Differential Immune-Reactivity and Subcellular Distribution Reveal the Multifunctional Character of Profilin in Pollen as Major Effect of Sequences Polymorphism

Trabajo presentado al Annual Meeting of the American Society of Agronomy and Crop Science Society and Soil Science Society of America, celebrado en Cincinnati (USA) del 21 al 24 de octubre de 2012.Profilin, one of the major allergen (Ole e 2) of olive (Olea europaea L.) pollen, are broadly distributed actin-monomer-binding proteins (ABP). They display a major regulatory role in actin cytoskeleton dynamics, driving cell morphogenesis, sexual reproduction, and translating signals into cellular responses to different environmental stresses. Plants exhibit multiple profilin isoforms w ith distinctive biochemical properties, and differentially regulated. How ever, it is still an open question w hether these profilin isoforms, generated by multiple gene sequence polymorphism, are functionally different, as well as the role of that polymorphism in pollen allergy. Particularly, in differential epitopes generation, profilin isoforms sensitization and cross-reactivity among cultivars, and even among species. In the present study, w e have used mature pollen from olive, birch, hazel, timothy-grass, and maize, in addition to olive germinating pollen and seeds, w ith the aim to analyze the immune-reactivity and subcellular localization of profilin by using polyclonal and specific isoforms antibodies against olive and maize profilins. The results show ed immune-reactivity differences betw een the five species analyzed, betw een olive cultivars, as w ell as between reproductive and vegetative profilins. Furthermore, the existence of different profilin isoforms w as revealed along pollen germination stages. A differential subcellular distribution of profilin isoforms w as found in olive pollen. They w ere localized in the nucleus, pollen aperture regions, pollen and tube w alls and pollen tip, in addition to a general cytoplasmic distribution, in comparison to controls. Data suggest that profilin family might contain numerous functionally distinctive isoforms, spatial-temporal differentially expressed and regulated during vegetative development, pollen maturation and pollen tube grow th. Furthermore, differential immune-reactivity revealed in the study might point out the involvement of common shared and specific epitopes, generated by sequence polymorphism, in differential olive pollen cultivar sensitization of allergenic patients, and cross-reaction to pollen from different species.This study was supported by the following European Regional Development Fund cofinanced grants: MCINN BFU 2004-00601/BFI, BFU 2008-00629, BFU2011-22779, CICE (Junta de Andalucía) P2010-CVI15767, P2010-AGR6274, P2011-CVI-7487, P2011-CVI-7487, and by the coordinated project Spain/Germany MEC HA2004-0094.Peer reviewe

The impact of silent vascular brain burden in cognitive impairment in Parkinson's disease

White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies

SARDINE FISHERIES: RESOURCE ASSESSMENT AND SOCIAL AND ECONOMIC SITUATION

This study describes fisheries, stock status, ICES advice and management measures for the Northern and Southern sardine stocks in EU Atlantic waters. Information on sardine biology and ecology is provided for a better understanding of stock development. Social and economic dimensions are addressed for sardine fisheries in France, Spain and Portugal. The study provides recommendations to improve knowledge on the species and indicates management measures which might be considered for the sustainability of the fisheries.Versión del edito

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration

Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I

We have previously shown that the administration of low doses of insulin-like growth factor-I (IGF-I) to CCl4-cirrhotic rats improves liver function and reduces fibrosis. To better understand the mechanisms behind the hepatoprotective effects of IGF-I, and to identify those genes whose expression is affected in cirrhosis and after IGF-1 treatment, we have performed differential display of mRNA analysis by means of polymerase chain reaction (PCR) in livers from control and CCl4-cirrhotic rats treated or not with IGF-I. We have identified 16 genes that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially normalized the expression of eight of these genes, including serine proteinase inhibitors such as serpin-2 and alpha-1-antichymotripsin, alpha-1-acid glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced the regenerative activity in the cirrhotic liver, as determined by the increased expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I treatment partially restored the expression of growth hormone receptor (GHR) and the levels of global genomic DNA methylation, which are reduced in human and experimental cirrhosis. Taken together, our observations confirm the hepatoprotective effects of IGF-I, and suggest that this action can be exerted in part through the normalization of liver gene expression, growth hormone (GH) responsiveness and global genomic DNA methylation

PET tracers for clinical imaging of breast cancer

Molecular imaging of breast cancer has undoubtedly permitted a substantial development of the overall diagnostic accuracy of this malignancy in the last years. Accurate tumour staging, design of individually suited therapies, response evaluation, early detection of recurrence and distant lesions have also evolved in parallel with the development of novel molecular imaging approaches. In this context, positron emission tomography (PET) can be probably seen as the most interesting molecular imaging technology with straightforward clinical application for such purposes. Dozens of radiotracers for PET imaging of breast cancer have been tested in laboratory animals. However, in this review we shall focus mainly in the smaller group of PET radiopharmaceuticals that have lead through into the clinical setting. PET imaging can be used to target general metabolic phenomena related to tumoural transformation, including glucose metabolism and cell proliferation, but can also be directed to specific hormone receptors that are characteristic of the breast cancer cell. Many other receptors and transport molecules present in the tumour cells could also be of interest for imaging. Furthermore, molecules related with the tumour microenvironment, tumour induced angiogenesis or even hypoxia could also be used as molecular biomarkers for breast cancer imaging

Tomografía por emisión de positrones en el cáncer de mama

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer

Early lung cancer detection using spiral computed tomography and positron emission tomography

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions

Rol de sCD40L en la predicción de súper-respuesta a la terapia de resincronización cardiaca

Background. The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor α, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Methods. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV ≥ 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. Results. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p=0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p<0.0001) and lateral (0 vs. 18%, p=0.03), inferior (4 vs. 33%, p=0.01) and posterior infarction (0 vs. 22%, p=0.01); absence of mitral regurgitation (47% vs. 22%, p=0.04), wider QRS width (157.7±22.9 vs. 140.8±19.2ms, p=0.01), higher concentrations of sCD40L (6.9±5.1 vs. 4.4±3.3 ng/mL, p=0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p=0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correlation with SR (r=0.39, p=0.02) and with the reduction of LVESV (r=0.44, p=0.02). Conclusion. sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.Fundamento. Analizar los biomarcadores Interleuquina 6, factor de necrosis tumoral α, sCD40L, troponina T hipersensible, proteína C-reactiva hipersensible y galectina-3 en la predicción de súper-respuesta (SR) a la terapia de resincronización cardiaca (TRC), ya que no han sido valorados con anterioridad. Material y métodos. Se recopilaron datos clínicos, electrocardiográficos y ecocardiográficos preimplante y al año. Se definió SR como disminución del VTSVI ≥ 30% al año de seguimiento. Las muestras sanguíneas fueron extraídas preimplante. Se realizó regresión logística multivariante y curvas ROC. Resultados. Se incluyeron 50 pacientes, 23 (46%) fueron SR.Las características relacionadas con la SR fueron: ser mujer (35 vs. 11%, p=0,04), sufrir menos cardiopatía isquémica (13 vs. 63%, p<0,0001) e infarto lateral (0 vs. 18%, p=0,03), inferior (4 vs. 33%, p=0,01) y posterior (0 vs. 22%, p=0,01); ausencia de insuficiencia mitral (47% vs. 22%, p=0,04), mayor anchura del QRS (157,7±22,9 vs. 140,8±19,2 ms, p=0,01), mayor concentración de sCD40L (6,9±5,1 vs. 4,4±3,3 ng/mL, p=0,02), y electrodo ventricular izquierdo más frecuentemente en posición lateral media (69 vs. 26%, p=0,002). El QRS, la posición lateral media del electrodo y la ausencia de insuficiencia mitral fueron predictores independientes de SR. sCD40L mostró una correlación moderada directa con SR (r=0,39, p=0,02) y con la disminución del VTSVI (r=0,44, p=0,02). Conclusiones. sCD40L se correlaciona significativamente con SR a la TRC. El QRS, la ausencia de insuficiencia mitral y la posición lateral media del electrodo son predictores independientes de SR en esta cohorte

The role of Prenatal Care and Social Risk Factors in the relationship between immigrant status and neonatal morbidity: A retrospective cohort study

Background and Aim Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity. Methods Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007–2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI). Results Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04–5.00), and crude OR for LBW was 1.77 (95% CI: 0.74–4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14–1.32); LBW = 0.48 (95% CI: 0.15–1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92–74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28–30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58– 18.62). Conclusions Prenatal care and social risk factors were major confounding variables in the relationship between immigrant status and neonatal morbidity