Acyclic, orally bioavailable ketone-based cathepsin K inhibitors

Starting from a potent ketone-based inhibitor with poor drug properties, incorporation of P(2)-P(3) elements from a ketoamide-based inhibitor led to the identification of a hybrid series of ketone-based cathepsin K inhibitors with better oral bioavailability than the starting ketone.     

The three-dimensional structure of the Moorella thermoacetica selenocysteine insertion sequence RNA hairpin and its interaction with the elongation factor SelB

Incorporation of the amino acid selenocysteine into a growing protein chain involves the interaction between a hairpin in the mRNA termed the selenocysteine insertion sequence (SECIS) and the special elongation factor SelB. Here we present the structure of the SECIS from the thermophilic organism Moorella thermoacetica (SECIS-MT) determined using nuclear magnetic resonance (NMR) spectroscopy. The SECIS-MT hairpin structure contains a pentaloop with the first and fourth nucleotides of the loop forming a noncanonical GC base pair; the fifth loop nucleotide is bulged out and unstructured. The G and U in positions two and three are on opposite sides of the loop and solvent exposed. The backbone resonances of the SECIS-binding domain from the M. thermoacetica SelB protein were assigned, and the degree of chemical shift perturbations that occur upon SECIS binding were mapped onto the structure of the complex. We demonstrate that a region in the third winged-helix domain of SelB, not previously implicated in binding, is affected by SECIS binding.     

Seed abortion in the sexual counterpart of <Emphasis Type="Italic">Brachiaria brizantha</Emphasis> apomicts (Poaceae)

Gametophytic organization, fertilization and reproductive success are described for the fertile diploid Brachiaria brizantha accession BRA-002747 which is being raised for use in Brachiaria breeding programs, as well as to understand and control of apomixis in this genus. The current paper reports on reproductive biology and analysis of seed set in field experiments during three consecutive years. Unsuccessful seed production in this plant is believed to correlate with early inbreeding depression, based on the reproductive features analyzed. Caryopsis development was observed using differential interference contrast microscopy with seed set determined by the number of self- and open-pollinated pistils that fully developed into viable seeds. Developing and mature female and male gametophytes were observed in the context of flower phenology, morphology and anthesis patterns. Pollen viability was determined by acetocarmine staining and by observation of germination in vivo, which was also used to observe pollen tube/pistil interaction. Although normal development was observed in floral structures, anthesis and gametophytes, seed set was low, with 2 and 6% in self- and open-pollination, respectively, producing seed. Variations observed in the female organs, such as the presence of a hermaphrodite flower in 50% of the inferior floscules and the presence of multiple embryo sacs of the Polygonum type within the same ovule in 15% of the pistils, are not related to low fertility. The majority of pollen grains are viable, in spite of the reduced number of pollen tubes within the style and ovary carpel, and a developing caryopsis was observed in 70% of self-pollinated pistils, indicating successful double fertilization from 2 days after anthesis (DAA). Nevertheless, abortion gradually increased from 2 until 7 DAA and remains elevated until 12 DAA, when caryopsis maturity is achieved. These data confirm low seed set in this accession and indicate that low fertility is not a consequence of abnormalities, either in the floral or gamete structures, or pollen tube rejection, but most likely a consequence of inbreeding depression.     

Effects of the fish-oil supplementation on the immune and inflammatory responses in elite swimmers

The effect of fish-oil supplementation (FO-S) on the immune responses of elite swimmers was investigated. In a randomized placebo-controlled trial, swimmers received either fish-oil capsules (n=10) containing long chain polyunsaturated fatty acids (FA) of n-3 (LCPUFA n-3) or placebo capsules (n=10), both for 6 weeks. Plasma FA, immunological markers, insulin and cortisol were evaluated. The FO-S resulted in an increase in LCPUFA n-3 and a decrease in arachidonic n-6 FA in plasma and a reduction in the production of interferon-gamma by cultured cells. A reduction in the production of tumor necrosis factor-alpha was observed in both groups. An increase in interleukin-2 production and no significant difference in interleukin-4 were also observed. FO-S was able to attenuate the exercise-induced increases in prostaglandin E2. Circulating concentrations of insulin did not change, while cortisol and glucose showed increase after the study period. These results suggest that FO-S influence exercise-associated immune responses in competitive swimmers.     

Development of a SCAR marker for the analysis of B chromosome presence in Partamona helleri (Hymenoptera, Apidae)

Chromosomes in hymenopteran insects cannot currently be analysed in adult individuals. The only available cytogenetic techniques need to be performed in larvae. Here we develop and implement a SCAR (Sequence Characterized Amplified Region) marker, associated with B chromosomes in the bee Partamona helleri, which has proven to be very useful to reveal B chromosome presence in adults from natural populations. The marker was tested in ten different colonies simultaneously analysed by both molecular (ten adults per colony) and cytogenetic (20 larvae per colony) techniques. The presence of the SCAR marker always showed the same pattern as B chromosome presence: both were present or absent in all individuals from a same colony, or both were present in only part of the individuals from a same colony. This molecular marker is thus a useful tool for analysing new aspects of this B chromosome system such as B frequency and geographical distribution, B transmission, or B effects in adult individuals.     

Effect of the microbial conditioning and temperature increase on the leaf consumption by shredders in Amazonian aquatic systems

Hydrobiologia - We used experimental chambers to evaluate the effect of the temperature increasing and microbial conditioning degree on the survival and leaf consumption of two plant species...     

Seasonality affects the parasitism levels in two fish species in the eastern Amazon region

Fish parasite communities have strong interactions with the environment, the host fish, and the aquatic invertebrate communities. Thus, factors directly involving their different life cycles, such as different host populations and environments, as well as seasonal fluctuations in water levels can cause different responses. The main factors structuring parasite communities may be the hydrodynamic variations, together with seasonal variations in the availability of infectious stages of parasites in the environment. The purpose of this study was therefore to investigate the influence of the rainy and dry seasons on parasite infracommunities in fish species in the Amazon River System of Brazil. Between October 2009 and April 2011, specimens of Colossoma macropomum and Colossoma macropomum × Piaractus brachypomus hybrids (tambatinga) were examined for the presence of parasites. The parasite communities were similar in these two species that both showed aggregate dispersion, although the hybrid specimens were less parasitized. For both hosts, the Brillouin diversity, species richness, evenness and Berger‐Parker dominance indices were similar in the rainy season and dry season, except that the Berger‐Parker dominance index for the C. macropomum × P. brachypomus hybrid was higher during the dry season. Ichthyophthirius multifiliis was the dominant parasite, followed by Piscinoodinium pillulare, in both hosts. However, C. macropomum had a higher prevalence and abundance in the dry season, while in the C. macropomum × P. brachypomus hybrid, only the I. multifiliis prevalence increased. The abundance of monogenean species (Anacanthorus spathulatus, Linguadactyloides brinkmanni, Mymarothecium and Notozothecium janauachensis) was higher during the dry season in the gills of C. macropomum. Despite overdispersion of the lernaeid Perulernaea gamitanae, a seasonal pattern was seen only in the C. macropomum × P. brachypomus hybrid, with higher prevalence in the rainy season. The low prevalence and abundance of the ectoparasites Tetrahymena sp., Trichodina sp. and Braga patagonica, as well as of the endoparasites Procamallalus (Spirocamallanus) inopinatus and Neoechinorhynchus buttnerae, were not affected by seasonality. This information is applicable in farming practice for these economically important fish, as it indicates the best time for prophylactic management and treatment against parasites, in order to prevent economic losses in fish farms.     

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley,Minas Gerais,Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.     

Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.