144 research outputs found
Extra-axial anaplastic astroblastoma in a 67-year-old woman
No full textAstroblastoma is a rare glial neoplasia of the central nervous system. It is histologically defined by the presence of neoplastic cells with non- or slightly tapering processes arranged around blood vessels (astroblastic rosettes) and conventionally subdivided into well-differentiated and anaplastic. It commonly affects children and young adults, although cases and due to its superficial location in the brain cortex, it can mimic an extra-axial mass on magnetic resonance imagining. Herein, we describe a unique case of pure extra-axial anaplastic astroblastoma in an elderly woman. Awareness that astroblastoma may be also extra-axial and affect older subjects, may be helpful for its identification and differential diagnosis toward more common entities at this site and age of onset, and for appropriate therapeutic management as well
Searching for Mechanisms Underlying the Assembly of Calcium Entry Units: The Role of Temperature and pH
No full textStore-operated Ca2+ entry (SOCE) is a mechanism that allows muscle fibers to recover external Ca2+, which first enters the cytoplasm and then, via SERCA pump, also refills the depleted intracellular stores (i.e., the sarcoplasmic reticulum, SR). We recently discovered that SOCE is mediated by Calcium Entry Units (CEUs), intracellular junctions formed by: (i) SR stacks containing STIM1; and (ii) I-band extensions of the transverse tubule (TT) containing Orai1. The number and size of CEUs increase during prolonged muscle activity, though the mechanisms underlying exercise-dependent formation of new CEUs remain to be elucidated. Here, we first subjected isolated extensor digitorum longus (EDL) muscles from wild type mice to an ex vivo exercise protocol and verified that functional CEUs can assemble also in the absence of blood supply and innervation. Then, we evaluated whether parameters that are influenced by exercise, such as temperature and pH, may influence the assembly of CEUs. Results collected indicate that higher temperature (36 °C vs. 25 °C) and lower pH (7.2 vs. 7.4) increase the percentage of fibers containing SR stacks, the n. of SR stacks/area, and the elongation of TTs at the I band. Functionally, assembly of CEUs at higher temperature (36 °C) or at lower pH (7.2) correlates with increased fatigue resistance of EDL muscles in the presence of extracellular Ca2+. Taken together, these results indicate that CEUs can assemble in isolated EDL muscles and that temperature and pH are two of the possible regulators of CEU formation
Phenotype and Genotype Expression in Pseudohomozygous Factor V <sup>LEIDEN</sup>
No full text
Abstract
—The presence of a DNA mutation is frequently used to define a disease or a risk state. Because DNA typing has become easy and convenient in contrast to protein characterization, it is generally assumed that a mutation if present (or not) at the DNA level will be also present (or not) in the corresponding protein. However, discrepancies between phenotype and genotype can occur. A point mutation in the coagulation factor V gene (G
1691
→A, resulting in an Arg
506
→Gln amino acid substitution in the factor V molecule [factor V
LEIDEN
], leading to activated protein C resistance) is the most common genetic risk factor for familial thrombophilia. A pseudohomozygous factor V
LEIDEN
phenotype would occur if a heterozygous individual for factor V
LEIDEN
also did not express the “normal” (non-Leiden) factor V allele. However, to date, no data have been available to confirm the presence of only the factor V
LEIDEN
form in the plasma of these individuals. Platelet mRNA from 2 presumed pseudohomozygous patients and their family members was isolated, the amplified partial cDNAs were sequenced or restricted, and the allelic bands were quantified. Both patients were found to be heterozygous for the G
1691
→A substitution at both the DNA and mRNA levels. The presence of either the normal or mutated form of factor V in the patients’ plasmas was investigated using a monoclonal antibody to factor V that recognizes an epitope located between residues 307 and 506 of the factor Va heavy chain. No normal factor V could be detected in the plasmas of the 2 propositi. The present data demonstrate absence of a correlation between genotype at position 1691 (at the DNA and mRNA levels) and the corresponding phenotype data found in the plasmas of patients with pseudohomozygous factor V
LEIDEN
. Overall, these data suggest the existence of heterogeneous genetic “lesions,” which interfere with factor V expression, processing, secretion, and/or stability. Because the presence of the factor V
LEIDEN
molecule in plasma is directly related to pathology, identification and quantification of the circulating forms of factor V in plasma may be required for the diagnosis of individuals with activated protein C resistance.
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A highly polymorphic microsatellite in the factor V gene is an informative tool for the study of factor V‐related disorders
No full textThe role of factor V (FV) mutations in activated protein C (APC) resistance and FV deficiency is well established. We report on the identification of a highly polymorphic (AT)n microsatellite marker in the FV gene, which represents an informative tool for the investigation of the origin and evolution of pathologically relevant FV genetic components. A high number of different microsatellite alleles were found to be associated with FV R506Q and FV H1299R, two single-origin mutations. An example of the use of the microsatellite marker in family studies of thrombophilia and FV deficiency is also provided
Generically distributed investments on flexible projects and endogenous growth
No full textIn this paper we study an endogenous growth model where investments are (generically) distributed over multi-period flexible projects leading to new capital once completed. Recently developed techniques in dynamic programming are adapted and used to unveil the global dynamics of this model. Based on this analytical ground, several numerical exercises are performed to show the quantitative relevance of the analytical findings with an emphasis on the relation between project features and economic growth and speed of convergence toward the balanced growth path. © 2015 The Author(s
Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family
No full textThe study of the molecular bases of thrombophilia in a large family with 4 symptomatic members is reported. Three thrombophilic genetic components (FV R506Q, FV H1299R, and PT 20210G/A), all affecting the activity of the prothrombinase complex, were detected alone and in combination in various family members. In addition, a newly identified missense mutation (factor V [FV] Y1702C), causing FV deficiency, was also present in the family and appeared to enhance activated protein C (APC) resistance in carriers of FV R506Q or FV H1299R by abolishing the expression of the counterpart FV allele. The relationships between complex genotypes, coagulation laboratory findings, and clinical phenotypes were analyzed in the family. All symptomatic family members were carriers of combined defects and showed APC resistance and elevated F1 + 2 values. Evidence for the causative role of the FV Y1702C mutation, which affects a residue absolutely conserved in all 3 A domains of FV, factor VIII, and ceruloplasmin, relies on (1) the absolute cosegregation between the mutation and FV deficiency, both in the family and in the general population; (2) FV antigen and immunoblot studies indicating the absence of Y1702C FV molecules in plasma of carriers of the mutation, despite normal levels of the FV Y1702C messenger RNA; and (3) molecular modeling data that support a crucial role of the mutated residue in the A domain structure. These findings help to interpret the variable penetrance of thrombosis in thrombophilic families and to define the molecular bases of FV deficiency
Classification of protein interaction sentences via gaussian processes
No full textThe increase in the availability of protein interaction studies in textual format coupled with the demand for easier access to the key results has lead to a need for text mining solutions. In the text processing pipeline, classification is a key step for extraction of small sections of relevant text. Consequently, for the task of locating protein-protein interaction sentences, we examine the use of a classifier which has rarely been applied to text, the Gaussian processes (GPs). GPs are a non-parametric probabilistic analogue to the more popular support vector machines (SVMs). We find that GPs outperform the SVM and na\"ive Bayes classifiers on binary sentence data, whilst showing equivalent performance on abstract and multiclass sentence corpora. In addition, the lack of the margin parameter, which requires costly tuning, along with the principled multiclass extensions enabled by the probabilistic framework make GPs an appealing alternative worth of further adoption
The Grouped Author-Topic Model for Unsupervised Entity Resolution
No full textThis paper describes a generative approach for tackling the problem of identity resolution in a completely unsupervised context with no fixed assumption regarding the true number of identities. The problem of entity resolution involves associating different references to authors (in a paper's author list, for example) with real underlying identities. The references may be written in differing forms or may have errors, and identical references may refer to different real identities. The approach taken here uses a generative model of both the abstract of a document and its list of authors to resolve identities in a corpus of documents. In the model, authors and topics are associated with latent groups. For each document, an abstract and an author list are generated conditioned on a given group. Results are presented on real-world datasets, and outperform the best performing unsupervised methods.</p
Store-Operated Ca2+ Entry in Skeletal Muscle Contributes to the Increase in Body Temperature during Exertional Stress
No full textExertional heat stroke (HS) is a hyperthermic crisis triggered by an excessive accumulation of Ca2+ in skeletal muscle fibers. We demonstrated that exercise leads to the formation of calcium entry units (CEUs), which are intracellular junctions that reduce muscle fatigue by promoting the recovery of extracellular Ca2+ via store-operated Ca2+ entry (SOCE). Here, we tested the hypothesis that exercise-induced assembly of CEUs may increase the risk of HS when physical activity is performed in adverse environmental conditions (high temperature and humidity). Adult mice were: (a) first, divided into three experimental groups: control, trained-1 month (voluntary running in wheel cages), and acutely exercised-1 h (incremental treadmill run); and (b) then subjected to an exertional stress (ES) protocol, a treadmill run in an environmental chamber at 34 °C and 40% humidity. The internal temperature of the mice at the end of the ES was higher in both pre-exercised groups. During an ES ex-vivo protocol, extensor digitorum longus(EDL) muscles from the trained-1 month and exercised-1 h mice generated greater basal tension than in the control and were those that contained a greater number of CEUs, assessed by electron microscopy. The data collected suggest that the entry of Ca2+ from extracellular space via CEUs could contribute to exertional HS when exercise is performed in adverse environmental conditions
Molecular bases of pseudo-homozygous APC resistance: The compound heterozygosity for FV R506Q and a FV null mutation results in the exclusive presence of FV Leiden molecules in plasma
No full textPseudo-homozygous APC resistance, the condition resulting from compound heterozygosity for FV R506Q (FV Leiden) and quantitative FV deficiency, provides a natural model to study the interaction between procoagulant and anticoagulant defects. This paper reports a complete FV characterization of a pseudo-homozygous APC resistant thrombotic patient. The expression of the patient's non-Leiden gene was found to be severely impaired both at the mRNA and protein levels. In particular, only FV Leiden molecules were detected in the patient's plasma by immunoblotting, which accounts for the observed marked APC resistance. Analysis of the FV cDNA obtained by reverse transcription of platelet RNA revealed that the mRNA of the non-Leiden gene was extremely reduced in amount. A PAC clone containing the whole FV gene was used to design primers for a complete FV exon scanning. A 2-bp insertion at nucleotide 3706 in the large exon 13 of the non-Leiden gene, predicting a frame-shift and premature termination of protein synthesis, was identified as responsible for the FV defect. Failure to find any case of pseudo-homozygous APC resistance in a large sample (6,804) of blood donors suggests that this condition is extremely rare among normal controls and that its detection is favoured by the thrombotic risk that it may confer
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