An ATP-regulated, inwardly rectifying potassium channel from rat kidney (ROMK)

Potassium channels exhibit a wide functional diversity making them well suited for their broad roles in renal (and other) cells [1, 2]. Potassium channels can be classified into two broad groups based on their functional/biophysical properties: the delayed or outward rectifiers that are activated by depolarizing potentials and the inward rectifiers that include the classical (strongly) inwardly rectifying K+ channel and the more weakly inwardly rectifying ATP-sensitive potassium (KATP) channels [1, 3–7]. The inward rectifiers are characterized by a lack of significant gating by voltage and by their ability to conduct potassium more readily in the inward than outward direction. The classical (strong) and KATP-type of inward rectifiers have been identified in a variety of excitable and nonexcitable cells. The strong inward rectifiers appear to function in maintaining the resting membrane potential and in regulating excitability (such as in cardiac muscle cells). ATP-sensitive potassium channels, on the other hand, open and close in response to cellular metabolic events and may serve important roles in some cells during ischemia. Renal KATP channels, while sharing many of the properties and characteristics of KATP channels found in other tissues (such as pancreatic β-cell and cardiac muscle cells [3]), lack sensitivity to TEA, have a much lower sensitivity to sulfonylureas (such as glyburide, a high affinity inhibitor of KATP channels found in heart and β-cells), and require higher (that is, mM) concentrations of ATP to inhibit channel activity [1, 7].In the kidney, the apical (K+ secretory) KATP channel serves a number of important roles in renal electrolyte transport [1]. In the thick ascending limb of Henle (TAL; both medullary, MTAL, and cortical, CTAL, segments; Fig. 1), KATP channels are the dominant conductance in apical plasma membranes and provide a crucial K+ efflux pathway for potassium entering cells via the apical Na+:K+:2Cl- cotransporter [1]. This recycling of potassium ensures that an adequate supply of luminal potassium is provided for efficient function of the Na+:K+:2Cl- cotransporter [1]. In addition, this channel mediates the apical component of a transcellular (basolateral-to-apical) current flow that returns to the basolateral side via the paracellular pathway predominantly as a sodium current [8]. This provides for one-half of the net transepithelial movement of sodium [9]. Two types of inwardly rectifying and ATP-sensitive K+ channels have been identified on apical membranes of TAL segments by patch clamp [10, 11]. Wang and coworkers [10] found a 20 to 30 pS K+ channel in rabbit TAL that had a high open probability (Po), was inhibited by ATP (mM) and not sensitive to TEA (referred to as the “low conductance” channel). On the other hand, a different KATP channel was identified on apical membranes of rat TAL by Greger and coworkers [11–13]; this channel also had a high Po and was ATP-sensitive but had a higher unitary conductance of ∼70 pS, was highly sensitive to reductions in cytosolic side pH (50% reduction in Po by a 0.2 pH unit decrease), and exhibited sensitivity to quinine or quinidine, TEA and Ca2+ (referred to as the “intermediate conductance” channel). Recently, Wang found both the low (∼30 pS) and intermediate (∼72 pS) conductance KATP channels in the same patches of rat TAL apical membranes [14]. He also confirmed that the intermediate conductance KATP channel is sensitive to quinidine and acidic pH while the low conductance channel is insensitive to quinidine. In addition, the low, but not the intermediate, conductance channel is inhibited by high (∼250 µM) gliburide. These studies demonstrate that there are two distinct channel types in apical membranes of TAL and that these channels can be distinguished by single channel conductances and their sensitivities to channel inhibitors.A functionally similar, if not identical, low conductance, inwardly rectifying KATP channel has been identified in apical membranes of principal cells in the cortical collecting duct (CCD) where it mediates K+ secretion into urine (Fig. 1) [1, 7, 15, 16]. The KATP channel in rat principal cells is dually regulated by ATP: high MgATP concentrations reversibly block channel activity (K1/2 = 0.6 to 1.0 mM) while lower concentrations of MgATP are required to maintain channel activity [1, 7, 17, 18]. The mechanism for ATP-mediated block of the principal cell KATP channel is unclear at present but may represent direct binding of nucleotide to the channel itself with a resulting change in channel conformation to the closed state and/or to altering the activity of the channel by regulating the phosphorylation of the channel itself, or some other protein involved to modulating channel activity. The stimulatory effect of low ATP concentration, however, clearly relates to regulation of channel activity by phosphorylation-dephosphorylation processes [18]: (i) channel activity rapidly diminishes (run-down) on patch excision unless the cytosolic face is exposed to low concentrations of MgATP; (ii) generally the catalytic subunit of cAMP-dependent protein kinase, PKA, is also required for channel maintenance and PKA, and together with MgATP can restore channel activity after run-down; (iii) non-hydrolyzable ATP analogues cannot maintain or restore channel activity; (iv) in patches in which channel activity is maintained by MgATP alone, the PKA inhibitor (PKI) reversibly reduces channel activity, providing evidence for an important role for endogenous PKA; and (v) PKC reversibly inhibits channel activity and antagonizes the stimulatory effect of PKA, a process that is Ca2+-dependent [19]. In further studies Wang and Giebisch [17, 18] demonstrated that the ratio of ATP to ADP and cell pH are also important regulators of the small conductance KATP channel in the apical membranes of principal cells. KATP channel activity in rat principal cells is also inhibited by activation of protein kinase C [19] or calcium-calmodulin-dependent kinase II [20] or by arachidonic acid [21].Much less is known about the regulation of the apical KATP channels in the TAL than in the CCD; however, we previously suggested that AVP (presumably cyclic AMP-dependent activation of PKA and subsequent phosphorylation of the channel or an associated regulatory protein) activated the K+ conductance of the apical membrane in mouse MTAL [22, 23]. Reeves and coworkers have provided more direct evidence for this [24]. They showed that Ba2+-sensitive, voltage-dependent 86Rb+ influx in membrane vesicles from rabbit outer medulla was activated by cAMP-dependent protein kinase. Wang [14] has confirmed this effect of cAMP-PKA by showing activation of the low conductance KATP channel in cell attached patches by AVP or cAMP and in excised patches by the catalytic subunit of PKA.Finally, it should be noted that large conductance (maxi-K+), Ca2+-activated K+ channels have been identified in apical membranes of both TAL [25, 26] and CCD [1, 27–29]. These voltage-gated channels are normally quiescent but can be activated by µM cytosolic Ca2+, are inhibited by TEA (more sensitive to TEA than the intermediate conductance KATP channel), and are insensitive to ATP. Since K+(Rb+) secretion and the transepithelial voltage in the CCD are not blocked by luminal TEA [16, 28], it is generally thought that this apical maxi-K+ channel is not directly involved in K+ secretion by this nephron segment. The maxi-K+ channel may function, however, as a K+ efflux pathway during cell swelling [1, 7, 30]

Association of Markers of Inflammation with Sleep and Physical Activity among People Living with HIV or AIDS

This study examined associations of sleep and minutes spent in moderate-vigorous physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6 among persons living with HIV (PLWH). Cross-sectional analyses (n=45) focused on associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived sleep duration, latency, and efficiency; bedtime; wake time; and wake-after-sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of sleep and MVPA were computed from general linear models. Individuals below the median of sleep duration, above the median for bedtime, and below the median of MVPA minutes had higher CRP or IL-6 levels. Generally, individuals with both low MVPA and poor sleep characteristics had higher inflammation levels than those with more MVPA and better sleep. Understanding the combined impact of multiple lifestyle/behavioral factors on inflammation could inform intervention strategies to reduce inflammation and therefore, chronic disease risk

Clinical Characteristics of the End-of-Life Phase in Children with Life-Limiting Diseases: Retrospective Study from a Single Center for Pediatric Palliative Care

Background: Data on the end-of-life phase of children receiving palliative care are limited. The purpose of this study is to investigate the spectrum of symptoms of terminally ill children, adolescents, and young adults, depending on their underlying disease. Methods: Findings are based on a 4.5-year retrospective study of 89 children who received palliative care before they died, investigating the symptomatology of the last two weeks before death. Results: In this study, the most common clinical symptomatology present in children undergoing end-of-life care includes pain, shortness of breath, anxiety, nausea, and constipation. Out of 89 patients included in this study, 47% suffered from an oncological disease. Oncological patients had a significantly higher symptom burden at the end of life (p < 0.05) compared to other groups, and the intensity of symptoms increased as the underlying disease progressed. The likelihood of experiencing pain and nausea/vomiting was also significantly higher in oncological patients (p = 0.016). Conclusions: We found that the underlying disease is associated with marked differences in the respective leading clinical symptom. Therefore, related to these differences, symptom management has to be adjusted according to the underlying disease, since the underlying disorder seems to exert an influence on the severity of symptoms and thereby on the modality and choice of treatment. This study is intended to aid underlying disease-specific symptom management at the end-of-life care for children, adolescents, and young adults, with a specific focus on end-of-life care in a home environment

Low fitness partially explains resting metabolic rate differences between African American and white women

Background High levels of obesity among African American women have been hypothesized to be partially resultant from a lower resting metabolic rate compared with white women. The aim of the current study was to determine if differences in cardiorespiratory fitness and moderate-to-vigorous physical activity are associated with differences in resting metabolic rate among free-living young adult African American women and white women. Methods Participants were 179 women (white women n = 141, African American women n = 38, mean age = 27.7 years). Resting metabolic rate was measured using indirect calorimetry, body composition using dual energy x-ray absorptiometry, cardiorespiratory fitness via maximal treadmill test, and moderate-to-vigorous physical activity using an activity monitor. Results African American women had higher body mass index, fat mass, and fat-free mass compared with white women but lower levels of cardiorespiratory fitness. No differences were observed between African American and white women in resting metabolic rate when expressed as kcal/day (1390.8 ± 197.5 vs 1375.7 ± 173.6 kcal/day, P =.64), but African American women had a lower resting metabolic rate when expressed relative to body weight (2.56 ± 0.30 vs 2.95 ± 0.33 mL/kg/min,

The Cancer Prevention and Control Research Network

The Cancer Prevention and Control Research Network is a national network recently established to focus on developing new interventions and disseminating and translating proven interventions into practice to reduce cancer burden and disparities, especially among minority and medically underserved populations. Jointly funded by the Centers for Disease Control and Prevention and the National Cancer Institute, the Cancer Prevention and Control Research Network consists of sites administered through Prevention Research Centers funded by the Centers for Disease Control and Prevention. The five sites are located in Kentucky, Massachusetts, South Carolina, Texas, Washington State, and West Virginia. The Cancer Prevention and Control Research Network's intervention areas include primary prevention of cancer through healthy eating, physical activity, sun avoidance, tobacco control, and early detection of cancer through screening. The Cancer Prevention and Control Research Network uses the methods of community-based participatory research and seeks to build on the cancer-relevant systematic reviews of the Guide to Community Preventive Services. Initial foci for the Cancer Prevention and Control Research Network's research work groups include projects to increase screening for breast, cervical, and colorectal cancers; to promote informed decision making for prostate cancer screening; and to validate educational materials developed for low-literacy populations

An Evaluation of the Causes, Consequences, and Potential Solutions to Increased Red River Flooding in the Caddo Parish Regions of Northwest Louisiana

Urban flooding is a challenge for many parts of the world, and Caddo Parish, Louisiana, is no exception. Caddo Parish, located in Northwestern Louisiana on the banks of the Red River, has been the subject of intense flooding for decades, issuing widespread devastation to many areas of the parish. As waters from rain events and upstream reservoirs deluged the Red River, countless individuals and communities were affected. In addition to damage and destruction of homes and personal belongings, sectors of the economy were also impacted, notably agriculture and industry. Rising waters jeopardized public infrastructure, affecting commerce throughout the parish, particularly waterway systems. This report, prepared by graduate students of the Bush School of Government and Public Service at Texas A&M University, per request of the Caddo Parish Sheriff’s Office, outlines policy solutions to protect the individuals and communities of Caddo Parish from future flooding

La industria de las flores en Colombia y el desarrollo de la cadena de suministro y logística en la actualidad

El presente documento describe el comportamiento y evolución de la industria floricultora colombiana, la cual alberga una evolución significativa en materia de desarrollo logístico empresarial y crecimiento económico para el país. Así mismo este análisis revela el desempeño evolutivo del país en cuestión logística y un comparativo de estrategias en materia de exportación de países en potencia mundial en floricultura, este comparativo no solo resalta el estado actual del país si no que evidencia las tendencias y estrategias de los países potencia en desarrollo, la estructura, las estrategias de mercado, la implementación de nuevos sistemas de desarrollo, el desempeño de carga y distribución entre otros factores importantes para analizar y optar hacia el desarrollo. Igualmente resalta el comportamiento evolutivo que ha tenido Colombia en la cadena de valor, como se integra con sus aleados, como forman estrategias para la competitividad y cómo pueden desarrollar proyectos que impulsan al sostenimiento en el mercado actual, el impacto de la venta de rosas y su importante contribución en crecimiento económico, estabilidad laboral, representación comercial entre otras, así mismo su impacto en la oferta de las flores y su penetración en mercados con nuevas especies y cómo es su acogida mundialThis document describes the behavior and evolution of the Colombian flower industry, which hosts a significant evolution in terms of business logistics development and economic growth for the country. Also this analysis reveals the evolutionary performance of the country in question logistics and a comparison of export strategies of countries in world power in floriculture, this comparative not only highlights the current state of the country but also evidence the trends and strategies of the countries power in development, structure, market strategies, implementation of new development systems, load performance and distribution among other important factors to analyze and opt for development. It also highlights the evolutionary behavior that Colombia has had in the value chain, how it integrates with its alloys, how they form strategies for competitiveness and how they can develop projects that encourage sustainability in the current market, the impact of the sale of roses and its important contribution in economic growth, labor stability, commercial representation among others, as well as its impact on the supply of flowers and its penetration in markets with new species and its worldwide acceptanc

Clustering of Unhealthy Behaviors in the Aerobics Center Longitudinal Study

Background Clustering of unhealthy behaviors has been reported in previous studies; however the link with all-cause mortality and differences between those with and without chronic disease requires further investigation. Objectives To observe the clustering effects of unhealthy diet, fitness, smoking, and excessive alcohol consumption in adults with and without chronic disease and to assess all-cause mortality risk according to the clustering of unhealthy behaviors. Methods Participants were 13,621 adults (aged 20–84) from the Aerobics Center Longitudinal Study. Four health behaviors were observed (diet, fitness, smoking, and drinking). Baseline characteristics of the study population and bivariate relations between pairs of the health behaviors were evaluated separately for those with and without chronic disease using cross-tabulation and a chi-square test. The odds of partaking in unhealthy behaviors were also calculated. Latent class analysis (LCA) was used to assess clustering. Cox regression was used to assess the relationship between the behaviors and mortality. Results The four health behaviors were related to each other. LCA results suggested that two classes existed. Participants in class 1 had a higher probability of partaking in each of the four unhealthy behaviors than participants in class 2. No differences in health behavior clustering were found between participants with and without chronic disease. Mortality risk increased relative to the number of unhealthy behaviors participants engaged in. Conclusion Unhealthy behaviors cluster together irrespective of chronic disease status. Such findings suggest that multi-behavioral intervention strategies can be similar in those with and without chronic disease