Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.

Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study.

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25–65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function

Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnA(loxP/loxP) females with GATA1-Cre males. FlnA(loxP/y) GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbalpha because they lack the normal cytoskeletal linkage of GPIbalpha to underlying actin filaments. This results in approximately 70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like-mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased alpha-granule secretion, integrin alphaIIbbeta3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C-gamma2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA-Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like-containing receptor signaling and platelet function.

The Physiological, Enzymatic, and Genetic Characterization of Staphylococcus sp. Chromium (VI) Reductase Function

A strain of Staphylococcus isolated by Dr. Fekete at the Sandia National Laboratory toxic metal dumping site in Sandia, New Mexico. has been found to reduce toxic Cr(VI) to the less toxic Cr(IlI) state. We have ascertained the environmental parameters for optimal bacterial growth and Cr(VI) reduction. This knowledge may be employed in a comprehensive bioremediation scheme designed to accelerate natural reparation of that Sandia ecosystem. In addition we have investigated the genetic and enzymatic basis for this Cr(VI) reducing ability. This information may allow us to create more effective bioremediation schemes based on the comprehensive knowledge of enzyme and gene function. Preliminary investigations have been carried out toward this end which may serve as the basis for a more thorough investigation.

Estimativas de parâmetros genéticos para produção de leite e persistência da lactação em vacas Gir, aplicando modelos de regressão aleatória

Com o objetivo de estimar parâmetros genéticos para a produção de leite no dia do controle (PLDC), foram usadas as 2.440 primeiras lactações de vacas da raça Gir leiteira, com partos registrados entre 1990 e 2005. As PLDC foram consideradas em dez classes mensais e analisadas por meio de modelo de regressão aleatória (MRA) utilizando-se como efeitos aleatórios o genético-aditivo, o de ambiente permanente e o residual e, como efeitos fixos, o grupo de contemporâneos (GC), a co-variável idade da vaca ao parto (efeito linear e quadrático) e a curva média de lactação da população. Os efeitos genético-aditivos e de ambiente permanente foram modelados utilizando-se as funções de Wilmink (WIL) e Ali e Schaeffer (AS). As variâncias residuais foram modeladas utilizando-se 1, 4, 6 ou 10 classes. Os grupos de contemporâneos foram definidos como rebanho-ano-estação do controle contendo no mínimo três animais. Os testes indicaram que o modelo com quatro classes de variâncias usando a função paramétrica AS foi o que melhor se ajustou aos dados. As estimativas de herdabilidade variaram de 0,21 a 0,33 para a função AS e de 0,17 a 0,30 para WIL e foram maiores na primeira metade da lactação. As correlações genéticas entre as PLDC foram positivas e elevadas entre os controles adjacentes e diminuiram quando a distância entre os controles aumentou. Para o melhor modelo, foram estimados os valores genéticos para a produção de leite acumulada até os 305 dias e, para períodos parciais da lactação, foram obtidas como médias dos valores genéticos preditos naquele período. Os valores genéticos foram comparados, por meio da correlação de posto, ao valor genético predito para a produção acumulada até os 305 dias, pelo método tradicional. As correlações entre os valores genéticos indicaram que podem ocorrer divergências na classificação dos animais pelos critérios estudados.

AI, LA, ALI e AQUI: gramaticalização de um paradigma emergente no domínio funcional da especificação nominal

In the light of the Functional Linguistic Theory, in its North-American version (HOPPER, 1987, 1991, 1998, 2008, 2010; GIVÓN, 2001; LEHMANN, 2002; HOPPER; TRAUGOTT, 2003; FURTADO DA CUNHA; OLIVEIRA; MARTELOTTA, 2003, among others), the general objective of this research is to demonstrate, based on morphosyntactic and semantic-pragmatic properties, that AQUI (HERE), AÍ, ALI and LÁ (THERE) are part of an emerging paradigm in Brazilian Portuguese recently constituted and still developing of forms indicating specificity in indefinite noun phrases (NP). The data that make up the corpus of this research were collected in the following large Brazilian oral corpora: the Corpus Discurso & Gramática: a língua falada e escrita na cidade de Natal (FURTADO DA CUNHA, 1998), the Banco Conversacional de Natal (FURTADO DA CUNHA, 2010), the Projeto Variação Linguística no Estado da Paraíba VALPB (HORA, 2005) and the Projeto Variação Linguística Urbana na Região Sul do Brasil VARSUL (VANDRESEN, 2002). Firstly, the behavior of the specificity markings AQUI, AÍ, ALI and LÁ is described with respect to many factors of morphosyntactic and semantic-pragmatic nature: type of construction in which the markers appeared; existence or not of intervening material between the specificity marker item and the NP s nuclear noun; type of noun to which AQUI, AÍ, ALI and LÁ are linked; syntactic function of the specified SN; informational status of the NP to which the specificity markers AQUI, AÍ, ALI and LÁ are attached; occurrence of conversational implicatures (GRICE, 1982) in the context of use of these specificity markers. Next, a possible grammaticalization trajectory is outlined, according to which AQUI, AÍ, ALI and LÁ would had gone from an early spatial deictic indication to the specificity indication. The results point to the existence of forms with varying degree of emergence in this new paradigm of nominal specification, with AÍ being, probably, the item most grammaticalized, followed by LÁ, then ALI and AQUI, which permanence in the paradigm do not yet appear to be consolidated

Combined exercise training in asymptomatic elderly with controlled hypertension: Effects on functional capacity and cardiac diastolic function

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Correlation between morphology and function of the upper lip: a longitudinal evaluation

In order to evaluate the relationship between the morphology of the upper lip and muscle activity in a sample of 38 subjects (17 males and 21 females) with Angle Class II division 1 malocclusions, cephalometric and electromyographic analyses were conducted. The sample was subdivided into either predominantly nose or mouth breathers. The individuals were evaluated at two different periods, with a 2 year interval. At the first observation, the subjects were 11 years to 14 years 11 months of age and at the second observation, 13 years 4 months to 16 years 6 months of age. Height and thickness of the upper lip were measured on lateral cephalograms with the aid of a digital pachymeter. For each individual, electromyographic records were obtained of the orbicularis oris superior muscle at rest and in a series of 12 movements. The electromyographic data were normalized as a function of amplitude, for achievement of the percentage value of each movement. Pearson and Spearman correlation tests were applied.The results showed some correlation between morphology and muscle function (at a confidence level of 95 per cent). However, as the values of the correlation coefficient (r) were too low to establish associations between variables, it was concluded that the dimensions of the upper lip are not correlated with muscle activity.

EFFECT OF AN LH-RH ANALOG ON CAT TESTIS AND ADRENAL-CORTEX FUNCTION

The LH-RH analog LH-RH-A (des-Gly10,[D-Trp6]-LH-RH ethylamide) was administered in pharmacological doses (20-mu-g/kg, sc) to adult male cats for 15 days and its effect on testis and adrenal function was determined. Daily administration of the analog promoted a 3-fold increase in plasma testosterone levels after 7 days, indicating a stimulatory effect of LH-RH-A (mean +/- SD for 6 treated cats, 1.88 +/- 0.35 vs 0.51 +/- 0.08 ng/ml for 6 control cats). After 15 days the LH-RH-A-treated group exhibited a similar plasma testosterone concentration as the control group (mean +/- SD, 0.96 +/- 0.35 ng/ml vs 0.88 +/- 0.39 ng/ml, respectively), similar testicular and adrenal weights and no significant differences in the spermatogenic process. However, semiquantitative analysis of the zona fasciculata of the adrenals from the LH-RH-A-treated group showed a significant accumulation of a substance not stained by hematoxylin-eosin or Schiff periodic acid (mean +/- SD of index of accumulation was 3.50 +/- 0.4 for treated cats vs 2.20 +/- 0.3 for control cats). The present results show that pharmacological doses of LH-RH-A have an effect on the adrenal cortex of cats without modifying spermatogenesis or plasma testosterone levels.

Performance of children with learning difficulties in fine motor function and handwriting

This study aimed to compare and characterize the fine, sensory and perceptive function performance and handwriting quality between students with learning difficulties and students with good academic performance. Methods: This study comprised 192 students from 2nd to 4th grades, both genders, whose ages ranged from 7 to 11 years old. The students were distributed into: GI, GII, GIII and GIV, comprising 96 students with learning difficulties, and groups GV, GVI, GVII, GVIII comprising 96 students with good academic performance. The students were submitted to evaluation of fine motor, sensorial and perception functions and handwriting evaluation under dictation. Results: The results showed that the students with learning difficulties, from 1st to 3rd grade, had lower performance on tests of fine motor, sensory and perceptive function, when compared to the students with good academic performance in the same grade; the students from 4th grade, both groups, did not show changes on fine motor, sensory and perceptive function; and only the students of GII showed dysgraphia. Conclusions: the results presented in this study suggest that the qualitative aspects of fine motor, sensory and perceptive skills reflect the integrity and maturity of central nervous system and can probably play an important role in early diagnosis of development disorders and consequently prevent academic disorders such as handwriting performance.

Diferentes abordagens para modelar a produção de leite de bovinos da raça Guzerá

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Bone Morphogenetic Proteins: Structure, biological function and therapeutic applications

Bone Morphogenetic Proteins (BMPs) are multifunctional secreted cytokines, which belong to the TGF-beta superfamily. These glycoproteins act as a disulfide-linked homo- or heterodimers, being potent regulators of bone and cartilage formation and repair, cell proliferation during embryonic development and bone homeostasis in the adult. BMPs are promising molecules for tissue engineering and bone therapy. The present review discusses this family of proteins, their structure and biological function, their therapeutic applications and drawbacks, their effects on mesenchymal stem cells differentiation, and the cell signaling pathways involved in this process. (C) 2014 Published by Elsevier Inc.

Parenteral administration of vitamins A, D and E on the oxidative metabolism and function of polymorphonuclear leukocytes in swine

The weaning period of piglets is characterized by physiological alterations, such as decreased weight gain, increased reactive oxygen species (ROS) and increased serum cortisol levels with possible effects on the immune response. The effect of parenteral administration of vitamins A, D and E on production performance, oxidative metabolism, and the function of polymorphonuclear leukocytes (PMNLs) was assessed in piglets during the weaning period. The sample was comprised of 20 male piglets that were given an injectable ADE vitamin combination (135,000 IU vitamin A, 40,000 IU vitamin D and 40mg vitamin E/animal) at 20 and 40 days of age. Weight gain, concentration of reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and the microbicidal and phagocytic activity of PMNLs were assessed. No difference was observed in the average piglet weight during the study; however, a greater percentage of weight gain was observed after weaning in the treated group. The concentrations of GSH and SOD did not differ between groups, although lipid peroxidation was greater in the control group at 60 days of age. The investigated variables of oxidative metabolism were correlated as follows: -0.41 for GSH and MDA, -0.54 for GSH and SOD and 0.34 for MDA and SOD. The intensity of intracellular ROS production, the percentage of ROS-producing PMNLs and the intensity of phagocytosis by PMNLs did not differ between treatment groups. Administration of the injectable ADE combination improved the percentage of weight gain between 20 and 40 days of age, decreased oxidative stress at 60 days of age and did not influence the function of PMNLs in piglets.

Association between chronic caregiving stress and impaired endothelial function in the elderly

We examined the relationship between chronic caregiving stress and endothelial function.

Pretransplant pulmonary hypertension and long-term allograft right ventricular function

Graft right ventricular (RV) function is compromised directly posttransplant, especially in heart transplantation (HTx) recipients with pretransplant pulmonary hypertension (PH). Graft RV size and systolic function, and the effect of the recipient's pulmonary haemodynamics on the graft extracellular matrix are not well characterised in the patients long-term after HTx.