S4 Movement in a Mammalian HCN Channel

Hyperpolarization-activated, cyclic nucleotide–gated ion channels (HCN) mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and the brain. HCN channels share sequence homology with depolarization-activated Kv channels, including six transmembrane domains and a positively charged S4 segment. S4 has been shown to function as the voltage sensor and to undergo a voltage-dependent movement in the Shaker K+ channel (a Kv channel) and in the spHCN channel (an HCN channel from sea urchin). However, it is still unknown whether S4 undergoes a similar movement in mammalian HCN channels. In this study, we used cysteine accessibility to determine whether there is voltage-dependent S4 movement in a mammalian HCN1 channel. Six cysteine mutations (R247C, T249C, I251C, S253C, L254C, and S261C) were used to assess S4 movement of the heterologously expressed HCN1 channel in Xenopus oocytes. We found a state-dependent accessibility for four S4 residues: T249C and S253C from the extracellular solution, and L254C and S261C from the internal solution. We conclude that S4 moves in a voltage-dependent manner in HCN1 channels, similar to its movement in the spHCN channel. This S4 movement suggests that the role of S4 as a voltage sensor is conserved in HCN channels. In addition, to determine the reason for the different cAMP modulation and the different voltage range of activation in spHCN channels compared with HCN1 channels, we constructed a COOH-terminal–deleted spHCN. This channel appeared to be similar to a COOH-terminal–deleted HCN1 channel, suggesting that the main functional differences between spHCN and HCN1 channels are due to differences in their COOH termini or in the interaction between the COOH terminus and the rest of the channel protein in spHCN channels compared with HCN1 channels

Design of Reliable Analog DMTL Phase Shifter with Improved Performance for Ku Band Applications

An analog phase shifter based on distributed MEMS transmission line (DMTL) is designed for Ku band applications. Traditional RF MEMS phase shifter comprising 6 switches has limited phase shift of 37.75° due to instability region. A new concept of stopper is incorporated to achieve high phase shift. In the present paper, optimisation of the analog phase shifter is done to increase its phase shift upto 88.63°. Phase shift is a strong function of capacitance ratio which is increased from 1.75 to 2.95. The maximum operating voltage and mechanical resonant frequency for the phase shifter are 16 V and 8.3 KHz, respectively. The switching time is calculated to 56 μs. The simulated insertion loss of the phase shifter is -1.75 dB with return loss of -20.49 dB at 17 GHz. The simulated results are verified with analytical modelling which are in close match

Studies on artemisinin, morphotypic and genetic characteristics of seventeen species of Artemisia growing in Indian Himalayan Region

272-279Seventeen species of Artemisia L. growing in the Indian Himalayan region were investigated for artemisinin content, morphological and genetic characters. During the investigation, artemisinin content was found to be in the range of trace to 0.12%. The highest was in A. dracunculus (0.12%) and A. roxburghiana (0.12%). The essential oil content was found in the range of 0.03-1.5%, A. dracunculus showed 1.5% oil (w/v) followed by A. nilagirica (0.6%) and A. maritima (0.6%). The AFLP analysis revealed 25.4% (Hind-ACC & Mse-CAC) to 67.38% (Hind-ACA & Mse-CAG) polymorphism while overall it was 51%. The dendrogram generated from AFLP data classified 8 species in one cluster (I) and 9 in another (II). The important pathway genes (HMGR, ADS and CYP71AV1) showed higher expression in A. dracunculus, A. roxburghiana and A. sieversiana. Based on the chemical analysis, the presence of a high amount of essential oil and artemisinin in A. dracunculus and A. roxburghiana suggested that these could be important medicinal plants for future research

Studies on artemisinin, morphotypic and genetic characteristics of seventeen species of Artemisia growing in Indian Himalayan Region

Seventeen species of Artemisia L. growing in the Indian Himalayan region were investigated for artemisinin content, morphological and genetic characters. During the investigation, artemisinin content was found to be in the range of trace to 0.12%. The highest was in A. dracunculus (0.12%) and A. roxburghiana (0.12%). The essential oil content was found in the range of 0.03-1.5%, A. dracunculus showed 1.5% oil (w/v) followed by A. nilagirica (0.6%) and A. maritima (0.6%). The AFLP analysis revealed 25.4% (Hind-ACC & Mse-CAC) to 67.38% (Hind-ACA & Mse-CAG) polymorphism while overall it was 51%. The dendrogram generated from AFLP data classified 8 species in one cluster (I) and 9 in another (II). The important pathway genes (HMGR, ADS and CYP71AV1) showed higher expression in A. dracunculus, A. roxburghiana and A. sieversiana. Based on the chemical analysis, the presence of a high amount of essential oil and artemisinin in A. dracunculus and A. roxburghiana suggested that these could be important medicinal plants for future research

Cost of fertility treatment and live birth outcome in women of different ages and BMI

Acknowledgements We thank the Aberdeen Fertility Centre Database Committee and the Aberdeen Maternal and Neonatal Databank Committee for giving us approval to use their databases. We thank the Data Management Team for extracting the required information from these databases. The views expressed in this paper represent the views of the authors and not necessarily the views of the funding bodies. Funding This study was partly funded by an NHS endowment grant (Grant Number 12/48) and DM by a Chief Scientist Office Postdoctoral Fellowship (Ref PDF/12/06).Peer reviewedPostprin

Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer?

A.M. and S.B. are co-applicants on the HTA/ NIHR grant, UK (ISCTRN-61225414) for E-Freeze Trial which is a randomised controlled trial comparing elective freezing of embryos with current policy of fresh embryo transfer. Otherwise the authors have no conflict of interest.Peer reviewedPostprin

Synthesis, Spectroscopic, and Antimicrobial Studies of Binuclear Metallocene (M = Ti, Zr, or Hf) Derivatives of Bis(mercaptoazoles)

The reactions of (η5 − C5H5)2MCl2 (M = Ti, Zr, or Hf) with mercaptoazoles (LH2), namely, bis(mercaptotriazoles), bis(mercap- tooxadiazoles), and bis(mercaptothiadiazoles) in 2 : 1 molar ratio, respectively, have been studied in dry tetrahydrofuran in the presence of n-butylamine and the binuclear complexes of the type [{(η − C5H5)2 M}2(L)] (M = Ti/Zr/Hf) are obtained. Tentative structural conclusions are drawn for the reaction products based upon elemental analysis, electrical conductance, magnetic moment, and spectral data (UV-Vis, IR, 1H NMR, and 13C NMR). FAB-mass spectra of few complexes of each series were also carried out to confirm the binuclear structures. Studies were conducted to assess the growth-inhibiting potential of the complexes synthesized, and the ligands against various fungal and bacterial strains

Gendered effects of COVID-19 school closures: India case study

This brief summarizes a case study that assessed the gendered impact of COVID-19 school closures on education, health, well-being, and protection of adolescents in India. Based on surveys and interviews in Bihar and Uttar Pradesh, findings point to the digital divide for girls as well as shared barriers to effective remote learning. Informed by the evidence, the study presents recommendations to scale up efforts to improve remote learning, reduce digital divide and strengthen teacher support, with a particular attention to addressing gendered differences