Compensatory up-regulation of angiotensin II subtype 1 receptors in alpha ENaC knockout heterozygous mice.

BACKGROUND: In mice, a partial loss of function of the epithelial sodium channel (ENaC), which regulates sodium excretion in the distal nephron, causes pseudohypoaldosteronism, a salt-wasting syndrome. The purpose of the present experiments was to examine how alpha ENaC knockout heterozygous (+/-) mice, which have only one allele of the gene encoding for the alpha subunit of ENaC, control their blood pressure (BP) and sodium balance. METHODS: BP, urinary electrolyte excretion, plasma renin activity, and urinary adosterone were measured in wild-type (+/+) and heterozygous (+/-) mice on a low, regular, or high sodium diet. In addition, the BP response to angiotensin II (Ang II) and to Ang II receptor blockade, and the number and affinity of Ang II subtype 1 (AT1) receptors in renal tissue were analyzed in both mouse strains on the three diets. RESULTS: In comparison with wild-type mice (+/+), alpha ENaC heterozygous mutant mice (+/-) showed an intact capacity to maintain BP and sodium balance when studied on different sodium diets. However, no change in plasma renin activity was found in response to changes in sodium intake in alpha ENaC +/- mice. On a normal salt diet, heterozygous mice had an increased vascular responsiveness to exogenous Ang II (P < 0.01). Moreover, on a normal and low sodium intake, these mice exhibited an increase in the number of AT1 receptors in renal tissues; their BP lowered markedly during the Ang II receptor blockade (P < 0.01) and there was a clear tendency for an increase in urinary aldosterone excretion. CONCLUSIONS: alpha ENaC heterozygous mice have developed an unusual mechanism of compensation leading to an activation of the renin-angiotensin system, that is, the up-regulation of AT1 receptors. This up-regulation may be due to an increase in aldosterone production.

Meat characteristics of chickens from an F1 cross of two improved Spanish breeds depending on slaughter age

The present study analysed the meat characteristics of i) improved Castellana Negra chickens slaughtered at 18 weeks (CN-18) and ii) F1 crossbred chickens from improved Castellana Negra hens and improved Penedesenca Negra cocks (CNPN) slaughtered at 12 weeks and 18 weeks of age (young and adult animals, respectively). Purebred and crossbred specimens were compared at similar weights (CN-18 and CNPN-12) and ages (CN-18 and CNPN-18). The protein content of the meat was similar for the three types of animals; heavier animals (CNPN-18) had more fat than those slaughtered at lower weights (CNPN-12 and CN-18). Adults had a higher saturated fatty acid content and the young CNPN chickens had more monounsaturated fatty acids than CN chickens. In the CNPN adults, less water was lost during cooking, which is directly related to the juiciness of the meat. With regard to sensory analysis, a darker colour was observed in the meat as much as the internal fat of adult animals, in addition to greater colour uniformity. The meat of young CNPN birds was juicier, whereas that of the CN chickens was more fibrous. Therefore, we conclude that meat from CNPN chickens presents chemical, physical, and sensorial characteristics that make these animals a genetic base for alternative poultry production.

Seleção de genótipos de pessegueiro F1 com baixa necessidade de frio hibernal

A baixa necessidade de frio é característica fundamental para que se possa cultivar economicamente o pessegueiro em condições de clima subtropical, devendo ser este, portanto, o principal objetivo dos programas de melhoramento nestas regiões. o objetivo deste trabalho foi avaliar e selecionar progênies de pessegueiro com baixa necessidade de frio hibernal por meio do método de ramos destacados e indicar o melhor genitor para utilização em programas de melhoramento, visando a esta característica. Foram avaliados 180 genótipos pertencentes a 25 populações de pessegueiro, sendo que o número de genótipos em cada população variou de três a dezenove. os ramos foram submetidos a 50; 100; 150; 200 e 400 unidades de frio, e, ao término de cada tratamento, os ramos foram transferidos para o interior da casa de vegetação. Após 21 dias, foram avaliados quanto às porcentagens de floração e brotação,e com os resultados obtidos, 5 populações e 29 genótipos de pessegueiro com baixa necessidade de frio hibernal foram selecionados. A cultivar Real mostrou-se eficiente na obtenção de pessegueiros com baixa necessidade de frio hibernal, quando utilizada como genitor feminino.

VARIABILIDAD GENÉTICA DE PARENTALES Y POBLACIONES F1 INTER E INTRAESPECÍFICAS DE Physalis peruviana L. Y P. floridana Rydb.

RESUMENLa uchuva, Physalis peruviana, es un frutal andino de importancia para la exportación; el principal limitante de su producción en Colombia es el marchitamiento vascular ocasionado por Fusarium oxysporum. En el presente trabajo se propuso generar poblaciones F1 entre parentales contrastantes por su respuesta a éste patógeno y evaluarlas molecularmente como apoyo al conocimiento y uso de los recursos genéticos de la especie. Para ello, cuatro genotipos de P. peruviana y uno de la especie relacionada P. floridana, fueron caracterizados a nivel morfo-agronómico empleando 34 variables cualitativas y 20 cuantitativas, y a nivel molecular con 328 marcadores tipoCOSII y 154 IRGs. Dichos genotipos se utilizaron como parentales para la generación y caracterización molecular de poblaciones F1. Las variables cuantitativas permitieron diferenciar las especies P. floridana y P. peruviana así como genotipos cultivados y silvestres dentro de P. peruviana. Se encontró un 100% de viabilidad en cruces F1 intraespecíficos y un 50% en interespecíficos, siendo viables aquellos donde P. floridana fue receptor de polen. A nivel molecular no se identificaron polimorfismos dentro de P. peruviana pero sí entre P. floridana y P. Peruviana. En una población F1 de 51 individuos generada entre las especies se encontró un total de 127 alelos con un promedio de 3,18 por locus, un PIC de 0,358 y altos valores de heterocigocidad (Ho: 0,737 y He: 0,449). Los análisis de PCA y agrupamiento permitieron discriminar la población F1 en tres grupos, en su mayoría con mayor similitud al parental P. floridana. Lo anterior se reflejó en una distorsión mendeliana del 75% favorecida por la presencia de un 63,75% de alelos maternos. El estudio aporta conocimiento sobre la cruzabilidad en uchuva y la variabilidad genética de genotipos parentales y poblaciones F1.

Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype.

Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B-cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (P<0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P=0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P=0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor.

Molecular profiling of non-small cell lung cancer by histologic subtype

Background: A substantial proportion of NSCLC has been shown to harbour specific molecular alterations affecting tumour proliferation and resulting in sensitivity to inhibition of the corresponding activated oncogenic pathway by targeted therapies. Comprehensive tumor profiling can diagnose such alterations and may identify new alterations opening additional treatment options for all distinct NSCLC subtypes. Methods: Over 6,700 non-small cell lung cancer cases referred to Caris Life Sciences between 2009 and 2014 were evaluated; clinical diagnoses and detailed tumor pathology were collected from referring physicians. Specific profiling was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification/rearrangement (CISH or FISH), and/or RNA fragment analysis within potential cancer-related genes and pathways. Results: Patients were grouped into cohorts according to histological subtype - adenocarcinoma (AD) (n=4,286), squamous cell carcinoma (SCC) (n=1,280), large cell carcinoma (LCC) (n=153) and bronchioalveolar carcinoma (BAC) (n=94). Protein overexpression of cMET (>2+ in >50% cells) was higher in AD (35.9%) compared to other subgroups (12-20%) while RRM1 and TOP2A levels were lower in AD. ALK or ROS1 were rearranged in 5.3% of patients with AD compared to 3.7% of patients with LCC and 1.2% of patients with SCC. EGFR mutations were found at low prevalence in both the LCC (0%) and SCC cohorts (2.8%) compared to 21% in AD. Similar lower rates of BRAF mutations were observed in the LCC and SCC cohorts compared to AD (0%, 1.1% and 5.1%). Pathway analysis showed activating mutations in the ERK pathway in 40% of patients with AD. Only 10-12% of patients with LCC or SCC had activating mutations in the ERK pathway. Conclusions: Despite the limitations of this retrospective series, we report comprehensive profiling of the largest cohort of NSCLC. Tumor profiling reveals that ADs may be more addicted to the ERK pathway than other histological subtypes. Drugs which target cMET may also have most utility in AD. Full analysis by histological subtype and additional correlative data on protein expression, gene copy number and mutations will be presented.

Mixed subtype of congenital mesoblastic nephroma with poor evolution: a case report and literature review

Abstract A male child born at 27 weeks, weighting 1305 g and presenting with a right-sided abdominal tumor. Computed tomography scan demonstrated the presence of a solid mass compressing the right kidney. Puncture biopsy revealed congenital mesoblastic nephroma. The patient underwent total right nephroureterectomy, and died on the second day after surgery.

Armazenamento sob condições ambiente e aceitabilidade do melão 'F1 Jangada' produzido em sistema hidropônico

O objetivo deste trabalho foi determinar o período de armazenamento pós-colheita e a aceitabilidade pelo consumidor de melão híbrido 'F1 Jangada' (Cucumis melo L.), produzido em sistema hidropônico, mantido em condições ambiente (22 ± 2 ºC e umidade relativa de 40 ± 5%). O experimento compreendeu o período de 21-6-2005 a 2-8-2005. Foi utilizado o esquema fatorial 5 x 2, em delineamento experimental inteiramente casualizado, com cinco períodos de armazenamento (0; 7; 21; 28 e 42 dias) e dois tipos de substrato (areia e fibra de coco), com três repetições, em que cada repetição consistiu em cinco frutos de meloeiro. Foram avaliados o pH, a acidez titulável, os sólidos solúveis, a perda de massa fresca, a análise sensorial e a decisão de compra dos melões. Foram verificados efeitos do tipo de substrato e tempo de armazenamento sobre os valores de pH dos melões. A acidez titulável dos melões diminuiu significativamente nos primeiros sete dias de armazenamento, em ambos os substratos. Não foram verificados efeitos do tipo de substrato e tempo de armazenamento nos sólidos solúveis dos melões durante o armazenamento. Não houve diferença de perda de massa fresca dos frutos produzidos nos dois substratos, sendo de 7,1 ± 0,2%, durante os 42 dias de armazenamento. O tipo de substrato não interferiu na aparência geral, cor, textura e sabor dos melões. Aos 42 dias de armazenamento, os melões produzidos nos dois tipos de substrato apresentaram-se aceitáveis pelo consumidor. No entanto, os produzidos no substrato com areia apresentaram melhor aceitabilidade e decisão de compra ao longo do armazenamento.

Karta öfver Finland (Sektionen F1)

1 kartta :, vär. ;, 51 x 42,8 cm, lehti 58 x 50,3 cm

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

Electrophysiological evidence for glial-subtype glutamate transporter functional expression in rat cerebellar granule neurons

A glutamate-sensitive inward current (Iglu) is described in rat cerebellar granule neurons and related to a glutamate transport mechanism. We examined the features of Iglu using the patch-clamp technique. In steady-state conditions the Iglu measured 8.14 ± 1.9 pA. Iglu was identified as a voltage-dependent inward current showing a strong rectification at positive potentials. L-Glutamate activated the inward current in a dose-dependent manner, with a half-maximal effect at about 18 µM and a maximum increase of 51.2 ± 4.4%. The inward current was blocked by the presence of dihydrokainate (0.5 mM), shown by others to readily block the GLT1 isoform. We thus speculate that Iglu could be attributed to the presence of a native glutamate transporter in cerebellar granule neurons.