First-principles quantum transport modeling of thermoelectricity in single-molecule nanojunctions with graphene nanoribbon electrodes

We overview nonequilibrium Green function combined with density functional theory (NEGF-DFT) modeling of independent electron and phonon transport in nanojunctions with applications focused on a new class of thermoelectric devices where a single molecule is attached to two metallic zigzag graphene nanoribbons (ZGNRs) via highly transparent contacts. Such contacts make possible injection of evanescent wavefunctions from ZGNRs, so that their overlap within the molecular region generates a peak in the electronic transmission. Additionally, the spatial symmetry properties of the transverse propagating states in the ZGNR electrodes suppress hole-like contributions to the thermopower. Thus optimized thermopower, together with diminished phonon conductance through a ZGNR/molecule/ZGNR inhomogeneous structure, yields the thermoelectric figure of merit ZT~0.5 at room temperature and 0.5<ZT<2.5 below liquid nitrogen temperature. The reliance on evanescent mode transport and symmetry of propagating states in the electrodes makes the electronic-transport-determined power factor in this class of devices largely insensitive to the type of sufficiently short conjugated organic molecule, which we demonstrate by showing that both 18-annulene and C10 molecule sandwiched by the two ZGNR electrodes yield similar thermopower. Thus, one can search for molecules that will further reduce the phonon thermal conductance (in the denominator of ZT) while keeping the electronic power factor (in the nominator of ZT) optimized. We also show how often employed Brenner empirical interatomic potential for hydrocarbon systems fails to describe phonon transport in our single-molecule nanojunctions when contrasted with first-principles results obtained via NEGF-DFT methodology.Comment: 20 pages, 6 figures; mini-review article prepared for the special issue of the Journal of Computational Electronics on "Simulation of Thermal, Thermoelectric, and Electrothermal Phenomena in Nanostructures", edited by I. Knezevic and Z. Aksamij

Aquaporin 2 promotes cell migration and epithelial morphogenesis

The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin beta 1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin beta 1 by mutating the RGD motif led to reduced endocytosis, retention of integrin beta 1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin beta 1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney

Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients

This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P-glycoprotein in human immunodeficiency virus (HIV)-infected patients receiving an antiretroviral therapy (ART) containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics. We measured activities of CYP3A, CYP2D6, and P-glycoprotein in 28 patients before and during ART using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P-glycoprotein were tested as covariates. Oral midazolam clearance (overall CYP3A activity) decreased to 0.19-fold (90% confidence interval (CI), 0.15-0.23), hepatic midazolam clearance and intestinal midazolam availability changed to 0.24-fold (0.20-0.29) and 1.12-fold (1.00-1.26), respectively. In CYP2D6 extensive metabolizers, the plasma ratio AUC(dextromethorphan)/AUC(dextrorphan) increased to 2.92-fold (2.31-3.69). Digoxin area under the curve (AUC)(0-12) (P-glycoprotein activity) increased to 1.81-fold (1.56-2.09). Covariates had no major influence on lopinavir and ritonavir pharmacokinetics. In conclusion, CYP3A, CYP2D6, and P-glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection

Diacylglycerol Kinase δ Suppresses ER-to-Golgi Traffic via Its SAM and PH Domains

We report here that the anterograde transport from the endoplasmic reticulum (ER) to the Golgi was markedly suppressed by diacylglycerol kinase δ (DGKδ) that uniquely possesses a pleckstrin homology (PH) and a sterile α motif (SAM) domain. A low-level expression of DGKδ in NIH3T3 cells caused redistribution into the ER of the marker proteins of the Golgi membranes and the vesicular-tubular clusters (VTCs). In this case DGKδ delayed the ER-to-Golgi traffic of vesicular stomatitis virus glycoprotein (VSV G) and also the reassembly of the Golgi apparatus after brefeldin A (BFA) treatment and washout. DGKδ was demonstrated to associate with the ER through its C-terminal SAM domain acting as an ER-targeting motif. Both of the SAM domain and the N-terminal PH domain of DGKδ were needed to exert its effects on ER-to-Golgi traffic. Kinase-dead mutants of DGKδ were also effective as the wild-type enzyme, suggesting that the catalytic activity of DGK was not involved in the present observation. Remarkably, the expression of DGKδ abrogated formation of COPII-coated structures labeled with Sec13p without affecting COPI structures. These findings indicate that DGKδ negatively regulates ER-to-Golgi traffic by selectively inhibiting the formation of ER export sites without significantly affecting retrograde transport

Probing for Membrane Domains in the Endoplasmic Reticulum: Retention and Degradation of Unassembled MHC Class I Molecules

Quality control of protein biosynthesis requires ER-retention and ER-associated degradation (ERAD) of unassembled/misfolded molecules. Although some evidence exists for the organization of the ER into functionally distinct membrane domains, it is unknown if such domains are involved in the retention and ERAD of unassembled proteins. Here, it is shown that unassembled MHC class I molecules are retained in the ER without accumulating at ER-exit sites or in the ERGIC of β2m(−/−) cells. Furthermore, these molecules did not cluster in the ER membrane and appeared to be highly mobile even when ERAD or their association with calnexin were inhibited. However, upon ATP depletion, they were reversibly segregated into an ER membrane domain, distinct from ER exit sites, which included calnexin and COPII, but not the ERGIC marker protein p58. This quality control domain was also observed upon prolonged inhibition of proteasomes. Microtubules were required for its appearance. Segregation of unfolded proteins, ER-resident chaperones, and COPII may be a temporal adaptation to cell stress