Characterization of DAG binding to TRPC channels by target-dependent cis–trans isomerization of OptoDArG

Azobenzene-based photochromic lipids are valuable probes for the analysis of ion channel–lipid interactions. Rapid photoisomerization of these molecules enables the analysis of lipid gating kinetics and provides information on lipid sensing. Thermal relaxation of the metastable cis conformation to the trans conformation of azobenzene photolipids is rather slow in the dark and may be modified by ligand–protein interactions. Cis photolipid-induced changes in pure lipid membranes as visualized from the morphological response of giant unilamellar vesicles indicated that thermal cis–trans isomerization of both PhoDAG-1 and OptoDArG is essentially slow in the lipid bilayer environment. While the currents activated by cis PhoDAG remained stable upon termination of UV light exposure (dark, UV-OFF), cis OptoDArG-induced TRPC3/6/7 activity displayed a striking isoform-dependent exponential decay. The deactivation kinetics of cis OptoDArG-induced currents in the dark was sensitive to mutations in the L2 lipid coordination site of TRPC channels. We conclude that the binding of cis OptoDArG to TRPC channels promotes transition of cis OptoDArG to the trans conformation. This process is suggested to provide valuable information on DAG–ion channel interactions and may enable highly selective photopharmacological interventions

A new icriodontid conodont cluster with specific mesowear supports an alternative apparatus motion model for Icriodontidae

Increasing numbers of conodont discoveries with soft tissue preservation, natural assemblages and fused clusters of the hard tissue have strengthened the hypothesis regarding the function and mechanism of the conodont feeding apparatus. Exceptional fossil preservation serves as a solid basis for modern reconstructions of the conodont apparatus illustrating the complex interplay of the single apparatus elements. Reliable published models concern the ozarkodinid apparatus of Pennsylvanian and Early Triassic conodonts. Recognition of microwear and mammal-like occlusion, especially of platform elements belonging to individuals of the genus Idiognathodus, allows rotational closure to be interpreted as the crushing mechanism of ozarkodinid platform (P1) elements. Here we describe a new icriodontid conodont cluster of Caudicriodus woschmidti that consists of one pair of icriodontan (I) and 10 pairs of coniform (C1\ue2\u80\u935) elements, with I elements being preserved in interlocking position. The special kind of element arrangement within the fused cluster provides new insights into icriodontid apparatus reconstruction and notation of elements. However, orientation of coniform elements is limited to a certain degree by possible preservational bias. Four possible apparatus models are introduced and discussed. Recognition of specific wear on denticle tips of one of the icriodontan elements forms the basis for an alternative hypothesis of apparatus motion. Analysis of tip wear suggests a horizontal, slightly elliptical motion of opposed, antagonistically operating I elements. This is supported by similar tip wear from much better preserved, but isolated, elements of Middle Devonian icriodontids. More detailed interpretation of the masticatory movement will allow enhanced understanding of anatomical specifications, diet and palaeobiology of different euconodont groups

Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

OBJECTIVE: To examine the association of six glutathione transferase (GST) gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357) with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006). CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer

Glutathione S-transferase (GST) genotype distribution.

<p>Glutathione S-transferase (GST) genotype distribution.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO2</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p

Patient characteristics at study entry.

<p>Patient characteristics at study entry.</p

<i>GSTT1, GSTP1, GSTO1, GSTO2, GSTM1</i> and <i>GSTA1</i> polymorphisms as the predictors for overall mortality among 101 patients with muscle invasive TCC after 5 yrs of follow-up by the Cox proportional hazards regression.

<p>Abbreviations: CI, Confidence Interval; HR, Hazard Ratio.</p>a<p>Adjusted for age and gender.</p>b<p>Adjusted for the covariates in Model 1 plus an additional adjustment for grade.</p

Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).

<p>Survival analysis Kaplan–Meier curves according to <i>GSTO1</i> polymorphism for overall mortality (A), as well as mortality of TCC patients on chemotherapy (B).</p

The state of the art in beyond 5G distributed massive multiple-input multiple-output communication system solutions

&lt;p&gt;Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.&lt;/p&gt