Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1

Pancreatic ductal adenocarcinoma (PDAC) has a 5 year survival rate post-diagnosis of \u3c 5%. Individuals with chronic pancreatitis (CP) are 20-fold more likely to develop PDAC, making it a significant risk factor for PDAC. While the relationship for the increased susceptibility to PDAC is unknown, loss of the acinar cell phenotype is common to both pathologies. Pancreatic acinar cells can dedifferentiate or trans-differentiate into a number of cell types including duct cells, β cells, hepatocytes and adipocytes. Knowledge of the molecular pathways that regulate this plasticity should provide insight into PDAC and CP. MIST1 (encoded by Bhlha15 in mice) is a transcription factor required for complete acinar cell maturation. The goal of this study was to examine the plasticity of acinar cells that do not express MIST1 (Mist1 -/-). The fate of acinar cells from C57Bl6 or congenic Mist1 -/- mice expressing an acinar specific, tamoxifen-inducible Cre recombinase mated to Rosa26 reporter LacZ mice (Mist1CreERT/- R26r) was determined following culture in a three-dimensional collagen matrix. Mist1CreERT/- R26r acini showed increased acinar dedifferentiation, formation of ductal cysts and transient increases in PDX1 expression compared to wild-type acinar cells. Other progenitor cell markers, including Foxa1, Sox9, Sca1 and Hes1, were elevated only in Mist1-/- cultures. Analysis of protein kinase C (PKC) isoforms by western blot and immunofluorescence identified increased PKCε accumulation and nuclear localization of PKCδ that correlated with increased duct formation. Treatment with rottlerin, a PKCδ-specific inhibitor, but not the PKCε-specific antagonist εV1-2, reduced acinar dedifferentiation, progenitor gene expression and ductal cyst formation. Immunocytochemistry on CP or PDAC tissue samples showed reduced MIST1 expression combined with increased nuclear PKCδ accumulation. These results suggest that the loss of MIST1 is a common event during PDAC and CP and events that affect MIST1 function and expression may increase susceptibility to these pathologies. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Effect of GnRH on scrotal surface temperature, testicular volume and spern parameters of bulls with poor semen quality.

Spermatogenesis is coordinated by the hypothalamic-pituitary-gonadal axis, mainly by GnRH secretion.Edição dos Proceedings of the 32nd Annual Meeting of the Brazilian Embryo Technology Society (SBTE)

Regional characterization of the structure and productivity of the vegetation of the Puna using MODIS images

La Puna es una región semiárida ubicada por encima de los 3300 m.s.n.m. en el noroeste argentino. Si bien existen descripciones florísticas parciales de la vegetación en el área, no existen trabajos que describan su fisonomía y su funcionamiento, aspectos claves para el manejo de la vegetación de la región. El objetivo de este trabajo fue cartografiar los diferentes tipos fisonómicos presentes y caracterizar su funcionamiento a partir de la estimación de la productividad primaria neta aérea (PPNA) en un área de 69210 km2 en las provincias de Salta y Jujuy. La aproximación metodológica combinó la utilización de datos provistos por sensores remotos, modelos biofísicos para estimar la productividad y censos fisonómico-florísticos. De las clases vegetadas, las estepas arbustivas (Estepa arbustiva densa y Estepa arbustiva rala) fueron las que ocuparon mayor proporción del territorio analizado, cubriendo entre ambas el 45% aproximadamente, mientras que las Estepas graminosas densas fueron las menos representadas, cubriendo poco más del 1%. Entre las clases no vegetadas el Suelo desnudo fue la clase más extendida, cubriendo aproximadamente 30% del área, seguida por la clase Salar, que ocupó 8.15%. El tipo fisonómico más productivo fue la Estepa graminosa densa (PPNA = 3900 kg MS.ha-1 .año-1), mientras que la Estepa arbustiva rala presentó la menor productividad (PPNA = 472 kg MS.ha-1.año-1). Los restantes tipos fisonómicos no superaron en promedio los 1000 kg MS.ha-1.año-1.The Puna is a semi-arid region located over 3300 m.a.s.l. in the northwestern portion of Argentina. Previous regional studies in Puna focused on the description of the floristic heterogeneity of relatively small portions of the territory. No integrative descriptions of the phisiognomy and functioning of the Puna ecosystems, two keys aspects for development of management actions, have been produced. In this article we generated a map of physonogmic types and we characterized above-ground net primary production (ANPP) of the different classes defined over an area of 69210 km2. The methodology to characterize vegetation structure (physiognomic units) combines remotely sensed data from MODIS sensor with field observations. Further, we applied biophysical models and satellite information to estimate ANPP. Among the classes with more than 5% of plant cover, shrub steppes (both sparse and dense) occuppied most of the area (45%). Dense grass steppes covered less than 1%. Bare soil covered most that 30% of the area, followed by Salt flats (8.15%). The most productive physiognomic type was the dense grass steppe (ANPP = 3900 kg DM.ha-1.year-1), while the sparse shrub steppe unit presented the lowest values (ANPP = 472 kg DM.ha-1.year-1). The remaining physiogmomic types presented ANPP values lower than 1000 kg DM.ha-1.year-1

Marker-Assisted Pyramiding of Blast-Resistance Genes in a japonica Elite Rice Cultivar through Forward and Background Selection

Rice blast, caused by Pyricularia oryzae, is one of the main rice diseases worldwide. The pyramiding of blast-resistance (Pi) genes, coupled to Marker-Assisted BackCrossing (MABC), provides broad-spectrum and potentially durable resistance while limiting the donor genome in the background of an elite cultivar. In this work, MABC coupled to foreground and background selections based on KASP marker assays has been applied to introgress four Pi genes (Piz, Pib, Pita, and Pik) in a renowned japonica Italian rice variety, highly susceptible to blast. Molecular analyses on the backcross (BC) lines highlighted the presence of an additional blast-resistance gene, the Pita-linked Pita2/Ptr gene, therefore increasing the number of blast-resistance introgressed genes to five. The recurrent genome was recovered up to 95.65%. Several lines carrying four (including Pita2) Pi genes with high recovery percentage levels were also obtained. Phenotypic evaluations confirmed the effectiveness of the pyramided lines against multivirulent strains, which also had broad patterns of resistance in comparison to those expected based on the pyramided Pi genes. The developed blast-resistant japonica lines represent useful donors of multiple blast-resistance genes for future rice-breeding programs related to the japonica group

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid

Impact of the introduction of organised screening for cervical cancer in Turin, Italy: cancer incidence by screening history 1992–98

After an organised cervical screening programme was introduced in Turin in 1992, the age-adjusted cervical cancer incidence ratio in 1992–98 was 0.81 (95% confidence interval (CI) 0.59–1.09) for invited vs not invited women and 0.25 (95% CI 0.13–0.50) for attenders vs non attenders. An organised screening programme can further reduce cervical cancer incidence in an area where substantial spontaneous activity was previously present