Bonaviri inedito

Book Reviews / Recension

Evaluation of a questionnaire to detect the risk of developing ESGD or EGGD in horses

Equine gastric ulcer syndrome (EGUS) affects various categories of horses worldwide. This syndrome is now divided into two different diseases, based on the presence of lesions on either the squamous (Equine Squamous Gastric Disease, ESGD) or the glandular (Equine Glandular Gastric Disease, EGGD) mucosa. Diagnosis is based on the evaluation of the presence of gastric lesions with gastroscopic examination. As a gastroscopy can be considered expensive by clients, therapy is started often on the basis of clinical signs only. The aim of this study was to validate a questionnaire to detect the risk of developing ESGD or EGGD. The owners of 418 horses that were submitted to gastroscopic evaluation were asked to answer a questionnaire on risk factors for ESGD and EGGD. Horses were divided into three groups based on the results of the questionnaire and their risk of developing gastric lesions. In our population the survey was not useful to detect the presence and the severity of the lesions detected during gastroscopic examination, however answers to some of the questions did correlate with the development of gastric lesions. The questionnaire could therefore be a useful tool to evaluate the risk of ESGD or EGGD. Having owners periodically complete the survey could also make them more aware of changes in the conditions of the horses that could lead to gastric lesions. This could then help them seek advice from veterinarians on how to manage this potential ris

Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis

The first IEEE workshop on the Future of Research Curation and Research Reproducibility

This report describes perspectives from the Workshop on the Future of Research Curation and Research Reproducibility that was collaboratively sponsored by the U.S. National Science Foundation (NSF) and IEEE (Institute of Electrical and Electronics Engineers) in November 2016. The workshop brought together stakeholders including researchers, funders, and notably, leading science, technology, engineering, and mathematics (STEM) publishers. The overarching objective was a deep dive into new kinds of research products and how the costs of creation and curation of these products can be sustainably borne by the agencies, publishers, and researcher communities that were represented by workshop participants.National Science Foundation Award #164101

Novel Phosphorylation Sites in the S. cerevisiae Cdc13 Protein Reveal New Targets for Telomere Length Regulation

The S. cerevisiae Cdc13 is a multifunctional protein with key roles in regulation of telomerase, telomere end protection, and conventional telomere replication, all of which are cell cycle-regulated processes. Given that phosphorylation is a key mechanism for regulating protein function, we identified sites of phosphorylation using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). We also determined phosphorylation abundance on both wild type (WT) and a telomerase deficient form of Cdc13, encoded by the cdc13-2 allele, in both G1 phase cells, when telomerase is not active, and G2/M phase cells, when it is. We identified 21 sites of in vivo phosphorylation, of which only five had been reported previously. In contrast, phosphorylation of two in vitro targets of the ATM-like Tel1 kinase, S249 and S255, was not detected. This result helps resolve conflicting data on the importance of phosphorylation of these residues in telomerase recruitment. multiple residues showed differences in their cell cycle pattern of modification. For example, phosphorylation of S314 was significantly higher in the G2/M compared to the G1 phase and in WT versus mutant Cdc13, and a S314D mutation negatively affected telomere length. Our findings provide new targets in a key telomerase regulatory protein for modulation of telomere dynamics. [Image: see text

Investigating the role of the Est3 protein in yeast telomere replication

The Est3 subunit of yeast telomerase, which adopts a predicted OB-fold, is essential for telomere replication. To assess the possible contributions that Est3 might make to enzyme catalysis, we compared telomerase activity from wild type and est3-Δ strains of Saccharomyces castellii, which revealed that loss of the Est3 subunit results in a 2- to 3-fold decline in nucleotide addition. This effect was not primer-specific, based on assessment of a panel of primers that spanned the template of the S. castellii telomerase RNA. Furthermore, using nuclear magnetic resonance chemical shift perturbation, no chemical shift change was observed at any site in the protein upon addition of single-stranded DNA, arguing against a role for Est3 in recognition of telomeric substrates by telomerase. Addition of exogenous Est3 protein, including mutant Est3 proteins that are severely impaired for telomere replication in vivo, fully restored activity in est3-Δ telomerase reactions. Thus, Est3 performs an in vivo regulatory function in telomere replication, which is distinct from any potential contribution that Est3 might make to telomerase activity

Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis

BACKGROUND: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis. METHODOLOGY/PRINCIPAL FINDINGS: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level. CONCLUSIONS: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden