Gene prioritization based on random walks with restarts and absorbing states, to define gene sets regulating drug pharmacodynamics from single-cell analyses.

Prioritizing genes for their role in drug sensitivity, is an important step in understanding drugs mechanisms of action and discovering new molecular targets for co-treatment. To formalize this problem, we consider two sets of genes X and P respectively composing the gene signature of cell sensitivity at the drug IC50 and the genes involved in its mechanism of action, as well as a protein interaction network (PPIN) containing the products of X and P as nodes. We introduce Genetrank, a method to prioritize the genes in X for their likelihood to regulate the genes in P. Genetrank uses asymmetric random walks with restarts, absorbing states, and a suitable renormalization scheme. Using novel so-called saturation indices, we show that the conjunction of absorbing states and renormalization yields an exploration of the PPIN which is much more progressive than that afforded by random walks with restarts only. Using MINT as underlying network, we apply Genetrank to a predictive gene signature of cancer cells sensitivity to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL), performed in single-cells. Our ranking provides biological insights on drug sensitivity and a gene set considerably enriched in genes regulating TRAIL pharmacodynamics when compared to the most significant differentially expressed genes obtained from a statistical analysis framework alone. We also introduce gene expression radars, a visualization tool embedded in MA plots to assess all pairwise interactions at a glance on graphical representations of transcriptomics data. Genetrank is made available in the Structural Bioinformatics Library (https://sbl.inria.fr/doc/Genetrank-user-manual.html). It should prove useful for mining gene sets in conjunction with a signaling pathway, whenever other approaches yield relatively large sets of genes.

Silage from heart-of-palm waste produced from Alexander palm tree / Ensilaje de residuos de palmito producidos a partir de Palma Real / Silagem de resíduos de palmito produzidos a partir da Palmeira Real

Abstract Background: Production of heart-of-palm from Alexander palm tree generates a waste that could be used as silage for feeding ruminants. Objective: To evaluate the chemical composition, fermentation parameters, and quality of silage made from waste of heart-of-palm production using Alexander palm. Methods: Three types of silage made from waste of heart-of-palm production were evaluated: 1) leaf silage, 2) sheath silage, and 3) compound (leaf + sheath) silage. The processed waste was packed in experimental silos and distributed in a completely randomized design with 10 replications. Means were compared pairwise using Tukey's test at the 5% significance level. Results: Leaf silage had the highest pH (p<0.05) and the lowest ammonia nitrogen (p<0.05) in relation to the other silages. No difference was observed (p>0.05) for lactic and butyric acids, whereas acetic acid was higher (p<0.05) in the sheath and compound silages. Dry matter and crude protein contents were the highest (p<0.05) in leaf silage. Neutral detergent fiber was higher (p<0.05) in sheath silage, followed by leaf and compound silages, respectively. The highest lignin content (p<0.05) was observed in sheath silage. Conclusions: Based on the fermentative parameters, waste from heart-of-palm from Alexander palm tree has potential for silage production. However, differences in silage composition at the time of feeding ruminants should be considered.

Resumen Antecedentes: Los residuos de la producción de palmito de Palma Real podrian utilizarse como ensilaje para alimentación de rumiantes. Objetivo: Determinar la composición, parámetros químicos de fermentación, y calidad del ensilaje elaborado a partir de residuos procedentes de la producción de palmito de Palma Real. Métodos: Tres tipos de ensilaje hechos con los residuos generados a partir de la producción de palmito fueron evaluados: 1) ensilaje de hojas, 2) ensilaje de vainas, y 3) ensilaje compuesto (hojas + vainas). Los residuos tratados fueron empacados en silos experimentales y distribuidos en un diseño completamente al azar con 10 repeticiones. Las medias fueron comparadas mediante la prueba de Tukey, con un nivel de significancia del 5%. Resultados: El ensilaje de hojas mostró el pH más alto (p<0,05) y el nivel más bajo de nitrógeno amoniacal (p<0,05) en comparación con los otros ensilajes. No se observaron diferencias (p>0,05) en los ácidos láctico y butírico, mientras que el ácido acético fue mayor en el ensilaje de vainas y en el compuesto en relación con el otro ensilaje. La materia seca (MS) y el contenido de proteína cruda (PC) fueron mayores (p<0,05) en el ensilaje de hojas. Los contenidos de fibra detergente neutra fueron mayores (p<0,05) en los ensilajes de vainas, seguido por los ensilajes de hojas y compuesto, respectivamente. El contenido de lignina fue más alto (p<0,05) en el ensilaje de vainas. Conclusiones: Según los parámetros fermentativos, los residuos de la producción de palmito de Palma Real tienen potencial para la producción de ensilaje. Sin embargo, se deben considerar las diferencias en la composición de los ensilajes al momento de alimentar rumiantes.

Resumo Antecedentes: Resíduos da produção de palmito da palmeira Real são um problema para a agroindústria devido sua falta de utilização e o seu uso na forma de silagem pode ser uma alternativa na alimentação de ruminantes. Objetivo: Avaliar a composição química e os parâmetros fermentativos, e verificar a qualidade da silagem produzida a partir do resíduo da produção de palmito da Palmeira Real Australiana. Métodos: Foram avaliadas três tipos de silagem de resíduo da produção de palmito da Palmeira Real: silagem de folha, silagem de bainha e silagem da composta (folha + bainha). O resíduo processado foi acondicionado em silos experimentais e distribuídos em um delineamento inteiramente casualizado com 10 repetições e as médias comparadas pelo teste de Tukey a 5% de significância. Resultados: A silagem de folha apresentou maior pH (p<0,05) em relação as demais silagens, enquanto para o nitrogênio amoniacal (p<0,05), apresentou menor teor em relação as demais silagens. Não observou-se diferença (p>0,05) para os ácidos lático e butírico, enquanto o ácido acético foi maior para as silagens de bainha e composta em relação as demais silagens. O teor de matéria seca (MS), proteína bruta (PB) foi maior (p<0,05) na silagem de folha em relação as demais silagens. A fibra em detergente neutro analisada estimada apresentou maiores valores (p<0,05) para a silagem de bainha, seguida pela silagem de folhas e silagem composta, respectivamente. O teor de lignina foi maior (p<0,05) para a silagem de bainha. Conclusões: De acordo com os parâmetros fermentativos, os resíduos da produção de palmito da Palmeira Real apresentam potencial para a produção de silagem. No entanto, as diferenças na composição das silagens devem ser consideradas quando oferecidas para animais ruminantes.

Dietary supplementation of heat-treated Gracilaria and Ulva seaweeds enhanced acute hypoxia tolerance in gilthead sea bream (Sparus aurata).

Intensive aquaculture practices involve rearing fish at high densities. In these conditions, fish may be exposed to suboptimal dissolved O2 levels with an increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW) contain biologically active substances with efficient antioxidant capacities. This study evaluated the effects of dietary supplementation of heat-treated SW (5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in sea bream subjected to a hypoxic challenge. 168 fish (104.5 g average weight) were distributed in 24 tanks, in which eight tanks were fed one of three experimental diets for 34 days: (i) a control diet without SW supplementation, (ii) a control diet supplemented with Ulva, or (iii) a control diet with Gracilaria Thereafter, fish from 12 tanks (n=4 tanks/dietary treatment) were subjected to 24 h hypoxia (1.3 mg O2 l-1) and subsequent recovery normoxia (8.6 mg O2 l-1). Hypoxic fish showed an increase in hematocrit values regardless of dietary treatment. Dietary modulation of the O2-carrying capacity was conspicuous during recovery, as fish fed SW supplemented diets displayed significantly higher haemoglobin concentration than fish fed the control diet. After the challenge, survival rates in both groups of fish fed SW were higher, which was consistent with a decrease in hepatic lipid peroxidation in these groups. Furthermore, the hepatic antioxidant enzyme activities were modulated differently by changes in environmental O2 condition, particularly in sea bream fed the Gracilaria diet. After being subjected to hypoxia, the gene expression of antioxidant enzymes and molecular chaperones in liver and heart were down regulated in sea bream fed SW diets. This study suggests that the antioxidant properties of heat-treated SW may have a protective role against oxidative stress. The nature of these compounds and possible mechanisms implied are currently being investigated.

Substituição do resíduo da produção de palmito da Palmeira Real Australiana (Archontophoenix alexandrae) na silagem de cana-de-açúcar em dietas de ovinos / Replacing of residue from production of palm Palm Royal Australian (Archontophoenix alexandrae) in silage of sugar cane in diets of sheep

Objetivou-se avaliar a composição química, consumo voluntário e digestibilidade aparente de dietas contendo resíduo oriundo da produção de palmito da palmeira Real Australiana (Archontophoenix alexandrae) em substituição à cana-de-açúcarem ovinos. Foram utilizados 12 ovinos com peso vivo médio de 23,3 ± 2,8 kg, mantidos em gaiolas metabólicas distribuídos em seis quadrados latinos 2x2 implementado em esquema fatorial 3 x 2 (três tipos de resíduo - folha, bainha e composta - e dois níveis de substituição do resíduo, 5% e 15%). Verificou-se maior consumo de matéria seca (MS), matéria orgânica (MO), carboidratos não fibrosos (CNF) na substituição pelo resíduo composta. Os valores médios de digestibilidade aparente da MS, MO, Proteína bruta (PB), fibra insolúvel em detergente neutro corrigido para cinzas e proteína(FDNcp) e nível dietético de NDT foram maiores para o resíduo folha. Constatou- se efeito de interação entre resíduo e o nível de substituição sobre as excreções urinárias de nitrogênio total (EUN), balanço nitrogenado aparente (BNA) e compostos nitrogenados microbianos (NMIC). Resíduos da produção de palmito oriundos da palmeira Real Australiana podem ser utilizados como alimentos volumosos na dieta de animais ruminantes, sendo destes, o resíduo folha e composta os que apresentaram melhores respostas nas características avaliadas.

The aim of this study was to evaluate the chemical composition, voluntary intake and apparent digestibility of the diets containing residue from palm heart of Australian Royal Palm (Archontophoenix alexandrae) to replace sugar cane on sheep. Twelve sheep were used with average live weight of 23,3 ± 2,8 Kg and they placed in metabolism cages and distributed in six latin square 2 x 2 in a factorial design 3 x 2 (three types of residue -sheet, bark and composed - and two levels of residue’s replacement, 5% and 15%). It was observed higher intake of dry matter (DM), organic matter (OM), nonfiber carbohydrates (NFC) by substitution of composed residue. The average values of apparent digestibility of DM, OM, crude protein (CP), neutral detergent fibre correct for ash and protein (NDFap) and total digestible nutrients (TDN) were higher for sheet residue. There was interaction between type of residue and level of residue’s replacement on the urinary excretion of total nitrogen (NUE), apparent nitrogen balance (BNA) and microbial nitrogen compost (NMIC). Residues from palm heart of Australian Royal Palm can be used as roughage in the ruminants’diet, and of these residues, the sheet and composed residue showed better response in the evaluated characteristics.

[Replacing of residue from production of palm Palm Royal Australian (Archontophoenix alexan- drae) in silage of sugar cane in diets of sheep]. / Substituição do resíduo da produção de palmito da Palmeira Real Australiana (Archontophoenix alexandrae) na silagem de cana-de-açúcar em dietas de ovinos.

The aim of this study was to evaluate the chemical composition, voluntary intake and apparent digestibility of the diets containing residue from palm heart of Australian Royal Palm (Archontophoenix alexandrae) to replace sugar cane on sheep. Twelve sheep were used with average live weight of 23.3 ± 2.8 Kg and they placed in metabolism cages and distributed in six latin square 2 x 2 in a factorial design 3 x 2 (three types of residue--sheet, bark and composed--and two levels of residue's replacement, 5% and 15%). It was observed higher intake of dry matter (DM), organic matter (OM), nonfiber carbohydrates (NFC) by substitution of composed residue. The average values of apparent digestibility of DM, OM, crude protein (CP), neutral detergent fibre correct for ash and protein (NDFap) and total digestible nutrients (TDN) were higher for sheet residue. There was interaction between type of residue and level of residue's replacement on the urinary excretion of total nitrogen (NUE), apparent nitrogen balance (BNA) and microbial nitrogen compost (NMIC). Residues from palm heart of Australian Royal Palm can be used as roughage in the ruminants'diet, and of these residues, the sheet and composed residue showed better response in the evaluated characteristics.

Intake and digestibility in cattle fed low-quality tropical forage and supplemented with nitrogenous compounds.

The effects of supplementation with nitrogenous compounds on intake, digestibility, and microbial protein synthesis in cattle fed low-quality tropical forage were assessed. Five rumen fistulated crossbred Holstein x Gir heifers were used, with initial average live weight of 180 +/- 21 kg. Signal grass (Brachiaria decumbens) hay (48.6 g kg(-1) of crude protein (CP), on a dry matter (DM) basis) was used as roughage. Five treatments were defined according to nitrogen supplementation level (0, 20, 40, 60, and 80 g of CP kg(-1) above the CP level of the hay). A mixture of urea, ammonium sulfate, and albumin at the ratios of 4.5:0.5:1.0, respectively, was used as nitrogen source. The experiment consisted of five experimental periods, according to a 5 x 5 Latin square design. The average CP contents in the diets were 51.9, 71.1, 86.0, 116.7, and 130.2 g kg(-1), on a DM basis. A quadratic effect was detected (P < 0.10) of the CP levels in the diets on DM and neutral detergent fiber intake (kg/day), with maximum response at the levels of 102.4 and 100.5 g CP kg(-1) DM, respectively. The average daily concentration of rumen ammonia nitrogen showed increasing linear pattern (P < 0.01) as function of CP levels in the diet, with estimated value of 9.64 mg dL(-1) equivalent to the maximum DM intake. Microbial nitrogen flow in the intestine was linearly and positively related (P < 0.01) with the CP levels in the diet.