Further evidence for a variable fine-structure constant from Keck/HIRES QSO absorption spectra

[Abridged] We previously presented evidence for a varying fine-structure constant, alpha, in two independent samples of Keck/HIRES QSO spectra. Here we present a detailed many-multiplet analysis of a third Keck/HIRES sample containing 78 absorption systems. We also re-analyse the previous samples, providing a total of 128 absorption systems over the redshift range 0.2<z_abs<3.7. All three samples separately yield consistent, significant values of da/a. The analyses of low- and high-z systems rely on different ions/transitions with very different dependencies on alpha, yet they also give consistent results. We identify additional random errors in 22 high-z systems characterized by transitions with a large dynamic range in apparent optical depth. Increasing the statistical errors on da/a for these systems gives our fiducial result, a weighted mean da/a=(-0.543+/-0.116)x10^-5, representing 4.7-sigma evidence for a smaller weighted mean alpha in the absorption clouds. Assuming that da/a=0 at z_abs=0, the data marginally prefer a linear increase in alpha with time: dota/a=(6.40+/-1.35)x10^-16 yr^-1. The two-point correlation function for alpha is consistent with zero over 0.2-13 Gpc comoving scales and the angular distribution of da/a shows no significant dipolar anisotropy. We therefore have no evidence for spatial variations in da/a. We extend our previous searches for possible systematic errors, identifying atmospheric dispersion and isotopic structure effects as potentially the most significant. However, overall, known systematic errors do not explain the results. Future many-multiplet analyses of QSO spectra from different telescopes and spectrographs will provide a now crucial check on our Keck/HIRES results.Comment: 31 pages, 25 figures (29 EPS files), 8 tables. Accepted by MNRAS. Colour versions of Figs. 6, 8 & 10 and text version of Table 3 available at http://www.ast.cam.ac.uk/~mim/pub.htm

Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination

Multiple sclerosis (MS) is a progressive inflammatory-demyelinating disease of the central nervous system. Increasing evidence suggests that vulnerable neurons in MS exhibit fatal metabolic exhaustion over time, a phenomenon hypothesized to be caused by chronic hyperexcitability. Axonal Kv7 (outward rectifying) and oligodendroglial Kir4.1 (inward rectifying) potassium channels have important roles in regulating neuronal excitability at and around nodes of Ranvier. Here, we studied the spatial and functional relationship between neuronal Kv7 and oligodendroglial Kir4.1 channels and assessed the transcriptional and functional signatures of cortical and retinal projection neurons under physiological and inflammatory-demyelinating conditions. We found that both channels became dysregulated in MS and experimental autoimmune encephalomyelitis (EAE) with Kir4.1 channels being chronically downregulated and Kv7 channel subunits being transiently upregulated during inflammatory demyelination. Further, we observed that pharmacological Kv7 channel opening with retigabine reduced neuronal hyperexcitability in human and EAE neurons, improved clinical EAE signs and rescued neuronal pathology in oligodendrocyte-Kir4.1-deficient mice. In summary, our findings indicate that neuron-oligodendrocyte compensatory interactions promote resilience through Kv7 and Kir4.1 channels and suggest pharmacological activation of nodal Kv7 channels as a neuroprotective strategy against inflammatory demyelination

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Notch1 control of oligodendrocyte differentiation in the spinal cord.

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo

Frequency and molecular epidemiology of class A ESBLs producing Enteroinvasive Escherichia coli (EIEC) isolates among patients with diarrhea

Aim: This study aimed to investigate the frequency and molecular epidemiology of class A ESBLs producing Enteroinvasive Escherichia coli (EIEC) isolates among patients with diarrhea. Background: Antibiotic resistance is widespread among diarrheagenic Escherichia coli (DEC) in developing countries. Information regarding Extended-Spectrum β-Lactamases (ESBLs) in diarrheagenic pathogens should be considered in clinical management when an optimal treatment is required. Methods: A total of 581 stool samples were collected from patients with diarrhea in Ahvaz, Iran. PCR was used for the presence of the ipaH gene to confirm EIEC strains. The antibiotic resistance pattern of all EIEC isolates was determined by the disk diffusion method. EIEC isolates were screened for class A β-lactamase genes. Genotyping of harboring β-lactamase genes was performed by Multi-Locus VNTR Analysis (MLVA). Results: Among 13 EIEC isolates, 9 isolates (69.2) were found ESBL positive by double-disk synergy test (DDST) and PCR. Furthermore, blaCTX-M-15 and blaCTX-M-1 genes were detected in 77.8 (n=7) and 44.5 (n=4) of the blaCTX-M-1 group. On the other hand, the blaTEM-1 gene was detected in 66.6 (n=6). None of the isolates had blaSHV-1, blaKPC, or blaGES genes. Six MLVA genotypes were identified. Conclusion: The current study revealed that the presence of ESBLs genes mediates the resistance of EIEC isolates to the majority of antibiotics in this region. The presence of ESBLs genes in different MLVA types showed that one specific clone was not responsible for spreading the EIEC isolates. © 2020 RIGLD, Research Institute for Gastroenterology and Liver Diseases

Molekulare Mechanismen und Genetik der Gliazelldifferenzierung. Teilprojekt C8 Abschlussbericht

Available from TIB Hannover: DtF QN1(48,13) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination

Abnormal cell loss is the common cause of a large number of developmental and degenerative diseases. To model such diseases in transgenic animals, we have developed a line of mice that allows the efficient depletion of virtually any cell type in vivo following somatic Cre-mediated gene recombination. By introducing the diphtheria toxin fragment A (DT-A) gene as a conditional expression construct (floxed lacZ-DT-A) into the ubiquitously expressed ROSA26 locus, we produced a line of mice that would permit cell-specific activation of the toxin gene. Following Cre-mediated recombination under the control of cell-type-specific promoters, lacZ gene expression was efficiently replaced by de novo transcription of the Cre-recombined DT-A gene. We provide proof of this principle, initially for cells of the central nervous system (pyramidal neurons and oligodendrocytes), the immune system (B cells), and liver tissue (hepatocytes), that the conditional expression of DT-A is functional in vivo, resulting in the generation of novel degenerative disease models

A transcriptional network coordinately determines transmitter and peptidergic fate in the dorsal spinal cord

Dorsal horn neurons express many different neuropeptides that modulate sensory perception like the sensation of pain. Inhibitory neurons of the dorsal horn derive from postmitotic neurons that express Pax2, Lbx1 and Lhx1/5, and diversify during maturation. In particular, fractions of maturing inhibitory neurons express various neuropeptides. We demonstrate here that a coordinate molecular mechanism determines inhibitory and peptidergic fate in the developing dorsal horn. A bHLH factor complex that contains Ptf1a acts as upstream regulator and initiates the expression of several downstream transcription factors in the future inhibitory neurons, of which Pax2 is known to determine the neurotransmitter phenotype. We demonstrate here that dynorphin, galanin, NPY, nociceptin and enkephalin expression depends on Ptf1a, indicating that these neuropeptides are expressed in inhibitory neurons. Furthermore, we show that Neurod1/2/6 and Lhx1/5, which act downstream of Ptf1a, control distinct aspects of peptidergic differentiation. In particular, the Neurod1/2/6 factors are essential for dynorphin and galanin expression, whereas the Lhx1/5 factors are essential for NPY expression. We conclude that a transcriptional network operates in maturing dorsal horn neurons that coordinately determines transmitter and peptidergic fate