the electromagnetic field effect via charge-dependent directed flow in heavy-ion collisions at the Relativistic Heavy Ion Collider

The deconfined quark-gluon plasma (QGP) created in relativistic heavy-ion collisions enables the exploration of the fundamental properties of matter under extreme conditions. Non-central collisions can produce strong magnetic fields on the order of $10^{18}$ Gauss, which offers a probe into the electrical conductivity of the QGP. In particular, quarks and anti-quarks carry opposite charges and receive contrary electromagnetic forces that alter their momenta. This phenomenon can be manifested in the collective motion of final-state particles, specifically in the rapidity-odd directed flow, denoted as $v_1(\mathsf{y})$. Here we present the charge-dependent measurements of $dv_1/d\mathsf{y}$ near midrapidities for $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ in Au+Au and isobar ($_{44}^{96}$Ru+$_{44}^{96}$Ru and $_{40}^{96}$Zr+$_{40}^{96}$Zr) collisions at $\sqrt{s_{\rm NN}}=$ 200 GeV, and in Au+Au collisions at 27 GeV, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The combined dependence of the $v_1$ signal on collision system, particle species, and collision centrality can be qualitatively and semi-quantitatively understood as several effects on constituent quarks. While the results in central events can be explained by the $u$ and $d$ quarks transported from initial-state nuclei, those in peripheral events reveal the impacts of the electromagnetic field on the QGP. Our data put valuable constraints on the electrical conductivity of the QGP in theoretical calculations