Regulation of sodium and body fluid homeostasis during development: Implications for the pathogenesis of hypertension

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Regulation of sodium and body fluid homeostasis during development: implications for the pathogenesis of hypertension.

The spontaneously hypertensive rat (SHR) is an important animal model of human essential hypertension. During the first month of life, increased retention of sodium is present in the SHR which appears to be mediated by the renin-angiotensin system. The present review will discuss the role that increased activity of the renin-angiotensin system plays in sodium/body fluid regulation during early development. It is hypothesized that disordered regulation of sodium/body fluid homeostasis during this stage leads to pathological cardiovascular regulation in adulthood. Through an understanding of the relationship between sodium/body fluid balance in the young and cardiovascular function in the adult insights may be gained into both the pathological state of hypertension and the critical role played by early development in shaping homeostatic mechanisms in adulthood.     

Spatial differences in rock uplift rates inferred from channel steepness indices along the northern flank of the Qilian Mountain, northeast Tibetan Plateau

The rate and distribution of deformation along the Qilian Mountain, on the northeastern Tibetan Plateau, is needed to understand the evolution of high topography associated with the plateau. Recently, a number of empirical studies have provided support for the contention, common to most models of fluvial incision, that rock uplift rate exerts a first-order control on the gradient of longitudinal river profiles. Along the northern Qilian Mountain, this method is used to extract information about the spatial patterns of differential rock uplift. Analysis of the longitudinal profiles of bedrock channels reveals systematic differences in the channel steepness index along the trend of the frontal ranges. Local comparisons of channel steepness reveal that lithology and precipitation have limited influence on channel steepness. Similarly, there is little evidence suggesting that channel steepness is influenced by differences in the sediment loads. We argue that the distribution of channel steepness in the Qilian Mountain is mostly the result of differential rates of rock uplift. Thus, channel steepness indices reveal a lower rock uplift rate in the eastern portion of the Qilian Mountain and a higher rate in the middle and west. The highest rates appear to occur in the middle-west portions of the range, just to the west of the Yumu Shan.     

Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations.     

Stress changes from the 2008 Wenchuan earthquake and increased hazard in the Sichuan basin

On 12 May 2008, the devastating magnitude 7.9 (Wenchuan) earthquake struck the eastern edge of the Tibetan plateau, collapsing buildings and killing thousands in major cities aligned along the western Sichuan basin in China. After such a large-magnitude earthquake, rearrangement of stresses in the crust commonly leads to subsequent damaging earthquakes. The mainshock of the 12 May earthquake ruptured with as much as 9 m of slip along the boundary between the Longmen Shan and Sichuan basin, and demonstrated the complex strike-slip and thrust motion that characterizes the region. The Sichuan basin and surroundings are also crossed by other active strike-slip and thrust faults. Here we present calculations of the coseismic stress changes that resulted from the 12 May event using models of those faults, and show that many indicate significant stress increases. Rapid mapping of such stress changes can help to locate fault sections with relatively higher odds of producing large aftershocks.