Screening for calreticulin mutations in a cohort of patients suspected of having a myeloproliferative neoplasm

Background. The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins. Over 36 types of CALR mutations have been identified, all causing a recurrent frameshift in the C-terminal domain affecting CALR’s localisation and calcium-binding function.Objective. To screen a cohort of 89 patients suspected of having an MPN for the CALR mutations.Methods. Capillary and gel electrophoresis were used in conjunction as confirmatory tests to screen the cohort of patients. Results. Of three samples containing a type 1 CALR mutation, two were heterozygous and one homozygous for a 52-base pair deletion in CALR.Conclusions. Most studies report CALR mutations to be present only in patients with primary myelofibrosis or essential thrombocythaemia, with mutual exclusivity to JAK2 mutations. The findings of this study indicate that JAK2 and CALR mutations are no longer considered mutually exclusive. Similarly, patients with a polycythaemia vera phenotype could also carry a CALR mutation

Screening for calreticulin mutations in a cohort of patients suspected of having a myeloproliferative neoplasm

Background. The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins. Over 36 types of CALR mutations have been identified, all causing a recurrent frameshift in the C-terminal domain affecting CALR’s localisation and calcium-binding function.Objective. To screen a cohort of 89 patients suspected of having an MPN for the CALR mutations.Methods. Capillary and gel electrophoresis were used in conjunction as confirmatory tests to screen the cohort of patients.Results. Of three samples containing a type 1 CALR mutation, two were heterozygous and one homozygous for a 52-base pair deletion in CALR.Conclusions. Most studies report CALR mutations to be present only in patients with primary myelofibrosis or essential thrombocythaemia, with mutual exclusivity to JAK2 mutations. The findings of this study indicate that JAK2 and CALR mutations are no longer considered mutually exclusive. Similarly, patients with a polycythaemia vera phenotype could also carry a CALR mutation

The determination of phosphorus in saliva and dentine

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Synthesis of triazole-linked 2-trichloromethylquinazolines and exploration of their efficacy against P. falciparum

Using 2-trichloromethylquinazoline as scaffold, seven novel triazole-linked compounds have been synthesized using CuAAC chemistry. The in vitrobiological activity of four of the compounds on the Plasmodium falciparumchloroquine-sensitive strain NF54 was then determined. The compounds which were tested showed moderate activity with 1.45 /iM as the lowest inhibitory concentration

Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment

Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic

Understanding the microstructure of mortars for cultural heritage using X-ray CT and MIP

In this study, the microstructure of mock-up mortar specimens for a historic environment, composed of different mixtures, was studied using mercury intrusion porosity (MIP) and micro-computed tomography (\ub5CT), highlighting the advantages and drawbacks of both techniques. Po-rosity, sphericity, and pores size distribution were studied, evaluating changes according to mortar composition (aerial and hydraulic binders, quartz sand, and crushed limestone aggregate). The \ub5CT results were rendered using 3D visualization software, which provides complementary information for the interpretation of the data obtained using 3D data-analysis software. Moreover, \ub5CT contrib-utes to the interpretation of MIP results of mortars. On the other hand, MIP showed significant ink-bottle effects in lime and cement mortars samples that should be taken into account when interpret-ing the results. Moreover, the MIP results highlighted how gypsum mortar samples display a porosity distribution that is best studied using this technique. This multi-analytical approach provides important insights into the interpretation of the porosimetric data obtained. This is crucial in the characterization of mortars and provides key information for the study of building materials and cultural heritage conservation

A review of bovine tuberculosis at the wildlife-livestock-human interface in sub-Saharan Africa

Infection of wild animals by bovine tuberculosis (bTB) is raising concern worldwide. This article reviews the current epidemiological situation, risk of emergence and control options at the wildlife-livestock-human interface in sub-Saharan Africa. In livestock, bTB has been confirmed in the majority of countries from all parts of the continent. Wildlife infection is confirmed in seven countries from southern and eastern Africa, apparently spreading in the southern Africa region. Mycobacterium bovis has been isolated from 17 wild mammal species, although only four are suspected to play a role as maintenance host. Zoonotic risks are a concern, but no direct spillover from wildlife to humans has been documented, and no case of bTB spillback from wildlife to livestock has been confirmed. In this paper we assess the main risk factors of bTB spillover at the wildlife-livestock-human interface and suggest several research themes which could improve the control of the disease in the African contex

Polarization transfer observables for quasielastic proton-nucleus scattering in terms of a complete Lorentz invariant representation of the NN scattering matrix

For the calculation of polarization transfer observables for quasielastic scattering of protons on nuclei, a formalism in the context of the Relativistic Plane Wave Impulse Approximation is developed, in which the interaction matrix is expanded in terms of a complete set of 44 independent invariant amplitudes. A boson-exchange model is used to predict the 39 amplitudes which were omitted in the formerly used five-term parameterization(the SPVAT form) of the nucleon-nucleon scattering matrix. Use of the complete set of amplitudes eliminates the arbitrariness of the five-term representation.Comment: 29 pages, 2 figure

Nuclear medium modifications of the NN interaction via quasielastic (p⃗,p⃗′\vec p,\vec p ') and (p⃗,n⃗\vec{p},\vec{n}) scattering

Within the relativistic PWIA, spin observables have been recalculated for quasielastic ($\vec p,\vec p '$) and ($\vec p,\vec n$) reactions on a $^{40}$Ca target. The incident proton energy ranges from 135 to 300 MeV while the transferred momentum is kept fixed at 1.97 fm^{-1}. In the present calculations, new Horowitz-Love--Franey relativistic NN amplitudes have been generated in order to yield improved and more quantitative spin observable values than before. The sensitivities of the various spin observables to the NN interaction parameters, such as (1) the presence of the surrounding nuclear medium, (2) a pseudoscalar versus a pseudovector interaction term, and (3) exchange effects, point to spin observables which should preferably be measured at certain laboratory proton energies, in order to test current nuclear models. This study also shows that nuclear medium effects become more important at lower proton energies ($\leq$ 200 MeV). A comparison to the limited available data indicates that the relativistic parametrization of the NN scattering amplitudes in terms of only the five Fermi invariants (the SVPAT form) is questionable.Comment: 10 pages, 6 Postscript figures, uses psfig.sty and article.sty, submitted to Phys. Rev.