Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño.

BackgroundGene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions.MethodsAllele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments.ResultsA total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates.DiscussionPrior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement.

BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty

Estrategias para ajustar el marco regulatorio de la nomenclatura del sistema vial en el corregimiento Barrio Colón (Distrito de La Chorrera, provincia de Panamá Oeste)

La investigación presentada es concerniente a la nomenclatura del sistema vial en el corregimiento Barrio Colón, distrito de La Chorrera, provincia de Panamá Oeste, cuyo fin es precisar estrategias como ajuste a su marco normativo. Su contribución responde a una necesidad urgente para una parte del sistema urbano, a pesar de la muy escaza literatura, motiva a ofrecer un aporte referente a la configuración del espacio geográfico en mención. En el campo de la geografía este tema se relaciona con el transporte. Su representatividad va de acuerdo a la jerarquía que asume, ya sea, por la representatividad local, regional o nacional permiten una comunicación gracias a la accesibilidad y conectividad que disponen. Si bien es cierto, al observar el plano callejero de este corregimiento que corresponde al eje urbano del distrito en mención, la nomenclatura está rotulada con su nombre respectivo. Sin embargo, al ir al terreno para su verificación, no existe, es decir, es nula la nomenclatura. Esto afecta la comunicación e identificación de la red vial, pues a través de ellas, la generación de productos y servicios que ofrecen a los múltiples usuarios, no permite observar su identificación, reduciendo así otras acciones como la conectividad y accesibilidad que hace una movilidad en beneficio a todos los actores pertenecientes al lugar como también, al resto de la sociedad. Esto ayudará a reducir los conflictos que confronta el ejido urbano a causa del ausentismo en la señalización de la nomenclatura del área seleccionada denominada, Barrio Coló

Estrategias para ajustar el marco regulatorio de la nomenclatura del sistema vial en el corregimiento Barrio Colón (Distrito de La Chorrera, provincia de Panamá Oeste)

La investigación presentada es concerniente a la nomenclatura del sistema vial en el corregimiento Barrio Colón, distrito de La Chorrera, provincia de Panamá Oeste, cuyo fin es precisar estrategias como ajuste a su marco normativo. Su contribución responde a una necesidad urgente para una parte del sistema urbano, a pesar de la muy escaza literatura, motiva a ofrecer un aporte referente a la configuración del espacio geográfico en mención. En el campo de la geografía este tema se relaciona con el transporte. Su representatividad va de acuerdo a la jerarquía que asume, ya sea, por la representatividad local, regional o nacional permiten una comunicación gracias a la accesibilidad y conectividad que disponen. Si bien es cierto, al observar el plano callejero de este corregimiento que corresponde al eje urbano del distrito en mención, la nomenclatura está rotulada con su nombre respectivo. Sin embargo, al ir al terreno para su verificación, no existe, es decir, es nula la nomenclatura. Esto afecta la comunicación e identificación de la red vial, pues a través de ellas, la generación de productos y servicios que ofrecen a los múltiples usuarios, no permite observar su identificación, reduciendo así otras acciones como la conectividad y accesibilidad que hace una movilidad en beneficio a todos los actores pertenecientes al lugar como también, al resto de la sociedad. Esto ayudará a reducir los conflictos que confronta el ejido urbano a causa del ausentismo en la señalización de la nomenclatura del área seleccionada denominada, Barrio Coló

Hydrography of the Pontevedra Ria: Intra-annual spatial and temporal variability in a Galician coastal system (NW Spain)

In order to ameliorate the dearth of existing scientific knowledge concerning the hydrography of the Pontevedra Ria, a systematic investigation was carried out between October 1997-98. Salinity variations were closely related to river discharge whereas bottom waters presented oceanic characteristics over the whole year. Current was controlled by tide, river discharge, and wind in the internal ria where the highest velocities were directed along the ria channel with a low transverse component. Favorable atmospheric conditions in spring induced coastal upwelling up the continental shelf. In May the upwelling was sufficiently strong to be detected in the inner ria and intensified in July and August, cooling the ria water to 12 degrees -14 degreesC. Upwelling ceased in September, and from November to March seawater transported by the poleward current (35.9; 15 degreesC) was detected on the shelf. From January until March, unanticipated favorable upwelling conditions provoked an influx of poleward inside the ria. Ria intrusion of poleward water and association with occasional winter upwelling conditions has not been observed previously. Isopycnic three-dimensional (3-D) surface and 2-D isopycnal maps show that with high river runoff or intense upwelling, lower-salinity water leaves the ria near the northern margin in the surface layer. Under negative upwelling conditions, the water is partially dammed inside the ria and exits the ria when the wind speed falls. During upwelling events, ENACW penetrated the ria, especially near the southern shore. Arrival of ENACW at the northern entrance impedes the outward water flow through this mouth

Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods: An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results: The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP) induces both NKx-2.5 and NF-kappaB translocations. Conclusion: This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders

Nuclear DNA Replication in Trypanosomatids:There Are No Easy Methods for Solving Difficult Problems

In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review focuses on the advances made in recent years regarding the differences and peculiarities of the replication machinery in trypanosomatids, including how such divergence might affect DNA replication dynamics and the replication stress response. Comparing the DNA replication machinery and processes of parasites and their hosts may provide a foundation for the identification of targets that can be used in the development of chemotherapies to assist in the eradication of diseases caused by these pathogens