Effects of Southern Hemisphere Wind Changes on the Meridional Overturning Circulation in Ocean Models.

Observations show that the Southern Hemisphere zonal wind stress maximum has increased significantly over the past 30 years. Eddy-resolving ocean models show that the resulting increase in the Southern Ocean mean flow meridional overturning circulation (MOC) is partially compensated by an increase in the eddy MOC. This effect can be reproduced in the non-eddy-resolving ocean component of a climate model, providing the eddy parameterization coefficient is variable and not a constant. If the coefficient is a constant, then the Southern Ocean mean MOC change is balanced by an unrealistically large change in the Atlantic Ocean MOC. Southern Ocean eddy compensation means that Southern Hemisphere winds cannot be the dominant mechanism driving midlatitude North Atlantic MOC variability.

Zfp423 binds autoregulatory sites in p19 cell culture model.

Zfp423 is a 30 zinc finger transcription factor that forms regulatory complexes with EBF family members and factors targeted by canonical signaling pathways. Zfp423 mutations produce a range of developmental abnormalities in mice and humans related to the ciliopathies. Surprisingly, computational analysis of clustered Zfp423 and partner motifs in conserved genomic sequences predicts enrichment in Zfp423 and Ebf genes. In cell culture models selected for Zfp423 and EBF expression, we identify strong and reproducible occupancy of two Zfp423 intronic sites using chromatin immunoprecipitation with multiple independent antibodies. Both sites are significantly enriched in either quantitative PCR or massively parallel sequencing assays. A site in intron 5 acts as a classical enhancer in transient assays, but does not require the consensus motif for activity, suggesting a redundant or modulatory role for Zfp423 binding in this context. We speculate that Zfp423 may repress this enhancer as part of a developmental ratchet.

The use of troponin in general practice.

BACKGROUND: General practitioners are able to measure cardiac troponin in order to help triage patients with symptoms suspicious of acute coronary syndrome. The aim of this study was to assess the utilisation of cardiac troponin testing in the community. METHODS: An audit of all cardiac troponin testing in an urban community from a single laboratory in 2010 was performed. Data regarding admissions and adverse events over a 6-month period was carried out in all patients. RESULTS: Cardiac troponin was measured during 2662 patient events during 2010. There were 223 patients episodes (8.4%) in which greater than and equal to 1 troponin result was elevated, 184 (82.5%) were admitted to hospital, 101 (54.9%) were diagnosed as acute coronary syndrome. Of the 2439 with normal troponin results, 344 (14.1%) were admitted, 42 (12.2%) were diagnosed as acute coronary syndrome. Only 12.1% had serial troponin measurements. The 6-month rates of death were 8.5% versus 1.1%, myocardial infarction were 2.2% versus 1.2%, revascularisation were 1.8% versus 0.7%, heart failure were 3.1% versus 1.0% in those with elevated versus normal troponin respectively. CONCLUSION: The use of troponin in the community appropriately triages patients regarding the need for admission. However, many patients had elevated troponin due to non-coronary causes. The indication for testing only in cases of suspected ACS and the use of serial cTn measurement in early presenters should be emphasised.

An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.

Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.

ROR alpha in genetic control of cerebellum development: 50 staggering years.

The staggerer mutation was first identified at the Jackson Laboratory in 1955. In the ensuing half-century, studies of staggerer mice have provided new insights into developmental neurobiology, gene regulatory networks, and circadian behavior. Recent work has expanded the role of RORalpha, the transcription factor mutated in staggerer, to peripheral tissues, including cholesterol and lipid metabolism, immune function, and bone development. This review focuses on the role of RORalpha in neural development and behavior revealed by the staggerer mutation and subsequent molecular studies.

Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation.

Neural stem cells and progenitors in the developing brain must choose between proliferation with renewal and differentiation. Defects in navigating this choice can result in malformations or cancers, but the genetic mechanisms that shape this choice are not fully understood. We show by positional cloning that the 30-zinc finger transcription factor Zfp423 (OAZ) is required for patterning the development of neuronal and glial precursors in the developing brain, particularly in midline structures. Mutation of Zfp423 results in loss of the corpus callosum, reduction of hippocampus, and a malformation of the cerebellum reminiscent of human Dandy-Walker patients. Within the cerebellum, Zfp423 is expressed in both ventricular and external germinal zones. Loss of Zfp423 results in diminished proliferation by granule cell precursors in the external germinal layer, especially near the midline, and abnormal differentiation and migration of ventricular zone-derived neurons and Bergmann glia.

An overview of chemotherapy-induced emesis highlighting the role of lorazepam as adjuvant therapy.

By preventing and optimizing emesis control in patients receiving chemotherapy, clinicians may significantly improve patients' functional status and quality of life. Improved tolerability may lead to greater patient acceptance of chemotherapy and prevent premature withdrawal or cessation of treatment. Controlling chemotherapy-induced emesis also helps to decrease the direct and indirect costs of managing cancer. This article reviews improvements made in antiemetic therapy and considers how the addition of lorazepam may further optimize the prevention and management of emesis at various stages of manifestation.