Cognitive dysfunction and psychopathology: a cohort study of adults with intellectual developmental disorder

Background: Cognitive impairment of intellectual developmental disorders (IDD) is determined by several different combinations of specific cognitive alterations. People with IDD present a rate of mental health problems that is up to 4 times higher than that of the general population. Despite this, the relationship between specific cognitive dysfunctions and co-occurring mental disorders has not been adequately studied. The aim of the present paper is to investigate the association between specific cognitive dysfunctions and specific psychiatric symptoms and syndromes in people with IDD. Methods: One hundred and twenty adults with mild to moderate IDD living in residential facilities underwent a clinical and instrumental assessment for specific cognitive and psychopathological features. Results: Participants with IDD and ASD have significantly lower scores compared to those without respect to who has not the diagnosis on the Processing Speed Index (PSI) and Perceptual Reasoning Index (PRI) on the WAIS-IV and higher time scores on the TMT A. Moreover, there is a significant association between years of hospitalisation and TMT B and TMT B A time scores; the longer a participant with IDD was hospitalised, the worse their performance on the TMT. Although not statistically significant, many psychopathological clusters showed substantial cognitive profiles. Conclusions: Although further research is needed, neuropsychological and IQ tests scores seem to be differently associated to various psychopathological conditions co-occurring with IDD, and with ASD especially. Cognitive assessment seems to support diagnosis and treatment of psychopathological co-occurrences in persons with IDD, also in consideration of indirect implications including a better knowledge of the patient's characteristics beyond IQ deficit

NADPH Oxidase 5 Is a Pro‐Contractile Nox Isoform and a Point of Cross‐Talk for Calcium and Redox Signaling‐Implications in Vascular Function

Background NADPH Oxidase 5 (Nox5) is a calcium‐sensitive superoxide‐generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro‐contractile signaling and vascular function. Methods and Results Transgenic mice expressing human Nox5 in a vascular smooth muscle cell–specific manner (Nox5 mice) and Rhodnius prolixus, an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5‐expressing mice, agonist‐induced vasoconstriction was exaggerated and endothelium‐dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N‐acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca2+]i, increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro‐contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild‐type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus, gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor). Conclusions Nox5 is a pro‐contractile Nox isoform important in redox‐sensitive contraction. This involves calcium‐calmodulin and endoplasmic reticulum–regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro‐contractile molecular machinery in vascular smooth muscle cells

Transformação genética de cana-de-açúcar por Agrobacterium tumefaciens.

RESUMO - A utilização das técnicas de modificação genética de plantas já são aplicadas comercialmente na agricultura há cerca de três décadas. No entanto, culturas como a cana-de-açúcar ainda se beneficiam pouco desta tecnologia. O presente trabalho descreve o processo de transformação genética de cana-de-açúcar, utilizando como vetor de transformação a Agrobacterium tumefaciens. Dentre as vantagens que se destacam nesse procedimento, podemos citar: simplicidade do procedimento; geração de eventos positivos com menor número de cópias do transgene de interesse; e integração do transgene em regiões mais ativas do genoma, características essas que favorecem o sucesso na obtenção de plantas geneticamente modificadas efetivamente funcionais e estáveis.CIIC 2018. Nº 17606. Na publicação: Juliana Erika Teixeira Yassitepe

NADPH oxidase 5 is a pro‐contractile Nox isoform and a point of cross‐talk for calcium and redox signaling‐implications in vascular function

Background: NADPH Oxidase 5 (Nox5) is a calcium‐sensitive superoxide‐generating Nox. It is present in lower forms and higher mammals, but not in rodents. Nox5 is expressed in vascular cells, but the functional significance remains elusive. Given that contraction is controlled by calcium and reactive oxygen species, both associated with Nox5, we questioned the role of Nox5 in pro‐contractile signaling and vascular function. Methods and Results: Transgenic mice expressing human Nox5 in a vascular smooth muscle cell–specific manner (Nox5 mice) and Rhodnius prolixus, an arthropod model that expresses Nox5 endogenoulsy, were studied. Reactive oxygen species generation was increased systemically and in the vasculature and heart in Nox5 mice. In Nox5‐expressing mice, agonist‐induced vasoconstriction was exaggerated and endothelium‐dependent vasorelaxation was impaired. Vascular structural and mechanical properties were not influenced by Nox5. Vascular contractile responses in Nox5 mice were normalized by N‐acetylcysteine and inhibitors of calcium channels, calmodulin, and endoplasmic reticulum ryanodine receptors, but not by GKT137831 (Nox1/4 inhibitor). At the cellular level, vascular changes in Nox5 mice were associated with increased vascular smooth muscle cell [Ca2+]i, increased reactive oxygen species and nitrotyrosine levels, and hyperphosphorylation of pro‐contractile signaling molecules MLC20 (myosin light chain 20) and MYPT1 (myosin phosphatase target subunit 1). Blood pressure was similar in wild‐type and Nox5 mice. Nox5 did not amplify angiotensin II effects. In R. prolixus, gastrointestinal smooth muscle contraction was blunted by Nox5 silencing, but not by VAS2870 (Nox1/2/4 inhibitor). Conclusions: Nox5 is a pro‐contractile Nox isoform important in redox‐sensitive contraction. This involves calcium‐calmodulin and endoplasmic reticulum–regulated mechanisms. Our findings define a novel function for vascular Nox5, linking calcium and reactive oxygen species to the pro‐contractile molecular machinery in vascular smooth muscle cells

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

A key aspect of nearly all single-cell sequencing experiments is dissociation of intact tissues into single-cell suspensions. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have on ex vivo gene expression. Here, we demonstrate that use of enzymatic dissociation on brain tissue induces an aberrant ex vivo gene expression signature, most prominently in microglia, which is prevalent in published literature and can substantially confound downstream analyses. To address this issue, we present a rigorously validated protocol that preserves both in vivo transcriptional profiles and cell-type diversity and yield across tissue types and species. We also identify a similar signature in postmortem human brain single-nucleus RNA-sequencing datasets, and show that this signature is induced in freshly isolated human tissue by exposure to elevated temperatures ex vivo. Together, our results provide a methodological solution for preventing artifactual gene expression changes during fresh tissue digestion and a reference for future deeper analysis of the potential confounding states present in postmortem human samples

Avaliação dos efeitos do flunixim meglumine sobre a concentração sérica de progesterona e ciclo estral em novilhas e vacas mestiças.

Resumo: Baseando-se nos mecanismos de interrupção da síntese de PGF2a em bovinos, objetivou-se com este estudo avaliar os efeitos do flunixin meglumine (FM) sobre o comprimento do ciclo estral e sobre os níveis de progesterona, em novilhas e vacas mestiças. Após sincronização dos estros, os animais foram divididos em grupos: controle (cinco vacas e quatro novilhas) e tratado (seis vacas e seis novilhas), sendo submetidos à colheita diária de sangue, até o estro subseqüente. Do 13o ao 18o dia, aplicou-se nos animais do grupo tratado 1,65 mg/kg intramuscular de FM, e nos do grupo controle, mesmo volume de solução fisiológica. A determinação da concentração sérica de progesterona foi realizada por RIA. Os resultados do comprimento do ciclo estral foram comparados entre os grupos e entre animais, pelo teste t de Student, enquanto a concentração de progesterona foi normalizada em relação à luteólise, e analisada entre os grupos pelo teste t de Tukey (SAS). Não se observou diferença (P>0,05) no comprimento do ciclo estral entre grupos e entre novilhas e vacas, tratadas e não tratadas. O dia do ciclo estral em relação à concentração de progesterona máxima e inferior a 1,0ng/mL, e a concentração sérica de progesterona entre os animais do grupo controle e tratado, também foram semelhantes entre os grupos (P>0,05). No entanto, observou-se diferença (P0.05). However, there was no difference concerning the concentration of progesterone decrease among theexperimental groups. It was concluded that, under the conditions this study was carried out, even though the effect of the treatment was observed, its action would be better characterized if the sample population were bigger.(AU

Physiological quality, content and activity of antioxidants in soybean seeds artificially aged.

ABSTRACT - The objective of this study was to evaluate physiological quality, content, and activity of antioxidants, in soybean seeds subjected to accelerated aging during different periods. Seeds of cultivars BRS 258, BRS 262 and BRS 268, subjected to accelerated aging during 12, 24, 36 and 48 hours and non-aged seeds were used. After each aging period, the seed were evaluated by tests of: germination; first count and tetrazolium. The total of phenolic compounds, total flavonoides, total of isoflavones, and activity for eliminating ABTS°+ radicals were quantified. There were differences among cultivars according to vigor and viability only after seeds were aged. Cultivars BRS 158 and BRS 268 have shown better seed physiological quality in each aging period; however, not presenting higher amounts of isoflavones and efficiency in removing free radicals. For all cultivars, the values for total of phenolic compounds, as well as total of flavonoids have shown quadratic positive behavior; the values for isoflavones remained constant and the vigor and viability showed contrary trend to activity of antioxidant agents. RESUMO: Qualidade fisiológica, conteúdo e atividade de antioxidantes presentes em sementes de soja envelhecidas artificialmente. O objetivo deste trabalho foi avaliar a qualidade fisiológica, o conteúdo e a atividade de agentes antioxidantes presentes em sementes de soja envelhecidas durante diferentes períodos. Foram utilizadas sementes das cultivares BRS 258, BRS 262 e BRS 268, envelhecidas durante 12, 24, 36 e 48 h e sementes não envelhecidas. Após cada período de envelhecimento, as sementes foram avaliadas pelo testes de: germinação; primeira contagem e tetrazólio. Foram quantificados: compostos fenólicos totais; flavonóides totais; total de isoflavonas e atividade eliminadora do radical ABTS°+. Houve diferença entre as cultivares em relação ao vigor e viabilidade somente quando foram envelhecidas. BRS 158 e BRS 268 apresentaram melhor qualidade fisiológica de sementes em cada período de envelhecimento, porém, não apresentaram maior quantidade de isoflavonas e eficiência no sequestro dos radicais livres. Para todas as cultivares, os valores de compostos fenólicos totais, assim como os flavonóides totais, apresentaram comportamento quadrático positivo; os valores das isoflavonas permaneceram constantes e o vigor e a viabilidade apresentaram tendência contrária à atividade dos agentes antioxidantes

Comparison of health conditions treated with traditional and biomedical health care in a Quechua community in rural Bolivia

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to reveal patterns in the treatment of health conditions in a Quechua-speaking community in the Bolivian Andes based on plant use data from traditional healers and patient data from a primary health care (PHC) service, and to demonstrate similarities and differences between the type of illnesses treated with traditional and biomedical health care, respectively.</p> <p>Methods</p> <p>A secondary analysis of plant use data from semi-structured interviews with eight healers was conducted and diagnostic data was collected from 324 patients in the community PHC service. Health conditions were ranked according to: (A) the percentage of patients in the PHC service diagnosed with these conditions; and (B) the citation frequency of plant use reports to treat these conditions by healers. Healers were also queried about the payment modalities they offer to their patients.</p> <p>Results</p> <p>Plant use reports from healers yielded 1166 responses about 181 medicinal plant species, which are used to treat 67 different health conditions, ranging from general symptoms (e.g. fever and body pain), to more specific ailments, such as arthritis, biliary colic and pneumonia. The results show that treatment offered by traditional medicine overlaps with biomedical health care in the case of respiratory infections, wounds and bruises, fever and biliary colic/cholecystitis. Furthermore, traditional health care appears to be complementary to biomedical health care for chronic illnesses, especially arthritis, and for folk illnesses that are particularly relevant within the local cultural context. Payment from patients to healers included flexible, outcome contingent and non-monetary options.</p> <p>Conclusion</p> <p>Traditional medicine in the study area is adaptive because it corresponds well with local patterns of morbidity, health care needs in relation to chronic illnesses, cultural perceptions of health conditions and socio-economic aspects of health care. The quantitative analysis of plant use reports and patient data represents a novel approach to compare the contribution of traditional and biomedical health care to treatment of particular health conditions.</p

Fungal diversity associated to the olive moth, prays oleae Bernard : a survey for potential entomopathogenic fungi

Olive production is one of the main agricultural activities in Portugal. In the region of Trás-os-Montes this crop has been considerably affected by Prays oleae. In order to evaluate the diversity of fungi on P. oleae population of Trás-os-Montes olive orchards, larvae and pupae of the three annual generations (phyllophagous, antophagous and carpophagous) were collected and evaluated for fungal growth on their surface. From the 3828 larvae and pupae, a high percentage of individuals exhibited growth of a fungal agent (40.6%), particularly those from the phyllophagous generation. From all the moth generations, a total of 43 species from 24 genera were identified, but the diversity and abundance of fungal species differed between the three generations. Higher diversity was found in the carpophagous generation, followed by the antophagous and phyllophagous generations. The presence of fungi displaying entomopathogenic features was highest in the phyllophagous larvae and pupae, being B. bassiana the most abundant taxa. The first report of B. bassiana presence on P. oleae could open new strategies for the biocontrol of this major pest in olive groves, since the use of an already adapted species increases the guarantee of success of a biocontrol approach. The identification of antagonistic fungi able to control agents that cause major olive diseases, such as Verticillium dahliae, will benefit future biological control approaches for limiting this increasingly spreading pathogen.This work was supported by Science and Technology Foundation (Fundação para a Ciência e Tecnologia – FCT) project PTDC/AGR-AAM/102600/2008 “Entomopathogenic fungi associated to olive pests: isolation, characterization and selection for biological control”. The first author is grateful to the Science and Technology Foundation for the PhD grant SFRH/BD/44265/2008