Genetic and oceanographic tools reveal high population connectivity and diversity in the endangered pen shell Pinna nobilis

For marine meta-populations with source-sink dynamics knowledge about genetic connectivity is important to conserve biodiversity and design marine protected areas (MPAs). We evaluate connectivity of a Mediterranean sessile species, Pinna nobilis. To address a large geographical scale, partial sequences of cytochrome oxidase I (COI, 590 bp) were used to evaluate phylogeographical patterns in the Western Mediterranean, and in the whole basin using overlapping sequences from the literature (243 bp). Additionally, we combined (1) larval trajectories based on oceanographic currents and early life-history traits and (2) 10 highly polymorphic microsatellite loci collected in the Western Mediterranean. COI results provided evidence for high diversity and low inter-population differentiation. Microsatellite genotypes showed increasing genetic differentiation with oceanographic transport time (isolation by oceanographic distance (IBD) set by marine currents). Genetic differentiation was detected between Banyuls and Murcia and between Murcia and Mallorca. However, no genetic break was detected between the Balearic populations and the mainland. Migration rates together with numerical Lagrangian simulations showed that (i) the Ebro Delta is a larval source for the Balearic populations (ii) Alicante is a sink population, accumulating allelic diversity from nearby populations. The inferred connectivity can be applied in the development of MPA networks in the Western MediterraneanProject MEDEICG funded by the Spanish Ministry of Economy and Competitiveness (CTM2009-07013)IEH was supported by Ramon y Cajal Fellowship RYC2014-14970Spanish Ministry of Economy, Industry and Competitiveness IFCT Investigator Programme-Career Development (IF/00998/2014)MGW and AHE was supported by FCT fellowships SFRH/BPD/63703/2009 and SFRH/BPD/107878/2015National Science Foundation (OCE-1419450)CCMAR team via excellence research line EXCL/AAG-GLO/0661/2012Ciencias del Ma

Avian adenovirus. Precipitants antibodies response

Se realizó la Inoculación experimental con Adenovirus aviar (serotipo 1) a pollos de 1 día de edad y adultos (11 a 24 semanas de edad). En los pollitos B.B. la respuesta de anticuerpos es más lenta (segunda semana postinoculación) comparado con la respuesta en animales de mayor edad, donde se hace evidente a la primera semana postinoculación. El titulo de anticuerpos es también mayor en animales adultos al igual que la proporción de animales infectados. Pollitos B.B. con anticuerpos maternales pueden ser infectados desarrollando anticuerpos más tardíamente (cuarta semana post-inoculación).Experimental inoculation with avian Adenovirus (serotvpe 1) was carried out in one day old chickens and in adults (eleven and twenty four weeks old). Response to antibodies is slower in B.B. chickens (second weeks postinoculation) as compared to response In older animals where this is evident in first week postinoculation. Not only the title of antibodies but also the proportion of infected animals is greater in adults animals. B. B. chickens with maternal antibodies may be Infected developing antibodies later (fourth week postinoculation).Facultad de Ciencias Veterinaria

Avian adenovirus. Precipitants antibodies response

Se realizó la Inoculación experimental con Adenovirus aviar (serotipo 1) a pollos de 1 día de edad y adultos (11 a 24 semanas de edad). En los pollitos B.B. la respuesta de anticuerpos es más lenta (segunda semana postinoculación) comparado con la respuesta en animales de mayor edad, donde se hace evidente a la primera semana postinoculación. El titulo de anticuerpos es también mayor en animales adultos al igual que la proporción de animales infectados. Pollitos B.B. con anticuerpos maternales pueden ser infectados desarrollando anticuerpos más tardíamente (cuarta semana post-inoculación).Experimental inoculation with avian Adenovirus (serotvpe 1) was carried out in one day old chickens and in adults (eleven and twenty four weeks old). Response to antibodies is slower in B.B. chickens (second weeks postinoculation) as compared to response In older animals where this is evident in first week postinoculation. Not only the title of antibodies but also the proportion of infected animals is greater in adults animals. B. B. chickens with maternal antibodies may be Infected developing antibodies later (fourth week postinoculation).Facultad de Ciencias Veterinaria

The Preclinical discovery and development of opicapone for the treatment of Parkinson's Disease

Introduction: Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson's disease (PD) associated with L-DOPA / L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Thus, OPC decreases fluctuation in L-DOPA plasma levels and favours more constant central dopaminergic receptor stimulation, thus improving PD symptomatology. Areas covered: This review evaluates the preclinical development, pharmacology, pharmacokinetics and safety profile of OPC. Data were extracted from published preclinical and clinical studies published on PUBMED and SCOPUS (Search period: 2000-2019). Clinical and post-marketing data were also evaluated. Expert opinion: OPC is a third generation COMT inhibitor with a novel structure. It has an efficacy and tolerability superior to its predecessors, tolcapone (TOL) and entacapone (ENT). It also provides a safe and simplified drug regimen that allows neurologists to individually adjust the existing daily administration of L-DOPA. OPC is indicated as an adjunctive therapy to L-DOPA/DDI in patients with PD and end-of-dose motor fluctuations who cannot be stabilised on those combinations. Abbreviations: 3-OMD, 3-O-methyldopa; 6-OHDA, 6-hydroxydopamine; BG, basal ganglia; COMT, Catechol-O-methyltransferase; DDI, decarboxylase inhibitors; ENT, Entacapone; FDA, Food and Drug Administration; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; OPC, Opicapone; PD, Parkinson's disease; TOL, Tolcapone; GDNF, Glial cell-line-derived neurotrophic factor; NTN, neurturin; ICV, Intracerebroventricular; PDUFA, Prescription Drug User Fees Act; EMA, European Medicine Administration; AE, Adverse event BG, Basal ganglia. QD, once a day

The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia

Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD) pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the 'peripheral' symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors

A metabolic perspective of late onset Alzheimer's disease

After decades of research, the molecular neuropathology of Alzheimer's disease (AD) is still one of the hot topics in biomedical sciences. Some studies suggest that soluble amyloid β (Aβ) oligomers act as causative agents in the development of AD and could be initiators of its complex neurodegenerative cascade. On the other hand, there is also evidence pointing to Aβ oligomers as mere aggravators, with an arguable role in the origin of the disease. In this line of research, the relative contribution of soluble Aβ oligomers to neuronal damage associated with metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity is being actively investigated. Some authors have proposed the endoplasmic reticulum (ER) stress and the induction of the unfolded protein response (UPR) as important mechanisms leading to an increase in Aβ production and the activation of neuroinflammatory processes. Following this line of thought, these mechanisms could also cause cognitive impairment. The present review summarizes the current understanding on the neuropathological role of Aβ associated with metabolic alterations induced by an obesogenic high fat diet (HFD) intake. It is believed that the combination of these two elements has a synergic effect, leading to the impairement of ER and mitochondrial functions, glial reactivity status alteration and inhibition of insulin receptor (IR) signalling. All these metabolic alterations would favour neuronal malfunction and, eventually, neuronal death by apoptosis, hence causing cognitive impairment and laying the foundations for late-onset AD (LOAD). Moreover, since drugs enhancing the activation of cerebral insulin pathway can constitute a suitable strategy for the prevention of AD, we also discuss the scope of therapeutic approaches such as intranasal administration of insulin in clinical trials with AD patients

Estudio de seroprevalencia de enfermedad de Chagas-Mazza en residentes del Cinturón Hortícola Platense

La Enfermedad de Chagas-Mazza, es silenciosa, frecuentemente ocasiona lesiones sin notables manifestaciones clínicas. Numerosas personas desconocen su condición de afectados por Tripanosoma cruzi. Cuando ellas tienen acceso a diagnósticos clínicos y seroepidemiológicos, puede ocurrir que haga ya muchos años que han sido afectados y haya daños orgánicos. En este estudio se realizaron actividades en territorio, en el cinturón frutihortícola platense en el que habitan personas provenientes de áreas endémicas de Enfermedad de Chagas-Mazza, como parte de un proyecto integral. Con consentimiento informado se realizaron extracciones y diagnósticos. Las personas seropositivas fueron luego estudiadas, seguidas y medicadas según cada caso siguiendo las indicaciones establecidas en los protocolos vigentes consensuados. Ellos no conocían su condición de afectados. Es necesario incrementar las acciones en el territorio a efectos de realizar diagnósticos tempranos y acciones oportunas.Chagas-Mazza disease is silent, frequently causes lesions without manifestations. notable clinical Many people are unaware of their status as affected by Trypanosoma cruzi. When they have access to clinical and seroepidemiological diagnoses, it may happen that they have been affected for years and there is organic damage. In this study, activities were carried out in the territory, in the La Plata fruit and vegetable belt where people from endemic areas of Chagas-Mazza disease live, as part of a comprehensive project. With informed consent, extractions and diagnoses were performed. The seropositive people were then studied, followed up and medicated according to each following the indications established in the current agreed protocols. They did not know their status as affected. It is necessary to increase actions in the territory in order to carry out early and timely actions.Facultad de Ciencias Veterinaria

Prevalence of vascular disruption anomalies and association with young maternal age: A EUROCAT study to compare the United Kingdom with other European countries

Background Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies. Methods All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom. Results There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands. Conclusion Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies.publishedVersio

Risk factors for non-diabetic renal disease in diabetic patients

Background. Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. Methods. Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. Results. In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 6 12.8 years, creatinine was 2.8 6 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2–5.4) g/24 h. About 39.5% (n ¼ 329) of patients had DN, 49.6% (n ¼ 413) NDRD and 10.8% (n ¼ 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n ¼ 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) ¼ 1.03, 95% CI: 1.02–1.05, P < 0.001], microhaematuria (OR ¼ 1.51, 95% CI: 1.03–2.21, P ¼ 0.033) and absence of diabetic retinopathy (DR) (OR ¼ 0.28, 95% CI: 0.19–0.42, P < 0.001) were independently associated with NDRD. Kaplan–Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P ¼ 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P ¼ 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P ¼ 0.002), higher creatinine (P ¼ 0.01) and DN (P ¼ 0.015) were independent risk factors for mortality. Conclusions. The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis