Sequence Stratigraphy and Evolution of a Basin-Slope Succession: The Late Proterozoic Wonoka Formation, Flinders Ranges, South Australia

A shelf to basin‐slope transition is vertically and laterally exposed within the Late Proterozoic Wonoka Formation in the northern Flinders Ranges of South Australia. The shelf to basin‐slope transition can be divided into four units (C to F) which are defined on the basis of facies, sedimentary structures, contacts, stratal geometry, and the type and abundance of down‐slope mass movement. The lowest unit (C) is mudstone dominated and parallel laminated with rare synsedimentary slides. Unit D, a thin, resedimented siliciclastic‐carbonate unit deposited on a sequence boundary at the end of unit C progradation, displays a lateral facies change from well bedded ‘outer shelf deposits in the east to basin‐slope debris flows in the west. Unit E forms a shallowing and coarsening upward succession from ‘outer shelf siltstone to ‘inner shelf storm wave influenced sandstone deposits. The unit thickens westwards, in the interpreted down‐slope direction, where it becomes finer grained and thinner bedded and displays an increasing abundance of synsedimentary slides. Unit F, deposited on an inferred shelf to basin‐slope transition, coarsens and shallows upward, thickens to the west and contains the highest percentage of sandstone and synsedimentary slides. Unit G, deposited at shelf depths, also shallows and coarsens upward from a thin, basal carbonate‐siliciclastic member, with sandstone increasing upsection to a gradational contact with the Pound Subgroup. Three sequences can be defined within this transition on the basis of facies, stratal terminations, and facies discontinuities at inferred sequence boundaries. Each sequence is marked by a transgressive base, overlain by a shallowing‐upward succession. On the inferred shelf and near the shelfbreak, toward the top of the succession, facies discontinuities at sequence boundaries are more obvious, with distinct contrasts in lithology and inferred palaeoenvironments; farther down‐slope and stratigraphically lower in the succession, the boundaries are cryptic, and only lateral tracing of the contacts from the shelf to the slope or the observation of stratal terminations permits them to be recognized

Working Hypotheses for the Origin of the Wonoka Canyons (Neoproterozoic), South Australia

Recent attempts to apply concepts of sequence stratigraphy to the Neoproterozoic Wilpena Group of the Adelaide "geosyncline" in South Australia have provided an important new method for improving the resolution of intrabasinal correlation in sparsely fossiliferous and unfossiliferous strata. Eight regional unconformities are now recognized within or bounding the Wilpena Group. The most prominent of these, at or near the base of the Wonoka Formation, is expressed by a series of spectacular incised valleys or canyons, some more than 1 km deep and dated as approx 630 to 580 Ma. The canyons developed following an interval of continental rifting that took place between about 800 and 700 Ma and prior to a second phase of accelerated subsidence of uncertain origin in Early Cambrian time (after about 560 Ma). Subsidence during the intervening span of more than 140 my was in part of thermal origin and in part due to the withdrawal of buried salt at depth, but it may also have involved additional extension for which little direct structural evidence is preserved. The canyons are incised into a succession of shallow marine mainly terrigenous strata that accumulated in a broad north- and east-facing ramp. They are exposed in two distinct belts within and east of the Flinders Ranges, in an area that is about 275 km in a north-south direction and about 175 km east-west. The canyons are inferred to have been filled by shallow marine sediments primarily on the basis of sedimentary structures interpreted as combined flow and oscillation ripples and hummocky cross-stratification. If this is correct, development of the canyons was related to regional lowering of depositional base level by more than 1 km. Recent work also indicates a second phase of valley incision at an unconformity immediately above the main canyons and involving a relative sealevel fall of at least 200 m. Two working hypotheses are advanced to account for the origin of the Wonoka canyons: regional uplift and an evaporitic lowering of sealevel in an isolated basin, analogous to the Messinian event in the Mediterranean. Any regional uplift would likely have been of tectonic origin. Diapirism associated with buried salt cannot account for the wide distribution of erosion or for pronounced uplift in an extensional setting lacking evidence for basin inversion or compressional deformation coeval with sedimentation. One possible mechanism for tectonic uplift involves inhomogeneous extension of the lithosphere, with the amount of extension balanced at all levels on a regional scale possibly by means of detachment faults. Possible difficulties with this hypothesis are the requirement of relatively uniform uplift over distances of hundreds of kilometers and the fact that repeated large-scale lowering of base level implies oscillatory vertical motions that are not readily explained. An evaporitic drawdown accounts for the wide distribution and scale of the canyons and for repeated lowering of base level. Possible difficulties in this case are the presence within the canyon fill of facies that have been interpreted to be of tidal origin; the fact that unlike the Messinian crisis in the Mediterranean, the Wonoka canyons do not appear to have been drowned rapidly; and the lack of direct evidence for evaporities of appropriate age. Neither hypothesis accounts for the apparent absence of appreciable meteoric diagenesis in areas far removea from sites of canyon incision. Two additional conclusions are as follows. First, neither of the hypotheses precludes eustasy as an important control on sedimentation. Sequence stratigraphic comparisons with other basins of the same general age should focus primarily on the time of formation of sequence boundaries not on the geometry of the boundaries or the facies involved. Second, a drawdown in excess of 1 km implies that the adjacent basin was originally at least this deep and hence likely underlain at least locally by highly attenuated continental crust or oceanic crust. Either hypothesis therefore has important implications for the tectonic development of the Adelaide geosyncline

Sympatho-renal axis in chronic disease

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney’s somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics—insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Microscopical methods for the localization of Na + , K + -ATPase

Na + , K + -ATPase plays a central role in the ionic and osmotic homeostasis of cells and in the movements of electrolytes and water across epithelial boundaries. Microscopic localization of the enzyme is, therefore, of crucial importance in establishing the subcellular routes of electrolyte flow across structurally complex and functionally polarized epithelia. Recently developed approaches to the localization of Na + , K + -ATPase are reviewed. These methods rely on different properties of the enzyme and encompass cytochemical localization of the K + -dependent nitrophenylphosphatase component of the enzyme, autoradiographic localization of tritiated ouabain binding sites, and immunocytochemical localization of the holoenzyme and of its catalytic subunit. The rationales for each of these techniques are outlined as are the critieria that have been established to validate each method. The observed localization of Na + , K + -ATPase in various tissues is discussed, particularly as it relates to putative and hypothetical mechanisms that are currently thought to mediate reabsorptive and secretory electrolyte transport.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42850/1/10735_2005_Article_BF01005056.pd

Metabolic phenotyping for discovery of urinary biomarkers of diet, xenobiotics and blood pressure in the INTERMAP Study: an overview

The etiopathogenesis of cardiovascular diseases (CVDs) is multifactorial. Adverse blood pressure (BP) is a major independent risk factor for epidemic CVD affecting ~40% of the adult population worldwide and resulting in significant morbidity and mortality. Metabolic phenotyping of biological fluids has proven its application in characterizing low-molecular-weight metabolites providing novel insights into gene-environmental-gut microbiome interaction in relation to a disease state. In this review, we synthesize key results from the INTERnational study of MAcro/micronutrients and blood Pressure (INTERMAP) Study, a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from Japan, the People's Republic of China, the United Kingdom and the United States. We describe the advancements we have made regarding the following: (1) analytical techniques for high-throughput metabolic phenotyping; (2) statistical analyses for biomarker identification; (3) discovery of unique food-specific biomarkers; and (4) application of metabolome-wide association studies to gain a better understanding into the molecular mechanisms of cross-cultural and regional BP differences