TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore.

Two-pore domain K+ channels (K2P) are responsible for background K+ currents and regulate the resting membrane potential and cellular excitability. Their activity is controlled by a large variety of physicochemical factors and intracellular signaling pathways. The majority of these effects converge on the intracellular C-terminus of the channels, resulting in the modification of the gating at the selectivity filter. Another gating mechanism, the activation gate at the helix bundle crossing is also well documented in other K+ channel families, however, it remains uncertain whether this type of gating is functional in K2P channels. The regulation of TWIK-related spinal cord K+ channel (TRESK) is different from the other K2P channels. Regulatory factors acting via the C-terminus are not known, instead channel activity is modified by the phosphorylation/dephosphorylation of the unusually long intracellular loop between the 2nd and 3rd transmembrane segments. These unique structural elements of the regulation lead us to examine channel gating at the bundle crossing region. Ba2+ was applied to the intracellular side of excised membrane patches and the characteristics of the channel block were determined. We compared the kinetics of the development of Ba2+ block when the channels were phosphorylated (inhibited) or dephosphorylated (activated) and also in different mutants mimicking the two functional states. Neither the phosphorylation/dephosphorylation nor the point mutations influenced the development of Ba2+ block, suggesting that the conformational changes of the bundle crossing region do not contribute to the phosphorylation-dependent gating of TRESK

Caring for the Uninsured and Underinsured

To the Editor. Access to health care is a significant problem for millions of Americans, particularly for those who are poor, homeless, lack health insurance, and are unemployed

It’s been mostly about money!: a multi-method research approach to the sources of institutionalization

Although much has been written about the process of party system insti- tutionalization in different regions, the reasons why some party systems institutionalize while others do not still remain a mystery. Seeking to fill this lacuna in the literature, and using a mixed-methods research approach, this article constitutes a first attempt to answer simultaneously the following three questions: (1) What specific factors help party systems to institutio- nalize (or not)? (2) What are the links (in terms of time and degree) as well as the causal mechanisms behind such relationships? and (3) how do they affect a particular party system? In order to do so, this article focuses on the study of party system development and institutionalization in 13 postcommunist democracies between 1990 and 2010. Methodologically, the article innovates in five respects. First, it continues the debate on the importance of ‘‘mixed methods’’ when trying to answer different research questions. Second, it adds to the as yet brief literature on the combination of process tracing and qualitative comparative analysis. Third, it constitutes the first attempt to date to use a most similar different outcome/most different same outcome pro- cedure in order to reduce causal complexity before undertaking a crisp-set qualitative comparative analysis. Third, it also shows the merits of combining both congruence and process tracing in the same comparative study. Finally, it also develops a novel ‘‘bipolar comparative method’’ to explain the extent to which opposite outcomes are determined by reverse conditions and conflicting intervening causal forces

Hyperspectral Microscopy of Near-Infrared Fluorescence Enables 17-Chirality Carbon Nanotube Imaging

The intrinsic near-infrared photoluminescence (fluorescence) of single-walled carbon nanotubes exhibits unique photostability, narrow bandwidth, penetration through biological media, environmental sensitivity, and both chromatic variety and range. Biomedical applications exploiting this large family of fluorophores will require the spectral and spatial resolution of individual (n,m) nanotube species € fluorescence and its modulation within live cells and tissues, which is not possible with current microscopy methods. We present a wide-field hyperspectral approach to spatially delineate and spectroscopically measure single nanotube fluorescence in living systems. This approach resolved up to 17 distinct (n,m) species (chiralities) with single nanotube spatial resolution in live mammalian cells, murine tissues ex vivo, and zebrafish endothelium in vivo. We anticipate that this approach will facilitate multiplexed nanotube imaging in biomedical applications while enabling deep-tissue optical penetration, and single-molecule resolution in vivo

Two-pore domain potassium channels (K2P) in GtoPdb v.2021.3

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two-pore domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below

Two-pore domain potassium channels (K2P) in GtoPdb v.2023.1

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two-pore domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below

Two P domain potassium channels in GtoPdb v.2021.2

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two P domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below

High Availability in the Future Internet

With the evolution of the Internet, a huge number of real- time applications, like Voice over IP, has started to use IP as primary transmission medium. These services require high availability, which is not amongst the main features of today’s heterogeneous Internet where fail- ures occur frequently. Unfortunately, the primary fast resilience scheme implemented in IP routers, Loop-Free Alternates (LFA), usually does not provide full protection against failures. Consequently, there has been a growing interest in LFA-based network optimization methods, aimed at tuning some aspect of the underlying IP topology to maximize the ratio of failure cases covered by LFA. The main goal of this chapter is to give a comprehensive overview of LFA and survey the related LFA network op- timization methods, pointing out that these optimization tools can turn LFA into an easy-to-deploy yet highly effective IP fast resilience scheme