Apoptosis in uterine epithelium and decidua in response to implantation: evidence for two different pathways

During the initial steps of implantation, the mouse uterine epithelium of the implantation chamber undergoes apoptosis in response to the interacting blastocyst. With progressing implantation, regression of the decidual cells allows a restricted and coordinated invasion of trophoblast cells into the maternal compartment. In order to investigate pathways of apoptosis in mouse uterine epithelium and decidua during early pregnancy (day 4.5–7.0 post coitum), we have investigated different proteins such as TNFalpha, TNF receptor1, Fas ligand, Fas receptor1, Bax and Bcl2 as well as caspase-9 and caspase-3 using immunohistochemistry. To detect cells undergoing apoptosis the Tunel assay was performed. Immunoreactivity for TNFalpha as well as for TNF receptor1 was observed exclusively in the epithelium of the implantation chamber and the adjacent luminal epithelium from day 4.5 post coitum onwards. In the developing decidua the Fas ligand, but not the Fas receptor, was expressed. Bax and Bcl2 revealed a complementary expression pattern with Bax in the primary and Bcl2 in the adjacent decidual zone. Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium. Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining. Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis

Efecto del sistema de labranza y la fertilización nitrogenada sobre el rendimiento de maíz (Zea mays l.) en un haplustol éntico de la región semiárida pampeana = Effect of tillage and nitrogen fertilization on corn yield (Zea mays l.) in an entic haplustol of the semiarid pampa

El objetivo de este trabajo fue evaluar el efecto de la fertilización nitrogenada sobre el rendimiento de maíz (Zea mays L.) en siembra directa (SD) y en siembra convencional (SC). Para ello se llevó a cabo un ensayo a campo en parcelas dividas en el cual el factor principal era sistema de labranza (SD, SC) y el factor secundario la dosis de fertilización nitrogenada (0, 60, 120 y 180 kg.ha-1). La determinación de humedad y de los contenidos de nitrógeno de nitratos en el suelo se realizó en intervalos de 20 cm hasta los 60 cm de profundidad. Los momentos de muestreo fueron en V2 (16/12), V6 (15/1), floración (11/2) y madurez fisiológica (28/4). La fertilización no afectó los rendimientos de maíz en SD cuando las dosis fueron bajas, pero a altas dosis los rendimientos fueron significativamente mayores. En SC los rendimientos variaron significativamente ante menores dosis. Los rendimientos fueron mayores en SD que en SC, comparando los mismos tratamientos de fertilización. Esto se pudo explicar ya que en siembra directa habría mayores contenidos hídricos, mayor mineralización del nitrógeno y menores pérdidas de este elemento por lixiviación.The objective of this study was to evaluate the effect of nitrogen (N) fertilization on corn grain yield (Zea mays L.) under zero tillage (SD) and conventional tillage (SC). For this purpose, a field assay using a split-plot experimental design was carried out relying on tillage system (SD, SC) as main factor and N fertilization rate (0, 60, 120, 180 kg N/ha) as secondary factor. Soil moisture and nitrate-N contents were determined at 20 cm intervals to a depth of 60 cm. This followed sampling done at crop phenological stages V2 (16 December), V6 (15 January), flowering (11 February) and physiological maturity (28 April). For SD system, corn yield was not affected by N fertilization at low rates but differed significantly at high rates, while yields for SC were different even at low rates. Considering the same fertilization treatments, yields for SD were always higher than those for SC. These results might be explained by the higher moisture contents and mineralization rates, and lower N lixiviation losses, for soil under SD system.EEA AnguilFil: Civalero, Agustín. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina.Fil: Kolman, Gabriel Yeshu. Universidad Nacional de La Pampa. Facultad de Agronomía; ArgentinaFil: Fernandez, Romina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Anguil; Argentina. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentina.Fil: Noellemeyer, Elke. Universidad Nacional de La Pampa. Facultad de Agronomía; Argentin

Efecto del sistema de labranza y la fertIización nitrogenada sobre el rendimiento de maíz (Zea mays l.) en un haplustol éntIco de la región semIárIda pampeana

El objetivo de este trabajo fue evaluar el efecto de la fertilización nitrogenada sobre el rendimiento de maíz (Zea mays L.) en siembra directa (SD) y en siembra convencional (SC). Para ello se llevó a cabo un ensayo a campo en parcelas dividas en el cual el factor principal era sistema de labranza (SD, SC) y el factor secundario la dosis de fertilización nitrogenada (0, 60, 120 y 180 kg.ha-1 ). La determinación de humedad y de los contenidos de nitrógeno de nitratos en el suelo se realizó en intervalos de 20 cm hasta los 60 cm de profundidad. Los momentos de muestreo fueron en V2 (16/12), V6 (15/1), floración (11/2) y madurez fisiológica (28/4). La fertilización no afectó los rendimientos de maíz en SD cuando las dosis fueron bajas, pero a altas dosis los rendimientos fueron significativamente mayores. En SC los rendimientos variaron significativamente ante menores dosis. Los rendimientos fueron mayores en SD que en SC, comparando los mismos tratamientos de fertilización. Esto se pudo explicar ya que en siembra directa habría mayores contenidos hídricos, mayor mineralización del nitrógeno y menores pérdidas de este elemento por lixiviación

Rapid and Efficient Invasion Assay of Glioblastoma in Human Brain Organoids

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Subfield profitability analysis reveals an economic case for cropland diversification

Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ∼3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010–2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US$ 250 ha−1 or more was negligible between 2010 and 2013 at 18 000–190 000 ha (\u3c2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services

Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma

Galectin-1 (Gal1) is a member of a highly conserved family of carbohydrate-binding proteins that modulates innate and adaptive immune responses and fosters tumor-immune escape. Hodgkin lymphoma (HL) Reed-Sternberg (RS) cells overexpress and secrete Gal1, which selectively kills Th1,Th17 and cytotoxic T cells and promotes the immunosuppressive Th2/Treg-predominant HL microenvironment. We developed a sandwich ELISA and assessed serum Gal1 levels in 315 newly diagnosed, previously untreated HL patients enrolled on 3 risk-adapted clinical trials. Serum Gal1 levels were significantly higher in HL patients than in normal controls (p < .0001). Gal1 serum levels also increased with Ann Arbor stage (p < .0001), areas of nodal involvement (p = .0001) and the International Prognostic Score (IPS) (2-7, p = .006). We conclude that Gal1 serum levels are significantly associated with tumor burden and additional adverse clinical characteristics in newly diagnosed HL Patients.Fil: Ouyang, Jing. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América;Fil: Plütschow, Annette. German Hodgkin Study Group; Alemania;Fil: Von Strandmann, Elke Pogge. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Reiners, Katrin S.. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Ponader, Sabine. German Hodgkin Study Group; Alemania;Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina;Fil: Neuberg, Donna. Dana-Farber Cancer Institute. Department of Biostatistics; Estados Unidos de América;Fil: Engert, Andreas. German Hodgkin Study Group; Alemania;Fil: Shipp, Margaret A.. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América

Protein Microarray-Guided Development of a Highly Sensitive and Specific Dipstick Assay for Glanders Serodiagnostics

Burkholderia mallei, the causative agent of glanders, is a clonal descendant of Burkholderia pseudomallei, the causative agent of melioidosis, which has lost its environmental reservoir and has a restricted host range. Despite limitations in terms of sensitivity and specificity, complement fixation is still the official diagnostic test for glanders. Therefore, new tools are needed for diagnostics and to study the B. mallei epidemiology. We recently developed a highly sensitive serodiagnostic microarray test for human melioidosis based on the multiplex detection of B. pseudomallei proteins. In this study, we modified our array tests by using anti-horse IgG conjugate and tested sera from B. mallei-infected horses (n = 30), negative controls (n = 39), and horses infected with other pathogens (n = 14). Our array results show a sensitivity of 96.7% (confidence interval [CI] 85.5 to 99.6%) and a specificity of 100.0% (CI, 95.4 to 100.0%). The reactivity pattern of the positive sera on our array test allowed us to identify a set of 12 highly reactive proteins of interest for glanders diagnosis. The B. mallei variants of the three best protein candidates were selected for the development of a novel dipstick assay. Our point-of-care test detected glanders cases in less than 15 min with a sensitivity of 90.0% (CI, 75.7 to 97.1%) and a specificity of 100.0% (CI, 95.4 to 100.0%). The microarray and dipstick can easily be adopted for the diagnosis of both B. mallei and B. pseudomallei infections in different animals. Future studies will show whether multiplex serological testing has the potential to differentiate between these pathogens

Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing

We have surveyed 191 prospectively sampled familial cancer patients with no previously detected pathogenic variant in the BRCA1/2, PTEN, TP53 or DNA mismatch repair genes. In all, 138 breast cancer (BC) cases, 34 colorectal cancer (CRC) and 19 multiple early-onset cancers were included. A panel of 44 cancer-predisposing genes identified 5% (9/191) pathogenic or likely pathogenic variants and 87 variants of uncertain significance (VUS). Pathogenic or likely pathogenic variants were identified mostly in familial BC individuals (7/9) and were located in 5 genes: ATM (3), BRCA2 (1), CHEK2 (1), MSH6 (1) and MUTYH (1), followed by multiple early-onset (2/9) individuals, affecting the CHEK2 and ATM genes. Eleven of the 87 VUS were tested, and 4/11 were found to have an impact on splicing by using a minigene splicing assay. We here report for the first time the splicing anomalies using this assay for the variants ATM c.3806A > G and BUB1 c.677C >T, whereas CHEK1 c.61G > A did not result in any detectable splicing anomaly. Our study confirms the presence of pathogenic or likely pathogenic variants in genes that are not routinely tested in the context of the above-mentioned clinical phenotypes. Interestingly, more than half of the pathogenic germline variants were found in the moderately penetrant ATM and CHEK2 genes, where only truncating variants from these genes are recommended to be reported in clinical genetic testing practice