De novo erythroleukemia chromosome features include multiple rearrangements, with special involvement of chromosomes 11 and 19

Erythroid leukemia (ERL or AML-M6) is an uncommon subtype of acute myeloid leukemia, the clinical, morphological, and genetic behavior of which needs further characterization. We analyzed a homogeneous group of 23 de novo AML-M6 patients whose bone marrow cells showed complex karyotypes. We also analyzed eight leukemia cell lines with erythroid phenotype, performing detailed molecular cytogenetic analyses, including spectral karyotyping (SKY) in all samples. The main features are: (1) A majority of patients (56%) had hypodiploidy. Loss of genetic material was the most common genetic change, especially monosomies of chromosome 7 or 18, and deletions of chromosome arm 5q. Taken together, 87% of the cases displayed aberrations involving chromosome 5 or 8. (2) We describe a novel, cryptic, and recurrent translocation, t(11;19)(p11.2;q13.1). Another translocation, t(12;21)(p11.2;q11.2), was found to be recurrent in a patient with ERL and in the K562 cell line. (3) MLL gene rearrangements were detected in 20% of cases (three translocations and three amplifications) and, overall, we defined 52 rearrangements (excluding deletions) with a mean of 2.3 translocations per patient. (4) Of the structural aberrations, 21% involved chromosomes 11 and 19. Most of the rearrangements were unbalanced; only 13 reciprocal translocations were observed. The general picture of chromosomal aberrations in cell lines did not reflect what occurred in patient samples. However, both primary samples and cell lines shared three common breakpoints at 19q13.1, 20q11.2, and 21q11.2. This is the first molecular cytogenetic description of the karyotype abnormalities present in patients with ERL. It should assist in the identification of genes involved in erythroleukemogenesis

Proceso agrario en Bolivia y América Latina

El material esta distribuido en cinco partes. La primera está referida a los resultados y perspectivas de la Reforma Agraria en Bolivia. Está dividida en tres temáticas: la Reforma Agraria en las Tierras Altas, la Reforma Agraria en las Tierras Bajas y la Reforma Agraria en el Chaco. La segunda parte contiene las intervenciones realizadas por los invitados extranjeros sobre los resultados y perspectivas de la Reforma Agraria en América Latina y en México, Perú y Ecuador. La tercera parte corresponde a las intervenciones de los representantes de las organizaciones indígenas y campesinas bolivianas, que fueron invitados para debatir el tema Tierra, Democracia y Poder. Esta parte esta precedida por un recuento general de la situación de los Movimientos Indígenas-Campesinos en América Latina y sus perspectivas. La cuarta da cuenta de las intervenciones hechas por los representantes de las organizaciones de productores agrarios, campesinos y empresarios, quienes fueron invitados para debatir el tema Tierra, Economía e Integración. La última parte es una síntesis de las ideas y aspectos relevantes producto de las exposiciones y de las preguntas de los asistentes al seminario, que dejaron una estela de inquietudes e iniciativas que son el eslabón para futuros debates en otros espacios de reflexión en diferentes lugares del país, con la participación de actores y pensadores, operadores y promotores del desarrollo rural.Presentación 7; Introducción 8; La Reforma Agraria abandonada: valles y altiplano, Miguel Urioste F. de C. 19; Medio siglo de Reforma Agraria boliviana, Danilo Paz Ballivián 53; La tierra es de quien la trabaja, René Salomón Vargas 65; La Reforma Agraria en las tierras bajas de Bolivia, Carlos Romero Bonifaz 83; Lógicas de ocupación territorial en la agricultura y la forestería empresarial en las tierras bajas, Alan Bojanic 127; Antecedentes, situación actual y recomendaciones en la tenencia de la tierra en el oriente boliviano, Cámara Agropecuaria del Oriente 137; 50 años de la Reforma Agraria en el Chaco boliviano, Oscar Bazoberry Chali 145; Resultados de los cambios introducidos por la Reforma Agraria, Erwin Galoppo von Borries 177; La Reforma Agraria en Bolivia y el MST, Ermelinda Fernández Bamba 191; La Reforma Agraria en América Latina, Jacques Chonchol 205; De rústicas revueltas: Añoranza y utopía en el México rural, Armando Bartra 223; Reforma y contrarreforma agraria en el Perú, Laureano del Castillo Pinto 255; Reforma Agraria en el Ecuador, Fausto Jordán B. 285; 50 años después, emergencia étnica, Xavier Albó 321; Tierra, mujer y desarrollo, María Machaca 329; Tierra y territorio comunitario, Bienvenido Zacu 333; Tierra, migración y colonización, José Luis Méndez Chaurara 341; Tierra, coca y desarrollo, Dionisio Núñez 355; Tierra para todos, Ángel Durán 359; Tierra y producción orgánica, Mario R. Cordero Camacho 367; Tierra y producción campesina, María Julia Jiménez 377; Tierra y Territorio y Políticas para la Tierra, Elizabeth Jiménez Zamora 385; Ideas y aspectos relevantes del Seminario, John D.Vargas Vega 429

The Black River: a comprehensive study of physical and chemical characteristics and their potential management implications.

An analysis of the Black River's biological and physicochemical characteristics was conducted for comparison to the model proposed by the river continuum theory. The theory specifies that the biological fauna, physical characteristics and chemical composition observed, are reflected in river order changes in terms of the presence, absence, or density of producer and consumer communities. The study reflected consistencies between the model and observed physical parameters and chemical attributes, but biological indicators were less corroborating. Physical characteristics such as temperature, depth, width, velocity, discharge, and suspended sediments increased with river mile and trends in the data became apparent. Chemical factors such as nitrates, dissolved oxygen, pH, alkalinity, and hardness, though not as clearly conclusive, show a gradient associated with river order transition. Biological indicators were not as conclusive in supporting the river continuum theory since there was no representation of shredders in the headwaters and predatory species were found at most sites. Management issues of the Black River address the control of soil erosion, species composition, and sedimentation as well as maintaining water temperature.http://deepblue.lib.umich.edu/bitstream/2027.42/54342/1/2778.pd

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas

Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non- BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitorsThis study was funded by the Fondo de Investigacio´n Sanitaria (FIS), Instituto de Salud Carlos III (grants CP07/00113 and PS09/01094

Prevalence of sarcopenic obesity according to different diagnostic methods and cut-off points in candidates for bariatric surgery

[EN] Background and aims: Sarcopenic obesity (SO) is defined as a combination of low strength and muscle mass along with excess adiposity. Our study aimed to determine the prevalence of sarcopenic obesity in candidates for bariatric surgery, according to ESPEN/EASO criteria using bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Methods: Retrospective study of adult patients (18-60 years) candidates for bariatric surgery (BMI ≥40 kg/m2 or ≥35 kg/m2 with associated complications). Adiposity was assessed by the percentage of fat mass by DXA, according to Gallagher's cut-off points. Muscle strength was measured by hand grip according to Sánchez-Torralvo, Dodds, and <-2SD cut-off points of healthy reference population. Muscle mass was determined by DXA (ALM/weight according to Batsis) and by BIA (SMM/weight according to Janssen and according to reference population). In addition, the agreement of the different diagnostic methods of sarcopenic obesity was analyzed. Results: A total of 124 subjects were included in the study, with 71.8 % being women. The overall mean age was 42.6 (SD 8.9) years. SO prevalence was found to be 13 %-22 % applying BIA with the SMM/weight equation according to Janssen, 14 %-23 % utilizing BIA with the SMM/weight equation according to the reference population, and 13 %-23 % employing DXA with the ALM/weight equation following Batsis criteria, depending on the specific hand grip strength cut-off points used. In general, we found good or very good concordances with the different diagnostic methods (with kappa values between 0.6 and 0.97). Conclusions: The prevalence of SO according to ESPEN/EASO criteria in candidates for bariatric surgery was 13 %-23 % based on the diagnostic method and cut-off points used.SIThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Insights gained from the reverse engineering of gene networks in keloid fibroblasts

<p>Abstract</p> <p>Background</p> <p>Keloids are protrusive claw-like scars that have a propensity to recur even after surgery, and its molecular etiology remains elusive. The goal of reverse engineering is to infer gene networks from observational data, thus providing insight into the inner workings of a cell. However, most attempts at modeling biological networks have been done using simulated data. This study aims to highlight some of the issues involved in working with experimental data, and at the same time gain some insights into the transcriptional regulatory mechanism present in keloid fibroblasts.</p> <p>Methods</p> <p>Microarray data from our previous study was combined with microarray data obtained from the literature as well as new microarray data generated by our group. For the physical approach, we used the fREDUCE algorithm for correlating expression values to binding motifs. For the influence approach, we compared the Bayesian algorithm BANJO with the information theoretic method ARACNE in terms of performance in recovering known influence networks obtained from the KEGG database. In addition, we also compared the performance of different normalization methods as well as different types of gene networks.</p> <p>Results</p> <p>Using the physical approach, we found consensus sequences that were active in the keloid condition, as well as some sequences that were responsive to steroids, a commonly used treatment for keloids. From the influence approach, we found that BANJO was better at recovering the gene networks compared to ARACNE and that transcriptional networks were better suited for network recovery compared to cytokine-receptor interaction networks and intracellular signaling networks. We also found that the NFKB transcriptional network that was inferred from normal fibroblast data was more accurate compared to that inferred from keloid data, suggesting a more robust network in the keloid condition.</p> <p>Conclusions</p> <p>Consensus sequences that were found from this study are possible transcription factor binding sites and could be explored for developing future keloid treatments or for improving the efficacy of current steroid treatments. We also found that the combination of the Bayesian algorithm, RMA normalization and transcriptional networks gave the best reconstruction results and this could serve as a guide for future influence approaches dealing with experimental data.</p

A homologous production system for Trichoderma reesei secreted proteins in a cellulase-free background

Recent demands for the production of biofuels from lignocellulose led to an increased interest in engineered cellulases from Trichoderma reesei or other fungal sources. While the methods to generate such mutant cellulases on DNA level are straightforward, there is often a bottleneck in their production since a correct posttranslational processing of these enzymes is needed to obtain highly active enzymes. Their production and subsequent enzymatic analysis in the homologous host T. reesei is, however, often disturbed by the concomitant production of other endogenous cellulases. As a useful alternative, we tested the production of cellulases in T. reesei in a genetic background where cellulase formation has been impaired by deletion of the major cellulase transcriptional activator gene xyr1. Three cellulase genes (cel7a, cel7b, and cel12a) were expressed under the promoter regions of the two highly expressed genes tef1 (encoding translation elongation factor 1-alpha) or cdna1 (encoding the hypothetical protein Trire2:110879). When cultivated on d-glucose as carbon source, the Δxyr1 strain secreted all three cellulases into the medium. Related to the introduced gene copy number, the cdna1 promoter appeared to be superior to the tef1 promoter. No signs of proteolysis were detected, and the individual cellulases could be assayed over a background essentially free of other cellulases. Hence this system can be used as a vehicle for rapid and high-throughput testing of cellulase muteins in a homologous background

Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and TGFβ1

BACKGROUND: Wounds in the nonglabrous skin of keloid-prone individuals tend to cause large disordered accumulations of collagen which extend beyond the original margins of the wound. In addition to abnormalities in keloid fibroblasts, comparison of dermal fibroblasts derived from nonwounded glabrous or nonglabrous skin revealed differences that may account for the observed location of keloids. METHODS: Fibroblast apoptosis and the cellular content of α-smooth-muscle actin, TGFβ1 receptorII and ED-A fibronectin were estimated by FACS analysis. The effects of TGFβ1 and serum were examined. RESULTS: In monolayer cultures non-glabrous fibroblasts were slower growing, had higher granularity and accumulated more α-smooth-muscle actin than fibroblasts from glabrous tissues. Keloid fibroblasts had the highest level of α-smooth-muscle actin in parallel with their expression level of ED-A fibronectin. TGFβ1 positively regulated α-smooth-muscle actin expression in all fibroblast cultures, although its effects on apoptosis in fibroblasts from glabrous and non-glabrous tissues were found to differ. The presence of collagen I in the ECM resulted in reduction of α-smooth-muscle actin. A considerable percentage of the apoptotic fibroblasts in attached gels were α-smooth-muscle actin positive. The extent of apoptosis correlated positively with increased cell and matrix relaxation. TGFβ1 was unable to overcome this apoptotic effect of matrix relaxation. CONCLUSION: The presence of myofibroblasts and the apoptosis level can be regulated by both TGFβ1 and by the extracellular matrix. However, reduction of tension in the matrix is the critical determinant. This predicts that the tension in the wound bed determines the type of scar at different body sites