Free diet selection by broilers as influenced by dietary macronutrient ratio and corticosterone supplementation. 1. Diet selection, organ weights, and plasma metabolites

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

β-conglycinin combined with fenofibrate or rosuvastatin have exerted distinct hypocholesterolemic effects in rats

Background: There is increasing interest in non-pharmacological control of cholesterol and triglyceride levels in the plasma and diet-drug association represent an important area of studies. The objective of this study was to observe the hypocholesterolemic effect of soybean β-conglycinin (7S protein) alone and combined with fenofibrate and rosuvastatin, two hypolipidemic drugs. Methods. The protein and drugs were administered orally once a day to rats and the effects were evaluated after 28 days. Wistar rats were divided into six groups (n = 9): hypercholesterolemic diet (HC), HC+7S protein (300 mg.kg-1 day-1) (HC-7S), HC+fenofibrate (30 mg.kg-1 day-1)(HC-FF), HC+rosuvastatin (10 mg.kg-1 day-1)(HC-RO), HC+7S+fenofibrate (HC-7S-FF) and HC+7S+rosuvastatin (HC-7S-RO). Results: Animals in HC-7S, HC-FF and HC-RO exhibited reductions of 22.9, 35.8 and 18.8% in total plasma cholesterol, respectively. In HC-7S-FF, animals did not show significant alteration of the level in HC+FF while the group HC-7S-RO showed a negative effect in comparison with groups taking only protein (HC-7S) or drug (HC-RO). The administration of the protein, fenofibrate and rosuvastatin alone caused increases in the plasma HDL-C of the animals, while the protein-drug combinations led to an increase compared to HC-FF and HC-RO. The plasma concentration of triacylgycerides was significantly reduced in the groups without association, while HC-7S-FF showed no alteration and HC-7S-RO a little reduction. Conclusion: The results of our study indicate that conglycinin has effects comparable to fenofibrate and rosuvastatin on the control of plasma cholesterol, HDL-C and triacylglycerides, when given to hypercholesterolemic rats, and suggests that the association of this protein with rosuvastatin alters the action of drug in the homeostasis of cholesterol. © 2012 Ferreira et al; licensee BioMed Central Ltd.

Annual reproductive cycle of males of the flat-faced fruit-eating bat, Artibeus planirostris (Chiroptera: Phyllostomidae)

Artibeus planirostris is an endemic species of Phyllostomid bat from the Neotropical region. Some studies have indicated that it exhibits seasonal bimodal polyestry; however, others postulate that it may be able to produce young at any time during the year. Thus, the aim of this study was to evaluate the annual variations in testicular and epididymal parameters of this species in southeast Brazil and try to understand how the reproduction of this species is regulated in this environment. Sixty mature male specimens, collected between June 2009 and May 2010, were submitted to morphometric and immunohistochemical analysis. Our study showed that A. planirostris presented a continuously active pattern of spermatogenesis throughout the year, presenting spermatozoa inside its cauda epididymis in all months, but with two pronounced peaks of spermatogenic production, one in September and other in February. We propose that the males developed these two peaks in order to produce sufficient sperm for the reproduction in a harem system and to synchronize with the female reproductive cycle, which had a bimodal polyestric pattern. Control of this variation is directly linked to the expression of the androgen receptor (AR) in Sertoli cells and to serum testosterone levels, which appear to synchronize to establish these two peaks. In the months preceding the two peaks, the testis have a higher expression of the AR, which possibly stimulates the increase in PCNA, and drives a gradual increase in the testicular parameters. Taken together the results suggest that if sperm storage happens in this species, it is of short duration. © 2013 Elsevier Inc.

Insulin and TOR pathways regulate cellular and organismal growth through the myc oncogene in Drosophila

A large body of literature documents in both mice and Drosophila the involvement of Insulin pathway in growth regulation, probably due to its role in glucose and lipid import, nutrient storage, and translation of RNAs implicated in ribosome biogenesis (Vanhaesebroeck et al. 2001). Moreover several lines of evidence implicate this pathway as a causal factor in cancer (Sale, 2008; Zeng and Yee 2007; Hursting et al., 2007; Chan et al., 2008). With regards to Myc, studies in cell culture have implied this family of transcription factors as regulators of the cell cycle that are rapidly induced in response to growth factors. Myc is a potent oncogene, rearranged and overexpressed in a wide range of human tumors and necessary during development. Its conditional knock-out in mice results in reduction of body weight due to defect in cell proliferation (Trumpp et al. 2001). Evidence from in vivo studies in Drosophila and mammals suggests a critical function for myc in cell growth regulation (Iritani and Eisenman 1999; Johnston et al. 1999; Kim et al. 2000; de Alboran et al. 2001; Douglas et al. 2001). This role is supported by our analysis of Myc target genes in Drosophila, which include genes involved in RNA binding, processing, ribosome biogenesis and nucleolar function (Orain et al 2003, Bellosta et al., 2005, Hulf et al, 2005). The fact that Insulin signaling and Myc have both been associated with growth control suggests that they may interact with each other. However, genetic evidence suggesting that Insulin signaling regulates Myc in vivo is lacking. In this work we were able to show, for the first time, a direct modulation of dMyc in response to Insulin stimulation/silencing both in vitro and in vivo. Our results suggest that dMyc up-regulation in response to DILPs signaling occurs both at the mRNA and potein level. We believe dMyc protein accumulation after Insulin signaling activation is conditioned to AKT-dependent GSK3β/sgg inactivation. In fact, we were able to demonstate that dMyc protein stabilization through phosphorylation is a conserved feature between Drosophila and vertebrates and requires multiple events. The final phosphorylation step, that results in a non-stable form of dMyc protein, ready to be degraded by the proteasome, is performed by GSK3β/sgg kinase (Sears, 2004). At the same time we demonstrated that CKI family of protein kinase are required to prime dMyc phosphorylation. DILPs and TOR/Nutrient signalings are known to communicate at several levels (Neufeld, 2003). For this reason we further investigated TOR contribution to dMyc-dependent growth regulation. dMyc protein accumulates in S2 cells after aminoacid stimulation, while its mRNA does not seem to be affected upon TORC1 inhibition, suggesting that the Nutrient pathway regulates dMyc mostly post-transcriptionally. In support to this hypothesis, we observed a TORC1-dependent GSK3β/sgg inactivation, further confirming a synergic effect of DILPs and Nutrients on dMyc protein stability. On the other hand, our data show that Rheb but not S6K, both downstream of the TOR kinase, contributes to the dMyc-induced growth of the eye tissue, suggesting that Rheb controls growth independently of S6K.. Moreover, Rheb seems to be able to regulate organ size during development inducing cell death, a mechanism no longer occurring in absence of dmyc. These observations suggest that Rheb might control growth through a new pathway independent of TOR/S6K but still dependent on dMyc. In order to dissect the mechanism of dMyc regulation in response to these events, we analyzed the relative contribution of Rheb, TOR and S6K to dMyc expression, biochemically in S2 cells and in vivo in morphogenetic clones and we further confirmed an interplay between Rheb and Myc that seems to be indipendent from TOR. In this work we clarified the mechanisms that stabilize dMyc protein in vitro and in vivo and we observed for the first time dMyc responsiveness to DILPs and TOR. At the same time, we discovered a new branch of the Nutrient pathway that appears to drive growth through dMyc but indipendently from TOR. We believe our work shed light on the mechanisms cells use to grow or restrain growth in presence/absence of growth promoting cues and for this reason it contributes to understand the physiology of growth control.

Volumetric and anatomical MRI for hypoxic-ischemic encephalopathy: relationship to hypothermia therapy and neurosensory impairments.

OBJECTIVE: To relate volumetric magnetic resonance imaging (MRI) findings to hypothermia therapy and neurosensory impairments. STUDY DESIGN: Newborns > or =36 weeks' gestation with hypoxic-ischemic encephalopathy who participated in the National Institute of Child Health and Human Development hypothermia randomized trial at our center were eligible. We determined the relationship between hypothermia treatment and usual care (control) to absolute and relative cerebral tissue volumes. Furthermore, we correlated brain volumes with death or neurosensory impairments at 18 to 22 months. RESULT: Both treatment groups were comparable before randomization. Total brain tissue volumes did not differ in relation to treatment assignment. However, relative volumes of subcortical white matter were significantly larger in hypothermia-treated than control infants. Furthermore, relative total brain volumes correlated significantly with death or neurosensory impairments. Relative volumes of the cortical gray and subcortical white matter also correlated significantly with Bayley Scales psychomotor development index. CONCLUSION: Selected volumetric MRI findings correlated with hypothermia therapy and neurosensory impairments. Larger studies using MRI brain volumes as a secondary outcome measure are needed.

Grain size composition of sediments from ODP Leg 164 sites

This research was designed to check the assumption of the grain-size control on a gas hydrate presence in the Blake Ridge sediments; the assumption had originated from the data gained at Deep Sea Drilling Project (DSDP) Site 533. Granulometric analysis (the combined pipette-sieve method) of the 345 sediment samples obtained after pore-water squeezing from Ocean Drilling Program (ODP) Sites 994, 995, and 997 has provided support for this assumption. The zone of negative anomalies of pore-water chlorinity, which is generally recognized to be gas hydrate bearing, is confined, as a whole, to the interval of comparatively coarse-grained sediments in each of the three site columns because content of the fine fractions <0.05, <0.01, <0.005, and <0.001 mm is lower there (although the character of this control changes from site to site). The individual chlorinity anomalies also coincide, for the most part, with relatively coarse-grained sediments.

A methodology for granularity-based control of parallelism in logic programs

Several types of parallelism can be exploited in logic programs while preserving correctness and efficiency, i.e. ensuring that the parallel execution obtains the same results as the sequential one and the amount of work performed is not greater. However, such results do not take into account a number of overheads which appear in practice, such as process creation and scheduling, which can induce a slow-down, or, at least, limit speedup, if they are not controlled in some way. This paper describes a methodology whereby the granularity of parallel tasks, i.e. the work available under them, is efficiently estimated and used to limit parallelism so that the effect of such overheads is controlled. The run-time overhead associated with the approach is usually quite small, since as much work is done at compile time as possible. Also,a number of run-time optimizations are proposed. Moreover, a static analysis of the overhead associated with the granularity control process is performed in order to decide its convenience. The performance improvements resulting from the incorporation of grain size control are shown to be quite good, specially for systems with medium to large parallel execution overheads.

Towards granularity based control of parallelism in logic programs

Several types of parallelism can be exploited in logic programs while preserving correctness and efficiency, i.e. ensuring that the parallel execution obtains the same results as the sequential one and the amount of work performed is not greater. However, such results do not take into account a number of overheads which appear in practice, such as process creation and scheduling, which can induce a slow-down, or, at least, limit speedup, if they are not controlled in some way. This paper describes a methodology whereby the granularity of parallel tasks, i.e. the work available under them, is efficiently estimated and used to limit parallelism so that the effect of such overheads is controlled. The run-time overhead associated with the approach is usually quite small, since as much work is done at compile time as possible. Also, a number of run-time optimizations are proposed. Moreover, a static analysis of the overhead associated with the granularity control process is performed in order to decide its convenience. The performance improvements resulting from the incorporation of grain size control are shown to be quite good, specially for systems with médium to large parallel execution overheads.

Modeling the control of DNA replication in fission yeast

A central event in the eukaryotic cell cycle is the decision to commence DNA replication (S phase). Strict controls normally operate to prevent repeated rounds of DNA replication without intervening mitoses (“endoreplication”) or initiation of mitosis before DNA is fully replicated (“mitotic catastrophe”). Some of the genetic interactions involved in these controls have recently been identified in yeast. From this evidence we propose a molecular mechanism of “Start” control in Schizosaccharomyces pombe. Using established principles of biochemical kinetics, we compare the properties of this model in detail with the observed behavior of various mutant strains of fission yeast: wee1− (size control at Start), cdc13Δ and rum1OP (endoreplication), and wee1− rum1Δ (rapid division cycles of diminishing cell size). We discuss essential features of the mechanism that are responsible for characteristic properties of Start control in fission yeast, to expose our proposal to crucial experimental tests.

Adaptive stepsize based on control theory for stochastic differential equations

The numerical solution of stochastic differential equations (SDEs) has been focussed recently on the development of numerical methods with good stability and order properties. These numerical implementations have been made with fixed stepsize, but there are many situations when a fixed stepsize is not appropriate. In the numerical solution of ordinary differential equations, much work has been carried out on developing robust implementation techniques using variable stepsize. It has been necessary, in the deterministic case, to consider the best choice for an initial stepsize, as well as developing effective strategies for stepsize control-the same, of course, must be carried out in the stochastic case. In this paper, proportional integral (PI) control is applied to a variable stepsize implementation of an embedded pair of stochastic Runge-Kutta methods used to obtain numerical solutions of nonstiff SDEs. For stiff SDEs, the embedded pair of the balanced Milstein and balanced implicit method is implemented in variable stepsize mode using a predictive controller for the stepsize change. The extension of these stepsize controllers from a digital filter theory point of view via PI with derivative (PID) control will also be implemented. The implementations show the improvement in efficiency that can be attained when using these control theory approaches compared with the regular stepsize change strategy. (C) 2004 Elsevier B.V. All rights reserved.

Upper-Pleistocene terrace deposits in Mediterranean climate: geomorphological and source-rock control on mineral and geochemical signatures (Betic Cordillera, SE Spain)

Mineral and chemical composition of alluvial Upper-Pleistocene deposits from the Alto Guadalquivir Basin (SE Spain) were studied as a tool to identify sedimentary and geomorphological processes controlling its formation. Sediments located upstream, in the north-eastern sector of the basin, are rich in dolomite, illite, MgO and KB2BO. Downstream, sediments at the sequence base are enriched in calcite, smectite and CaO, whereas the upper sediments have similar features to those from upstream. Elevated rare-earth elements (REE) values can be related to low carbonate content in the sediments and the increase of silicate material produced and concentrated during soil formation processes in the neighbouring source areas. Two mineralogical and geochemical signatures related to different sediment source areas were identified. Basal levels were deposited during a predominantly erosive initial stage, and are mainly composed of calcite and smectite materials enriched in REE coming from Neogene marls and limestones. Then the deposition of the upper levels of the alluvial sequences, made of dolomite and illitic materials depleted in REE coming from the surrounding Sierra de Cazorla area took place during a less erosive later stage of the fluvial system. Such modification was responsible of the change in the mineralogical and geochemical composition of the alluvial sediments.