Thermal conductivity, diffusivity and expansion of Avery Island salt at pressure and temperature

Preliminary data on the thermal properties of a coarse-grained rock salt from Avery Island, Louisiana, indicates that hydrostatic pressure to 50 MPa has little effect on the thermal conductivity, diffusivity and linear expansion at temperatures from 300 to 573 K. The measurements were made in a new apparatus under conditions of true hydrostatic loading. At room temperature and effective confining pressure increasing from 10 to 50 MPa, thermal conductivity and diffusivity are constant at roughly 7W/mK and 3.6 x 10/sup -6/ m/sup 2//s, respectively. At 50 MPa and temperature increasing from 300 to 573K, both conductivity and diffusivity drop by a factor of 2. Thermal linear expansion at 0 MPa matches that at 50 MPa, increasing from roughly 4.2 x 10/sup -5//K at 300 K to 5.5 x 10/sup -5/ at 573 K. The lack of a pressure effect on all three properties is confirmed by previous work. Simple models of microcracking suggest that among common geological materials the lack of pressure dependence is unique to rock salt

Specific Heterodimer Formation Is a Prerequisite for Uroplakins to Exit from the Endoplasmic Reticulum

Much of the lower urinary tract, including the bladder, is lined by a stratified urothelium forming a highly differentiated, superficial umbrella cell layer. The apical plasma membrane as well as abundant cytoplasmic fusiform vesicles of the umbrella cells is covered by two-dimensional crystals that are formed by four membrane proteins named uroplakins (UPs) Ia, Ib, II, and III. UPs are synthesized on membrane-bound polysomes, and after several co- and posttranslational modifications they assemble into planar crystals in a post-Golgi vesicular compartment. Distension of the bladder may cause fusiform vesicles to fuse with the apical plasma membrane. We have investigated the early stages of uroplakin assembly by expressing the four uroplakins in 293T cells. Transfection experiments showed that, when expressed individually, only UPIb can exit from the endoplasmic reticulum (ER) and move to the plasma membrane, whereas UPII and UPIII reach the plasma membrane only when they form heterodimeric complexes with UPIa and UPIb, respectively. Heterodimer formation in the ER was confirmed by pulse-chase experiment followed by coimmunoprecipitation. Our results indicate that the initial building blocks for the assembly of crystalline uroplakin plaques are heterodimeric uroplakin complexes that form in the ER

Loss-of-function mutations in <em>SLC30A8</em> protect against type 2 diabetes.

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 &times; 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 &times; 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention