Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients

Amyotrophic lateral sclerosis (ALS) is an incurable neuromuscular disease that leads to a profound loss of life quality and premature death. Around 10% of the cases are inherited and ALS8 is an autosomal dominant form of familial ALS caused by mutations in the vamp-associated protein B/C (VAPB) gene. The VAPB protein is involved in many cellular processes and it likely contributes to the pathogenesis of other forms of ALS besides ALS8. A number of successful drug tests in ALS animal models could not be translated to humans underscoring the need for novel approaches. The induced pluripotent stem cells (iPSC) technology brings new hope, since it can be used to model and investigate diseases in vitro. Here we present an additional tool to study ALS based on ALS8-iPSC. Fibroblasts from ALS8 patients and their non-carrier siblings were successfully reprogrammed to a pluripotent state and differentiated into motor neurons. We show for the first time that VAPB protein levels are reduced in ALS8-derived motor neurons but, in contrast to over-expression systems, cytoplasmic aggregates could not be identified. Our results suggest that optimal levels of VAPB may play a central role in the pathogenesis of ALS8, in agreement with the observed reduction of VAPB in sporadic ALS.

Increased Expression of GluR2-flip in the Hippocampus of the Wistar Audiogenic Rat Strain After Acute and Kindled Seizures

The Wistar Audiogenic Rat (WAR) is an epileptic-prone strain developed by genetic selection from a Wistar progenitor based on the pattern of behavioral response to sound stimulation. Chronic acoustic stimulation protocols of WARs (audiogenic kindling) generate limbic epileptogenesis, confirmed by ictal semiology, amygdale, and hippocampal EEG, accompanied by hippocampal and amygdala cell loss, as well as neurogenesis in the dentate gyrus (DG). In an effort to identify genes involved in molecular mechanisms underlying epileptic process, we used suppression-subtractive hybridization to construct normalized cDNA library enriched for transcripts expressed in the hippocampus of WARs. The most represented gene among the 133 clones sequenced was the ionotropic glutamate receptor subunit II (GluR2), a member of the a-amino-3-hydroxy-5-methyl-4-isoxazoleopropionic acid (AMPA) receptor. Although semiquantitative RT-PCR analysis shows that the hippocampal levels of the GluR2 subunits do not differ between naive WARs and their Wistar counterparts, we observed that the expression of the transcript encoding the splice-variant GluR2-flip is increased in the hippocampus of WARs submitted to both acute and kindled audiogenic seizures. Moreover, using in situ hybridization, we verified upregulation of GluR2-flip mainly in the CA1 region, among the hippocampal subfields of audiogenic kindled WARs. Our findings on differential upregulation of GluR2-flip isoform in the hippocampus of WARs displaying audiogenic seizures is original and agree with and extend previous immunohistochemical for GluR2 data obtained in the Chinese P77PMC audiogenic rat strain, reinforcing the association of limbic AMPA alterations with epileptic seizures. (C) 2009 Wiley-Liss, Inc.

Endurance training modulates lymphocyte function in rats with post-MI CHF

Purpose: Exercise training restores innate immune system cell function in post-myocardial infarction (post-MI) rats. However, studies of the involvement of lymphocyte (Ly) in the setting of the congestive heart failure (CHF) are few. To address this issue, we investigated the function of Ly obtained from cervical lymph nodes from post-MI CHF rats submitted to treadmill running training. Methods: Twenty-five male Wistar rats were randomly assigned to the following groups: rats submitted to ligation of the left coronary artery, which were sedentary (MI-S, N= 7, only limited activity) or trained (MI-T, N= 6, on a treadmill (0% grade at 13-20 m.m(-1)) for 60 min.d(-1), 5 d.wk(-1), for 8-10 wk); or sham-operated rats, which were sedentary (sham-S, N = 6) or trained (sham-T, N = 6). The incorporation of [2-C-14]-thymidine by Ly cultivated in the presence of concanavalin A (Con A) and lipopolysaccharide (LPS), cytokine production by Ly cultivated in the presence of phytohemagglutinin (PHA), and plasma concentration of glutamine were assessed in all groups, 48 h after the last exercise session. Results: Proliferative capacity was increased, following incubation with Con-A in the MI groups, when compared with the sham counterparts. When incubated in the presence of PHA, MI-S produced more IL-4 (96%) than sham-S (P < 0.001). The training protocol induced a 2.2-fold increase in the production of interleukin-2 (P < 0.001) of the cells obtained from the cervical lymph nodes of MI-T, compared with MI-S. Conclusion: The moderate endurance training protocol caused an increase in IL-2 production, and a trend toward the reversion of the Th-1/Th-2 imbalance associated with IL-4 production increased in the post-MI CHF animal model.

The Itajai foreland basin: a tectono-sedimentary record of the Ediacaran period, Southern Brazil

The Itajai Basin located in the southern border of the Luis Alves Microplate is considered as a peripheral foreland basin related to the Dom Feliciano Belt. It presents an excellent record of the Ediacaran period, and its upper parts display the best Brazilian example of Precambrian turbiditic deposits. The basal succession of Itajai Group is represented by sandstones and conglomerates (BaA(0) Formation) deposited in alluvial and deltaic-fan systems. The marine upper sequences correspond to the Ribeiro Carvalho (channelized and non-channelized proximal silty-argillaceous rhythmic turbidites), Ribeiro Neisse (arkosic sandstones and siltites), and Ribeiro do Bode (distal silty turbidites) formations. The ApiA(0)na Formation felsic volcanic rocks crosscut the sedimentary succession. The Cambrian Subida leucosyenogranite represents the last felsic magmatic activity to affect the Itajai Basin. The Brusque Group and the Florianpolis Batholith are proposed as source areas for the sediments of the upper sequence. For the lower continental units the source areas are the Santa Catarina, So Miguel and CamboriA(0) complexes. The lack of any oceanic crust in the Itajai Basin suggests that the marine units were deposited in a restricted, internal sea. The sedimentation started around 600 Ma and ended before 560 Ma as indicated by the emplacement of rhyolitic domes. The Itajai Basin is temporally and tectonically correlated with the Camaqu Basin in Rio Grande do Sul and the Arroyo del Soldado/Piriapolis Basin in Uruguay. It also has several tectono-sedimentary characteristics in common with the African-equivalent Nama Basin.

Deformation and geochronology of syntectonic granitoids emplaced in the Major Gercino Shear Zone, southeastern South America

The Major Gercino Shear Zone is one of the NE-SW lineaments that separate the Neoproterozoic Dom Feliciano Belt, of Brazil and Uruguay, into two different domains: a northwestern supracrustal domain from a southeastern granitoid domain. The shear zone, striking NE, is composed of protomylonites to ultramylonites with mainly dextral kinematic indicators. In Santa Catarina State, southern Brazil, the shear zone is composed of two mylonite belts. The mylonites have mineral orientations produced under greenschist fades conditions at a high strain rate. Strong flattening and coaxial deformation indicate the transpressive character, while the role of pure shear is emphasized by the orientation of the mylonite belts in relation to the inferred stress field component. The quartz microstructures point out that different dynamic recrystallization regimes and crystal plasticity were the dominant mechanisms of deformation during the mylonitization process. Additionally, the fabrics suggest that the glide systems are activated for deformation conditions compatible with the metamorphism in the middle greenschist facies. Elongated granitoid intrusions belonging to two petrographically, geochemically and isotopically distinct rock associations occur between the two mylonite belts. The structures observed in the granites result from a deformation range from magmatic to solid-state conditions points to a continuum of magma straining during and just after its crystallization. Conventional U-Pb analysis of multi-crystal zircon fractions yielded essentially identical ages of 609 +/- 16 Ma and 614 +/- 2 Ma for the two granitic associations, and constrain the transpressive phase of the shear zone. K-Ar ages of biotites between 585 and 560 Ma record the slow cooling and uplift of the intrusions. Some K-Ar ages of micas in regional mylonites are similar, suggesting that thermo-tectonic activity was intense up to this time, probably related to the agglutination of the granite belt to the supracrustal belt NW of the MGSZ. (C) 2009 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Wettability of Aqueous Rhamnolipids Solutions Produced by Pseudomonas aeruginosa LBI

The wetting behavior of rhamnolipids produced by Pseudomonas aeruginosa LBI strain grown on waste oil substrate and sodium dodecyl sulfate (SDS) on glass, polyethylene terephthalate (PET), poly(vinyl chloride) (PVC), poly(epsilon-caprolactone) (PCL) and polymer blend (PVC-PCL) was investigated by the measuring contact angle of sessile drops, to determine the wetting characteristics of rhamnolipids. The comparison of the wetting profiles showed that at low SDS and rhamnolipid concentrations, the contact angle increased and when the concentration of the surfactant increased further, the contact angle decreased. The blend surface (PVC-PCL) showed better wettability than the homopolymers themselves and the blend changed the surface hydrophobicity of the polymer, making it more hydrophilic. The rhamnolipids produced by the LBI strain exhibited superior wetting abilities than the chemical surfactant SDS one. This is the first work that evaluates the wetting properties of rhamnolipids on polymer blends.