Feeding graded levels of dried Sea buckthorn (Hippophaes rhamnoides) berries to broiler chickens

The aim of this study was to assess the effects of graded levels (0, 3, 6, 9 and 12 g/kg) of dry Sea buckthorn (SB) berries on growth performance, gastrointestinal tract (GIT) development, jejunal histomorphology, bird antioxidant status and caecal short-chain fatty acid concentration when fed to female Ross 308 broiler chickens. In addition, expression of cytokine biomarker genes in the jejunum was evaluated. The five experimental diets were fed from 7 to 21 days age to 8 pens (two birds in each) following randomisation. Feeding SB did not influence bird growth performance (p > .05). There was a linear decrease in butyric, acetic and valeric acid concentrations in caecal digesta (p < .05) and a decrease (p < .05) in crypt depth. The expression of IFNG and CD40LG responded quadratically (p < .05), peaking at 6–9 g/kg dietary inclusion of SB, respectively. Other studied variables were not affected by dietary SB inclusion (p > .05). Feeding dry SB berries up to 12 g/kg of diet did not improve the zootechnical variables of healthy commercial-strain broilers in this study.     

Blood System Formation in the Urochordate Ciona intestinalis Requires the Variable Receptor vCRL1

Adaptive immune systems are present only in vertebrates. How do all the remaining animals withstand continuous attacks of permanently evolving pathogens? Even in the absence of adaptive immunity, every organism must be able to unambiguously distinguish "self" cells from any imaginable "nonself." Here, we analyzed the function of highly polymorphic gene vCRL1, which is expressed in follicle and blood cells of Ciona intestinalis, pointing to possible recognition roles either during fertilization or in immune reactions. By using segregation analysis, we demonstrate that vCRL1 locus is not involved in the control of self-sterility. Interestingly, genetic knockdown of vCRL1 in all tissues or specifically in hemocytes results in a drastic developmental arrest during metamorphosis exactly when blood system formation in Ciona normally occurs. Our data demonstrate that vCRL1 gene might be essential for the establishment of a functional blood system in Ciona. Presumably, presence of the vCRL1 receptor on the surface of blood cells renders them as self, whereas any cell lacking it is referred to as nonself and will be consequently destroyed. We propose that individual-specific receptor vCRL1 might be utilized to facilitate somatic self/nonself discrimination.     

Discovery and structural characterization of an allosteric inhibitor of bacterial cis‐prenyltransferase

Undecaprenyl pyrophosphate synthase (UPPs) is an essential enzyme in a key bacterial cell wall synthesis pathway. It catalyzes the consecutive condensations of isopentenyl pyrophosphate (IPP) groups on to a trans-farnesyl pyrophosphate (FPP) to produce a C55 isoprenoid, undecaprenyl pyrophosphate (UPP). Here we report the discovery and co-crystal structures of a drug-like UPPs inhibitor in complex with Streptococcus pneumoniae UPPs, with and without substrate FPP, at resolutions of 2.2 and 2.1 Å, respectively. The UPPs inhibitor has a low molecular weight (355 Da), but displays potent inhibition of UPP synthesis in vitro (IC₅₀ 50 nM) that translates into excellent whole cell antimicrobial activity against pathogenic strains of Streptococcal species (MIC₉₀ 0.4 µg mL⁻¹). Interestingly, the inhibitor does not compete with the substrates but rather binds at a site adjacent to the FPP binding site and interacts with the tail of the substrate. Based on the structures, an allosteric inhibition mechanism of UPPs is proposed for this inhibitor. This inhibition mechanism is supported by biochemical and biophysical experiments, and provides a basis for the development of novel antibiotics targeting Streptococcus pneumoniae.     

Mitochondrial haplogroup N1a phylogeography,with implication to the origin of European farmers

Background  

Tracing the genetic origin of central European farmer N1a lineages can provide a unique opportunity to assess the patterns of the farming technology spread into central Europe in the human prehistory. Here, we have chosen twelve N1a samples from modern populations which are most similar with the farmer N1a types and performed the complete mitochondrial DNA genome sequencing analysis. To assess the genetic and phylogeographic relationship, we performed a detailed survey of modern published N1a types from Eurasian and African populations.     

3-Amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile

The optimization of compounds from the 3-amido-4-anilinoquinolines series of CSF-1R kinase inhibitors is described. The series has excellent activity and kinase selectivity. Excellent physical properties and rodent PK profiles were achieved through the introduction of cyclic amines at the quinoline 6-position. Compounds with good activity in a mouse PD model measuring inhibition of pCSF-1R were identified.     

Selective release and function of one of the two FMN groups in the cytoplasmic NAD+-reducing [NiFe]-hydrogenase from Ralstonia eutropha.

The soluble, cytoplasmic NAD+-reducing [NiFe]-hydrogenase from Ralstonia eutropha is a heterotetrameric enzyme (HoxFUYH) and contains two FMN groups. The purified oxidized enzyme is inactive in the H2-NAD+ reaction, but can be activated by catalytic amounts of NADH. It was discovered that one of the FMN groups (FMN-a) is selectively released upon prolonged reduction of the enzyme with NADH. During this process, the enzyme maintained its tetrameric form, with one FMN group (FMN-b) firmly bound, but it lost its physiological activity--the reduction of NAD+ by H2. This activity could be reconstituted by the addition of excess FMN to the reduced enzyme. The rate of reduction of benzyl viologen by H2 was not dependent on the presence of FMN-a. Enzyme devoid of FMN-a could not be activated by NADH. As NADH-dehydrogenase activity was not dependent on the presence of FMN-a, and because FMN-b did not dissociate from the reduced enzyme, we conclude that FMN-b is functional in the NADH-dehydrogenase activity catalyzed by the HoxFU dimer. The possible function of FMN-a as a hydride acceptor in the hydrogenase reaction catalyzed by the HoxHY dimer is discussed.     

Evolution of host specificity in fleas: is it directional and irreversible?

Evolutionary trends in the evolution of host specificity have been the focus of much discussion but little rigorous empirical testing. On the one hand, specialization is often presumed to lead irreversibly into evolutionary dead ends and little diversification; this would mean that generalists might evolve into specialists, but not vice versa. On the other hand, low host specificity may limit the risk of extinction and provide more immediate fitness benefits to parasites, such that selection may favour evolution toward a generalist strategy. Here, we test for directionality in the evolution of host specificity using a large data set and phylogenetic information on 297 species of fleas parasitic on small mammals. The analyses determined whether host specificity, measured both as the number of host species exploited and their taxonomic diversity, was related to clade rank of the flea species, or the number of branching events between an extant species and the root of the phylogenetic tree (i.e., the total path length from the root of the tree to the species). Based on regression analyses, we found positive relationships between the number of host species used and clade rank across all 297 species, as well as within one (Hystrichopsyllidae) of four large families and one of seven large genera investigated separately; in addition, we found a positive relationship between the taxonomic diversity of host species used and clade rank in another of the seven genera. These results suggest a slight evolutionary trend of decreasing host specificity. Using a much more conservative likelihood ratio test, however, a random walk, or null model, of evolution could not be discarded in favour of the directional trends in all cases mentioned above. Still, these results suggest that host specificity may have tended to decrease in many flea lineages, a process that could have been driven by the benefits of exploiting a wide range of host species.     

Urea potentiometric enzymatic biosensor based on charged biopolymers and electrodeposited polyaniline

A potentiometric biosensor based on urease was developed for the quantitative determination of urea concentration in aqueous solutions for biomedical applications. The urease was either physisorbed onto an electrodeposited polyaniline film (PANI), or immobilized on a layer-by-layer film (LbL) assembled over the PANI film, that was obtained by the alternate deposition of charged polysaccharides (carboxymethylpullulan (CMP) and chitosan (CHI)). In the latter case, the urease (Urs) enzyme was either physically adsorbed or covalently grafted to the LbL film using carbodiimide coupling reaction. Potentiometric responses of the enzymatic biosensors were measured as a function of the urea concentration in aqueous solutions (from 10(-6) to 10(-1) mol L(-1) urea). Very high sensitivity and short response time were observed for the present biosensor. Moreover, a stability study showed a higher stability over time for the potentiometric response of the sensor with the enzyme-grafted LbL film, testifying for the protective nature of the polysaccharide coating and the interest of covalent grafting.