HIF-2α downregulation in the absence of functional VHL is not sufficient for renal cell differentiation

<p>Abstract</p> <p>Background</p> <p>Mutational inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene has been linked to hereditary as well as sporadic clear cell renal carcinomas. The product of the VHL gene, pVHL, acts to target hypoxia-inducible factor alpha (HIF-α) subunits for ubiquitination and subsequent degradation. Using an RNA interference approach to lower levels of HIF-2α in two different renal cell lines that lack functional pVHL, we have tested the contribution of HIF-2α toward cellular pVHL activities.</p> <p>Results</p> <p>Knockdown of HIF-2α resulted in cell cycle arrest of renal cells that were grown on collagen I, indicating that this pVHL function is dependent on HIF-2α regulation. However, cellular morphological changes and downregulation of integrins α5 and β1, which were seen upon pVHL replacement, were not faithfully phenocopied by HIF-2α reduction. Moreover, fibronectin deposition and expression of renal cell differentiation markers were observed in cells containing replaced pVHL, but not in HIF-2α knockdown cells, indicating that these pVHL functions may occur independently of HIF-2α downregulation.</p> <p>Conclusion</p> <p>These results indicate that HIF-2α regulation is not sufficient for pVHL-induced renal cell differentiation. We hypothesize that in addition to HIF-2α dysregulation, abrogation of additional pVHL functions is required for the initiation of renal carcinogenesis.</p

Loop Order Analysis of Weft-Knitted Textiles

In this paper, we describe algorithms that perform loop order analysis of weft-knitted textiles, which build upon the foundational TopoKnit topological data structure and associated query functions. During knitting, loops of yarn may be overlayed on top of each other and then stitched together with another piece of yarn. Loop order analysis aims to determine the front-to-back ordering of these overlapping loops, given a stitch pattern that defines the knitted fabric. Loop order information is crucial for the simulation of electrical current, water, force, and heat flow within functional fabrics. The new algorithms are based on the assumption that stitch instructions are executed row-by-row and for each row the instructions can be executed in any temporal order. To make our algorithms knitting-machine-independent, loop order analysis utilizes precedence rules that capture the order that stitch commands are executed when a row of yarn loops are being knitted by a two-bed flat weft knitting machine. Basing the algorithms on precedence rules allows them to be modified to adapt to the analysis of fabrics manufactured on a variety of knitting machines that may execute stitch commands in different temporal orders. Additionally, we have developed visualization methods for displaying the loop order information within the context of a TopoKnit yarn topology graph

Loop Order Analysis of Weft-Knitted Textiles

In this paper, we describe algorithms that perform loop order analysis of weft-knitted textiles, which build upon the foundational TopoKnit topological data structure and associated query functions. During knitting, loops of yarn may be overlayed on top of each other and then stitched together with another piece of yarn. Loop order analysis aims to determine the front-to-back ordering of these overlapping loops, given a stitch pattern that defines the knitted fabric. Loop order information is crucial for the simulation of electrical current, water, force, and heat flow within functional fabrics. The new algorithms are based on the assumption that stitch instructions are executed row-by-row and for each row the instructions can be executed in any temporal order. To make our algorithms knitting-machine-independent, loop order analysis utilizes precedence rules that capture the order that stitch commands are executed when a row of yarn loops are being knitted by a two-bed flat weft knitting machine. Basing the algorithms on precedence rules allows them to be modified to adapt to the analysis of fabrics manufactured on a variety of knitting machines that may execute stitch commands in different temporal orders. Additionally, we have developed visualization methods for displaying the loop order information within the context of a TopoKnit yarn topology graph