Hedyphane from Nezilovo, Macedonia

Two different members of lead calcium arsenate series of apatite group from Nezilovo are found. According to the chemical formula (calculated on the basis of 10 cations), infra red absorption powder spectra, X-ray powder patterns and unit cell dimensions these are two distinct members of one mineral species. Unit cell dimensions are a=10.157(3), c=7.256(6) and a=10.154(2), c=7.191(3) A. The first sample has Pb:Ca ratio 7.35:2.59 and the second one 6.54:3.45, what is closer to ideal hedyphane formula (6:4)

Mutation to ispA Produces Stable Small-Colony Variants of Pseudomonas aeruginosa That Have Enhanced Aminoglycoside Resistance.

Pseudomonas aeruginosa is a major pathogen in burn wound infections. We present one of the first reports of small-colony variant (SCV) emergence of P. aeruginosa, taken from a patient under aminoglycosides for a persistent burn wound infection. We confirm the causative role of a single ispA mutation in SCV emergence and increased aminoglycoside resistance. IspA is involved in the synthesis of ubiquinone, providing a possible link between electron transport and SCV formation in P. aeruginosa

Parallel Evolution of Pseudomonas aeruginosa during a Prolonged ICU-Infection Outbreak.

Most knowledge about Pseudomonas aeruginosa pathoadaptation is derived from studies on airway colonization in cystic fibrosis; little is known about adaptation in acute settings. P. aeruginosa frequently affects burned patients and the burn wound niche has distinct properties that likely influence pathoadaptation. This study aimed to genetically and phenotypically characterize P. aeruginosa isolates collected during an outbreak of infection in a burn intensive care unit (ICU). Sequencing reads from 58 isolates of ST1076 P. aeruginosa taken from 23 patients were independently mapped to a complete reference genome for the lineage (H25338); genetic differences were identified and were used to define the population structure. Comparative genomic analysis at single-nucleotide resolution identified pathoadaptive genes that evolved multiple, independent mutations. Three key phenotypic assays (growth performance, motility, carbapenem resistance) were performed to complement the genetic analysis for 47 unique isolates. Population structure for the ST1076 lineage revealed 11 evolutionary sublineages. Fifteen pathoadaptive genes evolved mutations in at least two sublineages. The most prominent functional classes affected were transcription/two-component regulatory systems, and chemotaxis/motility and attachment. The most frequently mutated gene was oprD, which codes for outer membrane porin involved in uptake of carbapenems. Reduced growth performance and motility were found to be adaptive phenotypic traits, as was high level of carbapenem resistance, which correlated with higher carbapenem consumption during the outbreak. Multiple prominent linages evolved each of the three traits in parallel providing evidence that they afford a fitness advantage for P. aeruginosa in the context of human burn infection. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative pathogen causing infections in acutely burned patients. The precise mechanisms required for the establishment of infection in the burn setting, and adaptive traits underpinning prolonged outbreaks are not known. We have assessed genotypic data from 58 independent P. aeruginosa isolates taken from a single lineage that was responsible for an outbreak of infection in a burn ICU that lasted for almost 2.5 years and affected 23 patients. We identified a core set of 15 genes that we predict to control pathoadaptive traits in the burn infection based on the frequency with which independent mutations evolved. We combined the genotypic data with phenotypic data (growth performance, motility, antibiotic resistance) and clinical data (antibiotic consumption) to identify adaptive phenotypes that emerged in parallel. High-level carbapenem resistance evolved rapidly, and frequently, in response to high clinical demand for this antibiotic class during the outbreak

Malignant pleural mesothelioma co-opts BCL-XL and autophagy to escape apoptosis.

Escape from programmed cell death is a hallmark of cancer. In this study, we investigated the anti-apoptotic mechanisms and explored the therapeutic potential of BCL-2 homology domain-3 (BH3) mimetics in malignant pleural mesothelioma (MPM), a lethal thoracic malignancy with an extreme dearth of treatment options. By implementing integrated analysis of functional genomic data of MPM cells and quantitative proteomics of patients' tumors, we identified BCL-XL as an anti-apoptotic driver that is overexpressed and confers an oncogenic dependency in MPM. MPM cells harboring genetic alterations that inactivate the NF2/LATS1/2 signaling are associated with increased sensitivity to A-1155463, a BCL-XL-selective BH3 mimetic. Importantly, BCL-XL inhibition elicits protective autophagy, and concomitant blockade of BCL-XL and autophagic machinery with A-1155463 and hydroxychloroquine (HCQ), the US Food and Drug Administration (FDA)-approved autophagy inhibitor, synergistically enhances anti-MPM effects in vitro and in vivo. Together, our work delineates the molecular basis underlying resistance to apoptosis and uncovers an evasive mechanism that limits response to BH3 mimetics in MPM, suggesting a novel strategy to target this aggressive disease

Study of human liver disease with P-31 magnetic resonance spectroscopy.

Liver metabolism and energetics of 24 patients with liver disease were studied using phosphorus-31 magnetic resonance spectroscopy. Significant abnormalities were detected in the majority of these patients. A striking diversity in metabolic patterns was observed. Patients with acute viral hepatitis had low liver phosphodiesters and high phosphomonoesters, possibly phosphocholine and phosphoethanolamine. In alcoholic hepatitis phosphomonoesters were raised. Intracellular inorganic phosphate and inorganic phosphate/ATP ratios were decreased in primary biliary cirrhosis and in some patients with hepatitis. These spectroscopic results were evaluated in respect of the pattern of liver damage and cellular regeneration. Liver tumours had raised phosphomonoesters and also showed evidence for altered spin-lattice relaxation of the phosphorus nucleus in various metabolites. In iron overload the liver ATP resonances were broadened. The line broadening correlated with the degree of iron overload suggesting the potential use of P-31 magnetic resonance spectroscopy for measuring liver iron

Alpine high pressure evolution of the eastern Bitlis complex, SE Turkey

The Bitlis complex, SE Anatolia, constitutes a crystalline complex derived from the north of the Arabian Plate, accreted to the South Armenian block. Metamorphic studies in the cover sequences of the Bitlis complex allow constraining the thermal evolution of the massif by metamorphic index minerals. A regionally distributed low temperature-high pressure (LT-HP) metamorphic evolution is documented by glaucophane, relics of carpholite in chloritoid-bearing schists and pseudomorphs after aragonite in marbles. The metamorphic age of these HP assemblages is constrained by Ar isotope dating as 74 +/- 2 Ma. This indicates that (i) the Bitlis complex represents a terrane detached from the Arabian indenter that was subducted and stacked to form a nappe complex during the closure of the Neo-Tethys and (ii) that during Late Cretaceous to Cenozoic evolution the Bitlis complex never underwent temperatures over 450 degrees C. The consequences of the metamorphic evolution of the Bitlis complex (a cold continental block within a hot environment) for the Eastern Anatolian plateau are complied in a crustal section