Impact of common risk factors of fibrosis progression in chronic hepatitis C.

OBJECTIVE The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.

The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine

Nuclear factor-kappaB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-kappaB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and combined, on different stages of the NF-kappaB activation pathway, in primary and in transformed T cells. We show that NAC, contrary to its reported role as an NF-kappaB inhibitor, can actually enhance rather than inhibit IkappaB degradation and, most importantly, show that in all cases NAC exerts a dominant antagonistic effect on PDTC-mediated NF-kappaB inhibition. This was observed at the level of IkappaB degradation, NF-kappaB DNA binding, and HIV-LTR-driven reporter gene expression. NAC also counteracted growth arrest and apoptosis induced by dithiocarbamates. Antagonistic effects were further observed at the level of jun-NH2-terminal kinase, p38 and ATF-2 activation. Our findings argue against the widely accepted assumption that NAC inhibits all NF-kappaB activation pathways and shows that two compounds, previously thought to function through a common inhibitory mechanism, can also have antagonistic effects.

Tratamiento con ácido sulfúrico de semillas de la acacia blanca (Robinia pseudo acacia L.) cosechadas en Mendoza

The results obtained in germination test with seeds of "black locust" (Robinia Pseudo Acacia L) previously treated with sulphuric acid concentrated (d. 1.84) are given. Those test were made in order to get a good germination considering the water tight seed coat that those seeds have in a great percentage. The seeds were soaked in the solution for some minutes; the 180 and 210 minutes soaking (90 and 86.5 % respectively) gave the highest percentage and the fasted process of germination, which were higher than those obtained as efective by other researches. The test made would constitute another evidence of the effect of the locality of production upon the degree of water tightness of the Black locust seeds. The author suggests that the previous treatments of the seeds, the rusticity and quick growing of this species and the furrow system of irrigation so common in the zone will enable, perhaps with success the stablishment of woods of this valuable forestal species, by direct seeding.

Las fabulaciones de nuestra realidad. Apuntes para una poética del grupo leonés de J. P. Aparicio, L. M. Diez y J. M. Merino

Dentro de la llamada "generación del 68" en la narrativa española contemporánea, se ubica el "grupo leonés" de Juan Pedro Aparicio (1941), Luis Mateo Diez (1942) y José María Merino (1941), surgido en torno al filandón con una fuerte fascinación por los relatos de tradición oral y el compromiso con la reivindicación de la narratividad. Aunque han explorado mundos literarios muy distintos, su punto de conexión es un espacio que pertenece a la memoria de todos, y un personaje apócrifo común: Sabino Ordás, "patriarca de las letras leonesas". Estos escritores han producido, aparte del apócrifo, y paralelamente a su obra de ficción, un profuso material de reflexión crítica. Entre el discurso metatextual y el discurso narrativo se manifiesta una fuerte articulación cuyos mecanismos y estrategias nos permiten plantear una poética de la narrativa leonesa.

Las fabulaciones de nuestra realidad. Apuntes para una poética del grupo leonés de J. P. Aparicio, L. M. Diez y J. M. Merino

Dentro de la llamada "generación del 68" en la narrativa española contemporánea, se ubica el "grupo leonés" de Juan Pedro Aparicio (1941), Luis Mateo Diez (1942) y José María Merino (1941), surgido en torno al filandón con una fuerte fascinación por los relatos de tradición oral y el compromiso con la reivindicación de la narratividad. Aunque han explorado mundos literarios muy distintos, su punto de conexión es un espacio que pertenece a la memoria de todos, y un personaje apócrifo común: Sabino Ordás, "patriarca de las letras leonesas". Estos escritores han producido, aparte del apócrifo, y paralelamente a su obra de ficción, un profuso material de reflexión crítica. Entre el discurso metatextual y el discurso narrativo se manifiesta una fuerte articulación cuyos mecanismos y estrategias nos permiten plantear una poética de la narrativa leonesa.

Las fabulaciones de nuestra realidad. Apuntes para una poética del grupo leonés de J. P. Aparicio, L. M. Diez y J. M. Merino

Dentro de la llamada "generación del 68" en la narrativa española contemporánea, se ubica el "grupo leonés" de Juan Pedro Aparicio (1941), Luis Mateo Diez (1942) y José María Merino (1941), surgido en torno al filandón con una fuerte fascinación por los relatos de tradición oral y el compromiso con la reivindicación de la narratividad. Aunque han explorado mundos literarios muy distintos, su punto de conexión es un espacio que pertenece a la memoria de todos, y un personaje apócrifo común: Sabino Ordás, "patriarca de las letras leonesas". Estos escritores han producido, aparte del apócrifo, y paralelamente a su obra de ficción, un profuso material de reflexión crítica. Entre el discurso metatextual y el discurso narrativo se manifiesta una fuerte articulación cuyos mecanismos y estrategias nos permiten plantear una poética de la narrativa leonesa.

The California current predator diet database: synthesis of common forage species

Characterization of the diets of upper-trophic predators is a key ingredient in management including the development of ecosystem-based fishery management plans, conservation efforts for top predators, and ecological and economic modeling of predator prey interactions. The California Current Predator Diet Database (CCPDD) synthesizes data from published records of predator food habits over the past century. The database includes diet information for 100+ upper-trophic level predator species, based on over 200 published citations from the California Current region of the Pacific Ocean, ranging from Baja, Mexico to Vancouver Island, Canada. We include diet data for all predators that consume forage species: seabirds, cetaceans, pinnipeds, bony and cartilaginous fishes, and a predatory invertebrate; data represent seven discrete geographic regions within the CCS (Canada, WA, OR, CA-n, CA-c, CA-s, Mexico). The database is organized around predator-prey links that represent an occurrence of a predator eating a prey or group of prey items. Here we present synthesized data for the occurrence of 32 forage species (see Table 2 in the affiliated paper) in the diet of pelagic predators (currently submitted to Ecological Informatics). Future versions of the shared-data will include diet information for all prey items consumed, not just the forage species of interest.

Molecular and biochemical analyses of wounding in mesocarp of peach (Prunus persica L. Batsch) ripe fruits

The physiological and molecular responses of ripe fruit to wounding were evaluated in two peach (Prunus persica) varieties ('Glohaven', GH, melting and 'BigTop', BT, slow melting nectarine) by comparing mesocarp samples from wedges (as in minimal processing) and whole fruit as the control. Slight differences between the two varieties were detected in terms of ethylene production, whereas total phenol and flavonoid concentrations, and PPO and POD enzyme activities showed a general increase in wounded GH but not in BT. This was associated with the better appearance of the BT wedges at the end of the experimental period (72 h). Microarray (genome-wide ?PEACH3.0) analysis revealed that a total number of 2218 genes were differentially expressed (p < 0.01, log2 fold change expression ratio >1 or <-1) in GH 24 h after wounding compared to the control. This number was much lower (1208) in BT. According to the enrichment analysis, cell wall, plasma membrane, response to stress, secondary metabolic processes, oxygen binding were the GO categories over-represented among the GH up-regulated genes, whereas plasma membrane and response to endogenous stimulus were the categories over-represented among the down-regulated genes. Only 32 genes showed a common expression trend in the two varieties 24 h after wounding, whereas a total of 512 genes (with highly represented transcription factors), displayed opposite behavior. Quantitative RT-PCR analysis confirmed the microarray data for 18 out of a total of 20 genes selected. Specific WRKY, AP2/ERF and HSP20 genes were markedly up-regulated in wounded GH, indicating the activation of regulatory and signaling mechanisms probably related to different hormone categories. Compared to BT, the expression of specific genes involved in phenylpropanoid and triterpenoid biosynthetic pathways showed a more pronounced induction in GH, highlighting the difference between the two peach varieties in terms of molecular responses to wounding in the mesocarp tissue.

Abundance and sizes of European oak species (Quercus petraea (Matt.) Liebl., Quercus robur L.) in dependence of neighborhood and environmental factors

Quercus robur L. (pedunculate oak) and Quercus petraea (Matt.) Liebl. (sessile oak) are two European oak species of great economic and ecological importance. Even though both oaks have wide ecological amplitudes of suitable growing conditions, forests dominated by oaks often fail to regenerate naturally. The regeneration performance of both oak species is assumed to be subject to a variety of variables that interact with one another in complex ways. The novel approach of this research was to study the effect of many ecological variables on the regeneration performance of both oak species together and identify key variables and interactions for different development stages of the oak regeneration on a large scale in the field. For this purpose, overstory and regeneration inventories were conducted in oak dominated forests throughout southern Germany and paired with data on browsing, soil, and light availability. The study was able to verify the assumption that the occurrence of oak regeneration depends on a set of variables and their interactions. Specifically, combinations of site and stand specific variables such as light availability, soil pH and iron content on the one hand, and basal area and species composition of the overstory on the other hand. Also browsing pressure was related to oak abundance. The results also show that the importance of variables and their combinations differs among the development stages of the regeneration. Light availability becomes more important during later development stages, whereas the number of oaks in the overstory is important during early development stages. We conclude that successful natural oak regeneration is more likely to be achieved on sites with lower fertility and requires constantly controlling overstory density. Initially sufficient mature oaks in the overstory should be ensured. In later stages, overstory density should be reduced continuously to meet the increasing light demand of oak seedlings and saplings.

Increased CO2 modifies the carbon balance and the photosynthetic yield of two common Arctic brown seaweeds: Desmarestia aculeata and Alaria esculenta

Ocean acidification affects with special intensity Arctic ecosystems, being marine photosynthetic organisms a primary target, although the consequences of this process in the carbon fluxes of Arctic algae are still unknown. The alteration of the cellular carbon balance due to physiological acclimation to an increased CO2 concentration (1300 ppm) in the common Arctic brown seaweeds Desmarestia aculeata and Alaria esculenta from Kongsfjorden (Svalbard) was analysed. Growth rate of D. aculeata was negatively affected by CO2 enrichment, while A. esculenta was positively affected, as a result of a different reorganization of the cellular carbon budget in both species. Desmarestia aculeata showed increased respiration, enhanced accumulation of storage biomolecules and elevated release of dissolved organic carbon, whereas A. esculenta showed decreased respiration and lower accumulation of storage biomolecules. Gross photosynthesis (measured both as O2 evolution and 14C fixation) was not affected in any of them, suggesting that photosynthesis was already saturated at normal CO2 conditions and did not participate in the acclimation response. However, electron transport rate changed in both species in opposite directions, indicating different energy requirements between treatments and species specificity. High CO2 levels also affected the N-metabolism, and 13C isotopic discrimination values from algal tissue pointed to a deactivation of carbon concentrating mechanisms. Since increased CO2 has the potential to modify physiological mechanisms in different ways in the species studied, it is expected that this may lead to changes in the Arctic seaweed community, which may propagate to the rest of the food web.

Common depth points and associated geographic coordinates

Fluids in subduction zones can influence seismogenic behaviour and prism morphology. The Eastern Makran subduction zone, offshore Pakistan, has a very thick incoming sediment section of up to 7.5 km, providing a large potential fluid source to the accretionary prism. A hydrate-related bottom simulating reflector (BSR), zones of high amplitude reflectivity, seafloor seep sites and reflective thrust faults are present across the accretionary prism, indicating the presence of fluids and suggesting active fluid migration. High amplitude free gas zones and seep sites are primarily associated with anticlinal hinge traps, and fluids here appear to be sourced from shallow biogenic sources and migrate to the seafloor along minor normal faults. There are no observed seep sites associated with the surface expression of the wedge thrust faults, potentially due to burial of the surface trace by failure of the steep thrust ridge slopes. Thrust fault reflectivity is restricted to the upper 3 km of sediment and the deeper décollement is non-reflective. We interpret that fluids and overpressure are not common in the deeper stratigraphic section. Thermal modelling of sediments at the deformation front suggests that the deeper sediment section is relatively dewatered and not currently contributing to fluid expulsion in the Makran accretionary prism.

A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants

KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong dominant-negative effect on potassium currents by reducing the channel expression at the cell surface representing the first study to identify a trafficking-dependent dominant mechanism for the loss of KCNQ4 channel function in DFNA2. Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4 mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry. Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4 protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality control in the ER but does not reach the cell surface at normal levels. Currently we are investigating the trafficking behaviour and electrophysiological properties of several KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the common mechanism underlying DFNA2