What have proteomics taught us about Leishmania development?

Leishmania are obligatory intracellular parasitic protozoa that cycle between sand fly mid-gut and phagolysosomes of mammalian macrophages. They have developed genetically programmed changes in gene and protein expression that enable rapid optimization of cell function according to vector and host environments. During the last two decades, host-free systems that mimic intra-lysosomal environments have been devised in which promastigotes differentiate into amastigotes axenically. These cultures have facilitated detailed investigation of the molecular mechanisms underlying Leishmania development inside its host. Axenic promastigotes and amastigotes have been subjected to transcriptome and proteomic analyses. Development had appeared somewhat variable but was revealed by proteomics to be strictly coordinated and regulated. Here we summarize the current understanding of Leishmania promastigote to amastigote differentiation, highlighting the data generated by proteomics

Use of computational fluid dynamics to compare upper airway pressures and airflow resistance in brachycephalic, mesocephalic, and dolichocephalic dogs

Brachycephalic dog breeds are prone to breathing difficulties because of their upper airway anatomy. Several surgical techniques exist to correct anatomical pathologies and common surgical approaches aim to correct functional abnormalities in the nares and/or the soft palate. However, further research is needed to improve clinical outcomes. This study evaluated air pressure and airflow resistance in the upper airways and trachea in nine sedated, sternally recumbent dogs of different skull types (dolichocephalic, n = 3; mesocephalic, n = 3; brachycephalic, n = 3). CT images were acquired from the nostrils to the caudal border of the lungs and geometrical reconstruction of the upper airway and trachea was performed. Analysis of computational fluid dynamics was performed using inspiratory flow adapted to bodyweight for each dog. Flow (L/min) and pressure (cmH2O) were computed for the entire upper airway and trachea. Resistance (cmH2O/L/min) was calculated using pressure differences between the nose, larynx, and trachea. In this pilot study, statistical comparisons were not performed. Pressure maps, airflow, and resistance were similar in dolichocephalic and mesocephalic breeds. Median pressure difference (3.76 cmH2O) and resistance (0.154 cmH2O/L/min) between the nose and larynx were numerically higher in brachycephalic dogs than in other breeds (0.45 cmH2O and 0.016 cmH2O/L/min, respectively). Median pressure difference (0.205 cmH2O) and resistance (0.009 cmH2O/L/min) between the larynx and trachea was numerically similar in all dogs, except for the English bulldog. The methodology used in this preliminary study to quantify airflow characteristics such as pressure and resistance could improve the understanding of brachycephalic obstruction airway syndrome

Jack London and White Fang: a lost struggle

The California State Parks curators granted access to artifacts owned by Jack London that are in storage in their Sonoma Barracks in Sonoma, CA. A medicine case, drug vials, and various paper documents that covered the period of his life from 1906 to 1915 were examined for drug residues left on their surface. All the objects were tested with the non-invasive surface analysis EVA (ethylene-vinyl acetate) technology, which consist of a foil studded with ground mixed-bed cation/anion exchangers as well as with C$_{8}$ and C$_{18}$ resins. The harvested material collected by the foils was analysed via GC-MS and the following 12 drugs were identified: N-(4-ethoxyphenyl) acetamide, phenyl salicylic acid, morphine, 6-monoacetylmorphine, 3-acetylmorphine, diacetylmorphine, dipenteneglycol, quinine dihydrochloride, quinine base, atropine, scopolamine and hyoscyamine. Despite the claims by his biographers that he used opium, morphine, and heroin on a regular basis this assertion could not be confirmed by the chemical analyses of the objects here tested. Only two opioids were discovered, morphine and diacetylmorphine (heroin) both of which could have been derived from the use of common, legal (over-the-counter) flu and cough medications

Jack London and White Fang: a lost struggle

The California State Parks curators granted access to artifacts owned by Jack London that are in storage in their Sonoma Barracks in Sonoma, CA. A medicine case, drug vials, and various paper documents that covered the period of his life from 1906 to 1915 were examined for drug residues left on their surface. All the objects were tested with the non-invasive surface analysis EVA (ethylene-vinyl acetate) technology, which consist of a foil studded with ground mixed-bed cation/anion exchangers as well as with C$_{8}$ and C$_{18}$ resins. The harvested material collected by the foils was analysed via GC-MS and the following 12 drugs were identified: N-(4-ethoxyphenyl) acetamide, phenyl salicylic acid, morphine, 6-monoacetylmorphine, 3-acetylmorphine, diacetylmorphine, dipenteneglycol, quinine dihydrochloride, quinine base, atropine, scopolamine and hyoscyamine. Despite the claims by his biographers that he used opium, morphine, and heroin on a regular basis this assertion could not be confirmed by the chemical analyses of the objects here tested. Only two opioids were discovered, morphine and diacetylmorphine (heroin) both of which could have been derived from the use of common, legal (over-the-counter) flu and cough medications

Scalable Multiagent Planning using Probabilistic Inference

Multiagent planning has seen much progress with the development of formal models such as Dec-POMDPs. However, the complexity of these models—NEXP-Complete even for two agents— has limited scalability. We identify certain mild conditions that are sufficient to make multiagent planning amenable to a scalable approximation w.r.t. the number of agents. This is achieved by constructing a graphical model in which likelihood maximization is equivalent to plan optimization. Using the Expectation-Maximization framework for likelihood maximization, we show that the necessary inference can be decomposed into processes that often involve a small subset of agents, thereby facilitating scalability. We derive a global update rule that combines these local inferences to monotonically increase the overall solution quality. Experiments on a large multiagent planning benchmark confirm the benefits of the new approach in terms of runtime and scalability.

Análise de empresas de médias empresas da rússia na conexão dos distritos federais e principais municípios

The article examines the trends in the number of medium-sized enterprises in Russia, in the context of federal districts and major municipalities. Detailed information is provided on the number and dynamics of medium-sized enterprises in Russia by federal districts and the largest municipalities for the period from 2008 to 2017. The indicators of the number of employees, labor efficiency and revenues of medium-sized businesses are considered. Developed by the authors and presented in the article, the map of medium-sized businesses allows you to make both management decisions to state and municipal authorities, and make investment decisions.El artículo examina las tendencias en el número de empresas medianas en Rusia, en el contexto de los distritos federales y los principales municipios. Se proporciona información detallada sobre el número y la dinámica de las medianas empresas en Rusia por los distritos federales y los municipios más grandes durante el período de 2008 a 2017. Los indicadores de la cantidad de empleados, la eficiencia laboral y los ingresos de las medianas empresas son considerados. Desarrollado por los autores y presentado en el artículo, el mapa de las medianas empresas le permite tomar decisiones de gestión ante las autoridades estatales y municipales, y tomar decisiones de inversión.O artigo examina as tendências no número de empresas de médio porte na Rússia, no contexto de distritos federais e grandes municípios. Informações detalhadas sobre o número e a dinâmica das empresas de médio porte na Rússia são fornecidas pelos distritos federais e os maiores municípios durante o período de 2008 a 2017. Os indicadores do número de funcionários, a eficiência da mão-de-obra e a renda das medianas Empresas são consideradas. Desenvolvido pelos autores e apresentado no artigo, o mapa de empresas de médio porte permite que eles tomem decisões de gestão perante as autoridades estaduais e municipais e tomem decisões de investimento

Ingestão dietética de pacientes bariátricas femininas após gastroplastia anti-obesidade

PURPOSE: Roux-en-Y gastric bypass is a popular and successful operation for the treatment of morbid obesity. However, it greatly restricts ingestion and moderately interferes with absorption of food, thus potentially paving the way for undernutrition, especially during the first year before patients adapt to the new condition. Aiming to document actual dietary intake during this period, a prospective observational study was performed. METHODS: Forty consecutive patients were investigated using a 24-hour dietary recall technique every 3 months after surgery for 1 year. Females only were accepted for greater homogeneity of the sample. All received a vitamin and mineral supplement on a daily basis as a postoperative routine. A questionnaire was employed regarding general, nutritional, and gastrointestinal changes as well as consumption of medications. Dietary intake was analyzed after data processing using the Virtual Nutri software package (São Paulo, SP, Brazil). RESULTS: The surgical response was within the expected range, with about 67% excess weight loss at the end of the 1st year, and the same occurred with gastrointestinal symptoms and drug requirements. Daily energy intake on the 4 analyzed occasions was 529.4 ± 47.4, 710.9 ± 47.6, 833.2 ± 72.0, and 866.2 ± 95,1 kcal/day (mean ± SEM); protein intake was increased in the same proportion at 6 and 9 months, but reduced at 12 months. Thus, patients did not meet standard recommendations regarding calories and proteins, even at the end of the 1st year; iron and zinc intake were also inadequate, although deficiencies were probably staved off by the prescribed supplement preparation. CONCLUSIONS: 1) The risk for postoperative undernutrition was evidenced up to 1 year, while spontaneous improvement in food intake was slow and inefficient; 2) Specific protocols should be devised to improve nutrition and health during the postoperative phase until successful dietary adaptation is achieved.OBJETIVO: A gastroplastia com anastomose gastrojejunal em Y de Roux é uma operação popular e bem sucedida no tratamento da obesidade grave. Ela restringe seriamente a ingestão e moderadamente a absorção do alimento, potencialmente abrindo caminho para desnutrição especialmente no primeiro ano, antes que o paciente se adapte à nova condição. Com o propósito de documentar a real ingestão neste período, um estudo prospectivo observacional foi executado. MÉTODO: Quarenta pacientes consecutivos foram investigados por recordatório de 24 horas a cada três meses após a operação, até um ano. Apenas mulheres foram arroladas para maior homogeneidade da amostra. Todas receberam diariamente um suplemento vitamínico-mineral, como rotina pós-operatória. Um questionário foi empregado abordando alterações gerais, nutricionais e gastrointestinais assim como consumo de medicamentos. Os ganhos dietéticos foram analisados mediante o programa Virtual Nutri (São Paulo, SP, Brasil). RESULTADOS: A resposta cirúrgica situou-se dentro da faixa esperada, com perda de cerca de 67% do excesso de peso após um ano, e o mesmo ocorreu com sintomas gastrointestinais e necessidades medicamentosas. A quantidade de energia diária nas quatro ocasiões foi de 529,4±47,5, 710,9± 47,7, 833,2± 72,0 e 866,2± 95,1 kcal/dia (média ± erro padrão da média), e o aumento do consumo de proteína foi da mesma proporção nos 6 e 9 meses e com redução em 12 meses. Consequentemente mesmo após um ano as pacientes estavam abaixo das recomendações usuais de calorias e proteínas. A contribuição da dieta no tocante a ferro e zinco também mostrou-se inadequada, embora quadros deficitários tenham provavelmente sido abortados pelo suplemento utilizado. CONCLUSÕES: 1) O risco para desnutrição pos-operatória ficou demonstrado até um ano, e a melhora espontânea da ingestão de alimentos revelou-se lenta e ineficiente; 2) Protocolos específicos deveriam ser elaborados visando melhorar a nutrição e a saúde na fase pós-operatória, até que se verifique uma adaptação dietética satisfatória

A Translation Initiation Element Specific to mRNAs with Very Short 5′UTR that Also Regulates Transcription

Transcription is controlled by cis regulatory elements, which if localized downstream to the transcriptional start site (TSS), in the 5′UTR, could influence translation as well. However presently there is little evidence for such composite regulatory elements. We have identified by computational analysis an abundant element located downstream to the TSS up to position +30, which controls both transcription and translation. This element has an invariable ATG sequence, which serves as the translation initiation codon in 64% of the genes bearing it. In these genes the initiating AUG is preceded by an extremely short 5′UTR. We show that translation in vitro and in vivo is initiated exclusively from the AUG of this motif, and that the AUG flanking sequences create a strong translation initiation context. This motif is distinguished from the well-known Kozak in its unique ability to direct efficient and accurate translation initiation from mRNAs with a very short 5′UTR. We therefore named it TISU for Translation Initiator of Short 5′UTR. Interestingly, this translation initiation element is also an essential transcription regulatory element of Yin Yang 1. Our characterization of a common transcription and translation element points to a link between mammalian transcription and translation initiation