Physiological and metabolic changes in response to Boron levels are mediated by ethylene affecting tomato fruit yield.

Boron (B) is an essential nutrient for the plant, and its stress (both deficiency and toxicity) are major problems that affect crop production. Ethylene metabolism (both signaling and production) is important to plants' differently responding to nutrient availability. To better understand the connections between B and ethylene, here we investigate the function of ethylene in the responses of tomato (Solanum lycopersicum) plants to B stress (deficiency, 0 µM and toxicity, 640 µM), using ethylene related mutants, namely nonripening (nor), ripening-inhibitor (rin), never ripe (Nr), and epinastic (Epi). Our results show that B stress does not necessarily inhibit plant growth, but both B stress and ethylene signaling severely affected physiological parameters, such as photosynthesis, stomatal conductance, and chlorophyll a fluorescence. Under B toxicity, visible symptoms of toxicity appeared in the roots and margins of the older leaves through necrosis, caused by the accumulation of B which stimulated ethylene biosynthesis in the shoots. Both nor and rin (ethylene signaling) mutants presented similar responses, being these genotypes more sensitive and displaying several morphophysiological alterations, including fruit productivity reductions, in response to the B toxicity conditions. Therefore, our results suggest that physiological and metabolic changes in response to B fluctuations are likely mediated by ethylene signaling.

Fully automated deep-learning section-based muscle segmentation from CT images for sarcopenia assessment.

AIM: To develop a fully automated deep-learning-based approach to measure muscle area for assessing sarcopenia on standard-of-care computed tomography (CT) of the abdomen without any case exclusion criteria, for opportunistic screening for frailty. MATERIALS AND METHODS: This ethically approved retrospective study used publicly available and institutional unselected abdominal CT images (n=1,070 training, n=31 testing). The method consisted of two sequential steps: section detection from CT volume followed by muscle segmentation on single-section. Both stages used fully convolutional neural networks (FCNN), based on a UNet-like architecture. Input data consisted of CT volumes with a variety of fields of view, section thicknesses, occlusions, artefacts, and anatomical variations. Output consisted of segmented muscle area on a CT section at the L3 vertebral level. The muscle was segmented into erector spinae, psoas, and rectus abdominus muscle groups. Output was tested against expert manual segmentation. RESULTS: Threefold cross-validation was used to evaluate the model. Section detection cross-validation error was 1.41 ± 5.02 (in sections). Segmentation cross-validation Dice overlaps were 0.97 ± 0.02, 0.95 ± 0.04, and 0.94 ± 0.04 for erector spinae, psoas, and rectus abdominus, respectively, and 0.96 ± 0.02 for the combined muscle area, with R2 = 0.95/0.98 for muscle attenuation/area in 28/31 hold-out test cases. No statistical difference was found between the automated output and a second annotator. Fully automated processing took <1 second per CT examination. CONCLUSIONS: A FCNN pipeline accurately and efficiently automates muscle segmentation at the L3 vertebral level from unselected abdominal CT volumes, with no manual processing step. This approach is promising as a generalisable tool for opportunistic screening for frailty on standard-of-care CT.

Automatic 3D dense phenotyping provides reliable and accurate shape quantification of the human mandible.

Automatic craniomaxillofacial (CMF) three dimensional (3D) dense phenotyping promises quantification of the complete CMF shape compared to the limiting use of sparse landmarks in classical phenotyping. This study assesses the accuracy and reliability of this new approach on the human mandible. Classic and automatic phenotyping techniques were applied on 30 unaltered and 20 operated human mandibles. Seven observers indicated 26 anatomical landmarks on each mandible three times. All mandibles were subjected to three rounds of automatic phenotyping using Meshmonk. The toolbox performed non-rigid surface registration of a template mandibular mesh consisting of 17,415 quasi landmarks on each target mandible and the quasi landmarks corresponding to the 26 anatomical locations of interest were identified. Repeated-measures reliability was assessed using root mean square (RMS) distances of repeated landmark indications to their centroid. Automatic phenotyping showed very low RMS distances confirming excellent repeated-measures reliability. The average Euclidean distance between manual and corresponding automatic landmarks was 1.40 mm for the unaltered and 1.76 mm for the operated sample. Centroid sizes from the automatic and manual shape configurations were highly similar with intraclass correlation coefficients (ICC) of > 0.99. Reproducibility coefficients for centroid size were < 2 mm, accounting for < 1% of the total variability of the centroid size of the mandibles in this sample. ICC's for the multivariate set of 325 interlandmark distances were all > 0.90 indicating again high similarity between shapes quantified by classic or automatic phenotyping. Combined, these findings established high accuracy and repeated-measures reliability of the automatic approach. 3D dense CMF phenotyping of the human mandible using the Meshmonk toolbox introduces a novel improvement in quantifying CMF shape.

Combination anti-coronavirus therapies based on nonlinear mathematical models.

Using nonlinear mathematical models and experimental data from laboratory and clinical studies, we have designed new combination therapies against COVID-19.

Evaluation of reproductive and animal welfare parameters of swine females of different genetic lines submitted to different reproductive management and housing systems during pregnancy / [Avaliação de parâmetros reprodutivos e de bem-estar animal de fêmeas suínas de diferentes linhagens genéticas submetidas a diferentes sistemas de manejo reprodutivo e de alojamento durante a prenhez]

The aim of this study was to evaluate swine females of different genetic lines submitted to different reproductive management and housing systems during pregnancy on reproductive performance and animal welfare parameters. After artificial insemination protocol, 524 females were divided into two gestation housing systems: PEN1=animals housed in individual stalls during the breeding and after group-housed; PEN32=animals housed in individual stalls from breeding until 32 days of pregnancy and after group-housed. The number of piglets born, and the pregnancy and farrowing rates were evaluated. Welfare parameters related to the pregnancy phase were used. Females who weaned more piglets in the previous farrowing had a higher number of piglets born at the next farrowing. The pregnancy rate was affected by the number of semen doses. The farrowing rate was not influenced by the evaluated parameters, with average value of 91.36%. There was no effect of the gestation housing system and the genetic lines on pregnancy and farrowing rates, with values above 90.0%. The animal welfare indicators showed more compromised parameters in PEN1 system. PEN1 system did not impair the reproductive performance although it presented more compromised animal welfare parameters.(AU)

O objetivo deste estudo foi avaliar fêmeas suínas de diferentes linhagens genéticas submetidas a diferentes sistemas reprodutivos de manejo e alojamento durante a prenhez sobre parâmetros de desempenho reprodutivo e bem-estar animal. Após o protocolo de inseminação artificial, 524 fêmeas foram divididas em dois sistemas de alojamento de gestação: PEN1=animais alojados em baias individuais durante o protocolo de inseminação artificial e, depois, alojados em grupo; PEN32=animais alojados em baias individuais desde o protocolo de inseminação artificial até 32 dias de prenhez e, depois, alojados em grupo. O número de leitões nascidos e as taxas de prenhez e parto foram avaliados. Parâmetros de bem-estar relacionados à fase gestacional foram utilizados. As fêmeas que desmamaram mais leitões no parto anterior tiveram um maior número de leitões nascidos no próximo parto. A taxa de prenhez foi afetada pelo número de doses de sêmen. A taxa de parto não foi influenciada pelos fatores avaliados, com valor médio de 91,36%. Não houve efeito do sistema de alojamento gestacional e das linhas genéticas sobre as taxas de prenhez e parto, com valores acima de 90,0%. Os indicadores de bem-estar animal mostraram parâmetros mais comprometidos no sistema PEN1. O sistema PEN1 não prejudicou o desempenho reprodutivo, embora tenha apresentado parâmetros de bem-estar animal mais comprometidos.(AU)

Insulina e IGF-1 no meio extensor de criopreservação seminal bovina / Insulin and IGF-I in extender medium for bovine semen cryopreservation

Objetivou-se avaliar a condição metabólica e estrutural das células espermáticas bovinas após congelação, com adição prévia de IGF-I e insulina no meio diluidor seminal. Os ejaculados de seis touros Nelore foram submetidos a quatro tratamentos: controle; insulina (100µUI/mL); IGF-I (150ng/mL) e insulina + IGF-I (50µUI/mL e 75ng/mL, respectivamente). Após a congelação, realizaram-se os testes de termorresistência rápida, coloração pelo corante azul de tripan e Giemsa, além da análise computadorizada da motilidade espermática, da integridade das membranas plasmática e acrossomal, e da peça intermediária por meio de sondas fluorescentes. O teste de termorresistência rápida apresentou efeito dentro do tempo de cada tratamento, mas não entre os tratamentos. Na análise computadorizada da motilidade espermática, foram observados movimento, motilidade e velocidade espermáticos; não houve efeitos dos tratamentos sobre qualquer uma dessas variáveis. Respostas iguais foram obtidas com as sondas fluorescentes e o corante azul de tripan/Giemsa. A adição de insulina e IGF-I, de forma isolada ou combinada, ao meio diluidor para congelação de sêmen não produziu efeitos sobre as condições metabólica e estrutural das células espermáticas.(AU)

This study aimed to evaluate the metabolic and structural condition of the spermatic bovine cells after the freezing, with addition, previously, of IGF-I and Insulin in the seminal thinner medium. The semen of 6 Nellore bulls were submitted to four treatments: Control, Insulin (100µUI/mL); IGF-I (150ng/mL) and Insulin + IGF-I (50µUI/mL and 75ng/mL, respectively). After freezing, rapid resistance tests, Tripan and Giemsa Blue staining, and computerized analysis of sperm motility and integrity of the plasma and acrosomal membranes and the intermediate part were performed by fluorescent probes. The term rapid resistance test had effect within the time of each treatment, but not between treatments. In the computer analysis of sperm motility, sperm movement, motility and velocity no effects of treatments were observed on any of these variables. The same results were obtained with the fluorescent probes and the Blue dye Trypan / Giemsa. The addition of Insulin and IGF-I, alone or in combination, to the semen freezing dilution medium had no effect on the metabolic and structural condition of sperm cells.(AU)

Significant differences in access to tests and treatments for multiple myeloma between public and private systems in Latin America. Results of a Latin American survey. GELAMM (Grupo de Estudio Latino Americano de Mieloma Múltiple).

The incidence of multiple myeloma (MM) has increased in the last 20 years, particularly in middle and low-middle income countries. Access to diagnostic and prognostic tests and the availability of effective care is highly variable globally. Latin America represents 10% of the world population, distributed in countries of varied size, population, and socio-economic development. In the last decade, great improvements have been made in the diagnosis and treatment of MM. Applying these advances in real life is a challenge in our region. Local data regarding MM standards of care and outcomes are limited. A survey was carried out among hematologists from 15 Latin American countries to describe access to MM diagnostic and prognostic tests and the availability of effective care options. This study provides real-world data for MM in our region, highlighting striking differences between public and private access to essential analyses and therapeutic options.

Grazing criteria for perennial peanut (Arachis pintoi cv. Amarillo) consumed by sheep in rotational stocking / Critérios de pastejo para amendoim forrageiro (Arachis pintoi cv. Amarillo) consumido por ovelhas em sistema rotacionado

The objective of work was to study the productive profile of perennial peanut in a rotational stocking environment under different criteria. The treatments corresponded to pre-grazing height of 14 and 18cm or 95% of light interception (LI) distributed in a completely randomized design. The studied variables were forage mass, percentage of structural components, forage mass and the structural components in the lower and upper canopy strata. The entrance criterion of 18cm in height, despite having higher forage mass, presented lower percentage of leaves and higher percentage of stems and forage losses. The criteria of 14cm and 95% light interception presented similar production between them and the highest rate of forage accumulation. In all criteria, in the upper strata of pasture a higher percentage of leaves were found. The criteria of 95% LI and 14cm in height presented the best productive performances. The entry criterion of 18cm presented a higher mass of pre-grazing forage with lower percentage of dead material, but with higher forage losses, resulting from senescent leaves. Due to changes in the structural components, as grazing cycles increase, the interception of 95% of the incident light by the perennial peanut occurs at lower heights.(AU)

O objetivo do presente trabalho foi estudar o perfil produtivo do amendoim forrageiro em um ambiente rotacionado, sob diferentes critérios. Os tratamentos corresponderam à altura de pré-pastejo de 14 e 18cm ou 95% de intercepção de luz (LI), distribuídos em delineamento inteiramente ao acaso. As variáveis estudadas foram massa forrageira, porcentagem de componentes estruturais, densidade da massa forrageira e densidade dos componentes estruturais nos estratos do dossel inferior e superior. O critério de entrada de 18cm de altura, apesar de ter maior massa forrageira, apresentou menor porcentagem de folhas e maior porcentagem de hastes e perdas de forragem. Os critérios de interceptação de luz de 14cm e 95% apresentaram produção similar entre eles e a maior taxa de acumulação de forragem. Em todos os critérios, no estrato superior de pastagem, foi encontrada maior porcentagem de folhas. Os critérios de 95% LI e 14cm de altura apresentaram os melhores desempenhos produtivos. O critério de entrada de 18cm apresentou maior massa de forragem pré-pastagem com menor porcentagem de material morto, mas com maiores perdas de forragem, resultantes de folhas senescentes. Devido às mudanças nos componentes estruturais, à medida que os ciclos de pastagem aumentam, a intercepção de 95% da luz incidente pelo amendoim forrageiro ocorre em alturas mais baixas.(AU)

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Morphofunctional description of mucous cells in the gills of the Arapaimidae Arapaima gigas (Cuvier) during its development.

The gill structure of the Amazonian fish Arapaima gigas (Cuvier 1829) shows ontogenetic changes during development, particularly due the transition from the aquatic to the obligatory air breathing mode of respiration. However, three main cell types can be found in the gills: mitochondrial rich cells, pavement cells and mucous cells (MCs). The MCs are involved in the secretory pathway. The functions of the secreted molecules include mechanical protection of epithelia, protection against parasites and bacterial infection, and role on ion regulation. In this study, we analysed mucous cell location and mucous cell type, based on pH, during the development of A. gigas. Using samples obtained from the environment, gills were collected and fixed in buffered solution. Histological techniques for the identification of MCs were performed Alcian Blue (AB) and periodic acid-Schiff (PAS). The results showed the presence of PAS+ and AB+ cells in the whole filament in all examined fish. In animals less than 50 g, few MCs were present, and no differences were observed in AB+ and PAS+ cells. In animals weighing close to 500 g, more PAS+ cells than AB+ cells were observed, and in animals that weighed more than 1,000 g, more AB+ cells than PAS+ cells were observed. These observations may be a result of the ontogenetic changes in the gill epithelia, which can change the osmorespiratory compromise in ion regulation functions as well the glycosaminoglycans secreted by PAS cells, which in large animals can play a role in the protection against parasites and bacterial infection.

Valor nutritivo de gramíneas do gênero Cynodon consorciadas com amendoim forrageiro / Nutritive value of grasses of genus Cynodon mixed with forage peanut

O objetivo do presente estudo foi avaliar o valor nutritivo do consórcio forrageiro entre gramíneas do gênero Cynodon (cv. tifton 85 ou coastcross) com Arachis pintoi (amendoim forrageiro). O experimento foi conduzido na Universidade Tecnológica Federal do Paraná, Câmpus Dois Vizinhos, em área de aproximadamente 3000m2. O delineamento experimental foi de blocos ao acaso, com quatro tratamentos e três repetições. Os tratamentos foram: tifton 85 e coastcross em cultivo estreme, tifton 85 + AF e coastcross + AF. Foram avaliados os teores de PB, FDN, FDA, DIVMS, MM e MS das lâminas foliares, colmo+bainha, amendoim forrageiro e da MF disponível da simulação de pastejo. Foi observado que a coastcross tem menor teor de fibra, independentemente do tratamento. O avanço das estações do ano proporcionou menores valores de PB e DIVMS em todos os tratamentos. A simulação de pastejo demonstrou que a tifton 85 tem maiores teores de MS, assim como valores inferiores são encontrados para os consórcios. Quando consorciado com as gramíneas, o amendoim forrageiro reduziu os compostos fibrosos na pastagem, acrescentando maiores teores de PB em pastagem de gramíneas no final do ciclo produtivo.(AU)

The goal of this study was to evaluate the fodder performance and production of Cynodon (Cv. Tifton 85 or Coastcross) mixed with Arachis pintoi (Forage peanut). The experiment was conducted at the Universidade Tecnológica Federal do Paraná, Câmpus Dois Vizinhos, at an area of approximately 3000m2. A completely randomized block design was applied, with four treatments and three replicates. The treatments were: Tifton 85 and Coastcross in pure crop, Tifton 85 + AF and Coastcross + AF with rotated and successive implantation of one line to the grass and three consecutive lines to the legume. The content of CP, NDF, ADF, IVDMD ashe and DM of the leaf blades, stem of grasses forage peanut and total forage mass available of grazing simulation was evaluated. Coastcross has lower fibrous contents, regardless of treatment. The changing of the seasons during the year provided lower values of CP and IVDMD for all treatments. The evaluation of the grazing simulation showed that Tifton 85 has higher DM values just as the lower ones are found for consortia. When mixed with grasses, forage peanuts reduce the fibrous compounds on pasture, increasing the CP levels in grass pasture at the end of productive cycle.(AU)

Composição química da forragem e do ensilado de azevém anual em função de diferentes tempos de secagem e estádios fenológicos / Chemical composition of annual ryegrass forage and silage for different drying times and phenological phases

O objetivo do presente estudo foi determinar como o tempo de secagem e o estádio fenológico da planta influenciam na composição química e qualidade da silagem de azevém (Lolium multiflorum, Lam.). O delineamento experimental foi de blocos ao acaso, com seis tratamentos (vegetativo: cortar e ensilar; cortar + pré-secagem de 4 horas e ensilar; cortar + pré-secagem de 7 horas e ensilar; pré-florescimento: ensilagem, cortar e ensilar e pré-secagem de 4 horas; florescimento: cortar e ensilar) e quatro repetições, com quatro meses de conservação da silagem. Foram determinados: desaparecimento de massa após o corte, rendimento de massa seca, proteína bruta e frações fibrosas. Além disso, foram determinados na silagem: pH, lipídios totais, nitrogênio insolúvel em detergente neutro e ácido. O manejo empregado auxilia na desidratação da forragem, com perda na quantidade de nitrogênio no vegetativo. No pré-florescimento, essa perda não ocorre. O avanço do ciclo da forrageira ocasiona diminuição na quantidade de nutrientes na biomassa, entretanto a produção de forragem é aumentada. A silagem apresentou composição bromatológica semelhante à observada na massa verde de azevém, o que demonstra a eficiência do método de conservação. A ensilagem em estádios mais avançados é aconselhada quando se busca maior quantidade de biomassa ensilada, porém com qualidade inferior.(AU)

The aim was how to define the effect of pre-drying time and the plant phase's influence on chemical composition and quality of ryegrass silage. The experimental design was randomized blocks with six treatments (Vegetative: Cut and ensiled; cut + pre-drying 4 hours and ensiled and; cut + pre-drying of 7 hours and ensiled; Pre-flowering: Silage cutting and ensiled and pre-drying 4 hours Flowering:. cut and ensiled) and four repetitions. The silage was stowed for four months. It were determined the mass disappearance after cutting, dry matter yield, crude protein and fiber fractions. Moreover, it was determined on silage pH, total lipids and insoluble protein content. The management used aids in dehydration of fodder, resulting in losses on the amount of nitrogen on vegetative phase. For pre-flowering, this loss has not occur. The advance of fodder cycle causes a decrease in the amount of nutrients in biomass, but fodder yield increased. Ryegrass silage presented chemical composition similar to that observed on green mass of ryegrass, evinced the efficiency of fodder conservation method. The silage in more advanced phases is advised when seeking greater amount of ensiled biomass, but lower quality.(AU)

A physical model for dementia.

Aging associated brain decline often result in some kind of dementia. Even when this is a complex brain disorder a physical model can be used in order to describe its general behavior. A probabilistic model for the development of dementia is obtained and fitted to some experimental data obtained from the Alzheimer's Disease Neuroimaging Initiative. It is explained how dementia appears as a consequence of aging and why it is irreversible.

Self-similar conductance patterns in graphene Cantor-like structures.

Graphene has proven to be an ideal system for exotic transport phenomena. In this work, we report another exotic characteristic of the electron transport in graphene. Namely, we show that the linear-regime conductance can present self-similar patterns with well-defined scaling rules, once the graphene sheet is subjected to Cantor-like nanostructuring. As far as we know the mentioned system is one of the few in which a self-similar structure produces self-similar patterns on a physical property. These patterns are analysed quantitatively, by obtaining the scaling rules that underlie them. It is worth noting that the transport properties are an average of the dispersion channels, which makes the existence of scale factors quite surprising. In addition, that self-similarity be manifested in the conductance opens an excellent opportunity to test this fundamental property experimentally.

Amendoim forrageiro manejado com baixos resíduos de pastejo por ovinos / Perennial peanut handled with low grazing waste by sheep

O objetivo do trabalho foi estudar o comportamento produtivo do amendoim forrageiro (Arachis pintoi cv. Amarillo) sob diferentes intensidades de pastejo por ovinos em ambiente rotativo. Os tratamentos corresponderam a quatro intensidades de pastejo (muito leniente - ML, leniente - L, moderado - M e severo - S) representadas pelas alturas de resíduo de 11,2; 8,4; 5,9 e 3,2cm, que foram alocadas segundo um delineamento inteiramente ao acaso, com quatro repetições. As variáveis estudadas no pré e no pós-pastejo foram: massa de forragem, percentual de folhas e caules e índice de área foliar. Ao final do experimento, foi calculada a massa de forragem total acumulada, a taxa de acúmulo e a massa de forragem desaparecida. Os dados foram submetidos à análise de variância e ao teste de comparação de médias de Tukey (P< 0,05). Foi verificado que a intensidade de pastejo modifica a composição dos componentes morfológicos e a massa de forragem acumulada pelo amendoim forrageiro, todavia o índice de área foliar no pré-pastejo não é alterado. O amendoim forrageiro não deve ser utilizado sob pastejo intenso. Intensidades de pastejo de moderada a muito leniente proporcionam maior massa de forragem pré-pastejo e total acumulada, associada a menores intervalos entre pastejos.(AU)

This research aimed to study the productive behavior of perennial peanut (Arachis pintoi cv. Amarillo) under different grazing intensities by sheep in a rotation environment. The treatments consisted of four grazing intensity levels (very lenient - VL, lenient - L, moderate - M, and severe - S) represented by the residues 11.2; 8.4; 5.9 and 3.2cm, and allocated randomly with four replications. The variables studied in the pre-grazing and post-grazing were: forage mass, percentage of leaves and stems and leaf area index. At the end of the experiment, total accumulated forage mass, accumulation rate, and mass of missing forage were calculated. The data was submitted to a variance analysis and comparison to a Tukey's test, with a 5% significance level. Grazing intensity was found to modify the composition of morphological components and the forage mass accumulated by peanuts; however, the leaf area index in pre-grazing remained constant. Perennial peanut should not be used under intensive grazing. Grazing intensity from moderate to very lenient provides greater mass of pre-grazing forage and total accumulated forage, combined with shorter intervals between grazing.(AU)

Diethylcarbamazine attenuates LPS-induced acute lung injury in mice by apoptosis of inflammatory cells.

BACKGROUND: Acute lung injury (ALI) is characterized by extensive neutrophil infiltration, and apoptosis delay considered part of the pathogenesis of the condition. Despite great advances in treatment strategies, few effective therapies are known for ALI. Diethylcarbamazine (DEC) is used against lymphatic filariasis, a number of studies have described its anti-inflammatory activities and pro-apoptotic effect. These properties have been associated with nuclear factor kappa-B inactivation. The aim of the present study was to investigate the effect of DEC on ALI induced by lipopolysaccharide (LPS) in mice. METHODS: DEC effect was evaluated by histological and ultrastructural analysis, immunohistochemistry and western blot (WB). Also TUNEL assays were performed and as well as myeloperoxidase (MPO) levels and nitric oxide (NO) were measured. RESULTS: The results demonstrate that LPS induced histological and ultrastructural changes with tissue damage, intense cell infiltration and pulmonary edema, and also increased levels of MPO and NO. DEC reversed these effects, confirming its anti-inflammatory action. DEC pro-apoptotic activity was also evaluated. The expression of TUNEL-positive cells and caspase-3 was increased in DEC treated group. Furthermore, immunohistochemical and WB analysis showed that DEC increased the expression of pro-apoptotic proteins in both the intrinsic (Bax, cytochrome c and caspase-9) and the extrinsic pathways of apoptosis (Fas, FADD and caspase-8). Additionally, DEC reduced the expression of the anti-apoptotic protein Bcl-2. CONCLUSION: Our results suggest that DEC attenuates ALI through the prevention of inflammatory cells accumulation by stimulating apoptosis. DEC accelerates the resolution of inflammation and may be a potential pharmacological treatment for ALI.

Association between the thrombophilic polymorphisms MTHFR C677T, Factor V Leiden, and prothrombin G20210A and recurrent miscarriage in Brazilian women.

Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations - factor V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T - in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling.

O uso de ducha: efeito sobre o bem-estar e a qualidade da carcaça e da carne em suínos transportados para o abate / Use of shower: the effect on welfare and carcass and meat quality of pigs transported to slaughter

O objetivo deste trabalho foi avaliar os efeitos do uso da ducha de água, antes e após o transporte, sobre o bem-estar dos animais e a qualidade da carne dos suínos. Foram utilizados 384 animais (fêmeas e machos castrados), frutos de cruzamento industrial e provenientes de 16 granjas de Santa Catarina/Brasil. O delineamento experimental foi em um fatorial 2x4, com duas distâncias da granja até o frigorífico (menos de 50km; mais de 50km) e quatro protocolos de ducha, que consistiram em: suínos não molhados na granja e no frigorífico (NMG_NMF); não molhados na granja e molhados no frigorífico (NMG_MOF); molhados na granja e não molhados no frigorífico (MOG_NMF); molhados na granja e molhados no frigorífico (MOG_MOF). Nenhum dos fatores teve influência (P>0,05) sobre as variáveis fisiológicas relacionadas ao estresse (cortisol e lactato sanguíneo), ao número de lesões na carcaça e às características de qualidade da carne.(AU)

This study was carried out to evaluate the effects of a shower before and after pig transportation on welfare, meat and carcass quality. We used 384 crossbreeding animals (females and castrated males), from 16 farms in Santa Catarina State, Brazil. A 2x4 factorial arrangement of treatments was employed with two distances from farm to slaughter plant (less than 50km and more than 50km) and four showering protocols. These protocols were applied on pigs: no showering at farm or slaughter plant (Control), no showering at farm but showering at the plant (NMG_MOF); showering at the farm and no showering at the plant (MOG_NMF); showering at the farm and plant (MOG_MOF). None of the factors influenced (P>0.05) physiological variables related to stress (cortisol and lactate in blood samples), number of carcass lesions and the characteristics of meat quality.(AU)

Potential of UCHL1 as biomarker for destruction of pancreatic beta cells.

There is a clinical need for plasma tests for real-time detection of beta cell destruction, as surrogate endpoint in islet transplantation and immunoprevention trials in type 1 diabetes. This study reports on the use of label-free LC-MS/MS proteomics for bottom-up selection of candidate biomarkers. Ubiquitin COOH-terminal hydrolase 1 (UCHL1) was identified as abundant protein in rat and human beta cells, showing promising beta cell-selectivity, and was selected for further validation in standardized toxicity models. In vitro, H2O2-induced necrosis of INS-1 cells and human islets resulted in intracellular UCHL1 depletion and its extracellular discharge. In vivo, streptozotocin progressively depleted UCHL1 from islet cores and in 50% of animals, an associated plasma UCHL1 surge was detected preceding the GAD65 peak. UCHL1 was cleared with a half-life of 20min. Whole-body dynamic planar imaging of (99m)-Technetium-labeled UCHL1 indicated a rapid UCHL1 uptake in the liver and spleen, followed by urinary excretion of mainly proteolytic UCHL1 fragments. We conclude that LC-MS/MS proteomics is a useful tool to prioritize biomarkers for beta cell injury with promising molar abundance. Despite its consistent UCHL1 discharge by damaged beta cells in vitro, its in vivo use might be restrained by its rapid elimination from plasma. BIOLOGICAL SIGNIFICANCE: Our bottom-up LC-MS/MS proteomics represents a pragmatic approach to identify protein-type biomarkers of pancreatic beta cell injury. UCHL1 successfully passed sequential validation steps of beta cell-selectivity, antigenicity and toxic discharge in vitro. Whole-body dynamic planar imaging of radiolabeled recombinant UCHL1 indicated rapid clearance through the liver, spleen and urinary excretion of proteolytic fragments, likely explaining non-consistent detection in vivo. Integration of kinetic biomarker clearance studies in the a priori selection criteria is recommended before engaging in resource-intensive custom development of sensitive immunoassays for clinical translation.

p53 signaling pathway polymorphisms associated to recurrent pregnancy loss.

The p53 protein is known for performing essential functions in the maintenance of genomic stability in somatic cells and prevention of tumor formation. Studies of the p53 signaling pathway have suggested associations between some polymorphisms and infertility, post-in vitro fertilization implantation failure and recurrent abortions. The TP53 Pro72Arg polymorphism has been implicated as a risk factor for recurrent pregnancy loss (RPL); however, the association is controversial. In this study, our objective was to evaluate selected polymorphisms in genes of the p53 signalling pathway [TP53 c.215G>C (Pro72Arg), MDM2 c.14+309T>G (SNP309) and LIF c.1414T>G in the region 3' UTR] and determine their effect as risk factors for RPL. In a case-control study, we investigated 120 women with two or more pregnancy losses and 143 fertile control women reporting at least two live births and no history of pregnancy loss. When analyzed separately, the allele and genotype distributions of the polymorphisms in the two groups were not different. However, in a multivariate analysis adjusted for alcohol consumption, smoking, ethnicity, and number of pregnancies, the interaction between the genotypes TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) showed to be associated to RPL, increasing the risk for this condition (OR = 2.58, 95% CI: 1.31-5.07, p = 0.006). In conclusion, our study indicates that the combination of TP53 Arg/Arg (rs1042522) and MDM2 TT (rs2279744) genotypes may be a risk factor for RPL.