The Z-Pattern and the PKD Family
The Z-Pattern is best suited for landing pages that are looking to encourage users to take action. This layout is unique in that it anticipates how users will scan a site, making it more likely they will see your call to action.
See how Studio Z Design Concepts transformed this Bethesda home in the winter issue of Home & Design magazine. Click the link below to read the full article.
PKD1 is a large and complex gene that encodes proteins that function in the formation of renal primary cilia. Mutations in this gene result in autosomal dominant polycystic kidney disease (ADPKD). PKD1 has also been shown to be essential for normal tubular morphogenesis.
Complexity analyses of PKD1 demonstrated that breakpoints in the CC*GG dinucleotide sequence of its poly(R*Y) tract usually occur near homologous nucleotides in the vector and often are followed by short direct repeats. In addition, tri-, tetra-, and penta-nucleotide direct repeats cluster in specific regions of the 2.5-kb PKD1 segment.
Family studies have shown that nontruncating PKD1 pathogenic variants are associated with much less severe disease than truncating variants. Bioinformatic analysis has divided these nontruncating variants into two mutation strength groups based on the extent of substitutions in well-conserved sites in orthologs and domains: those with conservative substitutions (MSG1; NT1) cause more severe disease, while those with more nonconservative substitutions (MSG2; NT2) cause milder disease.
The PKD2 gene encodes polycystin-2, a non-selective calcium-permeable cation channel. The channel has six transmembrane domains and is a member of the TRP family of channels that are activated by extracellular Ca2+. Polycystin-2 has a large extracellular loop and an inactivating domain that are distinct from the voltage-sensing domain found in other TRP family members. Polycystin-2 is also different from other ion channels, as it does not display spontaneous ion channel opening or closing in isolated membranes.
The protein is expressed in the epithelial cells that form primary cilia. Together with PKD1, it forms a complex that senses fluid shear and regulates mechanotransductive signaling in the cilium. It also plays a role in left-right axis patterning by sensing nodal flow during spermatogenesis. Mutations in PKD2 can lead to renal tubule cyst formation and progression of ADPKD.
The PKD family members are serine/threonine protein kinases that function in diverse cellular processes. They are activated by various stimuli, including growth factors and hormones, diacylglycerol, and oxidative stress. They are also involved in EMT, cell migration/invasion, and apoptosis.
In MDA-MB-231 cells stably depleted of PKD3, the expression of several surface proteins was dysregulated compared with control cells (shNon_CTRL). In addition, PKD3 deficiency reduced GEF-H1 activity and YAP/TAZ signaling.
We show that PKD3 is an Hsp90 client and that the chaperone-client interaction plays a key role in promoting prostate cancer metastasis. Treatment with the Hsp90 inhibitor ganetespib significantly attenuated PKD3-induced cell migratory behaviors in both DU145 and PC3 cells, indicating that PKD3 depends on Hsp90 for its migratory functions. Moreover, PKD3 siRNA and ganetespib treatment both attenuated the increased sphere formation of EGFP-PKD3 transfected PC3 cells, demonstrating that oncosphere formation depends on PKD3 stability.
PKD5 is involved in primary cilium formation (PubMed:19852954, PubMed:28530676). It also localizes to centrioles and to the distal ends of basal bodies. Defects in PKD5 are associated with polycystic kidney disease (PubMed:28530676).
z design aims to propose an alternative to the current housing paradigm in Israel. Most residential prototypes in the city tend to be dull and repetitive extrusions with facades reflecting their real-estate value. This building, located in the center of Holon, addresses the issue by articulating the basic residential”aggregate”- the apartment, almost as an independent unit. By doing so, every second floor gains a large 30 sqm “roof terrace” as an integral part of the building mass, and the rich volumetric composition is almost a by-product of this simple shift. This feature makes this building a new language for urban housing in the Mediterranean climate.