Jesse James: Last Rebel of the Civil War

Review of: Jesse James: Last Rebel of the Civil War. Stiles, T. J

Jesse James: Last Rebel of the Civil War

Review of: Jesse James: Last Rebel of the Civil War. Stiles, T. J

Activation of the Unfolded Protein Response (UPR) Is Associated with Cholangiocellular Injury, Fibrosis and Carcinogenesis in an Experimental Model of Fibropolycystic Liver Disease

Fibropolycystic liver disease is characterized by hyperproliferation of the biliary epithelium and the formation of multiple dilated cysts, a process associated with unfolded protein response (UPR). In the present study, we aimed to understand the mechanisms of cyst formation and UPR activation in hepatocytic c-Jun N-terminal kinase 1/2 (Jnk1/2) knockout mice. Floxed JNK1/2 (Jnkf/f) and Jnk∆hepa animals were sacrificed at different time points during progression of liver disease. Histological examination of specimens evidenced the presence of collagen fiber deposition, increased α-smooth muscle actin (αSMA), infiltration of CD45, CD11b and F4/80 cells and proinflammatory cytokines (Tnf, Tgfβ1) and liver injury (e.g., ALT, apoptosis and Ki67-positive cells) in Jnk∆hepa compared with Jnkf/f livers from 32 weeks of age. This was associated with activation of effectors of the UPR, including BiP/GRP78, CHOP and spliced XBP1. Tunicamycin (TM) challenge strongly induced ER stress and fibrosis in Jnk∆hepa animals compared with Jnkf/f littermates. Finally, thioacetamide (TAA) administration to Jnk∆hepa mice induced UPR activation, peribiliary fibrosis, liver injury and markers of biliary proliferation and cholangiocarcinoma (CCA). Orthoallografts of DEN/CCl4-treated Jnk∆hepa liver tissue triggered malignant CCA. Altogether, these results suggest that activation of the UPR in conjunction with fibrogenesis might trigger hepatic cystogenesis and early stages of CCA

The number and profile of reactive NADH-d and NADPH-d neurons of myenteric plexus of six-month-old rats are different in the cecum portions

Whole-mount preparations were prepared and submitted to NADH-diaphorase and NADPH-diaphorase histochemistry techniques. The myenteric plexus arrangement and the number of neurons were comparatively evaluated among the different portions of the cecum. The neurons from the apical and basal regions were distributed in classes at intervals of 100µm², the means of the corresponding intervals being compared. The ganglia, in both techniques, were often connected by fine bundles, which became thicker in the mesenteric region and in the region next to the cecal ampulla. The number of positive NADH-d neurons was higher than that of NADPH-d neurons in all portions, from both regions. The numbers of reactive NADH-d e NADPH-d neurons were significantly different among the different portions of the cecum, except for the antimesenteric basal and intermediate basal regions, considering the NADH-d neurons. The profile area for the reactive NADH-d e NADPH-d neurons was higher in the apical region than in the basal area. Differences in arrangement, distribution and size of positive NADH-d e NADPH-d neurons in the different cecum portions evidenced the importance of the subdivision of the analyzed organ.Estudaram-se o arranjo do plexo mioentérico, o número de neurônios e a área do perfil do corpo celular (µm²) dos neurônios mioentéricos, nas regiões apical e basal do ceco de ratos Wistar com 6 meses de idade. Estas regiões foram subdivididas nas seguintes porções: apical mesentérica (AM); apical intermediária (AI); apical antimesentérica (AA); próximo à ampola cecal (PA); basal intermediária (BI), e basal antimesentérica (BA). Foram montados preparados de membrana que receberam as técnicas histoquímica de NADH-diaforase (NADH-d) e NADPH-diaforase (NADPH-d). O arranjo do plexo mioentérico e o número de neurônios foram avaliados comparativamente entre as diferentes porções das regiões do ceco. Os neurônios das regiões apical e basal foram distribuídos em classes com intervalos de 100µm², sendo comparadas às médias da mensuração dos pares. Os gânglios, em ambas as técnicas, apresentavam-se, em geral, conectados por feixes delicados, tornando-se mais espessos na porção mesentérica e naquela próxima à ampola cecal. O número de neurônios NADH-d positivos foi maior do que o de NADPH-d em todas as porções, de ambas as regiões. O número de neurônios reativos a NADH-d e NADPH-d foi significativamente diferente entre as diferentes porções do ceco, com exceção das comparações entre as porções basal antimesentérica e basal intermediária, para os primeiros; e entre a basal intermediária e porção próxima à ampola cecal, e comparando-se a apical mesentérica e porção próxima à ampola cecal, para os neurônios NADPH-d positivos. A área do perfil dos neurônios NADH-d e NADPH-d reativos foi maior na região apical do que na basal. Pela primeira vez, o número de neurônios do plexo mioentérico é reportado em porções pré-estabelecidas do ceco de ratos. Nossos resultados reiteram a importância da indicação precisa da porção estudada em pesquisas envolvendo este segmento intestinal

A population genomics approach shows widespread geographical distribution of cryptic genomic forms of the symbiotic fungus Rhizophagus irregularis.

Arbuscular mycorrhizal fungi (AMF; phylum Gomeromycota) associate with plants forming one of the most successful microbe-plant associations. The fungi promote plant diversity and have a potentially important role in global agriculture. Plant growth depends on both inter- and intra-specific variation in AMF. It was recently reported that an unusually large number of AMF taxa have an intercontinental distribution, suggesting long-distance gene flow for many AMF species, facilitated by either long-distance natural dispersal mechanisms or human-assisted dispersal. However, the intercontinental distribution of AMF species has been questioned because the use of very low-resolution markers may be unsuitable to detect genetic differences among geographically separated AMF, as seen with some other fungi. This has been untestable because of the lack of population genomic data, with high resolution, for any AMF taxa. Here we use phylogenetics and population genomics to test for intra-specific variation in Rhizophagus irregularis, an AMF species for which genome sequence information already exists. We used ddRAD sequencing to obtain thousands of markers distributed across the genomes of 81 R. irregularis isolates and related species. Based on 6 888 variable positions, we observed significant genetic divergence into four main genetic groups within R. irregularis, highlighting that previous studies have not captured underlying genetic variation. Despite considerable genetic divergence, surprisingly, the variation could not be explained by geographical origin, thus also supporting the hypothesis for at least one AMF species of widely dispersed AMF genotypes at an intercontinental scale. Such information is crucial for understanding AMF ecology, and how these fungi can be used in an environmentally safe way in distant locations

Dispersion and energy compensation in high-gradient linacs for lepton colliders

The shape of an rf pulse is distorted due to dispersion encountered in acceleration through traveling-wave linear accelerator structures. Simulations are made to ascertain the severity of this distortion in cavities designed to operate at various group velocities. The pulse suffers maximum degradation when propagated through accelerating cavities with a phase advance per cell in the vicinity of π, where the group velocity reaches its minimum value. Several cavities are simulated to study the pulse distortion and compared with experiments performed on a high phase advance structure H60VG3, which has a phase advance of 5π/6 per cell. A circuit model and a mode matching code are used to perform these simulations on accelerating structures consisting of multiple cells. Beam loading is taken into account and the implications on energy dispersion are also analyzed. Means of mitigating for this energy deviation are discussed