Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of Ca2+ Activation of the NADPH Oxidase 5 (NOX5)*

NADPH oxidase 5 (NOX5) is a homologue of the gp91phox subunit of the phagocyte NADPH oxidase. NOX5 is expressed in lymphoid organs and testis and distinguished from the other NADPH oxidases by its unique N terminus, which contains three canonical EF-hands, Ca2+-binding domains. Upon heterologous expression, NOX5 was shown to generate superoxide in response to intracellular Ca2+ elevations. In this study, we have analyzed the mechanism of Ca2+ activation of NOX5. In a cell-free system, Ca2+ elevations triggered superoxide production by NOX5 (Km = 1.06 μm) in an NADPH- and FAD-dependent but cytosol-independent manner. That result indicated a role for the N-terminal EF-hands in NOX5 activation. Therefore, we generated recombinant proteins of NOX5 N terminus and investigated their interactions with Ca2+. Flow dialysis experiments showed that NOX5 N terminus contained four Ca2+-binding sites and allowed us to define the hitherto unidentified fourth, non-canonical EF-hand. The EF-hands of NOX5 formed two pairs: the very N-terminal pair had relatively low affinity for Ca2+, whereas the more C-terminal pair bound Ca2+ with high affinity. Ca2+ binding caused a marked conformation change in the N terminus, which exposed its hydrophobic core, and became able to bind melittin, a model peptide for calmodulin targets. Using a pull-down assay, we demonstrate that the regulatory N terminus and the catalytic C terminus of NOX5 interact in a Ca2+-dependent way. Our results indicate that the Ca2+-induced conformation change of NOX5 N terminus led to enzyme activation through an intra-molecular interaction. That represents a novel mechanism of activation among NAD(P)H oxidases and Ca2+-activated enzymes.
In Practice CKD – Mineral and Bone Disorder Management in Kidney Transplant Recipients

Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD–mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD–mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23– parathyroid hormone–vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease. Am J Kidney Dis. xx(x):xxx. © 2012 by the National Kidney Foundation, Inc.
Identification of mycoplasma colonies by immunobinding

An immunobinding assay was developed to identify mycoplasma colonies on agar in pure and mixed cultures. Mycoplasma colonies on agar were transferred to nitrocellulose. The nitrocellulose was treated with specific rabbit antisera against mycoplasmas, peroxidase-conjugated goat anti-rabbit immunoglobulin G, 4-chloro-1-naphthol, and H2O2. Purple developed in the presence of specific reactions. The procedure was superior to epifluorescence.
AMP‐activated protein kinase in BK‐channel regulation and protection against hearing loss following acoustic overstimulation

The energy‐sensing AMP‐activated serine/threonine protein kinase (AMPK) confers cell survival in part by stimulation of cellular energy production and limitation of cellular energy utilization. AMPK‐sensitive functions further include activities of epithelial Na+ channel ENaC and voltage‐gated K+ channel KCNE1/KCNQ1. AMPK is activated by an increased cytosolic Ca2+ concentration. The present study explored whether AMPK regulates the Ca2+‐sensitive large conductance and voltage‐gated potassium (BK) channel. cRNA encoding BK channel was injected into Xenopus oocytes with and without additional injection of wild‐type AMPK (AMPKα1+AMPKβ1+AMPKγ1), constitutively active AMPKγR70Q, or inactive AMPKαK45R. BK‐channel activity was determined utilizing the 2‐electrode voltage‐clamp. Moreover, BK‐channel protein abundance in the cell membrane was determined by confocal immunomicroscopy. As BK channels are expressed in outer hair cells (OHC) of the inner ear and lack of BK channels increases noise vulnerability, OHC BK‐channel expression was examined by immunohistochemistry and hearing function analyzed by auditory brain stem response measurements in AMPKα1‐deficient mice (ampk–/–) and in wild‐type mice (ampk+/+). As a result, coexpression of AMPK or AMPKγR70Q but not of AMPKαK45R significantly enhanced BK‐channel‐mediated currents and BK‐channel protein abundance in the oocyte cell membrane. BK‐channel expression in the inner ear was lower in ampk–/– mice than in ampk+/+ mice. The hearing thresholds prior to and immediately after an acoustic overexposure were similar in ampk–/– and ampk+/+ mice. However, the recovery from the acoustic trauma was significantly impaired in ampk–/–mice compared to ampk+/+ mice. In summary, AMPK is a potent regulator of BK channels. It may thus participate in the signaling cascades that protect the inner ear from damage following acoustic overstimulation. —Föller, M. , Jaumann, M. , Dettling, J., Saxena, A. , Pakladok, T. , Munoz, C. , Ruth, P., Sopjani, M. , Seebohm, G. , Rüttiger, L. , Knipper, M. , Lang, F. AMP‐activated protein kinase in BK‐channel regulation and protection against hearing loss following acoustic overstimulation. FASEB J. 26, 4243–4253 (2012). www.fasebj. org
Pathogenic characterization in mice of Neospora caninum isolates obtained from asymptomatic calves

SUMMARY In this study, we characterized 8 new isolates obtained from healthy but congenitally infected calves using a BALB/c mouse model. Neospora caninum-infected mice survived without exhibiting any clinical signs of disease. Nevertheless, differences among isolates in parasite organ distribution, parasite burden and the severity of histopathological lesions were determined. Mice infected with the Nc-Spain 5H, Nc-Spain 7 and Nc-Spain 9 isolates showed higher parasite burdens and more severe brain lesions during the late phase of infection compared to mice infected with the Nc-Spain 2H, Nc-Spain 3H or Nc-Spain 6 isolates. Furthermore, differences in the immunoglobulin IgG1 and IgG2a isotype kinetics induced by these isolates were observed, with a more rapid IgG2a response seen in mice infected with the Nc-Spain 2H and Nc-Spain 3H isolates. These results confirm the intra-species variability of N. caninum pathogenicity.
Lack of segmental selectivity in elimination of synapses from soleus muscle of new‐born rats.

The elimination of polyneuronal innervation from neonatal rat soleus muscle was studied by comparing the extent of synapse loss by motor neurones emerging through each of the two spinal nerves (L4 and L5) supplying the muscle. The fraction of muscle fibres receiving innervation from the L4 spinal nerve declined from an average of 75% in 6‐day‐old animals (when all fibres are polyneuronally innervated) to 18% in animals older than 16 days (when almost all muscle fibres are singly innervated). By comparison innervation by the L5 spinal nerve declined from 99% of the fibres at 6 days to 83% of the fibres after 16 days. As a result of synapse elimination there is a greater reduction in the innervation of the muscle by the L4 nerve. The difference in loss of muscle fibres innervated by L4 vs. L5 was not, however, due to a greater degree of synapse elimination of L4 motor nerve terminals. As shown by measurements of the sizes of motor units, both L4 and L5 have units which on average are about four to five times larger at 6 days than at the conclusion of synapse elimination. Thus L4 and L5 motor neurones undergo approximately the same degree of size reduction. The apparently disproportionate loss of muscle innervation by the L4 nerve is explained by the fact that L4 usually contains only a small portion of the total of soleus motor neurones. I therefore conclude that there is no selective loss of synapses based on spinal origin of motor neurones.
Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES Muscle wasting, a common complication in chronic kidney disease (CKD), contributes to poor outcomes. Mitochondrial biogenesis is critical for the maintenance of skeletal muscle function and structural integrity. The present study--a secondary analysis from a published randomized controlled trial--examined the effect of resistance exercise training on skeletal muscle mitochondrial (mt)DNA copy number and determined its association with skeletal muscle phenotype (muscle mass and strength). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Twenty-three patients with moderate-to-severe CKD were randomized to resistance training (n = 13) or an attention-control (n = 10) group for 12 weeks. After a run-in period of a low-protein diet that continued during the intervention, mtDNA copy number in the vastus lateralis muscle was estimated by quantitative real-time PCR at baseline and 12 weeks. RESULTS Participants mean age was 64 +/- 10 (SD) years and median (interquartile range, IQR) GFR 27.5 (37.0) ml/min. There were no differences between groups at baseline. Median (IQR) mtDNA copy number was 13,713 (10,618). There was a significant increase in muscle mtDNA with exercise compared with controls (1306 [13306] versus -3747 [15467], P = 0.01). The change in muscle mtDNA copy number was positively correlated with previously reported changes in types I and II muscle fiber cross-sectional area. CONCLUSIONS In this pilot study, resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. This finding suggests that the mitochondrial dysfunction observed with chronic disease could potentially be restored with this exercise modality and should be investigated further.
Trisectors like Bisectors with equilaterals instead of Points

Spiridon A. KuruklisEurobank,Group IT Security and Risk Management DivisionAthens, GREECEskuruklis@gmail.comABSTRACTIt is established that among all Morley triangles of △ABC the only equilaterals are theones determined by the intersections of the proximal to each side of △ABC trisectorsof either interior, or exterior, or one interior and two exterior angles. It is showedthat these are in fact equilaterals, with uniform proofs. It is then observed that theintersections of the interior trisectors with the sides of the interior Morley equilateralform three equilaterals. These along with Pasch’s axiom are utilized in showing thatMorley’s theorem does not hold if the trisectors of one exterior and two interior anglesare used in its statement.RESUMENSe establece que entre todos los tri´angulos de Morley de △ABC, los u´nicos equil´aterosson theones determinados por las intersecciones del proximal a cada lado de los trisec-tores △ABC de angulos interior, o exterior, o uno interior y dos exteriores. Se muestraque estos estan en tri´angulos equil´ateros de facto con demostraciones uniformes. Luego,se observa que las intersecciones de trisectores interiores con los lados de un equil´ateroMorley interior forman tres tri´angulos equil´ateros. Junto con el axioma de Pasch, seutilizan para probar que el Teorema de Morley no se satisface si se usan los trisectoresde un angulo exterior y dos interiores.Keywords and Phrases: Angle trisection, Morley’s theorem, Morley trisector theorem, Morleytriangle, Morley interior equilateral, Morley central equilateral, Morley exterior equilateral, Pasch’saxiom, Morley’s magic, Morley’s miracle, Morley’s mystery.2010 AMS Mathematics Subject Classiﬁcation: 51M04
PULMONARY VASCULAR REACTIVITY OF SPONTANEOUSLY HYPERTENSIVE RATS IS EXACERBATED IN RESPONSE TO THE CENTRAL ADMINISTRATION OF EXOGENOUS NITRIC OXIDE

1 Centrally, nitric oxide (NO) is a sympathoinhibitory substance. Spontaneously hypertensive rats (SHR) have an impaired central nitroxidergic system and, consequently, NO‐mediated decrease in sympathetic activity is exacerbated in SHR compared with Wistar‐Kyoto (WKY) rats. We have demonstrated previously that acute hypoxic pulmonary vasoconstriction (HPV) is enhanced by central NO administration. Therefore, in the present study, we hypothesized that accentuation of the HPV by NO would be exacerbated in SHR compared with WKY rats. 2 Mean pulmonary arterial pressure, systemic mean arterial blood pressure, cardiac output and heart rate were measured in pentobarbitone‐anaesthetized, artificially ventilated, male SHR and WKY rats. The brief, transient response to a bolus intracerebroventricular (i.c.v.) dose of NG‐nitro‐l‐arginine methyl ester (l‐NAME; 150 µg in 10 µL) was recorded in all rats. Upon recovery, rats were exposed to acute hypoxia (10% O2 for 4 min) before and after the i.c. v. administration of the NO donor 3‐[4‐morpholinyl]‐sydnonimine‐hydrochloride (SIN‐1; 100 µg in 10 µL). 3 In WKY rats, central inhibition of NO synthesis by l‐NAME caused a mild increase in tonic pulmonary vascular tone and induced a large systemic pressor response. These responses were not observed in SHR. In contrast, SIN‐1 failed to alter tonic pulmonary vascular tone, although it enhanced the HPV in WKY rats and, significantly more so, in SHR. 4 These results confirm that accentuation of the HPV by NO is exacerbated in SHR compared with WKY rats. The mechanism(s) by which the HPV is accentuated by central NO remains to be fully elucidated, but is likely to be associated with the sympathoinhibitory effects of NO and, if so, supports the idea that the nitroxidergic system of the SHR is impaired. Further electrophysiological studies are essential to confirm these assumptions.
Language Dominance and PerformanceOutcomes in Bilingual Pronunciation

A significant body of experimental and naturalistic studies has demonstrated that bilingual speakers of Romance language–English pairings are capable of creating separate phonetic categories for the production of voiceless stops, measured as voiced onset time (VOT), across their languages (Caramazza, Yeni-Komshian, Zurif & Carbone, 1973; Flege & Eefting, 1987: Major, 1992, interalia). However, bilinguals equally tend to show altered, either converged or exaggerated VOT values in one or both of their languages relative to the those of monolingual speakers. Sancier and Fowler’s (1997) case study of a Portuguese-English bilingual suggests that a bilingual’s VOT values are not fixed; rather they tend to drift according to the ambient speech environment. They label the phenomenon observed in their study as “gestural drift” because the gradient changes to VOT are observed in both the speaker’s L1 (Portuguese) and L2 (English). Gestural drift is consistent with Grosjean’s (2001) notion of “language mode” and with Escudero and Boersma’s (2002) “perceptual mode. ” Such research contends that bilinguals’ language use is malleable in that they may behave differently according to which language they are producing or perceiving at a given time. The focus of the present study is to examine the effect of language mode on VOT production in real time via the use of a linguistic code-switching task. As code-switching arguably requires bilinguals to activate both languages simultaneously, it is expected that speakers should manifest VOT values in code-switched tasks that differ significantly from their productions in monolingual modes. At issue is the extent to which each of a bilingual’s component languages is affected by code-switching. Gestural drift implies that they should be equally vulnerable to inter-linguistic influence. But if phonetic categories are established early in childhood then we would expect that bilinguals’ L1 categories should be resistant to incursions from the L2 but not vice-versa.
Material science and device physics in SiC technology for high-voltage power devices

Power semiconductor devices are key components in power conversion systems. Silicon carbide (SiC) has received increasing attention as a wide-bandgap semiconductor suitable for high-voltage and low-loss power devices. Through recent progress in the crystal growth and process technology of SiC, the production of medium-voltage (600–1700 V) SiC Schottky barrier diodes (SBDs) and power metal–oxide–semiconductor field-effect transistors (MOSFETs) has started. However, basic understanding of the material properties, defect electronics, and the reliability of SiC devices is still poor. In this review paper, the features and present status of SiC power devices are briefly described. Then, several important aspects of the material science and device physics of SiC, such as impurity doping, extended and point defects, and the impact of such defects on device performance and reliability, are reviewed. Fundamental issues regarding SiC SBDs and power MOSFETs are also discussed.
Perceived rate of monotic and dichotically alternating clicks.

Subjects compared the apparent repetition rates of trains of dichotically alternating clicks, presented at 1–40/sec, with the apparent rates of monotic trains. All dichotic rates were underestimated, the degree of underestimation varying from a few percent at 1/sec to 35%–40% from about 7.5/sec onward. The latter rate corresponds to the switching rates producing minimal intelligibility of speech presented alternately to the two ears. Unlike the results of switched‐speech experiments, however, the present results appear to be unequivocally interpretable as indicating a difficulty in integrating dichotically alternating inputs into a single percept.
Experimental spinal cord angiography.

Abstract The clinical value of selective spinal cord angiography in the management of arteriovenous malformations and tumours of the spinal cord is well established. It is obvious, however, that two conditions must be met if this method is to become a more frequently used diagnostic procedure. The technique needs to be simplified, and its clinical indications must be expanded to include the common and important obstructive vascular disease. To attain the two above-mentioned goals, we have been carrying our experimental spinal cord angiography in 82 rhesus monkeys. Successful demonstration of the spinal cord vessels has been obtained with both techniques tested: Vasopressor potentiation and abdominal compression aortography. In vivo angiographic and “post-mortem” microangiographic studies have also been carried out after surgical occlusion of the major thoracolumbar spinal cord arteries. Particular emphasis has been placed upon the recognition of collateral circulation patterns. Effects of the surgically a.
Measuring the Welfare Effects of Residential Energy Efficiency Programs

This paper sets out a framework to evaluate the welfare impacts of residential energy efficiency programs in the presence of imperfect information, behavioral biases, and externalities, then estimates key parameters using a 100,000-household field experiment. Several results run counter to conventional wisdom: we find no evidence of informational or behavioral failures thought to reduce program participation, there are large unobserved benefits and costs that traditional evaluations miss, and realized energy savings are only 58 percent of predictions. In the context of the model, the two programs we study reduce social welfare by $0.18 per subsidy dollar spent, both because subsidies are not well-calibrated to estimated externality damages and because of self-selection induced by subsidies that attract households whose participation generates low social value. However, the model predicts that perfectly calibrated subsidies would increase welfare by $2.53 per subsidy dollar, revealing the potential of energy efficiency programs.
Estradiol‐17β‐D‐glucuronide (E‐17G) cholestasis in perfused rat liver: Fate of E‐17G and choleretic responses to bile salts

This study was designed to test the hypothesis that increasing the infusion rate of bile salts could overcome drug‐induced cholestasis. Cholestasis was induced by administration of 17.5 μmol/L estradiol‐17β‐D‐glucuronide during the infusion of taurocholate, tauroursodeoxycholate or dehydrocholate at 20 nmol/min/gm liver. After 30 min, a bolus of 10 μmol of the bile salts was added to the perfusate, and the infusion rate of each bile salt was increased. Taurocholate at a rate of 62 or 125 nmol/min/gm liver, caused a prompt dose‐dependent increase of the depressed bile flow and bile salt excretion. A higher rate of taurocholate infusion (180 nmol/min/gm liver) was less effective than either the 62 or 125 rate in increasing bile flow. Infusion of tauroursodeoxycholate at 250 or 390 nmol/min/gm liver also led to a dose‐dependent recovery. Further increase of tauroursodeoxycholate infusion rate to 580 nmol/min/gm liver did not provide any additional recovery in bile flow. Dehydrocholate, at rates of 62 or 125 nmol/min/gm liver, gave only a slight enhancement of bile flow. Both taurocholate and tauroursodeoxycholate caused a marked removal of the estradio‐17β‐D‐glucuronide, which had accumulated in the liver. At lower taurocholate infusion rates, the estradiol‐17β‐D‐glucuronide was excreted mainly in the bile. At the highest rate, however, biliary excretion of estradiol‐17β‐D‐glucuronide declined significantly, and a marked back‐efflux of the estrogen into the perfusate was noted. In contrast, tauroursodeoxycholate led to enhanced biliary estradiol‐17β‐D‐glucuronide excretion at all increased tauroursodeoxycholate infusion rates and to only a small increase in back‐efflux of estradiol‐17β‐D‐glucuronide at the two highest tauroursodeoxycholate infusion rates. Dehydrocholate, at higher infusion rates, did not enhance estradiol‐17β‐D‐glucuronide biliary transport or regurgitation. The effects of taurocholate, tauroursodeoxycholate and dehydrocholate on bile flow, bile salt secretion and estrogen excretion during estradiol‐17β‐D‐glucuronide cholestasis paralleled their relative hydrophobicity and detergent effect. Taurocholate infusion also decreased the adverse effect of estradiol‐17β‐D‐glucuronide on sucrose clearance. Among the bile salts used, taurocholate was the most effective in increasing bile flow during estradiol‐17β‐D‐glucuronide cholestasis but showed some toxicity. Although less effective, tauroursodeoxycholate did not exert adverse effects. Accordingly, tauroursodeoxycholate has a higher therapeutic index that might be relevant in efforts to treat estrogen‐induced cholestasis by administration of bile salts. (HEPATOLOGY 1990; 11:735‐742.)