The Caenorhabditis elegans vulva: A post-embryonic gene regulatory network controlling organogenesis

The Caenorhabditis elegans vulva is an elegant model for dissecting a gene regulatory network (GRN) that directs postembryonic organogenesis. The mature vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique pattern of spatial and temporal gene expression. The mechanisms that specify these cell types in a precise spatial pattern are not well understood. Using reverse genetic screens, we identified novel components of the vulval GRN, including nhr-113 in vulA. Several transcription factors (lin-11, lin-29, cog-1, egl-38, and nhr-67) interact with each other and act in concert to regulate target gene expression in the diverse vulval cell types. For example, egl-38 (Pax2/5/8) stabilizes the vulF fate by positively regulating vulF characteristics and by inhibiting characteristics associated with the neighboring vulE cells. nhr-67 and egl-38 regulate cog-1, helping restrict its expression to vulE. Computational approaches have been successfully used to identify functional cis-regulatory motifs in the zmp-1 (zinc metalloproteinase) promoter. These results provide an overview of the regulatory network architecture for each vulval cell type

Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes

Sincronización de los ritmos circadianos en el movimiento de las hojas de Solanum tuberosum mediada por el phy A

Los ritmos circadianos son oscilaciones generadas por un reloj endógeno que normalmente es sicronizado por los ciclos naturales de luz-oscuridad. Los fotorreceptores involucrados en la sincronización de los ritmos no fueron aún identificados en plantas, animales o microorganismos. Plantas de papa transgenicas con niveles de fitocromo A (phy A) inferiores al normal (plantas subexpresantes) y con niveles superiores al normal (plantas sobreexpresantes) fueron utilizadas para analizar la participación del phy A en la percepción de las señales lumínicas que ponen en fase los ritmos circadianos en el movimiento de las hojas. Plantas subexpresantes cultivadas bajo un fotoperíodo natural tratadas durante la segunda mitad de la noche con una mezcla de rojo (R) y rojo lejano (RL) similar ala del sol no son capaces de desfasar el ritmo del movimiento de las hojas. Plantas con niveles de phy A normales (WT) y sobreexpresantes bajo el mismo tratamiento, modifican la fase del ritmo en aproximadamente 6 horas. De la misma manera, las plantas WT y sobreexpresantes responden a tratamientos con RL, R+RL, R+RL+ azul desfasando el ritmo circadiano del movimiento de las hojas bajo condiciones de libre curso con luz continua. Solo el tratamiento con R+RL+azul modifica la fase del ritmo circadiano, bajo condiciones de libre curso, en plantas subexpresantes. Por ultimo, tratamientos con pulsos de RL cambian la fase de los ritmos en la misma magnitud que el RL continuo, mostrando la participación de respuestas muy sensibles del phy A como las respuesta de muy bajo flujo. Se puede concluir entonces que el phy A y un fotorreceptor específico de luz azul participan en la sincronización y el desfasaje del reloj circadiano que controla los ritmosFil: Wagmaister, Javier Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Multiculturalidad : desafíos de las empresas argentinas en un proceso de internacionalización

Fil: Wagmaister, Martín. Universidad de San Andrés. Escuela de Administración y Negocios; Argentina.Dvoskin, Robert

Prophylactic Effect of Ethyl Pyruvate on Renal Ischemia/Reperfusion Injury Mediated Through Oxidative Stress

PURPOSE: As oxidative stress (OXS) has been shown to play a primary role in renal ischemia/reperfusion injury (RIRI), we investigated whether antioxidant such as ethyl pyruvate (EPy) might effectively prevent RIRI. Possible prophylactic effects of EPy and mannitol (Mann), one of perioperative agents often used, were tested against harmful OXS in vitro. METHODS: Hydrogen peroxide (H2O2) was used to exert OXS on the renal proximal tubular MDCK cells. Severity of OXS and protective effects of EPy and Mann were assessed by lipid peroxidation assay and cell viability test, respectively. The cytotoxic mechanism of H2O2 was explored by examining the status of glycolysis, metabolic signaling pathways, cell cycle, and induction of apoptosis. RESULTS: Although H2O2 (500 microM) increased OXS by ~ 3.5 times of controls, EPy (1 mM) fully reduced it to the basal level. Cell viability declined to merely 10% by H2O2 was regained to \u3e 90% with EPy. Hexokinase activity and ATP level also declined significantly by H2O2, but they sustained 80-90% with EPy. Additionally, H2O2 led to the modulations of metabolic signaling regulators, a G1 cell cycle arrest, and induction of apoptosis, which were yet prevented with EPy. Unlike EPy, Mann had virtually little effects. CONCLUSIONS: OXS can indeed lead to the significant cell viability reduction through its adverse cellular effects, ultimately resulting in RIRI. However, EPy appears to prevent these effects and protect MDCK cells, while Mann does not. Thus, EPy could be a more effective prophylactic renoprotective agent (than Mann) against oxidative renal cell injury including RIRI

Phytochrome A resets the circadian clock and delays tuber formation under long days in potato

Transgenic potatoes (Solanum tuberosum) with either increased (sense transformants) or reduced (antisense transformants) phytochrome A (phyA) levels were used, in combination with specific light treatments, to investigate the involvement of phyA in the perception of signals that entrain the circadian clock. Far-red or far-red plus red light treatments given during the night reset the circadian rhythm of leaf movements in wild-type plants and phyA over-expressors, but had little effect in phyA under-expressors. Far-red light was also able to reset the rhythm of leaf movement in wild-type Arabidopsis thaliana but was not effective in mutants without phyA. Blue light was necessary to reset the rhythm in phyA-deficient potato plants. Resetting of the rhythm by far-red plus red light was only slightly affected in transgenic plants with reduced levels of phytochrome B. The production of tubers was delayed by day extensions with far-red plus red light, but this effect was reduced in transgenic lines deficient in phyA. We conclude that phyA is involved in resetting the circadian clock controlling leaf movements and in photoperiod sensing in light-grown potato plants

Contemporary Trends in Percutaneous Nephrolithomy Across New York State: A Review of the Statewide Planning and Research Cooperative System

Introduction and Objectives: Percutaneous nephrolithotomy (PCNL) is a complex multistep surgery that has shown a steady increase in use for the past decade in the United States. We sought to evaluate the trends and factors associated with PCNL usage across New York State (NYS). Our goal was to characterize patient demographics and socioeconomic factors across high-, medium-, and low-volume institutions. Materials and Methods: We searched the NYS, Statewide Planning and Research Cooperative System (SPARCS) database from 2006 to 2014 using ICD-9 Procedure Codes 55.04 (percutaneous nephrostomy with fragmentation) for all hospital discharges. Patient demographics including age, gender, race, insurance status, and length of hospital stay were obtained. We characterized each hospital as a low-, medium-, or high-volume center by year. Patient and hospital demographics were compared and reported using chi-square analysis and Student\u27s t-test for categorical and continuous variables, respectively, with statistical significance as a p-value of \u3c0.05. Results: We identified a total of 4576 procedures performed from 2006 to 2014 at a total of 77 hospitals in NYS (Table 1). Total PCNL volume performed across all NYS hospitals increased in the past decade, with the greatest number of procedures performed in 2012 to 2013. Low-volume institutions were more likely to provide care to minority populations (21.4% vs 17.3%, p \u3c 0.001) and those with Medicaid (25.5% vs 21.5%, p \u3c 0.001). High-volume institutions provided care to patients with private insurance (42.1% vs 34.0%, p \u3c 0.001) and had a shorter length of stay (3.3 days vs 4.1 days, p \u3c 0.001). Conclusion: Our data provide insight into the patient demographics of those treated at high-, medium-, and low-volume hospitals for PCNL across NYS. Significant differences in race, insurance status, and length of stay were noted between low- and high-volume institutions, indicating that racial and socioeconomic factors play a role in access to care at high-volume centers