A Minimalist Approach to Clitics and Clitic Doubling in Spanish

This dissertation addresses questions concerning cliticisation within the framework of the minimalist approach as presented, among others, by Chomsky (1995a). Chapter 1 presents the basic tenets underlying the minimalist approach. It also briefly discusses the historical developments within generative grammar which have led to the adoption of a minimalist approach. Chapter 2 presents general background on cliticisation and clitic doubling, including theories such as the Movement and Base generation theories which have been advanced to account for the behaviour of clitics. The theory of Clitic Voices presented by Sportiche (1992), a synthesis of previous analyses, is also presented and adopted as providing a more principled account of clitics in clitic-doubling constructions. In Chapter 3 the traditional classification of clitics in terms of their Case properties is abandoned in favour of a more fundamental one based on other features of clitics such as [± person] and [± number]. This characterisation leads to the postulation of a maximum of two clitic phrases for Spanish, each associated with different feature compositions. This feature system takes into account both phi-features and aspectual features of the predicate associated with the clitics. This proposal allows a unified analysis of a number of constructions, previously viewed as distinct, under the more general umbrella of clitic doubling. Chapter 4 provides an account of the alternation between enclisis and proclisis found in Spanish as well as other Romance languages. This alternation is explained by reference to the features present on the verbal host which trigger movement in cases of enclisis. In an extension of the analysis of the relation between a clitic and its host, an account of interpolation in Old Spanish is also discussed. Chapter 5 discusses the restrictions apparent in instances of clitic doubling with respect to the features of the doubling element, e.g. [± pronominal], [± human], and [± specific]. A parallel is drawn between these restrictions and similar patterns found in ergative languages. Finally, Chapter 6 shows how the conclusions reached in this thesis can be seen to apply to broader concerns of language acquisition and language impairment

Linoleic acid enhances the secretion of plasminogen activator inhibitor type 1 by HepG2 cells.

This study was undertaken in order to assess whether triglycerides and/or their fatty acids directly influence the secretion of plasminogen activator inhibitor type 1 (PAI-1) in HepG2 cells. To this end, subconfluent HepG2 cells were incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16 h, and PAI-1 levels were determined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid composition at the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L) increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mumol/L). Incorporation of LA into cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [14C]LA. LA accumulated in all lipid classes including diacylglycerol, the incorporated LA being converted into arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid methyl esters. It is concluded that PAI-1 secretion in HepG2 cells is modulated by triacylglycerols and by linoleic acid and/or its metabolic products

Reprint of: Proteomics in cardiovascular diseases::Unveiling sex and gender differences in the era of precision medicine

Cardiovascular diseases (CVDs) represent the most important cause of mortality in women and in men. Contrary to the long-standing notion that the effects of the major risk factors on CVD outcomes are the same in both sexes, recent evidence recognizes new, potentially independent, sex/gender-related risk factors for CVDs, and sex/gender-differences in the clinical presentation of CVDs have been demonstrated. Furthermore, some therapeutic options may not be equally effective and safe in men and women. In this context, proteomics offers an extremely useful and versatile analytical platform for biomedical researches that expand from the screening of early diagnostic and prognostic biomarkers to the investigation of the molecular mechanisms underlying CDVs. In this review, we summarized the current applications of proteomics in the cardiovascular field, with emphasis on sex and gender-related differences in CVDs

Educación bilingüe en Argentina – Programas y docentes

Actualmente, existe una gran variedad de programas de educación bilingüe a nivel mundial y Argentina no es una excepción. Allí, la etiqueta “educación bilingüe” suele aplicarse a una amplia gama de programas que abarcan diversas poblaciones y necesidades específicas.El educador se presenta como elemento clave, así como la importancia de su formación docente que, en algunos casos, ha sufrido modificaciones en los últimos años. Estos cambios se han dado de forma paulatina y como consecuencia de políticas educativas que, además, asisten en la búsqueda de docentes con perfiles específicos.Este artículo presenta un estado de la cuestión actualizado en lo referido a los programas considerados “bilingües” en Argentina. Se detallaron los objetivos y alcances de cada uno de los programas. En segundo lugar, se describieron las características de los docentes que se desempeñan en estos contextos y el tipo de formación que reciben en la actualidad. Por último, se analizaron las posibles áreas de convergencia de los programas bilingües en Argentina, a saber, la relación de poder relativa de las lenguas involucradas y las áreas de base de conocimiento que resultan indispensables para enseñar en los diversos programas de educación bilingüe de Argentina.There is a wide variety of bilingual education programmes around the world and Argentina is no exception. In the latter, the label “bilingual education” is applied to a vast range of programmes that cater for diverse populations and specific needs.The teacher is the key constituent among these programmes as well as his/her teacher training programme, which has undergone changes in the last few years. These changes have been implemented in due time and as a consequence of educational policies which, in turn, assist in the search of educators with a specific profile.This article proposes a current state of the art on the situation of the vast range of programmes considered “bilingual” in Argentina. As a starting point, we presented the objectives and main features of the different bilingual programmes. In the second place, we described the characteristics of the teachers who belong in this context and the type of teacher education they receive. Finally, we looked at those areas that can help towards analysing possible points in common between minority and prestigious bilingual programmes, i.e. the power relations of the languages involved in the different programmes and the knowledge that teachers and other staff members on bilingual programmes require

Pro-oxidant and pro-inflammatory effects of glycated albumin on cardiomyocytes.

Human serum albumin (HSA) is the most abundant circulating protein in the body and presents an extensive range of biological functions. As such, it is prone to undergo post-translational modifications (PTMs). The non-enzymatic early glycation of HSA, one of the several PTMs undergone by HSA, arises from the addition of reducing sugars to amine group residues, thus modifying the structure of HSA. These changes may affect HSA functions impairing its biological activity, finally leading to cell damage. The aim of this study was to quantitate glycated-HSA (GA) levels in the plasma of heart failure (HF) patients and to evaluate the biological effects of GA on HL-1 cardiomyocytes. Plasma GA content from HF patients and healthy subjects was measured by direct infusion electrospray ionization mass spectrometry (ESI-MS). Results pointed out a significant increase of GA in HF patients with respect to the control group (p < 0.05). Additionally, after stimulation with GA, proteomic analysis of HL-1 secreted proteins showed the modulation of several proteins involved, among other processes, in the response to stress. Further, stimulated cells showed a rapid increase in ROS generation, higher mRNA levels of the inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), and higher levels of the oxidative 4-HNE-protein adducts and carbonylated proteins. Our findings show that plasma GA is increased in HF patients. Further, GA exerts pro-inflammatory and pro-oxidant effects on cardiomyocytes, which suggest a causal role in the etiopathogenesis of HF

Data for proteomic analysis of murine cardiomyocytic HL1 cells treated with siRNA against tissue factor

YesThis data article is related to the research article entitled Proteomics of Tissue Factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control by Lento et al [1]. Tissue Factor (TF) is the key player in the coagulation cascade, but it has additional functions ranging from angiogenesis, tumor invasion and, in the heart, the maintenance of the integrity of cardiac cells. This article reports the nano-LC-MSE analysis of the cardiomyocytic HL-1 cell line proteome and describes the results obtained from a Gene Ontology analysis of those proteins affected by TF-gene silencing

Multicomponent Synthesis of Polyphenols and Their In Vitro Evaluation as Potential \u3b2-Amyloid Aggregation Inhibitors

While plant polyphenols possess a variety of biological properties, exploration of chemical diversity around them is still problematic. Here, an example of application of the Ugi multicomponent reaction to the combinatorial assembly of artificial, yet \u201cnatural-like\u201d, polyphenols is presented. The synthesized compounds represent a second-generation library directed to the inhibition of \u3b2-amyloid protein aggregation. Chiral enantiopure compounds, and polyphenol-\u3b2-lactam hybrids have been prepared too. The biochemical assays have highlighted the importance of the key pharmacophores in these compounds. A lead for inhibition of aggregation of truncated protein A\u3b2pE3-42 was selected

Veno-occlusive disease nurse management: Development of a dynamic monitoring tool by the GITMO nursing group

Veno-occlusive disease (VOD) is a complication arising from the toxicity of conditioning regimens that have a significant impact on the survival of patients who undergo stem cell transplantation. There are several known risk factors for developing VOD and their assessment before the start of conditioning regimens could improve the quality of care. Equally important are early identification of signs and symptoms ascribable to VOD, rapid diagnosis, and timely adjustment of support therapy and treatment. Nurses have a fundamental role at the stages of assessment and monitoring for signs and symptoms; therefore, they should have documented skills and training. The literature defines nurses' areas of competence in managing VOD, but in the actual clinical practice, this is not so clear. Moreover, there is an intrinsic difficulty in managing VOD due to its rapid and often dramatic evolution, together with a lack of care tools to guide nurses. Through a complex evidence-based process, the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), cellule staminali emopoietiche e terapia cellulare nursing board has developed an operational flowchart and a dynamic monitoring tool applicable to haematopoietic stem cell transplantation patients, whether they develop this complication or not

Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control

YesIt has long been known that Tissue Factor (TF) plays a role in blood coagulation and has a direct thrombotic action that is closely related to cardiovascular risk, but it is becoming increasingly clear that it has a much wider range of biological functions that range from inflammation to immunity. It is also involved in maintaining heart haemostasis and structure, and the observation that it is down-regulated in the myocardium of patients with dilated cardiomyopathy suggests that it influences cell-to-cell contact stability and contractility, and thus contributes to cardiac dysfunction. However, the molecular mechanisms underlying these coagulation-independent functions have not yet been fully elucidated. In order to analyse the influence of TF on the cardiomyocitic proteome, we used functional biochemical approaches incorporating label-free quantitative proteomics and gene silencing, and found that this provided a powerful means of identifying a new role for TF in regulating splicing machinery together with the expression of several proteins of the spliceosome, and mRNA metabolism with a considerable impact on cell viability

Sensitivity to Entrectinib Associated with a Novel LMNA-NTRK1 Gene Fusion in Metastatic Colorectal Cancer

In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2cm in longest diameter to 4.7 and 4.3cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib