Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis

Peroxisome proliferator-activated receptor gamma (PPARgamma) has been proposed as a therapeutic target for neurodegenerative diseases because of its anti-inflammatory action in glial cells. However, PPARgamma agonists preventbeta-amyloid (Abeta)-induced neurodegeneration in hippocampal neurons, and PPARgamma is activated by the nerve growth factor (NGF) survival pathway, suggesting a neuroprotective anti-inflammatory independent action. Here we show that the PPARgamma agonist rosiglitazone (RGZ) protects hippocampal and dorsal root ganglion neurons against Abeta-induced mitochondrial damage and NGF deprivation-induced apoptosis, respectively, and promotes PC12 cell survival. In neurons and in PC12 cells RGZ protective effects are associated with increased expression of the Bcl-2 anti-apoptotic protein. NGF-differentiated PC12 neuronal cells constitutively overexpressing PPARgamma are resistant to Abeta-induced apoptosis and morphological changes and show functionally intact mitochondria and no increase in reactive oxygen species when challenged with up to 50 microM H2O2. Conversely, cells expressing a dominant negative mutant of PPARgamma show increased Abeta-induced apoptosis and disruption of neuronal-like morphology and are highly sensitive to oxidative stress-induced impairment of mitochondrial function. Cells overexpressing PPARgamma present a 4- to 5-fold increase in Bcl-2 protein content, whereas in dominant negative PPARgamma-expressing cells, Bcl-2 is barely detected. Bcl-2 knockdown by small interfering RNA in cells overexpressing PPARgamma results in increased sensitivity to Abeta and oxidative stress, further suggesting that Bcl-2 up-regulation mediates PPARgamma protective effects. PPARgamma prosurvival action is independent of the signal-regulated MAPK or the Akt prosurvival pathways. Altogether, these data suggest that PPARgamma supports survival in neurons in part through a mechanism involving increased expression of Bcl-2.     

Sleep in brain development

With the discovery of rapid eye movement (REM) sleep, sleep was no longer considered a homogeneous state of passive rest for the brain. On the contrary, sleep, and especially REM sleep, appeared as an active condition of intense cerebral activity. The fact that we get large amounts of sleep in early life suggested that sleep may play a role in brain maturation. This idea has been investigated for many years through a large number of animal and human studies, but evidence remains fragmented. The hypothesis proposed was that REM sleep would provide an endogenous source of activation, possibly critical for structural maturation of the central nervous system. This proposal led to a series of experiments looking at the role of REM sleep in brain development. In particular, the influence of sleep in developing the visual system has been highlighted. More recently, non-REM (NREM) sleep state has become a major focus of attention. The current data underscore the importance of both REM sleep and NREM sleep states in normal synaptic development and lend support to their functional roles in brain maturation. Both sleep states appear to be important for neuronal development, but the corresponding contribution is likely to be different.     

IDconverter and IDClight: Conversion and annotation of gene and protein IDs

Background  

Researchers involved in the annotation of large numbers of gene, clone or protein identifiers are usually required to perform a one-by-one conversion for each identifier. When the field of research is one such as microarray experiments, this number may be around 30,000.     

Intertissue mechanical stress affects Frizzled-mediated planar cell polarity in the Drosophila notum epidermis

Frizzled/planar cell polarity (Fz/PCP) signaling controls the orientation of sensory bristles and cellular hairs (trichomes) along the anteroposterior axis of the Drosophila thorax (notum). A subset of the trichome-producing notum cells differentiate as "tendon cells," serving as attachment sites for the indirect flight muscles (IFMs) to the exoskeleton. Through the analysis of chascon (chas), a gene identified by its ability to disrupt Fz/PCP signaling under overexpression conditions, and jitterbug (jbug)/filamin, we show that maintenance of anteroposterior planar polarization requires the notum epithelia to balance mechanical stress generated by the attachment of the IFMs. chas is expressed in notum tendon cells, and its loss of function disturbs cellular orientation at and near the regions where IFMs attach to the epidermis. This effect is independent of the Fz/PCP and fat/dachsous systems. The chas phenotype arises during normal shortening of the IFMs and is suppressed by genetic ablation of the IFMs. chas acts through jbug/filamin and cooperates with MyosinII to modulate the mechanoresponse of notum tendon cells. These observations support the notion that the ability of epithelia to respond to mechanical stress generated by one or more interactions with other tissues during development and organogenesis influences the maintenance of its shape and PCP features.     

Formulation and drying of alginate beads for controlled release and stabilization of invertase

Several alternatives to the conventional alginate beads formulation were studied for encapsulation of invertase. Pectin was added to the alginate/enzyme solution while trehalose and β-cyclodextrin were added to the calcium gelation media. The effect of composition changes, freezing, drying methods (freeze, vacuum, or air drying), and thermal treatment were evaluated on invertase stability and its release kinetics from beads. The enzyme release mechanism from wet beads depended on pH. The addition of trehalose, pectin, and β-cyclodextrin modified the bead structure, leading in some cases to a release mechanism that included the relaxation of the polymer chains, besides Fickian diffusion. Enzyme release from vacuum-dried beads was much faster than from freeze-dried beads, probably due to their higher pore size. The inclusion of β-cyclodextrin and especially of pectin prevented enzyme activity losses during bead generation, and trehalose addition was fundamental for achieving adequate invertase protection during freezing, drying, and thermal treatment. Present results showed that several alternatives such as drying method, composition, as well as pH of the relese medium can be managed to control enzyme release.     

Phenotypic analysis of first-year traits in a pseudo-backcross {(slash x loblolly) x slash} and the open-pollinated families of the pure-species progenitors

A single test, including one pseudo-backcross (Pinus elliottii x Pinus taeda) x P. elliottii and open-pollinated families of the pure species progenitors, was established in North Central Florida in December 2007 to study the transfer of the fast-growing characteristics from a P. taeda L. (loblolly pine) parent into the P. elliottii Engelm. (slash pine) background. Several traits were measured in the first growing season: height growth, phenology, tip moth incidence, stem traits, crown architectural and needle traits. Heterosis was evaluated for each trait using analyses of variance by fitting a linear mixed model. All traits were significantly (p value < 0.05) different among families while the significance for heterosis varied by trait. Positive heterosis was found for average rate of shoot elongation (ASRE), total growth (TG), total height and number of needles per fascicle while the opposite was true for base diameter, top diameter, fascicle length, fascicle diameter, crown projected area and phenological traits (cessation, duration and day to reach 50% of the height). Average performance (i.e., no heterosis) was found for initiation of growth, number of branches, number of nodes, tip moth incidence, sheath length and specific leaf area. The analyses indicated that introgression of loblolly pine alleles into slash pine was effective and novel trait combinations were achieved. The pseudo-backcross had larger variation in early height growth than the slash pine families and was taller than all open-pollinated families at the end of the first season. Tip moth incidence was much lower than the loblolly pine family.     

Cellulosomics, a gene-centric approach to investigating the intraspecific diversity and adaptation of Ruminococcus flavefaciens within the rumen

Background

The bovine rumen maintains a diverse microbial community that serves to break down indigestible plant substrates. However, those bacteria specifically adapted to degrade cellulose, the major structural component of plant biomass, represent a fraction of the rumen microbiome. Previously, we proposed scaC as a candidate for phylotyping Ruminococcus flavefaciens, one of three major cellulolytic bacterial species isolated from the rumen. In the present report we examine the dynamics and diversity of scaC-types both within and between cattle temporally, following a dietary switch from corn-silage to grass-legume hay. These results were placed in the context of the overall bacterial population dynamics measured using the 16S rRNA.

Principal Findings

As many as 117 scaC-types were estimated, although just nineteen were detected in each of three rumens tested, and these collectively accounted for the majority of all types present. Variation in scaC populations was observed between cattle, between planktonic and fiber-associated fractions and temporally over the six-week survey, and appeared related to scaC phylogeny. However, by the sixth week no significant separation of scaC populations was seen between animals, suggesting enrichment of a constrained set of scaC-types. Comparing the amino-acid translation of each scaC-type revealed sequence variation within part of the predicted dockerin module but strong conservation in the N-terminus, where the cohesin module is located.

Conclusions

The R. flavefaciens species comprises a multiplicity of scaC-types in-vivo. Enrichment of particular scaC-types temporally, following a dietary switch, and between fractions along with the phylogenetic congruence suggests that functional differences exist between types. Observed differences in dockerin modules suggest at least part of the functional heterogeneity may be conferred by scaC. The polymorphic nature of scaC enables the relative distribution of R. flavefaciens strains to be examined and represents a gene-centric approach to investigating the intraspecific adaptation of an important specialist population.