Microbiology: breaking down biofilms

Biofilms--adherent bacterial communities embedded in a polymer matrix--are common in nature and can cause persistent human infections that are highly resistant to antibiotics. Recent work provides insight into how these communities develop and function, and offers clues to combating them.     

Some properties of peptidase from rat heart, breaking down luliberin

The properties of rat heart peptidase hydrolyzing luliberin were studied. This peptidase was shown to be a sulfhydryl metalloenzyme with m.w. of about 100000. The maximal enzyme activity was observed at neutral values of pH Ca2+ (5 X 10(-6) M) increased the enzyme activity by 50%, thus being indicative of an anomalous dependence of the enzyme activity of substrate concentration. At luliberin concentrations of 10(-7)-10(-6) M the enzyme activation by Ca2+ was considerably reduced and returned to the initial level when the peptide concentration was increased up to 10(-5) M. It was assumed that the peptidase under study is a regulatory enzyme whose activity depends on concentrations of Ca2+ and of the reaction substrate, luliberin.     

Brains, islands and evolution: breaking all the rules

The announcement in 2004 that a small-brained hominin, Homo floresiensis, had been discovered on the island of Flores, Indonesia, was hailed as a major scientific breakthrough because it challenged preconceptions about the evolution of our closest relatives. Now, just over two years later, questions raised by the interpretation of the fossil abound. In a series of recent papers, critics have questioned the interpretation of the small brain volume of the fossil as that of a new hominin species, suggesting instead that it was due to microcephaly. The arguments raised by critics and advocates alike prompt a re-examination of ideas about what is possible during the evolution of the brain.     

Multiple orientations in a physiological complex: the pyruvate-ferredoxin oxidoreductase-ferredoxin system

Ferredoxin I from Desulfovibrio africanus (Da FdI) is a small acidic [4Fe-4S] cluster protein that exchanges electrons with pyruvate-ferredoxin oxidoreductase (PFOR), a key enzyme in the energy metabolism of anaerobes. The thermodynamic properties and the electron transfer between PFOR and either native or mutated FdI have been investigated by microcalorimetry and steady-state kinetics, respectively. The association constant of the PFOR-FdI complex is 3.85 x 10(5) M(-1), and the binding affinity has been found to be highly sensitive to ionic strength, suggesting the involvement of electrostatic forces in formation of the complex. Surprisingly, the punctual or combined neutralizations of carboxylate residues surrounding the [4Fe-4S] cluster slightly affect the PFOR-FdI interaction. Furthermore, hydrophobic residues around the cluster do not seem to be crucial for the PFOR-FdI system activity; however, some of them play an important role in the stability of the FeS cluster. NMR restrained docking associated with site-directed mutagenesis studies suggested the presence of various interacting sites on Da FdI. The modification of additional acidic residues at the interacting interface, generating a FdI pentamutant, evidenced at least two distinct FdI binding sites facing the distal [4Fe-4S] cluster of the PFOR. We also used a set of various small acidic partners to investigate the specificity of PFOR toward redox partners. The remarkable flexibility of the PFOR-FdI system supports the idea that the specificity of the physiological complex has probably been "sacrificed" to improve the turnover rate and thus the efficiency of bacterial electron transfer.     

Understanding and breaking down the reproductive barrier between Asian and African cultivated rice: a new start for hybrid rice breeding

<正>Oryza sativa and O. glaberrima, commonly known as Asian and African cultivated rice, are two domesticated rice species in Oryza genus. Asian cultivated rice may produce higher yields with better quality, whereas African cultivated rice shows a wide range of tolerance to abiotic and biotic stresses.Interspecific hybrids between O. sativa and O. glaberrima would show strong heterosis and thus increasing production because of their distant genetic diversity and complementary agronomic traits. However, reduced fertility is observed in hybrids from interspecific crosses; this hinders further uti-     

Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors

The innate immune pathways that contribute to the potent immunogenicity of recombinant adenovirus (rAd) vaccine vectors remain largely undefined. Previous studies assessing innate immunity triggered by vaccine vectors have largely focused on in vitro studies involving antigen-presenting cells and on early in vivo inflammatory responses. Here, we systematically explore the Toll-like receptor (TLR) signaling requirements for the generation of cellular immune responses by intramuscular immunization with common and alternative serotype rAd vectors in mice. Antigen-specific CD8(+) T-lymphocyte responses elicited by these rAd vectors were significantly diminished in MyD88(-/-) mice but not in TRIF(-/-) or TLR3(-/-) mice, suggesting the importance of MyD88-dependent TLR signaling. However, the absence of each individual TLR resulted in minimal to no effect on vaccine-elicited cellular immune responses. Moreover, responses were not diminished in IL-1R(-/-) or IL-18R(-/-) mice. These data suggest that rAd vectors engage multiple MyD88-dependent signaling pathways, none of which are individually critical; rather, they are integrated to contribute to the potent immunogenicity of rAd vectors. Stimulation of multiple innate immune mechanisms may prove a generalizable property of potent vaccines, and this strategy could be harnessed in the development of next-generation vaccine vectors and adjuvants.     

Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain

Down syndrome (DS, trisomy 21) is the most frequent genetic cause of mental retardation. Although known for more than a hundred years the underlying pathomechanisms for the phenotype and impaired brain functions remain elusive. Performing protein hunting in fetal DS brain, we detected a series of cytoskeleton proteins with aberrant expression in fetal DS cortex. Fetal brain cortex samples of controls and DS of the early second trimenon of gestation were used for the experiments. We applied two-dimensional electrophoresis with in-gel digestion of protein spots, subsequent mass spectroscopical (MALDI) identification, and quantification of spots using specific software. Centractin alpha, F-actin capping protein alpha-1, alpha-2 and beta subunits were significantly reduced in fetal DS cortex, whereas dynein intermediate clear 2, dynein intermediate chain 2, and kinesin light chain protein levels were unchanged. Centractins and F-actin capping proteins are major determinants of the cytoskeleton and are involved in pivotal functions including cellular, organelle, and nuclear motility. Deranged centractins and F-actin capping proteins may represent or induce deficient axonal transport and may well contribute to deterioration of the cytoskeleton's mitotic functions in trisomy 21.     

Language development: breaking the code

This paper reviews the major achievements of the preschool years regarding language acquisition. Although most children appear to master their native language with little apparent effort, learning a language is a complex task. It requires the ability to extract clues from environmental stimuli and to discover how those stimuli convey meanings and are modified according to the meaning conveyed. In general, language learning follows a similar sequence regardless of the language being learned. The major accomplishments in the areas of speech perception, early sound production, phonology, lexicon, syntax, and morphology are described, with specific examples from recent studies of acquisition of French in young children from Québec. These examples confirm major milestones observed in other languages, but also illustrate how comparisons across languages and across children learning the same language can be challenging. For each area, current issues are identified regarding the bases (neurological, genetic) of language development, as well as the processes (social, cognitive, linguistic) involved. Current hypotheses regarding language acquisition and language disorders are briefly discussed.     

Cadherin function: breaking the barrier

Three desmoglein isoforms collaborate with desmocollins to build the adhesive core of desmosomes. A recent study has shown that altering the ratio of desmoglein isoforms influences epidermal barrier function, suggesting distinct roles for these cadherins that extend beyond adhesion.