All patients had longer go process duration in general and in particular, as a proactive control, as demonstrated by the increase in RT after erroneously performed stop trials. Further, they were defective in the slope of the psychometric function indicating a difficulty on triggering the stop process, although the SSRT did

not differ from controls. Notably, their performance was worse when lesions affected deep cerebellar nuclei. Our results support the hypothesis that the cerebellum regulates the executive control of voluntary actions. We speculate that its activity is attributed to specific cerebellar influence over the cortico-striatal loop.”
“Older adults are vastly underrepresented in clinical trials in spite of shouldering a disproportionate burden of disease and consumption find more URMC-099 supplier of prescription drugs and therapies, restricting treatments’ generalizability, efficacy, and safety. Eliminating Disparities in Clinical Trials, a national initiative comprising a stake-holder network of researchers, community advocates, policymakers, and federal representatives, undertook a critical analysis of older adults’ structural barriers to clinical trial participation. We present practice and policy change recommendations emerging from this process and their rationale, which spanned

multiple themes: (1) decision making with cognitively impaired patients; (2) pharmacokinetic differences and physiological age; (3) health literacy, communication, and aging; (4) geriatric training; (5) federal monitoring

and accountability; (6) clinical trial costs; and (7) cumulative effects of aging and ethnicity. (Am J Public Health. 2010;100:S105-S112. doi:10.2105/AJPH.2009.162982)”
“Twenty patients affected by chronic venous disease check details (CVD) in tertiary venous network and/or saphenous vein were analyzed before surgical ablation by echo-color-doppler for the hemodynamic parameters reflux time (RT) and resistance index (RI), a negative and a positive prognostic factor, respectively. RT and RI were next correlated with relevant in vitro parameters of venous endothelial cells (VEC) obtained from surgical specimens, such as cell migration in response to serum gradient, proliferation index, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression, as well as cytokines release. Of interest, ICAM-1 expression in patient-derived VEC cultures correlated positively with RT and negatively with RI. Moreover, RT showed a positive correlation with the baseline osteoprotegerin (OPG) expression by VEC and an inverse correlation with VEC proliferation index. On the other hand, RI correlated positively with TNF-related apoptosis inducing ligand (TRAIL) expression.

\n\nMethods: We reviewed the outcome of seventy-four bilateral Ilizarov tibial lengthenings for short stature in thirty-seven patients. The mean age at the time of surgery was 21.7 years (range, thirteen to thirty-one years), and the mean duration of follow-up was forty-five months. Proximal GSK2879552 migration of the fibula was assessed with changes in the malleolar tip distance.

A valgus change of 5 in the tibiotalar angle was regarded as ankle valgus deformity following tibial lengthening.\n\nResults: The average length gain was 6.9 cm (range, 4.7 to 11.5 cm), and the average lengthening index was 1.5 mo/cm. Valgus deformity developed in six ankles (8%) and fibular nonunion developed in ten (14%). Proximal migration of the lateral malleolus of mm was related to valgus talar tilting. Bifocal tibial lengthening, rapid distraction rate of the fibula (>1 mm per day), and development of a fibular

nonunion were factors associated with proximal migration of the distal end of the fibula of mm, which suggests that regenerated bone of poor quality in the distraction gap may cause proximal migration of the distal end of the fibula following tibial lengthening.\n\nConclusions: LY411575 in vivo Proximal migration of the distal end of the fibula following tibial lengthening may occur even with the use of an llizarov ring fixator. This migration seems to be caused by collapse of regenerated bone of poor quality or fibular nonunion. Proximal migration of mm is associated with the risk of valgus talar tilting. Surgeons should consider earlier intervention with bone-grafting if there are conditions that compromise regenerated bone formation in the fibular distraction gap, such as can occur with extensive tibial lengthening by bifocal corticotomy.\n\nLevel of Evidence: Therapeutic Level III. See Instructions to Authors for Vorinostat cost a complete description of levels of evidence.”
“Iterative decoding of an irregular variable-length coding (IrVLC) scheme

concatenated with precoded fast frequency-hopping (FFH) M-ary frequency-shift keying (MFSK) is considered. We employ EXtrinsic Information Transfer (EXIT) charts to investigate the three-stage concatenation of the FFH-MFSK demodulator, the rate-1 decoder, and the outer IrVLC decoder. The proposed joint source and channel coding scheme is capable of operating at low signal-to-noise ratios (SNRs) in Rayleigh fading channels contaminated by partial-band noise jamming (PBNJ). The IrVLC scheme is composed of a number of component variable-length coding (VLC) codebooks employing different coding rates that encode particular fractions of the input source symbol stream. These fractions may be chosen with the aid of EXIT charts to shape the inverted EXIT curve of the IrVLC codec so that it can be matched with the EXIT curve of the inner decoder.

We present here initial results to show that NO can be generated in the region around F1 in the right parietal ganglion and that NO and cGMP directly hyperpolarize this neuron. For example, application of the NO-donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP; 200 mu M) can cause a mean hyperpolarization of 41.7 mV, while 2 mM 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) produced Vorinostat a mean hyperpolarization of 33.4 mV.

Additionally, pre-exposure to NO-donors or cGMP appears to significantly reduce or even eliminates the normal hyperpolarizing K+-mediated response to dopamine (DA) by this neuron; 200 mu M SNAP abolishes a standard response to 0.5 mu M DA while 1 mM 8-bromo-cGMP reduces it 62 %.”
“AasP, an autotransporter serine protease of Actinobacillus pleuropneumoniae, has been shown to be expressed in necrotic porcine lung GW786034 manufacturer tissue. Based on the hypothesis that AasP might play an important role in A. pleuropneumoniae adhesion and virulence by processing other surface-associated proteins, the predicted catalytic site of AasP was deleted and the isogenic mutant, AP76 Delta aasP, was compared to

the wild-type strain in a biofilm assay as well as an aerosol infection model. AP76 Delta aasP showed increased adherence compared to the wild-type strain under standard culturing conditions as well as under NAD restriction. No significant differences between AP76 wild-type and AP76 Delta aasP were observed upon experimental infection of pigs, indicating that AasP does not play a crucial role in A. pleuropneumoniae virulence. (C) 2009 Elsevier B.V. All rights reserved.”
“Aim Liver cirrhosis (LC) is the end stage of chronic liver disease. No definitive pharmacological treatment is currently available. We previously reported that thrombopoietin (TPO) promoted liver regeneration and improved liver cirrhosis by increasing platelet count. TPO is therefore considered to be a therapeutic

agent for LC; however, it is unclear whether TPO has proliferative effects on hepatocellular CCI-779 carcinoma (HCC), which arises frequently in cirrhotic livers. In this study, we examined the effects of TPO on growth of HCC. Methods Expression of the TPO receptor, myeloproliferative leukemia virus oncogene (MPL) was examined in various liver tumor cell lines and liver cell types. In an in vitro study, the effects of TPO on signal transduction, cell proliferation, migration and invasion were examined in Huh7 cells, in which MPL is highly expressed. In an in vivo study, we subcutaneously transplanted Huh7 cells into nude mice that were divided into a TPO-treated group and a control group, and the tumor volume of each group was measured. Results MPL was expressed strongly in hepatocytes but not in other cell types. Among liver tumor cell lines, Huh7 showed the highest expression of MPL.

The active force-length relationships of the contractile component determined with model [CC] agree better with the theoretical sarcomere force-length relationship.”
“Objective: Epidemiological studies on psychiatric disorders are quite rare in the Arab World. This article reviews epidemiological studies on ADHD in all the Arab countries. Method: FDA-approved Drug Library All epidemiological studies on ADHD conducted from 1966 through th present were reviewed. Samples were drawn from the general community, primary

care clinical settings, and populations of traumatized children. Data on prevalence, gender differences, risk factors, comorbidity, and burden of ADHD were reviewed. Results: ADHD rates in Arab populations were similar to those in other cultures. Comparisons within Arab studies were difficult given the variability of methodology and instruments used. Conclusion: There is an important need for research on ADHD in the Arab World, not only to assess the national prevalence in children and adolescents, but also to look at the differential burden and treatment of this disorder, which has high levels of mental comorbidities and high impact across the life span. (J. of Att. Dis. 2009; 13(3) 211-222)”
“This study was carried out to investigate the effects of fluctuate lighting on performance of laying hens. Two programs were applied with 16 hours daily lighting: step-up (normal) lighting program as the control treatment and a fluctuate

lighting program AZD8931 datasheet of 2 W/m(2) for 45 min and 6 W/m(2) for 15 min. Egg weight, feed consumption, feed conversion ratio, hen-day egg production and hen-housed egg production of the laying hens were recorded for 46 weeks. No significant difference for hen-day and hen-housed egg production between the step up and fluctuate lighting programs learn more (P>0.05) were found. However, fluctuate lighting program resulted in

a significant increase in egg weight (P<0.05). Moreover, hens in the fluctuate lighting program consumed significantly less amount of feed and had a better feed conversion ratio than hens in the step-up lighting program (P<0.01). The results of the present study indicate that fluctuate lighting can be used for a profitable egg production.”
“Objectives: To reveal the success of boomerang-shaped chondroperichondrial graft (BSCPG) in pediatric chronic otitis media cases. Methods: A total of 43 pediatric patients (age 7-16 years) who had undergone type 1 tympanoplasty with the diagnosis of chronic otitis media between March 2010 and March 2013 were included in this retrospective study. The main outcome measures were the graft success rate and level of hearing improvement. Results: Graft intake success rate was 90.7%. Mean preoperative and postoperative air-bone gap values were 20.51 +/- 4.34 dB SPL and 9.32 +/- 5.64 dB SPL, respectively (p smaller than 0.001). Mean preoperative and postoperative pure tone average values were 28.6 +/- 3.52 and 12.24 +/- 5.

SbE had little anti-proliferative effect on the colorectal cancer cells; cancer cell growth was even observed at certain concentrations. ARF exerted potent anti-proliferative effects on the cancer cells. By contrast, BF increased cancer cell growth. ARF arrested cells in the S and G2/M phases, increased the expression of cyclins A and B1, and significantly induced cell apoptosis. Multiple genes in the mitochondrial

pathway are involved in ARF-induced apoptosis, and subsequent cellular functional analysis validated the involvement of this pathway. These results suggest that removing baicalin from SbE produces an ARF that significantly inhibits the growth of colorectal cancer cells, and that the mitochondrial apoptotic pathway plays a role in hydrophobic flavonoid-induced apoptosis.”
“Estrogen treatment exerts SB202190 solubility dmso a protective effect on experimental autoimmune encephalomyelitis (EAE) and is under clinical trial for multiple sclerosis therapy. Estrogens have been suspected to protect from CNS autoimmunity through their capacity to exert anti-inflammatory as well as neuroprotective effects. Despite the obvious impacts of estrogens on the pathophysiology of multiple sclerosis and EAE, the dominant cellular target that orchestrates the anti-inflammatory effect of 17 beta-estradiol

(E2) in EAE is still ill defined. Using conditional estrogen receptor (ER) alpha-deficient mice and bone marrow chimera experiments, we show that expression of ER alpha is critical in hematopoietic cells but not in endothelial ones to AG-014699 molecular weight mediate the E2 inhibitory effect on Th1 and Th17 cell priming, resulting in EAE protection. Furthermore, using newly created cell type-specific ER alpha-deficient mice, we demonstrate that ERa is required

in T lymphocytes, but neither in macrophages nor dendritic cells, for E2-mediated inhibition of Th1/Th17 cell differentiation and protection from EAE. Lastly, in absence of ERa in host nonhematopoietic tissues, we further show that ERa signaling in T cells is necessary and sufficient to mediate the inhibitory effect of E2 on EAE development. These data uncover T lymphocytes as a major and nonredundant cellular target responsible for the anti-inflammatory selleck chemicals effects of E2 in Th17 cell-driven CNS autoimmunity. The Journal of Immunology, 2011, 187: 2386-2393.”
“Argulosis hampers aquaculture production and alters the host physiology and growth. Azadirachtin is recognized as a potential antiparasitic agent against Argulus sp. The present study aimed to investigate the effect of different concentration of azadirachtin solution on haematological and serum biochemical parameters of Argulus-infested goldfish Carassius auratus. Ninety Argulus-infested goldfish were randomly divided into six equal groups.

Here, using a transgenic Arabidopsis line harboring the stress-inducible RESPONSIVE TO DEHYDRATION29A (RD29A) promoter-LUCIFERASE find more (LUC) reporter gene and

the cauliflower mosaic virus 35S promoter (35S)-NEOMYCIN PHOSPHOTRANSFERASE II (NPTII) antibiotic resistance marker gene, we characterize a ROS locus, ROS5, that encodes a protein in the small heat shock protein family. ROS5 mutations lead to the silencing of the 35S-NPTII transgene due to DNA hypermethylation but do not affect the expression of the RD29A-LUC transgene. ROS5 physically interacts with the histone acetyltransferase ROS4/INCREASED DNA METHYLATION1 (IDM1) and is required to prevent the DNA hypermethylation of some genes that are also regulated by ROS1 and IDM1. We propose that ROS5 regulates DNA demethylation by interacting with

IDM1, thereby creating a chromatin environment that facilitates the binding of ROS1 to erase DNA methylation.”
“PurposeTo develop and validate a respiratory motion compensation method for free-breathing cardiac cine imaging. MethodsA free-breathing navigator-gated cine steady-state free precession acquisition (Cine-Nav) was developed which preserves the equilibrium state of the net magnetization vector, maintains the high spatial and temporal resolutions of standard breath-hold (BH) acquisition, and images entire cardiac cycle. Cine image data is accepted only from cardiac cycles occurring entirely during end-expiration. Prospective validation was performed in 10 patients by obtaining in each three complete ventricular image stacks with different respiratory motion JNK-IN-8 compensation approaches: (1) BH, (2) free-breathing with 3 signal averages (3AVG), and (3) free-breathing with Cine-Nav. ResultsThe subjective

image quality score (1=worst, 4=best) for Cine-Nav (3.80.4) was significantly better than for 3AVG (2.2 +/- 0.5, P=0.002), and similar to BH (4.0 +/- 0.0, P=0.13). The blood-to-myocardium contrast ratio for Cine-Nav (6.3 +/- 1.5) was similar to selleck compound BH (5.9 +/- 1.6, P=0.52) and to 3AVG (5.6 +/- 2.5, P=0.43). There were no significant differences between Cine-Nav and BH for the ventricular volumes and mass. In contrast, there were significant differences between 3AVG and BH in all of these measurements but right ventricular mass. ConclusionFree-breathing cine imaging with Cine-Nav yielded comparable image quality and ventricular measurements to BH, and was superior to 3AVG. Magn Reson Med 73:1555-1561, 2015. (c) 2014 Wiley Periodicals, Inc.”
“Background Remifentanil has been suggested for the induction of general anaesthesia for caesarean section. We aimed to define remifentanil effects on maternal stress response as well as neonatal effects. Methods Relevant articles were retrieved by a systematic literature search. Randomized, controlled trials comparing remifentanil use before delivery with placebo were selected.

The present study indicates that NMN. produces significant beneficial effects by attenuating apoptosis and improving energy metabolism in a cellular model of PD. These results suggest that NMN may become a promising therapeutic drug for PD.”
“Ribosomal Protein L22 (RPL22) encodes a protein that is a component of the 60S subunit of

the ribosome. Variants in this gene have recently been linked to cancer development. Mutations in an A8 repeat in exon 2 were found in a recent study in 52% of microsatellite-unstable endometrial tumors. These tumors are particularly prone to mutations in repeats due to mismatch repair deficiency. We screened this coding repeat in our collection of microsatellite-unstable endometrial tumors (EC) and colorectal VDA inhibitor tumors (CRC). We found 50% mutation frequency for EC and 77% mutation frequency for CRC. These results confirm the previous study on the involvement of RPL22 in EC and, more importantly, reports for the first time such high mutation frequency in this gene in colorectal cancer. Furthermore, considering the high mutation frequency found,

our data point toward an important role for RPL22 in microsatellite instability carcinogenesis.”
“CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A Alisertib mouse ubiquitylation on lysine 124 (K124) and CENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone

chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A EVP4593 inhibitor K124R to centromeres and the interaction with HJURP, indicating that “signaling” ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.”
“Extra-axial ependymomas are exceedingly rare neuroectodermal tumors that arise outside the central nervous system. The majority behave in a benign clinical fashion. In this case, an elderly woman developed an intraperitoneal ependymoma that after surgical excision recurred twice over a period of twenty four years. At each presentation, the tumor demonstrated identical histologic appearances with prominent rosettes as well as perivascular pseudorosettes. Immunohistochemistry showed strong positivity for glial fibrilary acidic protein, estrogen receptors, CAM 5.2 and CD99 with weak staining for pankeratin.

Of note, MR revealed restricted diffusion within the mass. The presumptive diagnosis of dermoid tumor was made and the patient was scheduled for surgical resection. On operative exploration, a 1 cm thrombosed

aneurysm was revealed. Thrombosed aneurysms must be considered in the differential diagnosis for midline cerebral masses with negative angiogram and restricted diffusion. This distinction has implications for the clinical management of the patient.”
“Magnetic resonance image (MRI) systems with a much higher magnetic flux density were developed and applied for potential use in medical diagnostic. Recently,much attention has been paid to the biological effects of static, strong magnetic fields (SMF). With the 13 T SMF facility in the Institute of Plasma Physics, Chinese Academy of selleckchem Sciences, the present study focused on the cellular effects INCB024360 manufacturer of the SMF with 13 T on the cell viability and the cell cycle distribution in immortalized hamster cells, such as human-hamster hybrid (A(L)) cells, Chinese hamster ovary (CHO) cells,

DNA double-strand break repair deficient mutant (XRS-5) cells, and human primary skin fibroblasts (AG1522) cells. It was found that the exposure of 13 T SMF had less effect on the colony formation in either nonsynchronized or synchronized A(L) cells. Moreover, as compared to non-exposed groups, the re were slight differences Selleck Sapanisertib in the cell cycle distribution no matter in either synchronized or nonsynchronized immortalized hamster cells after exposure to 13 T SMF. However,it should be noted that the percentage of exposed AG1522 cells at G0/G1 phase was decreased by 10% as compared to the controls. Our data indicated that although

13 T SMF had minimal effects in immortalized hamster cells, the cell cycle distribution was slightly modified by SMF in human primary fibroblasts.”
“Obesity and adiponectin depletion have been associated with the occurrence of nonalcoholic fatty liver disease (NAFLD). The goal of this study was to identify the relationship between weight gain, adiponectin signaling, and development of nonalcoholic steatohepatitis (NASH) in an obese, diabetic mouse model. Leptin-receptor deficient (Lepr(db/db)) and C57BL/6 mice were administered a diet high in unsaturated fat (HF) (61%) or normal chow for 5 or 10 weeks. Liver histology was evaluated using steatosis, inflammation, and ballooning scores. Serum, adipose tissue, and liver were analyzed for changes in metabolic parameters, messenger RNA (mRNA), and protein levels. Lepr(db/db) HF mice developed marked obesity, hepatic steatosis, and more than 50% progressed to NASH at each timepoint. Serum adiponectin level demonstrated a strong inverse relationship with body mass (r = -20.82; P smaller than 0.0001) and adiponectin level was an independent predictor of NASH (13.6 mu g/mL; P smaller than 0.

Phosphorus, potassium, calcium, sodium and magnesium contents were 5020 ppm, 5576 ppm, 3562 ppm, 780 ppm and 372 ppm,

respectively wb% (wet basis) at the initial moisture content. The antioxidant activity and phenolic content of the grains were found to be 56.62% and 24.82 mu g GAE/mg db., respectively at the initial moisture content.”
“The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts BI 2536 datasheet with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition,

structure, stiffness and abundance contributes to several pathological find more conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.”
“Membrane proteins account for nearly a quarter of all genes, but their structure and function remain incompletely understood. Most membrane proteins have transmembrane (TM) domains made up of bundles of hydrophobic alpha-helices. The lateral association of TM helices within the lipid bilayer is a key stage see more in the

folding of membrane proteins. It may also play a role in signaling across cell membranes. Dimerization of TM helices is a simple example of such lateral association.\n\nMolecular dynamics (MD) simulations have been used for over a decade to study membrane proteins in a lipid bilayer environment. However, direct atomistic (AT) MD simulation of self-assembly of a TM helix bundle remains challenging. AT-MD may be complemented by coarse-grained (CG) simulations, in which small numbers of atoms are grouped together into particles. In this Account, we demonstrate how CG-MD may be used to simulate formation of dimers of TM helices. We also show how a serial combination of CG and AT simulation provides a multiscale approach for generating and refining models of TM helix dimers.\n\nThe glycophorin A (GpA) TM helix dimer represents a paradigm for helix-helix packing, mediated by a GxxxG sequence motif. It is well characterized experimentally and so is a good test case for evaluating computational methods. CG-MD simulations in which two separate TM helices are inserted in a lipid bilayer result in spontaneous formation of a right-handed GpA dimer, in agreement with NMR structures. CG-MD models were evaluated via comparison with data on destabilizing mutants of GpA. Such mutants increased the conformational flexibility and the dissociation constants of helix dimers.

These results provide new insights into metazoan GST diversity and the biochemical mechanisms used by marine organisms to cope with their chemically

defended prey. (c) 2008 Elsevier Inc. All rights reserved.”
“Austroplenckia populnea (Celastraceae), known as “marmelinho do campo”, Vorinostat mouse is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial. antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried Out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound

selleck products 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC(50) values of 0.7 mu g mL(-1) and 5.5 mu g mL(-1), respectively, while amphotericin B showed an IC(50) value of 0.1 mu g mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC(50) value of 52 mu g mL(-1), while compounds 2 and 3 displayed an IC(50) value of 18 mu g mL(-1). In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was

evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested.”
“Gating of ion channels by ligands is fundamental to cellular function, and ATP serves as both an energy source and a signaling molecule that modulates BMS-777607 purchase ion channel and transporter functions. The slowly activating K+ channel I-Ks in cardiac myocytes is formed by KCNQ1 and KCNE1 subunits that conduct K+ to repolarize the action potential. Here we show that intracellular ATP activates heterologously coexpressed KCNQ1 and KCNE1 as well as I-Ks in cardiac myocytes by directly binding to the C terminus of KCNQ1 to allow the pore to open. The channel is most sensitive to ATP near its physiological concentration, and lowering ATP concentration in cardiac myocytes results in I-Ks reduction and action potential prolongation. Multiple mutations that suppress I-Ks by decreasing the ATP sensitivity of the channel are associated with the long QT (interval between the Q and T waves in electrocardiogram) syndrome that predisposes afflicted individuals to cardiac arrhythmia and sudden death.