Respiratory responses of three Antarctic ascidians and a sea pen to increased sediment concentrations

Glacial retreat and subglacial bedrock erosion are consequences of rapid regional warming on the West Antarctic Peninsula. Sedimentation of fine-grained eroded particles can impact the physiology of filter-feeding benthic organisms. We investigated the effect of increasing concentrations of sediment on the oxygen consumption of suspension feeding species, the ascidians Molgula pedunculata, Cnemidocarpa verrucosa, Ascidia challengeri, and the pennatulid Malacobelemnon daytoni in Potter Cove (South Shetland Islands, Antarctica). In A. challengeri and C. verrucosa, oxygen consumption increased gradually up to a critical sediment concentration (C _crit) where species oxygen consumption was maximal (O _max in mg O₂?g^?1dm?day^?1) and further addition of sediments decreased respiration. C _crit was 200?mg?L^?1 for A. challengeri (O _max of 0.651?±?0.238) and between 100 and 200?mg?L^?1 for C. verrucosa (O _max of 0.898?±?0.582). Oxygen consumption of M. pedunculata increased significantly even at low sediment concentrations (15–50?mg sediment?L^?1). Contrary to the ascidians, sediment exposure did not affect oxygen consumption of the sea pen. The tiered response to sedimentation in the four species corroborates recent field observations that detected a reduction in the abundance of the sensitive ascidian M. pedunculata from areas strongly affected by glacial sediment discharge, whereas sea pens are increasing in abundance. Our investigation relates consequences (population shifts in filter-feeder communities) to causes (glacial retreat) and is of importance for modelling of climate change effects in Antarctic shallow coastal areas.     

Combined effect of temperature and salinity on the Thermotolerance and osmotic pressure of juvenile white shrimp litopenaeus vannamei (Boone)

Thermotolerance (CTMax) was determined in L. vannamei in three salinities and five acclimation temperatures 20, 23, 26, 29 and 32 °C. In white shrimp, the CTMax was not significantly affected by salinity (P>0.05). A direct relationship was obtained between CTMax and acclimation temperature. The end point of the CTMax in L. vannamei exposed to different combinations of temperature and salinity was defined as the loss of the righting response (LRR). The acclimation response ratio (ARR) for the juveniles of white shrimp ranged from 0.42 to 0.49; values in agreement with other crustaceans from tropical and sub tropical climates. The osmotic pressure of the hemolymph was measured in control organisms and in organisms exposed to CTMax; significant differences were found in organisms maintained in 10 and 40 psu, but there were no significant differences in hemolymph osmotic pressure in those that were acclimated to 26 psu.     

Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB(1) receptors

Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481-488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB(1) receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB(1) receptors modulate baroreflex activity. We found that bilateral microinjection of the CB(1) receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB(1) receptors, which modulate local glutamate release.     

Heterogeneity of the digestible insoluble fiber of selected forages in situ

Long-term in situ incubations were performed to verify the likelihood of the heterogeneity concept of the potentially digestible fraction of the insoluble fiber (NDFom) by fitting both heterogeneous and homogeneous potentially digestible NDFom versions of a generalized compartmental model of digestion (GCMD). Corn silage and eleven tropical grasses and alfalfa hay were studied. Data were gathered from a study in which forage samples in nylon bags were incubated in rumen cannulated steers so that three profiles per forage were generated. The incubation endpoint was used to form sets of time profiles. The original set consisted of profiles ending at 1440 h, and the other two were formed by using 96 and 240 h as the incubation endpoints, respectively. The indigestible residue was estimated using nonlinear least squares or by assuming it to be 2.4 times lignin determined by the sulphuric acid method (Lignin (sa)). Therefore, eight different models were evaluated by combining end points of digestion, and the homogeneous and heterogeneous versions of GCMD with the two ways of estimating the indigestible residue. The likelihood of the models was assessed by computing Akaike information criteria. The effects of forage, model, and their interaction were analyzed by taking model as a repeated measurement. Heterogeneity of the potentially degradable fraction for NDFom was detected with long-term incubation trials (up to 1440 h) for some forages, and the introduction of the 2.4×Lignin (sa) as a direct measure of the indigestible residue improved the likelihood of the heterogeneous version of GCMD. The forage by model interaction was significant for many comparable parameter estimates, which means that specific and inconsistent results for models within forages were produced depending on the definition of the incubation end-point. The indigestible residue was overestimated with short-term incubation profiles, but the overestimation was lower for the profiles ending at 240 h whether compared to profiles ending at 96 h. Given the likelihood of the heterogeneous version of GCMD fitted to profiles ending at 1440 h and at 240 h for some forages, the heterogeneity concept should be investigated whenever the research interest relies on estimating the kinetic attributes of the degradation profiles of the NDFom in situ.     

POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria

Mutations in POLG account for one of the most frequent nuclear encoded causes of mitochondrial disorders to date. Individuals harboring POLG mutations exhibit fairly heterogeneous clinical presentations leading to increasing difficulties in classifying these patients into defined clinical phenotypes. This study aims to investigate the molecular basis of a mitochondrial cytopathy in a patient with 3-methylglutaconic aciduria and to expand the clinical phenotype associated with POLG mutations. Clinical, molecular and genetic analyses as well as neurophysiological examinations were carried out for a 23-year-old woman of mixed Caucasian and Latin American ancestry with a history of cataracts diagnosed at age 1 year, she had onset of distal muscle weakness at age 2 years progressing to atrophy and ovarian dysgenesis at puberty. The patient was found to have 3-methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A (p.Y951N) was found which is predicted to be deleterious. There are limited reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This case report of a young woman with a heterozygous mutation in POLG, presenting with muscle weakness and atrophy at a young age aims to aid clinicians in similar challenging diagnostic situations as well as enhances our understanding of POLG-related disease phenotypes.     

Different mutation profiles associated to P53 accumulation in colorectal cancer

This paper analyzes the DNA code of several species in the perspective of information content. For that purpose several concepts and mathematical tools are selected towards establishing a quantitative method without a priori distorting the alphabet represented by the sequence of DNA bases. The synergies of associating Gray code, histogram characterization and multidimensional scaling visualization lead to a collection of plots with a categorical representation of species and chromosomes.     

Influence of stent configuration on cerebral aneurysm fluid dynamics

Embolic coiling is the most popular endovascular treatment available for cerebral aneurysms. Nevertheless, the embolic coiling of wide-neck aneurysms is challenging and, in many cases, ineffective. Use of highly porous stents to support coiling of wide-neck aneurysms has become a common procedure in recent years. Several studies have also demonstrated that high porosity stents alone can significantly alter aneurysmal hemodynamics, but differences among different stent configurations have not been fully characterized. As a result, it is usually unclear which stent configuration is optimal for treatment. In this paper, we present a flow study that elucidates the influence of stent configuration on cerebral aneurysm fluid dynamics in an idealized wide-neck basilar tip aneurysm model. Aneurysmal fluid dynamics for three different stent configurations (half-Y, Y and, cross-bar) were first quantified using particle image velocimetry and then compared. Computational fluid dynamics (CFD) simulations were also conducted for selected stent configurations to facilitate validation and provide more detailed characterizations of the fluid dynamics promoted by different stent configurations. In vitro results showed that the Y stent configuration reduced cross-neck flow most significantly, while the cross-bar configuration reduced velocity magnitudes within the aneurysmal sac most significantly. The half-Y configuration led to increased velocity magnitudes within the aneurysmal sac at high parent-vessel flow rates. Experimental results were in strong agreement with CFD simulations. Simulated results indicated that differences in fluid dynamic performance among the different stent configurations can be attributed primarily to protruding struts within the bifurcation region.     

Translesion Synthesis across 1,N6-(2-Hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA) Adducts by Human and Archebacterial DNA Polymerases

The 1,N⁶-(2-Hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N⁶-γ-HMHP-dA) adducts are formed upon bifunctional alkylation of adenine nucleobases in DNA by 1,2,3,4-diepoxybutane, the putative ultimate carcinogenic metabolite of 1,3-butadiene. The presence of a substituted 1,N⁶-propano group on 1,N⁶-γ-HMHP-dA is expected to block the Watson-Crick base pairing of the adducted adenine with thymine, potentially contributing to mutagenesis. In this study, the enzymology of replication past site-specific 1,N⁶-γ-HMHP-dA lesions in the presence of human DNA polymerases (hpols) β, η, κ, and ι and archebacterial polymerase Dpo4 was investigated. Run-on gel analysis with all four dNTPs revealed that hpol η, κ, and Dpo4 were able to copy the modified template. In contrast, hpol ι inserted a single base opposite 1,N⁶-γ-HMHP-dA but was unable to extend beyond the damaged site, and a complete replication block was observed with hpol β. Single nucleotide incorporation experiments indicated that although hpol η, κ, and Dpo4 incorporated the correct nucleotide (dTMP) opposite the lesion, dGMP and dAMP were inserted with a comparable frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed the ability of bypass polymerases to insert dTMP, dAMP, or dGMP opposite 1,N⁶-γ-HMHP-dA and detected large amounts of −1 and −2 deletion products. Taken together, these results indicate that hpol η and κ enzymes bypass 1,N⁶-γ-HMHP-dA lesions in an error-prone fashion, potentially contributing to A→T and A→C transversions and frameshift mutations observed in cells following treatment with 1,2,3,4-diepoxybutane.     

Sorafenib sensitizes hepatocellular carcinoma cells to physiological apoptotic stimuli

Sorafenib increases survival rate of patients with advanced hepatocellular carcinoma (HCC). The mechanism underlying this effect is not completely understood. In this work we have analyzed the effects of sorafenib on autocrine proliferation and survival of different human HCC cell lines. Our results indicate that sorafenib in vitro counteracts autocrine growth of different tumor cells (Hep3B, HepG2, PLC-PRF-5, SK-Hep1). Arrest in S/G2/M cell cycle phases were observed coincident with cyclin D1 down-regulation. However, sorafenib's main anti-tumor activity seems to occur through cell death induction which correlated with caspase activation, increase in the percentage of hypodiploid cells, activation of BAX and BAK and cytochrome c release from mitochondria to cytosol. In addition, we observed a rise in mRNA and protein levels of the pro-apoptotic "BH3-domain only" PUMA and BIM, as well as decreased protein levels of the anti-apoptotic MCL1 and survivin. PUMA targeting knock-down, by using specific siRNAs, inhibited sorafenib-induced apoptotic features. Moreover, we obtained evidence suggesting that sorafenib also sensitizes HCC cells to the apoptotic activity of transforming growth factor-β (TGF-β) through the intrinsic pathway and to tumor necrosis factor-α (TNF) through the extrinsic pathway. Interestingly, sensitization to sorafenib-induced apoptosis is characteristic of liver tumor cells, since untransformed hepatocytes did not respond to sorafenib inducing apoptosis, either alone or in combination with TGF-β or TNF. Indeed, sorafenib effectiveness in delaying HCC late progression might be partly related to a selectively sensitization of HCC cells to apoptosis by disrupting autocrine signals that protect them from adverse conditions and pro-apoptotic physiological cytokines.     

Early carbon mobilization and radicle protrusion in maize germination

Considerable amounts of information is available on the complex carbohydrates that are mobilized and utilized by the seed to support early seedling development. These events occur after radicle has protruded from the seed. However, scarce information is available on the role of the endogenous soluble carbohydrates from the embryo in the first hours of germination. The present work analysed how the soluble carbohydrate reserves in isolated maize embryos are mobilized during 6-24 h of water imbibition, an interval that exclusively embraces the first two phases of the germination process. It was found that sucrose constitutes a very significant reserve in the scutellum and that it is efficiently consumed during the time in which the adjacent embryo axis is engaged in an active metabolism. Sucrose transporter was immunolocalized in the scutellum and in vascular elements. In parallel, a cell-wall invertase activity, which hydrolyses sucrose, developed in the embryo axis, which favoured higher glucose uptake. Sucrose and hexose transporters were active in the embryo tissues, together with the plasma membrane H(+)-ATPase, which was localized in all embryo regions involved in both nutrient transport and active cell elongation to support radicle extension. It is proposed that, during the initial maize germination phases, a net flow of sucrose takes place from the scutellum towards the embryo axis and regions that undergo elongation. During radicle extension, sucrose and hexose transporters, as well as H(+)-ATPase, become the fundamental proteins that orchestrate the transport of nutrients required for successful germination.