Procoagulant Microparticles in Dogs with Immune-Mediated Hemolytic Anemia

BACKGROUND: Studies of some human prothrombotic diseases suggest that phosphatidylserine-positive (PS+) and tissue factor-positive (TF+) microparticles (MPs) might play a role in the pathogenesis of thrombosis or serve as biomarkers of thrombotic risk. HYPOTHESIS/OBJECTIVES: To determine if circulating levels of PS+MP and procoagulant activity (PCA) associated with PS+MPs and TF+ MPs are increased in dogs with IMHA. ANIMALS: Fifteen dogs with primary or secondary IMHA and 17 clinically healthy dogs. METHODS: Prospective case-controlled observational study. Circulating PS+MPs were measured by flow cytometry. PCA associated with PS+MPs and TF+MPs was measured by thrombin and Factor Xa generating assays, respectively. RESULTS: Circulating numbers of PS+MPs were not significantly higher in dogs with IMHA [control median 251,000/μL (36,992-1,141,250/μL); IMHA median 361,990/μL (21,766-47,650,600/μL) P = .30]. However, PS+MP PCA [control median 2.2 (0.0-16.8) nM PS eq; IMHA median 8.596, (0-49.33 nM PS eq) P = .01] and TF+MP PCA [control median 0.0, (0.0-0.0 pg/mL); IMHA median 0.0; (0-22.34 pg/mL], P = .04) were increased. Intravascular hemolysis, which we showed might increase PS+ and TF+MP PCA, was evident in 3 of 5 dogs with PS+MP PCA and 2 of 4 dogs with TF+MP PCA higher than controls. Underlying disease in addition to IMHA was detected in 1 of 5 dogs with PS+PCA and 3 of 4 dogs with TF+MP PCA higher than controls. CONCLUSIONS AND CLINICAL IMPORTANCE: TF+ and PS+MP PCA is increased in some dogs with IMHA. Further studies that determine if measuring TF+ and PS+ MP PCA can help identify dogs at risk for thrombosis are warranted

Indirect monitoring shot-to-shot shock waves strength reproducibility during pump-probe experiments

We present an indirect method of estimating the strength of a shock wave, allowing on line monitoring of its reproducibility in each laser shot. This method is based on a shot-to-shot measurement of the X-ray emission from the ablated plasma by a high resolution, spatially resolved focusing spectrometer. An optical pump laser with energy of 1.0 J and pulse duration of ∼660 ps was used to irradiate solid targets or foils with various thicknesses containing Oxygen, Aluminum, Iron, and Tantalum. The high sensitivity and resolving power of the X-ray spectrometer allowed spectra to be obtained on each laser shot and to control fluctuations of the spectral intensity emitted by different plasmas with an accuracy of ∼2%, implying an accuracy in the derived electron plasma temperature of 5%-10% in pump-probe high energy density science experiments. At nano- and sub-nanosecond duration of laser pulse with relatively low laser intensities and ratio Z/A ∼ 0.5, the electron temperature follows Te ∼ Ilas2/3. Thus, measurements of the electron plasma temperature allow indirect estimation of the laser flux on the target and control its shot-to-shot fluctuation. Knowing the laser flux intensity and its fluctuation gives us the possibility of monitoring shot-to-shot reproducibility of shock wave strength generation with high accuracy.T. A. Pikuz, A. Ya. Faenov, N. Ozaki, N. J. Hartley, B. Albertazzi, T. Matsuoka, K. Takahashi, H. Habara, Y. Tange, S. Matsuyama, K. Yamauchi, R. Ochante, K. Sueda, O. Sakata, T. Sekine, T. Sato, Y. Umeda, Y. Inubushi, T. Yabuuchi, T. Togashi, T. Katayama, M. Yabashi, M. Harmand, G. Morard, M. Koenig, V. Zhakhovsky, N. Inogamov, A. S. Safronova, A. Stafford, I. Yu. Skobelev, S. A. Pikuz, T. Okuchi, Y. Seto, K. A. Tanaka, T. Ishikawa, and R. Kodama, "Indirect monitoring shot-to-shot shock waves strength reproducibility during pump–probe experiments", Journal of Applied Physics 120, 035901 (2016) https://doi.org/10.1063/1.4958796

Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in <it>GFAP </it>that cause this disease, cases of adult-onset ALX have been increasingly reported.</p> <p>Case Presentation</p> <p>We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the <it>GFAP </it>gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX.</p> <p>Conclusion</p> <p>The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the <it>GFAP </it>gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX.</p

Srebrna spremnica za klupko djelo majstora Antona Fuchsa u Kiseku

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is widely used to build optoelectronic devices. However, as a hygroscopic water-based acidic material, it brings major concerns for stability and degradation, resulting in an intense effort to replace it in organic photovoltaic (OPV) devices. In this work, we focus on the perfluorinated ionomer (PFI) polymeric additive to PEDOT:PSS. We demonstrate that it can reduce the relative amplitude of OPV device burn-in, and find two distinct regimes of influence. At low concentrations there is a subtle effect on wetting and work function, for instance, with a detrimental impact on the device characteristics, and above a threshold it changes the electronic and device properties. The abrupt threshold in the conducting polymer occurs for PFI concentrations greater than or equal to the PSS concentration and was revealed by monitoring variations in transmission, topography, work-function, wettability and OPV device characteristics. Below this PFI concentration threshold, the power conversion efficiency (PCE) of OPVs based on poly(3-hexylthiophene-2,5-diyl):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) are impaired largely by low fill-factors due to poor charge extraction. Above the PFI concentration threshold, we recover the PCE before it is improved beyond the pristine PEDOT:PSS layer based OPV devices. Supplementary to the performance enhancement, PFI improves OPV device stability and lifetime. Our degradation study leads to the conclusion that PFI prevents water from diffusing to and from the hygrosopic PEDOT:PSS layer, which slows down the deterioration of the PEDOT:PSS layer and the aluminum electrode. These findings reveal mechanisms and opportunities that should be taken into consideration when developing components to inhibit OPV degradation.Comment: 14 pages, 9 figures, 1 table, Journal of Materials Chemistry A 201

Diversity in Functional Organization of Class I and Class II Biotin Protein Ligase

The cell envelope of Mycobacterium tuberculosis (M.tuberculosis) is composed of a variety of lipids including mycolic acids, sulpholipids, lipoarabinomannans, etc., which impart rigidity crucial for its survival and pathogenesis. Acyl CoA carboxylase (ACC) provides malonyl-CoA and methylmalonyl-CoA, committed precursors for fatty acid and essential for mycolic acid synthesis respectively. Biotin Protein Ligase (BPL/BirA) activates apo-biotin carboxyl carrier protein (BCCP) by biotinylating it to an active holo-BCCP. A minimal peptide (Schatz), an efficient substrate for Escherichia coli BirA, failed to serve as substrate for M. tuberculosis Biotin Protein Ligase (MtBPL). MtBPL specifically biotinylates homologous BCCP domain, MtBCCP87, but not EcBCCP87. This is a unique feature of MtBPL as EcBirA lacks such a stringent substrate specificity. This feature is also reflected in the lack of self/promiscuous biotinylation by MtBPL. The N-terminus/HTH domain of EcBirA has the self-biotinable lysine residue that is inhibited in the presence of Schatz peptide, a peptide designed to act as a universal acceptor for EcBirA. This suggests that when biotin is limiting, EcBirA preferentially catalyzes, biotinylation of BCCP over self-biotinylation. R118G mutant of EcBirA showed enhanced self and promiscuous biotinylation but its homologue, R69A MtBPL did not exhibit these properties. The catalytic domain of MtBPL was characterized further by limited proteolysis. Holo-MtBPL is protected from proteolysis by biotinyl-5′ AMP, an intermediate of MtBPL catalyzed reaction. In contrast, apo-MtBPL is completely digested by trypsin within 20 min of co-incubation. Substrate selectivity and inability to promote self biotinylation are exquisite features of MtBPL and are a consequence of the unique molecular mechanism of an enzyme adapted for the high turnover of fatty acid biosynthesis

Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study

BACKGROUND: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. METHODS: HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. RESULTS: We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). CONCLUSION: This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs