(E)-1-(4-Meth­oxy­phen­yl)-3-(3,4,5-trimeth­oxy­phen­yl)prop-2-en-1-one

The title compound, C19H20O5, was synthesized by reaction of 4-meth­oxy­acetophenone and 3,4,5-trimeth­oxy-benzaldehyde. The aromatic rings form a dihedral angle of 36.39 (7)°. Two intramolecular C—H⋯O hydrogen bonds occur. The crystal packing features weak C—H⋯O inter­actions

Resurrection of Anopheles goeldii from synonymy with Anopheles nuneztovari (Diptera, Culicidae) and a new record for Anopheles dunhami in the Brazilian Amazon

Nucleotide sequences of the internal transcribed spacer 2 (ITS2) rDNA and partial sequences of the cytochrome coxidase subunit I (COI) mtDNA and white gene nDNA were obtained from specimens of Anopheles nuneztovari A collected in Macapá (state of Amapá), Óbidos, Prainha and Almeirim (state of Pará), Itacoatiara and Parintins (state of Amazonas), Brazil, and compared with previously published sequences of A. nuneztovari s.l. Results of the Bayesian phylogenetic analyses performed using either COI or combined ITS2, COI and white gene sequences suggest that An. nuneztovari B/C is distinct from specimens obtained in the Amazonas/Solimões River basin. Anopheles goeldii, currently in synonymy with An. nuneztovari, was described from individuals collected in Belterra (= Fordlândia) in the Tapajós River, state of Pará, Southern Amazonas River. Morphological comparisons of the characteristics of the male genitalia indicated that An. nuneztovari A and An. goeldii are similar but distinct from An. nuneztovariB/C by the apex of the aedeagus. In considering the results of the phylogenetic analyses and morphological comparisons, An. goeldii is resurrected from synonymy with An. nuneztovari. Additionally, Anopheles dunhamiis reported for the first time in Parintins. This species can be distinguished from An. goeldiiby characters of the male genitalia and molecular dataFAPESP 05/53973-0, CNPq 472485/2006-

Accreting Protoplanets in the LkCa 15 Transition Disk

Exoplanet detections have revolutionized astronomy, offering new insights into solar system architecture and planet demographics. While nearly 1900 exoplanets have now been discovered and confirmed, none are still in the process of formation. Transition discs, protoplanetary disks with inner clearings best explained by the influence of accreting planets, are natural laboratories for the study of planet formation. Some transition discs show evidence for the presence of young planets in the form of disc asymmetries or infrared sources detected within their clearings, as in the case of LkCa 15. Attempts to observe directly signatures of accretion onto protoplanets have hitherto proven unsuccessful. Here we report adaptive optics observations of LkCa 15 that probe within the disc clearing. With accurate source positions over multiple epochs spanning 2009 - 2015, we infer the presence of multiple companions on Keplerian orbits. We directly detect H{\alpha} emission from the innermost companion, LkCa 15 b, evincing hot (~10,000 K) gas falling deep into the potential well of an accreting protoplanet.Comment: 35 pages, 3 figures, 1 table, 9 extended data item

A Cell Permeable Peptide Targeting the Intracellular Loop 2 of Endothelin B Receptor Reduces Pulmonary Hypertension in a Hypoxic Rat Model

Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH). These therapies have had success but have been accompanied by adverse reactions. Also, unlike the CPP which target specific signaling cascades, the antagonists target the entire function of the receptor. Using the CPP strategy of biased antagonism of the ETB receptor’s intracellular loop 2 (ICB2), we demonstrate blunting of hypoxic pulmonary hypertension (HPH) in the rat, including indices of pulmonary arterial pressure, right ventricular hypertrophy and pulmonary vascular remodeling. Further, ex vivo analysis of the pulmonary artery treated with the IC2B peptide upon injection manifests marked reductions in Akt and ERK activation. Both kinases have been intimately related to cell proliferation and vascular contraction, the hallmarks of PAH. These observations in sum illustrate an involvement of the ETB receptor in HPH and furthermore provide a basis for a novel, CPP-based, strategy in the treatment of PAH, ultimately able to target not only ET-1, but also other factors involved in the development of PAH

Tratamento térmico em sementes de macaúba visando a superação da dormência.

O objetivo deste trabalho foi avaliar a germinação e o desenvolvimento in vitro de plântulas oriundas de diferentes acessos nativos de macaúba. Projeto Fontes alternativas de matéria prima para produção de biocombustíveis

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM

Risk factors associated with calcinosis of juvenile dermatomyositis

OBJETIVO: Identificar fatores de risco associados à calcinose em crianças e adolescentes com dermatomiosite juvenil. MÉTODOS: Prontuários de 54 pacientes com dermatomiosite juvenil foram estudados. Foram avaliados dados demográficos; características clínicas: grau de força muscular (I a V do Medical Research Council), presença de comprometimentos pulmonar (distúrbio ventilatório restritivo com presença ou ausência do anticorpo anti-Jo-1), gastrointestinal (refluxo gastroesofágico) e cardíaco (pericardite e/ou miocardite); exames laboratoriais: elevação de enzimas musculares (creatinoquinase, aspartato aminotransferase, alanina aminotransferase e desidrogenase lática) e terapias utilizadas: corticoterapia isolada ou associada à cloroquina e/ou imunossupressor. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de calcinose e foram avaliados através de análise univariada e multivariada. RESULTADOS: Calcinose foi evidenciada em 23 (43%) pacientes, sendo em seis (26%) antes do diagnóstico e em 17 (74%) após. A análise univariada revelou que comprometimentos cardíaco (p = 0,01) e pulmonar (p = 0,02) e necessidade da utilização de um ou mais imunossupressores (metotrexato, ciclosporina A e/ou pulsoterapia com ciclofosfamida endovenosa) no tratamento da dermatomiosite juvenil (p = 0,03) foram associados com uma maior incidência de calcinose. A análise multivariada mostrou que comprometimento cardíaco (OR = 15,56; IC95% 1,59-152,2) e uso de um ou mais imunossupressores (OR = 4,01; IC95% 1,08-14,87) foram as únicas variáveis independentes associadas à presença de calcinose. CONCLUSÕES: O aparecimento da calcinose foi freqüente na dermatomiosite juvenil, habitualmente na evolução da doença. A calcinose foi associada aos casos mais graves, que apresentaram envolvimento cardíaco e necessitaram da utilização de imunossupressores no seu tratamento.OBJECTIVE: To identify risk factors associated with calcinosis in children and adolescents with juvenile dermatomyositis. METHODS: A review was carried out of the medical records of 54 patients with juvenile dermatomyositis. Data were collected on demographic characteristics, clinical features: muscle strength (stages I to V of the Medical Research Council scale), pulmonary involvement (restrictive pulmonary disease with presence or absence of anti-Jo1 antibodies), gastrointestinal problems (gastroesophageal reflux) and/or heart disease (pericarditis and/or myocarditis); laboratory tests: elevated muscle enzyme levels in serum (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase and/or lactate dehydrogenase); and on the treatments given: corticoid therapy in isolation or associated with hydroxychloroquine and/or immunosuppressants. The patients were divided into two groups, depending on presence or absence of calcinosis and data were evaluated by both univariate and multivariate analyses. RESULTS: Calcinosis was identified in 23 (43%) patients, and in six (26%) patients it had emerged prior to diagnosis while in 17 (74%) it was post diagnosis. The univariate analysis revealed that cardiac (p = 0.01) and pulmonary (p = 0.02) involvement and the need for one or more immunosuppressor (methotrexate, cyclosporine A and/or pulse therapy with intravenous cyclophosphamide) to treat juvenile dermatomyositis (p = 0.03) were all associated with an increased incidence of calcinosis. The multivariate analysis then demonstrated that only cardiac involvement (OR = 15.56; 95%CI 1.59-152.2) and the use of one or more immunosuppressor (OR = 4.01; 95%CI 1.08-14.87) were independently associated with the presence of calcinosis. CONCLUSIONS: Calcinosis was a frequent development among these juvenile dermatomyositis cases, generally emerging as the disease progressed. Calcinosis was associated with the more severe cases that also had cardiac involvement and where immunosuppressors had to be included in the treatment

Responsiveness to exercise training in juvenile dermatomyositis: a twin case study

<p>Abstract</p> <p>Background</p> <p>Patients with juvenile dermatomyositis (JDM) often present strong exercise intolerance and muscle weakness. However, the role of exercise training in this disease has not been investigated.</p> <p>Purpose</p> <p>this longitudinal case study reports on the effects of exercise training on a 7-year-old patient with JDM and on her unaffected monozygotic twin sister, who served as a control.</p> <p>Methods</p> <p>Both the patient who was diagnosed with JDM as well as her healthy twin underwent a 16-week exercise training program comprising aerobic and strengthening exercises. We assessed one repetition-maximum (1-RM) leg-press and bench-press strength, balance, mobility and muscle function, blood markers of inflammation and muscle enzymes, aerobic conditioning, and disease activity scores. As a result, the healthy child had an overall greater absolute strength, muscle function and aerobic conditioning compared to her JDM twin pair at baseline and after the trial. However, the twins presented comparable relative improvements in 1-RM bench press, 1-RM leg press, VO_2peak, and time-to-exhaustion. The healthy child had greater relative increments in low-back strength and handgrip, whereas the child with JDM presented a higher relative increase in ventilatory anaerobic threshold parameters and functional tests. Quality of life, inflammation, muscle damage and disease activity scores remained unchanged.</p> <p>Results and Conclusion</p> <p>this was the first report to describe the training response of a patient with non-active JDM following an exercise training regimen. The child with JDM exhibited improved strength, muscle function and aerobic conditioning without presenting an exacerbation of the disease.</p