Factors influencing the development and carbohydrate metabolism of Echinococcus granulosus in dogs

Echinococcus granulosus adult worms, 35 days postinfection, were measured for dispersion in the intestines of 10 dogs, a range of morphological characters, and the excreted end products of carbohydrate catabolism following 4 hr incubation in vitro. Most worms were found in the proximal sections of the small intestine, but the pattern of dispersion differed between dogs. Worm development varied both between dogs and between different regions of the small intestine of individual dogs. Overall there was a high level of variability with no simple patterns. Worm metabolism was related to worm development and, also independently, to local population density within the intestine. Larger, more mature worms produced less lactate and, at higher densities. worms tended to produce more acetate and succinate (pathways with a higher energy yield than lactate) and less ethanol. Thus, both more developed worms and high population density are associated with a shift from cytosolic to mitochondrial metabolism. The variation between worm populations along the small intestine along with the observed variation between worm populations from sibling dogs infected with genetically identical parasites suggests that the local host environment has a significant effect on parasite development

Synthesis and evaluation of influenza A viral neuraminidase candidate inhibitors based on a bicyclo[3.1.0]hexane scaffold

We describe the synthesis of constrained oseltamivir analogues designed to mimic the proposed boat conformation of the enzymatic transition state

Observation of a Tricyclic[4.1.0.0 2,4]heptane During a Michael Addition-Ring Closure Reaction and a Computational Study on Its Mechanism of Formation

We describe the formation of a bis-cyclopropane product, a tricyclic[4.1.0.02,4]heptane, that is formed during a Johnson-Corey-Chaykovsky reaction on a cyclopentenone. Two (of four possible) bicyclic products are selectively formed by addition of a COOEt-stabilized sulfur ylide onto the Michael acceptor. The tricyclic product is formed subsequently via a retro Michael elimination of a hindered ether followed by addition of a further cyclopropyl moiety, affecting only one of the two bicyclic products initially formed. The experimental reaction outcome was rationalized using density functional theory (DFT), investigating the different Michael-addition approaches of the sulfur ylide, the transition state (TS) energies for the formation of possible zwitterionic intermediates and subsequent reactions that give rise to cyclopropanation. Selective formation of only two of the four possible products occurs due to the epimerization of unreactive intermediates from the other two pathways, as revealed by energy barrier calculations. The formation of the tricyclic product was rationalized by evaluation of energy barriers for proton abstraction required to form the intermediate undergoing the second cyclopropanation. The selectivity-guiding factors discussed for the single and double cyclopropanation of this functionalized Michael-acceptor will be useful guidelines for the synthesis of future singly and doubly cyclopropanated compounds

Design and synthesis of constrained bicyclic molecules as candidate inhibitors of influenza A neuraminidase

The rise of drug-resistant influenza A virus strains motivates the development of new antiviral drugs, with different structural motifs and substitution. Recently, we explored the use of a bicyclic (bicyclo[3.1.0]hexane) analogue of sialic acid that was designed to mimic the conformation adopted during enzymatic cleavage within the neuraminidase (NA; siali-dase) active site. Given that our first series of compounds were at least four orders of magnitude less active than available drugs, we hypothesized that the new carbon skeleton did not elicit the same interactions as the cyclohexene frameworks used previously. Herein, we tried to address this critical point with the aid of molecular modeling and we proposed new structures with different functionalization, such as the introduction of free ammonium and guanidinium groups and ether side chains other than the 3-pentyl side chain, the characteristic side chain in Oseltamivir. A highly simplified synthetic route was developed, starting from the cyclopropanation of cyclopentenone and followed by an aziridination and further functionalization of the five-member ring. This allowed the efficient preparation of a small library of new bicyclic ligands that were characterized by enzyme inhibition assays against influenza A neuraminidases N1, its H274Y mutant, and N2. The results show that none of the new structural variants synthesized, including those containing guanidinium groups rather than free ammonium ions, displayed activity against influenza A neuraminidases at concentrations less than 2 mM. We conclude that the choice and positioning of functional groups on the bicyclo[3.1.0]hexyl system still need to be properly tuned for producing complementary interactions within the catalytic site

Quantum superpositions of clockwise and counterclockwise supercurrent states in the dynamics of a rf-SQUID exposed to a quantized electromagnetic field

The dynamical behavior of a superconducting quantum interference device (a rf-SQUID) irradiated by a single mode quantized electromagnetic field is theoretically investigated. Treating the SQUID as a flux qubit, we analyze the dynamics of the combined system within the low lying energy Hilbert subspace both in the asymmetric and in the symmetric SQUID potential configurations. We show that the temporal evolution of the system is dominated by an oscillatory behavior characterized by more than one, generally speaking, incommensurable Rabi frequencies whose expressions are explicitly given. We find that the external parameters may fixed in such a way to realize a control on the dynamical replay of the total system which, for instance, may be forced to exhibit a periodic evolution accompanied by the occurrence of an oscillatory disappearance of entanglement between the two subsystems. We demonstrate the possibility of generating quantum maximally entangled superpositions of the two macroscopically distinguishable states describing clockwise and counterclockwise supercurrents in the loop. The experimental feasibility of our proposal is briefly discussed.Comment: 16 pages, 7 figures, submitted to PR

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective leg blood flow (LBF), muscle microvascular blood volume (MBV) and MPS were measured under postabsorptive and postprandial (I.V glamin, dextrose to sustain glucose ~7.5 mmol·l-1) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time as nutrition began. Leg [femoral artery] blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound (CEUS) using DefinityTM perflutren contrast agent and MPS using [1, 2-13C2] leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism

Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis

BACKGROUND: People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU. METHODS AND FINDINGS: We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence. CONCLUSIONS: 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes

The SARAO MeerKAT 1.3 GHz Galactic Plane Survey

We present the SARAO MeerKAT Galactic Plane Survey (SMGPS), a 1.3 GHz continuum survey of almost half of the Galactic Plane (251○ ≤l ≤ 358○ and 2○ ≤l ≤ 61○ at |b| ≤ 1 5). SMGPS is the largest, most sensitive and highest angular resolution 1 GHz survey of the Plane yet carried out, with an angular resolution of 8″ and a broadband RMS sensitivity of ∼10–20 μJy beam−1. Here we describe the first publicly available data release from SMGPS which comprises data cubes of frequency-resolved images over 908–1656 MHz, power law fits to the images, and broadband zeroth moment integrated intensity images. A thorough assessment of the data quality and guidance for future usage of the data products are given. Finally, we discuss the tremendous potential of SMGPS by showcasing highlights of the Galactic and extragalactic science that it permits. These highlights include the discovery of a new population of non-thermal radio filaments; identification of new candidate supernova remnants, pulsar wind nebulae and planetary nebulae; improved radio/mid-IR classification of rare Luminous Blue Variables and discovery of associated extended radio nebulae; new radio stars identified by Bayesian cross-matching techniques; the realisation that many of the largest radio-quiet WISE H II region candidates are not true H II regions; and a large sample of previously undiscovered background H I galaxies in the Zone of Avoidance

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema