Bactericidal disruption of magnesium metallostasis in Mycobacterium tuberculosis is counteracted by mutations in the metal ion transporter CorA

A defining characteristic of treating tuberculosis is the need for prolonged administration of multiple drugs. This may be due in part to subpopulations of slowly replicating or nonreplicating Mycobacterium tuberculosis bacilli exhibiting phenotypic tolerance to most antibiotics in the standard treatment regimen. Confounding this problem is the increasing incidence of heritable multidrug-resistant M. tuberculosis. A search for new antimycobacterial chemical scaffolds that can kill phenotypically drug-tolerant mycobacteria uncovered tricyclic 4-hydroxyquinolines and a barbituric acid derivative with mycobactericidal activity against both replicating and nonreplicating M. tuberculosis. Both families of compounds depleted M. tuberculosis of intrabacterial magnesium. Complete or partial resistance to both chemotypes arose from mutations in the putative mycobacterial Mg2+/Co2+ ion channel, CorA. Excess extracellular Mg2+, but not other divalent cations, diminished the compounds’ cidality against replicating M. tuberculosis. These findings establish depletion of intrabacterial magnesium as an antimicrobial mechanism of action and show that M. tuberculosis magnesium homeostasis is vulnerable to disruption by structurally diverse, nonchelating, drug-like compounds

Response of the ATLAS tile calorimeter prototype to muons

A study of high energy muons traversing the ATLAS hadron Tile calorimeter in the barrel region in the energy range between 10 and 300~GeV is presented. Both test beam experimental data and Monte Carlo simulations are given and show good agreement. The Tile calorimeter capability of detecting isolated muons over the above energy range is demonstrated. A signal to background ratio of about 10 is expected for the nominal LHC luminosity ($10^{34} cm^{-2} sec^{-1}$). The photoelectron statistics effect in the muon shape response is shown. The e/mip ratio is found to be $0.81 \pm 0.03$; the e/$\mu$ ratio is in the range 0.91 - 0.97. The energy loss of a muon in the calorimeter, dominated by the energy lost in the absorber, can be correlated to the energy loss in the active material. This correlation allows one to correct on an event by event basis the muon energy loss in the calorimeter and therefore reduce the low energy tails in the muon momentum distribution

Results from a combined test of an electromagnetic liquid argon calorimeter with a hadronic scintillating-tile calorimeter

The first combined test of an electromagnetic liquid argon accordion calorimeter and a hadronic scintillating-tile calorimeter was carried out at the CERN SPS. These devices are prototypes of the barrel calorimeter of the future ATLAS experiment at the LHC. The energy resolution of pions in the energy range from 20 to 300~GeV at an incident angle $\theta$ of about 11$^\circ$ is well-described by the expression \sigma/E = ((46.5 \pm 6.0)\%/\sqrt{E} +(1.2 \pm 0.3)\%) \oplus (3.2 \pm 0.4)~\mbox{GeV}/E. Shower profiles, shower leakage, and the angular resolution of hadronic showers were also studied

A measurement of the energy loss spectrum of 150 GeV muons in iron

The energy loss spectrum of 150 GeV muons has been measured with a prototype of the ATLAS hadron calorimeter in the H8 beam of the CERN SPS.\\ The differential probability $dP/dv$ per radiation length of a fractional energy loss $v = \Delta E_{\mu} / E_{\mu}$ has been measured in the range $v = 0.01 \div 0.95$; it is then compared with the theoretical predictions for energy losses due to bremsstrahlung and production of electron-positron pairs or of energetic knock-on electrons.\\ The integrated probability $\int_{0.01}^{0.95} (dP/dv) dv$ is $(1.610\pm0.015_{stat.}\pm0.105_{syst.})\cdot10^{-3}$ in agreement with the theoretical predictions of $1.556\cdot10^{-3}$ and $1.619\cdot10^{-3}$. %7.8.96 - start Agreement with theory is also found in two intervals of $v$ where production of electron-positron pairs and knock-on electrons dominates. In the region of bremsstrahlung dominance ($v = 0.12\div0.95$) the measured integrated probability $(1.160\pm0.040_{stat}\pm0.075_{syst})\cdot 10^{-4}$ is in agreement with the theoretical value of $1.185 \cdot 10^{-4}$, obtained using Petrukhin and Shestakov's \cite{PS} description of the bremsstrahlung process. The same result is about 3.6 standard deviations (defined as the quadratic sum of statistical and systematic errors) lower than the theoretical prediction of $1.472\cdot 10^{-4}$, obtained using Tsai's \cite{TS} description of bremsstrahlung

The Vein Patterning 1 (VEP1) Gene Family Laterally Spread through an Ecological Network

Lateral gene transfer (LGT) is a major evolutionary mechanism in prokaryotes. Knowledge about LGT— particularly, multicellular— eukaryotes has only recently started to accumulate. A widespread assumption sees the gene as the unit of LGT, largely because little is yet known about how LGT chances are affected by structural/functional features at the subgenic level. Here we trace the evolutionary trajectory of VEin Patterning 1, a novel gene family known to be essential for plant development and defense. At the subgenic level VEP1 encodes a dinucleotide-binding Rossmann-fold domain, in common with members of the short-chain dehydrogenase/reductase (SDR) protein family. We found: i) VEP1 likely originated in an aerobic, mesophilic and chemoorganotrophic α-proteobacterium, and was laterally propagated through nets of ecological interactions, including multiple LGTs between phylogenetically distant green plant/fungi-associated bacteria, and five independent LGTs to eukaryotes. Of these latest five transfers, three are ancient LGTs, implicating an ancestral fungus, the last common ancestor of land plants and an ancestral trebouxiophyte green alga, and two are recent LGTs to modern embryophytes. ii) VEP1's rampant LGT behavior was enabled by the robustness and broad utility of the dinucleotide-binding Rossmann-fold, which provided a platform for the evolution of two unprecedented departures from the canonical SDR catalytic triad. iii) The fate of VEP1 in eukaryotes has been different in different lineages, being ubiquitous and highly conserved in land plants, whereas fungi underwent multiple losses. And iv) VEP1-harboring bacteria include non-phytopathogenic and phytopathogenic symbionts which are non-randomly distributed with respect to the type of harbored VEP1 gene. Our findings suggest that VEP1 may have been instrumental for the evolutionary transition of green plants to land, and point to a LGT-mediated ‘Trojan Horse’ mechanism for the evolution of bacterial pathogenesis against plants. VEP1 may serve as tool for revealing microbial interactions in plant/fungi-associated environments

Brain inflammation is accompanied by peripheral inflammation in Cstb(-/-) mice, a model for progressive myoclonus epilepsy

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.Peer reviewe

Effect of synthesis methods and a comparative study of structural and magnetic properties of zinc ferrite

Zinc ferrite samples were prepared by two different routes which are chemical co-precipitation and standard solid state double sintering method. Structural properties of ZnFe2O4 were determined, and initial particle size was found as 5 nm in the samples prepared by chemical co-precipitation technique. The XRD patterns showed the single phase of ZnFe2O4 spinel structure and confirmed by the lattice parameter and the unmixed hkl values for both the synthesis techniques. M-H curves at room temperature showed superparamagnetic nature of the samples sintered from 200°C to 600°C, synthesized by chemical co-precipitation technique. The Mössbauer analysis at room temperature showed a doublet which is the signature of superparamagnetic nature, and it is in agreement with the acquired M-H curves. The magnetization of ZnFe2O4 synthesized by chemical co-precipitation method was found higher than the magnetization of ZnFe2O4 synthesized by the solid-state double sintering method in the sintering temperature from 1100°C to 1300°C

Investigation of various magnetic features of spinel type cobalt ferrite (CoFe2O4) nanoparticles tuned by annealing temperature

Cobalt ferrite (CoFe2O4) nanoparticles synthesized by chemical co-precipitation method were studied to see the effect of annealing temperatures on the structural parameters and magnetic properties of the sample. X-ray powder diffraction (XRD), transmission electron microscope (TEM) and SAD pattern demonstrated that single face (fcc) spinel structure of CoFe2O4 has been formed showing particles in completely crystalline state which was further confirmed by the lattice parameter and the unmixed hkl values. The particle size is in the range of about 5-10 nm depending on the annealing temperature from 200°C to 400°C. The grain growth occurred monotonically with the increase of annealing temperature. The magnetic properties demonstrated a strong dependence on particle size. The saturation magnetization Ms, remanent ratio Mr/Ms and coercivity Hc increased with the increase of particle size. The hysteresis curves for samples of different grain size showed the ferrimagnetic behavior which is completely analogous to the slow relaxation sextet peaks of Mössbauer spectroscopy. Other parameters such as chemical shift, quadruple splitting and hyperfine field and site occupancy of Fe3+ were determined by Mössbauer spectroscopy. Ferrimagnetic to superparamagnetic transition temperature known as blocking temperature TB was determined from the temperature dependent magnetization curves. With the increase of grain size, Blocking temperature also increases. Maximum entropy changes due to magnetic phase transition were also observed for mentioned annealing temperatures in the context of Magnetocaloric effect

Ultra-soft magnetic properties and correlated phase analysis by 57Fe Mössbauer spectroscopy of Fe74Cu0.8Nb2.7Si15.5B7 alloy

A detailed study of magnetic softness has been performed on FINEMENT type of ribbons by investigating the BH loop with maximum applied field of 960 A/m. The ribbon with the composition of Fe74Cu0.8Nb2.7Si15.5B7 was synthesized by rapid solidification technique and the compositions volume fraction was controlled by changing the annealing condition. Detail phase analysis was performed through X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Vibrating sample magnetometer (VSM) and Mössbauer spectroscopy in order to correlate the ultrasoft magnetic properties with the volume fraction of amorphous and α-Fe(Si) soft nano composites. Bright (BF) and dark field (DF) image with selective area diffraction (SAD) patterns by the transmission electron microscopy (TEM) of the sample annealed for the optimized annealed condition at 853 K for 3 min reveals nanocrystals with an average size between 10-15 nm possessing the bcc structure which matches with the grain size revealed by the X-ray diffraction. Kinetics of crystallization of α-Fe(Si) phases has been determined by DSC curves. Extremely small coercivity of 30.9 A/m and core loss of 2.5 W/Kg for the sample annealed at 853 K for 3 min was found. Similar values for other crystalline conditions were determined by using BH loop tracer with a maximum applied field of around 960 A/m. Mössbauer spectroscopy was used to determine chemical shift, hyperfine field distribution (HFD), and peak width of different phases. The volume fractions of the relative amount of amorphous and crystalline phases are also determined by Mössbauer spectroscopy. High saturation magnetization along with ultrasoft magnetic properties exhibits very high potentials technological applications