Genome-Wide Tissue-Specific Occupancy of the Hox Protein Ultrabithorax and Hox Cofactor Homothorax in Drosophila

The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Hydrothermal alteration and mineralisation at the Mt Carlton high-sulphidation Au- Ag-Cu epithermal deposit (NE Queensland, Australia)

The Mt Carlton high-sulphidation Au-Ag-Cu deposit is located in the northern Bowen Basin, NE Queensland (Australia). High-grade mineralisation is confined to NE-trending, steeply dipping (75-90°) structures, and is hosted in a rhyodacitic unit of the Lizzie Creek Volcanic Group (Early Permian). The core of the hydrothermal system shows silicic alteration, with variable amounts of alunite (disseminated-and vein-type), anhydrite and pyrite. Outwards, the silicic zone progressively grades into an envelope of quartz- alunite-barite-pyrite → quartz-dickite-kaolinite-pyrite → illite-montmorillonite-pyrite alteration. After the alteration, the majority of metals were deposited in an initial stage of high-sulphidation mineralisation, dominated by enargite-luzonite-pyrite. This stage is overprinted by two intermediate-sulphidation stages, one Zn-Pb-Au rich (sphalerite-galena-electrum) and one Cu-(Au) rich (tennantite), respectively. The known mineralisation along ~800m strike length shows a distinct metal zonation from NE to SW of Cu-Au→ Cu+Zn+Pb+Ag →Ag+Pb →Ag. This metal zonation is mainly linked to the mineralogy of the initial high- sulphidation ore stage. Ar-Ar dating of alunite from the Mt Carlton lithocap gives an age of 284.3 ± 2.0 Ma. It is not distinguishable from U-Pb ages of the Lizzie Creek volcanic rocks (283-287 ± 2-4 Ma), indicating that the mineralisation occurred shortly after the formation of the host rocks. Stable isotope analyses (S, O, H) of sulfates (alunite, anhydrite and barite) and coeval pyrite suggest that they formed from a SO42- -dominated fluid with a mixed magmatic-meteoric signature. Thermometric calculations based on S isotope pairs indicate a temperature range of ~220-130 °C for the hydrothermal alteration stage (alunite-pyrite), and ~130-115 °C for late, intermediate-sulphidation ore (sphalerite-galena, sphalerite-pyrite). The combined petrographic and isotopic evidence thus suggest that a cooling fluid that evolved from high - to intermediate-sulphidation states was involved in the genesis of the Mt Carlton deposit

Estudio de las deleciones de los genes GSTM1 y GSTT1 y del polimorfismo Ile105Val del gen GSTP1 en pacientes con enfermedad ósea de Paget

Fundamento: La enfermedad ósea de Paget (EOP) es un trastorno focal del hueso con aumento el número, tamaño y actividad de los osteoclastos. Algunos datos epidemiológicos apoyan la teoría de su relación con agentes ambientales tóxicos o infecciosos. Su interacción con algunas alteraciones genéticas predisponentes conducirían a la EOP. Las glutatión-S-transferasas (GST) intervienen en la metabolización de toxinas, al catalizar el ataque nucleofílico del sustrato fisiológico, glutatión reducido o GSH (g-Glu-Cys-Gly) sobre el centro electrófilo de un gran número de estructuras tóxicas. Estudiamos si la variabilidad de los genes GSTM1, GSTP1 y GSTT1 se relaciona con el riesgo a desarrollar EOP.Pacientes y métodos: Analizamos a 148 pacientes diagnosticados de EOP y a 207 individuos controles pareados en sexo y edad sin antecedentes de alteraciones óseas. Con DNA genómico obtenido de sangre periférica se estudió la presencia-ausencia de deleción en los genes GSTM1 y GSTT1, mediante PCR multiplex. El estudio del polimorfismo Ile105Val del gen GSTP1 se llevó a cabo mediante PCR y posterior digestión con la enzima de restricción BsmaI. Se analizó la distribución de genotipos mediante el test chi-cuadrado de Pearson. Cuando se encontraron diferencias estadísticamente significativas, realizamos una regresión logística multivariante para conocer el riesgo que puede generar la presencia de un determinado genotipo. Utilizamos el programa SPSS 21.0. Se consideraron diferencias estadísticamente significativas aquéllas con valores de p<0,05. Resultados: Encontramos diferencias en la distribución de la presencia-ausencia de deleción en el gen GSTM1; no ser portador de la deleción o serlo en heterocigosis en el gen GSTM1 confiere un menor riesgo a desarrollar EOP (OR=0,56, IC 95%: 0,36-0,87; p=0,011). En el estudio de los genes GSTT1 y GSTP1 no hubo diferencias significativas. Conclusión: La actividad detoxificadora disminuye cuando se heredan las dos copias delecionadas del gen GSTM1 al disminuir la actividad enzimática; se ha asociado con una mayor susceptibilidad para algunos tumores, hepatopatía alcohólica y otros problemas inflamatorios. No conocemos descripción de su asociación con la EOP. En los individuos portadores del gen GSTM1 delecionado en homocigosis se observa con más frecuencia EOP. Este hecho podría explicar los hallazgos epidemiológicos que asocian la EOP a la exposición a determinados agentes ambientales