YqiC of Salmonella enterica serovar Typhimurium is a membrane fusogenic protein required for mice colonization

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>serovar Typhimurium is an intracellular bacterial pathogen which can colonize a variety of hosts, including human, causing syndromes that vary from gastroenteritis and diarrhea to systemic disease.</p> <p>Results</p> <p>In this work we present structural information as well as insights into the <it>in vivo </it>function of YqiC, a 99-residue protein of <it>S</it>. Typhimurium, which belongs to the cluster of the orthologous group 2960 (COG2960). We found that YqiC shares biophysical and biochemical properties with <it>Brucella abortus </it>BMFP, the only previously characterized member of this group, such as a high alpha helix content, a coiled-coil domain involved in trimerization and a membrane fusogenic activity <it>in vitro</it>. In addition, we demonstrated that YqiC localizes at cytoplasmic and membrane subcellular fractions, that a <it>S</it>. Typhimurium <it>yqiC </it>deficient strain had a severe attenuation in virulence in the murine model when inoculated both orally and intraperitoneally, and was impaired to replicate at physiological and high temperatures <it>in vitro</it>, although it was still able to invade and replicate inside epithelial and macrophages cell lines.</p> <p>Conclusion</p> <p>This work firstly demonstrates the importance of a COG2960 member for pathogen-host interaction, and suggests a common function conserved among members of this group.</p

GRACKLE: a chemistry and cooling library for astrophysics

We present the Grackle chemistry and cooling library for astrophysical simulations and models. Grackle provides a treatment of non-equilibrium primordial chemistry and cooling for H, D, and He species, including H2 formation on dust grains; tabulated primordial and metal cooling; multiple UV background models; and support for radiation transfer and arbitrary heat sources. The library has an easily implementable interface for simulation codes written in C, C++, and Fortran as well as a Python interface with added convenience functions for semi-analytical models. As an open-source project, Grackle provides a community resource for accessing and disseminating astrochemical data and numerical methods. We present the full details of the core functionality, the simulation and Python interfaces, testing infrastructure, performance, and range of applicability. Grackle is a fully open-source project and new contributions are welcome.Comment: 20 pages, 8 figures, accepted for publication in MNRAS. For more info, visit grackle.readthedocs.i

FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention

Artificial gauge fields for the Bose-Hubbard model on a checkerboard superlattice and extended Bose-Hubbard model

We study the effects of an artificial gauge field on the ground-state phases of the Bose-Hubbard model on a checkerboard superlattice in two dimensions, including the superfluid phase and the Mott and alternating Mott insulators. First, we discuss the single-particle Hofstadter problem, and show that the presence of a checkerboard superlattice gives rise to a magnetic flux-independent energy gap in the excitation spectrum. Then, we consider the many-particle problem, and derive an analytical mean-field expression for the superfluid-Mott and superfluid--alternating-Mott insulator phase transition boundaries. Finally, since the phase diagram of the Bose-Hubbard model on a checkerboard superlattice is in many ways similar to that of the extended Bose-Hubbard model, we comment on the effects of magnetic field on the latter model, and derive an analytical mean-field expression for the superfluid-insulator phase transition boundaries as well.Comment: 8 pages, 5 figures and 1 table; to appear in EPJ

Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro

Oligodendrocytes: biology and pathology

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation, migration, differentiation, and myelination to finally produce the insulating sheath of axons. Due to this complex differentiation program, and due to their unique metabolism/physiology, oligodendrocytes count among the most vulnerable cells of the CNS. In this review, we first describe the different steps eventually culminating in the formation of mature oligodendrocytes and myelin sheaths, as they were revealed by studies in rodents. We will then show differences and similarities of human oligodendrocyte development. Finally, we will lay out the different pathways leading to oligodendrocyte and myelin loss in human CNS diseases, and we will reveal the different principles leading to the restoration of myelin sheaths or to a failure to do so