Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry

RATIONALE: Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i) decreased production; ii) increased utilization; iii) increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. OBJECTIVES: This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. FINDINGS: The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i) increased number of platelets with high FSC and high SSC, ii) a significant number of those gigantic platelets had strong fluorescent signal (IgG bound), iii) very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv) significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. CONCLUSIONS: This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses

Vanadium-rich Muscovite from Austria: Crystal Structure, Chemical Analysis, and Spectroscopic Investigations

The crystal structure of a green, transparent, vanadium-rich muscovite-2M_1 (V_2O_3 = 11.35 wt.%, one of the highest amounts reported to date in muscovite) with the optimized formula (K_(0.94)Na_(0.06))M2(Al_(1.20)V^(3+)_(0.61)Mg_(0.12)Cr^(3+)_(0.07))T1(Si^(1.54)Al_(0.46))T2(Si_(1.54)Al_(0.46))O_(10)(OH)_2 and space group C2/c, a 5.2255(6), b 9.0704(10), c 20.0321(21) Å, β 95.773(2)°, Z = 4 has been refined to R = 6.97% for 1070 unique reflections (MoKα). This muscovite, which occurs in small quartz veins in graphite schist from Weinberg mountain, near the village of Amstall, Lower Austria, is distinctly low in Cr (Cr_2O_3 ∼1.4 wt.%) and Mg (MgO ∼1.1 wt.%); Fe, Mn, and Ti are below detection limit. All octahedral cations occupy the M2 site, and the average octahedral bond (M2–O) distance is 1.953 Å. Structural distortions include α = 8.89° and Δz = 0.193 Å, resulting in an interlayer spacing of 3.35 Å. The optical absorption spectrum of this V-rich muscovite shows absorption features at 427 and 609 nm that define a transmission window centered at 523 nm. These absorption features are consistent with those expected for V^(3+) in mica, but the 609 nm band has a slightly longer wavelength than in low-V micas

A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.</p

The Ursinus Weekly, April 18, 1949

Council adopts petitions for \u2749 coed elections • Junior men to elect annual prom queen • Black-faced belles plan initial debut for minstrel frolic • Organizations seek support of students in worthy projects • Y commission lists letters, trip, talk in year\u27s activities • Sororities plan party for frosh; Movie, social to highlight affair • FTA elects Heist to presidency for \u2749-\u2750 schedule of activities • What do you demand of your ideal man? • Bruins drop 4-3 decision in ten inning ball game • Five sports events fill week\u27s roster • Sixteen get awards for winter sports • Students find appeal in Curtain Club actshttps://digitalcommons.ursinus.edu/weekly/1614/thumbnail.jp

The constrained-monad problem

In Haskell, there are many data types that would form monads were it not for the presence of type-class constraints on the operations onthat data type. This is a frustrating problem in practice, because there is a considerable amount of support and infrastructure for monads that these data types cannot use. Using several examples,we show that a monadic computation can be restructured into a normal form such that the standard monad class can be used. The technique is not specific to monads, and we show how it can also be applied to other structures, such as applicative functors. One significant use case for this technique is domain-specific languages,where it is often desirable to compile a deep embedding of a computation to some other language, which requires restricting the types that can appear in that computation

Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria

Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homogentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was performed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. In total, we observed 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2–16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2–0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia