Electric field of a pointlike charge in a strong magnetic field and ground state of a hydrogenlike atom

In an external constant magnetic field, so strong that the electron Larmour length is much shorter than its Compton length, we consider the modification of the Coulomb potential of a point charge owing to the vacuum polarization. We establish a short-range component of the static interaction in the Larmour scale, expressed as a Yukawa-like law, and reveal the corresponding "photon mass" parameter. The electrostatic force regains its long-range character in the Compton scale: the tail of the potential follows an anisotropic Coulomb law, decreasing away from the charge slower along the magnetic field and faster across. In the infinite-magnetic-field limit the potential is confined to an infinitely thin string passing though the charge parallel to the external field. This is the first evidence for dimensional reduction in the photon sector of quantum electrodynamics. The one-dimensional form of the potential on the string is derived that includes a delta-function centered in the charge. The nonrelativistic ground-state energy of a hydrogenlike atom is found with its use and shown not to be infinite in the infinite-field limit, contrary to what was commonly accepted before, when the vacuum polarization had been ignored. These results may be useful for studying properties of matter at the surface of extremely magnetized neutron stars.Comment: 45 pages, 6 figures, accepted to Phys. Rev.

Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.

Most neurodegenerative disorders are associated with accumulation of disease-relevant proteins. Among them, Huntington disease (HD) is of particular interest because of its monogenetic nature. HD is mainly caused by cytotoxicity of the defective protein encoded by the mutant Huntingtin gene (HTT). Thus, lowering mutant HTT protein (mHTT) levels would be a promising treatment strategy for HD. Here we report two kinases HIPK3 and MAPK11 as positive modulators of mHTT levels both in cells and in vivo. Both kinases regulate mHTT via their kinase activities, suggesting that inhibiting these kinases may have therapeutic values. Interestingly, their effects on HTT levels are mHTT-dependent, providing a feedback mechanism in which mHTT enhances its own level thus contributing to mHTT accumulation and disease progression. Importantly, knockout of MAPK11 significantly rescues disease-relevant behavioral phenotypes in a knockin HD mouse model. Collectively, our data reveal new therapeutic entry points for HD and target-discovery approaches for similar diseases

Sequential Assembly of Centromeric Proteins in Male Mouse Meiosis

The assembly of the mitotic centromere has been extensively studied in recent years, revealing the sequence and regulation of protein loading to this chromosome domain. However, few studies have analyzed centromere assembly during mammalian meiosis. This study specifically targets this approach on mouse spermatocytes. We have found that during prophase I, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The last proteins to be assembled are the outer kinetochore proteins BubR1 and CENP-E. All these proteins are not detected at the centromere during anaphase/telophase I and are then reloaded during interkinesis. The loading sequence of the analyzed proteins is similar during prophase I and interkinesis. These findings demonstrate that the interkinesis stage, regularly overlooked, is essential for centromere and kinetochore maturation and reorganization previous to the second meiotic division. We also demonstrate that Shugoshin 2 is necessary for the loading of MCAK at the inner centromere, but is dispensable for the loading of the outer kinetochore proteins BubR1 and CENP-E

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Excitation of the Madden–Julian Oscillation in Atmospheric Adjustment to Equatorial Heating

International audienceAbstract We study the adjustment of the tropical atmosphere to localized surface heating using a Lagrangian atmospheric model (LAM) that simulates a realistic Madden–Julian oscillation (MJO)—the dominant, eastward-propagating mode of tropical intraseasonal variability modulating atmospheric convection. Idealized warm sea surface temperature (SST) anomalies of different aspect ratios and magnitudes are imposed in the equatorial Indian Ocean during MJO-neutral conditions and then maintained for 15 days. The experiments then continue for several more months. Throughout these experiments, we observe a robust generation of an MJO event, evident in precipitation, velocity, temperature, and moisture fields, which becomes a key element of atmospheric adjustment along with the expected Kelvin and Rossby waves. The MJO circulation pattern gradually builds up during the first week, and then starts to propagate eastward at a speed of 5–7 m s −1 . The upper-level quadrupole circulation characteristic of the MJO becomes evident around day 14, with two anticyclonic gyres generated by the Gill-type response to convective heating and two cyclonic gyres forced by the excited Kelvin waves and extratropical Rossby wave trains. A moisture budget analysis shows that the eastward propagation of the MJO is controlled largely by the anomalous advection of moisture and by the residual between anomalous moisture accumulation due to converging winds and precipitation. The initial MJO event is followed by successive secondary events, maintaining the MJO for several more cycles. Thus, this study highlights the fundamental role that the MJO can play in the adjustment of the moist equatorial atmosphere to localized surface heating

Excitation of the Madden–Julian Oscillation in Atmospheric Adjustment to Equatorial Heating

International audienceAbstract We study the adjustment of the tropical atmosphere to localized surface heating using a Lagrangian atmospheric model (LAM) that simulates a realistic Madden–Julian oscillation (MJO)—the dominant, eastward-propagating mode of tropical intraseasonal variability modulating atmospheric convection. Idealized warm sea surface temperature (SST) anomalies of different aspect ratios and magnitudes are imposed in the equatorial Indian Ocean during MJO-neutral conditions and then maintained for 15 days. The experiments then continue for several more months. Throughout these experiments, we observe a robust generation of an MJO event, evident in precipitation, velocity, temperature, and moisture fields, which becomes a key element of atmospheric adjustment along with the expected Kelvin and Rossby waves. The MJO circulation pattern gradually builds up during the first week, and then starts to propagate eastward at a speed of 5–7 m s −1 . The upper-level quadrupole circulation characteristic of the MJO becomes evident around day 14, with two anticyclonic gyres generated by the Gill-type response to convective heating and two cyclonic gyres forced by the excited Kelvin waves and extratropical Rossby wave trains. A moisture budget analysis shows that the eastward propagation of the MJO is controlled largely by the anomalous advection of moisture and by the residual between anomalous moisture accumulation due to converging winds and precipitation. The initial MJO event is followed by successive secondary events, maintaining the MJO for several more cycles. Thus, this study highlights the fundamental role that the MJO can play in the adjustment of the moist equatorial atmosphere to localized surface heating