bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional activation of the anchoring protein SAP97 by heat shock factor (HSF)‐1 stabilizes Kv1.5 channels in HL‐1 cells
Authors: Ting YK , Morikawa K , Kurata Y , Li P , Bahrudin U , Mizuta E , Kato M , Miake J , Yamamoto Y , Yoshida A , Murata M , Inoue T , Nakai A , Shiota G , Higaki K , Nanba E , Ninomiya H , Shirayoshi Y , Hisatome I 
Published: January 2011

BACKGROUND AND PURPOSEThe expression of voltage‐dependent K+channels (Kv) 1.5 is regulated by members of the heat shock protein (Hsp) family. We examined whether the heat shock transcription factor 1 (HSF‐1) and its inducer geranylgeranylacetone (GGA) could affect the expression of Kv1.5 channels and its anchoring protein, synapse associated protein 97 (SAP97).EXPERIMENTAL APPROACHTransfected mouse atrial cardiomyocytes (HL‐1 cells) and COS7 cells were subjected to luciferase reporter gene assay and whole‐cell patch clamp. Protein and mRNA extracts were subjected to Western blot and quantitative real‐time polymerase chain reaction.KEY RESULTSHeat shock of HL‐1 cells induced expression of Hsp70, HSF‐1, SAP97 and Kv1.5 proteins. These effects were reproduced by wild‐type HSF‐1. Both heat shock and expression of HSF‐1, but not the R71G mutant, increased the SAP97 mRNA level. Small interfering RNA (siRNA) against SAP97 abolished HSF‐1‐induced increase of Kv1.5 and SAP97 proteins. A luciferase reporter gene assay revealed that the SAP97 promoter region (from −919 to −740) that contains heat shock elements (HSEs) was required for this induction. Suppression of SIRT1 function either by nicotinamide or siRNA decreased the level of SAP97 mRNA. SIRT1 activation by resveratrol had opposing effects. A treatment of the cells with GGA increased the level of SAP97 mRNA, Kv1.5 proteins and IKurcurrent, which could be modified with either resveratrol or nicotinamide.CONCLUSIONS AND IMPLICATIONSHSF‐1 induced transcription of SAP97 through SIRT1‐dependent interaction with HSEs; the increase in SAP97 resulted in stabilization of Kv1.5 channels. These effects were mimicked by GGA.
Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy
Authors: Meng LQ , Tang JW , Wang Y , Zhao JR , Shang MY , Zhang M , Liu SY , Qu L , Cai SQ , Li XM 
Published: January 2011

BACKGROUND AND PURPOSE The combination of Chinese herbs, Astragali Radix and Angelicae Sinensis Radix, could alleviate renal interstitial fibrosis. Astragaloside IV (AS‐IV) and ferulic acid (FA) are the two major active constituents in this combination. In this study, we employed rats with unilateral ureteral obstruction to determine whether AS‐IV and FA have the same renoprotective effects and investigated the mechanisms of this action.EXPERIMENTAL APPROACH Renal pathological changes were evaluated after treatment with AS‐IV, FA or AS‐IV + FA (AF) for 10 days. Meanwhile, the expression of transforming growth factor β1 (TGF‐β1), fibronectin, α‐smooth muscle actin (α‐SMA), phosphorylation of c‐Jun NH2‐terminal kinase (p‐JNK) and nitric oxide (NO) production in kidney were determined. The expressions of fibronectin, α‐SMA, mitogen‐activated protein kinases [JNK, extracellular signal‐regulated kinases (ERK), P38] in TGF‐β1‐treated NRK‐49F cells or interleukin‐1‐treated HK‐2 cells after AS‐IV, FA or AF were assessed.KEY RESULTS AF alleviated the infiltration of mononuclear cells, tubular atrophy and interstitial fibrosis; reduced the expression of fibronectin, α‐SMA, TGF‐β1 and p‐JNK; and dramatically increased the production of NO in obstructed kidneys. Neither AS‐IV nor FA alone improved renal damage, but both increased NO production. AF inhibited α‐SMA and fibronectin expression in NRK‐49F or HK‐2 cells. Furthermore, AF significantly inhibited IL‐1β‐induced JNK phosphorylation, without affecting ERK or P38 phosphorylation. Neither AS‐IV nor FA alone had any effect on the cells.CONCLUSIONS AND IMPLICATIONS AS‐IV synergizes with FA to alleviate renal tubulointerstitial fibrosis; this was associated with inhibition of tubular epithelial–mesenchymal transdifferentiation (EMT) and fibroblast activation, as well as an increase in NO production in the kidney.
Different sensitivities of rat skeletal muscles and brain to novel anti‐cholinesterase agents, alkylammonium derivatives of 6‐methyluracil (ADEMS)
Authors: Petrov Konstantin A , Yagodina Lilia O , Valeeva Guzel R , Lannik Natalya I , Nikitashina Alexandra D , Rizvanov Albert A , Zobov Vladimir V , Bukharaeva Ellya A , Reznik Vladimir S , Nikolsky Eugeny E , Vyskočil František 
Published: January 2011

BACKGROUND AND PURPOSEThe rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6‐methyluracil (ADEMS). This study evaluated several possible reasons for differing sensitivity between the diaphragm and limb muscles and between the muscles and the brain.EXPERIMENTAL APPROACHIncreased amplitude and prolonged decay time of miniature endplate currents were used to assess anti‐cholinesterase activity in muscles. In hippocampal slices, induction of synchronous network activity was used to follow cholinesterase inhibition. The inhibitor sensitivities of purified AChE from the EDL and brain were also estimated.KEY RESULTSThe intermuscular difference in sensitivity to ADEMS is partly explained caused by a higher level of mRNA and activity of 1,3‐bis[5(diethyl‐o‐nitrobenzylammonium)pentyl]‐6‐methyluracildibromide (C‐547)‐resistant BuChE in the diaphragm. Moreover, diaphragm AChE was more than 20 times less sensitive to C‐547 than that from the EDL. Sensitivity of the EDL to C‐547 dramatically decreased after treadmill exercises that increased the amount of PRiMA AChE(G4), but not ColQ AChE(A12) molecular forms. The A12 form present in muscles appeared more sensitive to C‐547. The main form of AChE in brain, PRiMA AChE(G4), was apparently less sensitive because brain cholinesterase activity was almost three orders of magnitude more resistant to C‐547 than that of the EDL.CONCLUSIONS AND IMPLICATIONSOur findings suggest that ADEMS compounds could be used for the selective inhibition of AChEs and as potential therapeutic tools.
Capsaicin in the periaqueductal gray induces analgesia via metabotropic glutamate receptor‐mediated endocannabinoid retrograde disinhibition
Authors: Liao H‐T , Lee H‐J , Ho Y‐C , Chiou L‐C 
Published: January 2011

BACKGROUND AND PURPOSECapsaicin, an agonist of transient receptor potential vanilloid 1 (TRPV1) channels, is pro‐nociceptive in the periphery but is anti‐nociceptive when administered into the ventrolateral periaqueductal gray (vlPAG), a midbrain region for initiating descending pain inhibition. Here, we investigated how activation of TRPV1 channels in the vlPAG leads to anti‐nociception.EXPERIMENTAL APPROACHWe examined synaptic transmission and neuronal activity using whole‐cell recordings in vlPAG slicesin vitroand hot‐plate nociceptive responses in rats after drug microinjection into the vlPAGin vivo.KEY RESULTSCapsaicin (1–10 µM) depressed evoked GABAergic inhibitory postsynaptic currents (eIPSCs) in vlPAG slices presynaptically, while increasing miniature excitatory PSC frequency. Capsaicin‐induced eIPSC depression was antagonized by cannabinoid CB1and metabotropic glutamate (mGlu5) receptor antagonists, and prevented by inhibiting diacylglycerol lipase (DAGL), which converts DAG into 2‐arachidonoylglycerol (2‐AG), an endocannabinoid. Capsaicin induced membrane depolarization in 2/3 neurons recorded but, overall, increased neuronal firings by increasing evoked postsynaptic potentials. Intra‐vlPAG capsaicin reduced hot‐plate responses in rats, effects blocked by CB1and mGlu receptor antagonists. Effects of capsaicin were antagonized by SB 366791, a TRPV1 channel antagonist.CONCLUSIONS AND IMPLICATIONSCapsaicin activated TRPV1s on glutamatergic terminals to release glutamate which activated postsynaptic mGlu5receptors, yielding 2‐AG from DAG by DAGL hydrolysis. 2‐AG induces retrograde inhibition (disinhibition) of GABA release via presynaptic CB1receptors. This disinhibition in the vlPAG leads to anti‐nociception by activating the descending pain inhibitory pathway. This is a novel TRPV1 channel‐mediated anti‐nociceptive mechanism in the brain and a new interaction between vanilloid and endocannabinoid systems.
An Explorative Study of Australian Nursing Scholars and Contemporary Scholarship
Authors: Stockhausen Lynette , Turale Sue 
Published: January 2011

Abstract Purpose: To explore Australian nurse scholars’ personal and professional perspectives on the nature and development of contemporary Australian scholarship, including its facilitators and barriers. Design and Methods: A qualitative exploratory design, with snowball sampling, identified 13 well‐regarded nurse scholars from Australian universities or clinical health services. Semistructured, in‐depth interviews were conducted in 2008–2009, and transcripts of data were subjected to Morse's content analysis method. Results: Four themes with supporting subthemes emerged: Views on Scholarship; Locations; Facilitators and Barriers; and Visioning the Future. New and reinforced information about Australian nursing scholarship was revealed. Conclusions: The study revealed contemporary Australian perspectives on nursing scholarship. It included participants’ personal and professional histories; definitions of the attributes of scholars; mentoring; and that educational and practice maturity contribute to contemporary definitions of nursing scholarship. Scholars, working in either academic or practice environments, provided points of difference on scholarship. High workloads associated with curricula, lack of recognition of a scholar's achievements, and securing research funding were seen as barriers to scholarship. Moreover, current scholars are aging, and there is a looming shortage of scholars prepared for the future. Urgent attention needs to be paid to capacity building of clinicians and academics for the future scholarship of Australian nursing. Clinical Relevance: Scholarship is seen as the hallmark of the intellectual pursuit of knowledge and understanding and is essential for the practice of nursing and improvements to health. Educators, policy makers, and nursing leaders need to clearly develop strategies to sustain Australian nursing scholarship for the future.
Faint resonantly scattered Lyα emission from the absorption troughs of damped Lyα systems at z ∽ 3
Authors: Rauch Michael , Haehnelt Martin G. 
Published: January 2011

Abstract
We demonstrate that the Lyα emission in the absorption troughs of a large sample of stacked damped Lyα absorption systems (DLAS) presented by Rahmani et al. is consistent with the spectral profiles and luminosities of a recently detected population of faint Lyα emitters at z∼ 3. This result supports the suggestion that the faint emitters are to be identified with the host galaxies of DLAS at these redshifts.
Near opposition photometry of comet C/2007 N3 (Lulin)
Authors: Joshi U. C. , Ganesh S. , Baliyan K. S. 
Published: January 2011

Abstract
Observations of comet C/2007 N3 (Lulin) were made at phase angles close to opposition (). Photometric observations were carried out during 2009 February 24–28, in the International Halley Watch (IHW) blue and red continuum and R broad-band using a photopolarimeter mounted on the 1.2-m telescope at Mount Abu Infrared Observatory. In all the bands, a significant linear increase in brightness with decreasing phase angle is detected for the above phase angle range. The phase coefficient [β= 0.040 ± 0.001 mag deg−1 estimated in the IHW red (6840 Å) filter band] is found to be independent of wavelength. No non-linear opposition surge is observed for phase angle . The linear increase in brightness with decreasing phase angle in the range mentioned earlier can be explained using the shadow hiding model. The colour of the comet is found to be similar to the solar colour, indicating the dominance of grains larger than 0.1 μm. A dip in the brightness of about 0.20 mag is seen at the phase angle .
Mechanism of cytochrome P450-3A inhibition by ketoconazole
Authors: Greenblatt David J , Zhao Yanli , Venkatakrishnan Karthik , Duan Su X , Harmatz Jerold S , Parent Sarah J , Court Michael H , von Moltke Lisa L 
Published: January 2011

AbstractObjectivesKetoconazole is extensively used as an index inhibitor of cytochrome P450-3A (CYP3A) activity in vitro and in vivo, but the mechanism of ketoconazole inhibition of CYP3A still is not clearly established.MethodsInhibition of metabolite formation by ketoconazole (seven concentrations from 0.01 to 1.0 µm) was studied in human liver microsomes (n = 4) at six to seven substrate concentrations for triazolam, midazolam, and testosterone, and at two substrate concentrations for nifedipine.Key findingsAnalysis of multiple data points per liver sample based on a mixed competitive–noncompetitive model yielded mean inhibition constant Ki values in the range of 0.011 to 0.045 µm. Ketoconazole IC50 increased at higher substrate concentrations, thereby excluding pure noncompetitive inhibition. For triazolam, testosterone, and midazolam α-hydroxylation, mean values of α (indicating the ‘mix’ of competitive and noncompetitive inhibition) ranged from 2.1 to 6.3. However, inhibition of midazolam 4-hydroxylation was consistent with a competitive process. Determination of Ki and α based on the relation between 50% inhibitory concentration values and substrate concentration yielded similar values. Pre-incubation of ketoconazole with microsomes before addition of substrate did not enhance inhibition, whereas inhibition by troleandomycin was significantly enhanced by pre-incubation.ConclusionsKetoconazole inhibition of triazolam α- and 4-hydroxylation, midazolam α-hydroxylation, testosterone 6β-hydroxylation, and nifedipine oxidation appeared to be a mixed competitive–noncompetitive process, with the noncompetitive component being dominant but not exclusive. Quantitative estimates of Ki were in the low nanomolar range for all four substrates.
Modulated pharmacokinetics and increased small intestinal toxicity of methotrexate in bilirubin-treated rats
Authors: Yokooji Tomoharu , Mori Nobuhiro , Murakami Teruo 
Published: January 2011

AbstractObjectivesThe effect of bilirubin treatment on the pharmacokinetics and small intestinal toxicity of methotrexate was evaluated in rats, since bilirubin and its glucuronide conjugates can suppress multidrug resistance-associated protein-mediated transport.MethodsRats were treated intravenously with bilirubin and the various clearances and tissue distribution of methotrexate were estimated under a steady-state plasma concentration. Intestinal toxicity induced by methotrexate was also evaluated by measuring the leakage of alkaline phosphatase (ALP) activity. Probenecid, an inhibitor for multidrug resistance-associated protein and organic anion transporters, was used for comparison.Key findingsThe treatment with bilirubin increased the steady-state plasma concentration and reduced biliary excretion clearance, urinary excretion clearance and intestinal exsorption clearance of methotrexate, as did treatment with probenecid. The intestinal absorption and jejunum distribution of methotrexate also significantly increased in bilirubin- and probenecid-treated rats. A greater leakage of ALP activity to the luminal fluid, with a lower ALP activity in the intestinal mucosal membrane after intestinal perfusion of methotrexate, was observed in bilirubin- and probenecid-treated rats.ConclusionsHyperbilirubinemia, which is involved under various disease states, may increase the small intestinal accumulation and toxicities of methotrexate, since high plasma concentrations of conjugated bilirubin can suppress the function of multidrug resistance-associated proteins, which facilitate the efflux of methotrexate out of cells.
Hospital Epidemiology and Infection Control in Acute-Care Settings
Authors: Sydnor Emily R. M. , Perl Trish M. 
Published: January 2011

SUMMARY
Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program.
Zoonotic Potential and Molecular Epidemiology ofGiardiaSpecies and Giardiasis
Authors: Feng Yaoyu , Xiao Lihua 
Published: January 2011

SUMMARYMolecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission ofGiardiaspecies and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution ofGiardia duodenalisgenotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for someG. duodenalisgenotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics ofG. duodenalisin humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of variousG. duodenalisgenotypes, and the ecology of environmental contamination.
Real-Time Quantitative PCR Assay for Monitoring of Nervous Necrosis Virus Infection in Grouper Aquaculture
Authors: Kuo Hsiao-Che , Wang Ting-Yu , Chen Peng-Peng , Chen Young-Mao , Chuang Hui-Ching , Chen Tzong-Yueh 
Published: January 2011

ABSTRACT

Viral nervous necrosis caused by nervous necrosis virus (NNV) exacts a high mortality and results in huge economic losses in grouper aquaculture in Taiwan. The present study developed a real-time quantitative PCR (qPCR) method for NNV monitoring. The assay showed a strong linear correlation (
r
2
= 0.99) between threshold cycle (

C
T

) and RNA quantities, which allowed identification of infected groupers by the

C
T

value and could be exploited to warn of NNV infection prior to an outbreak in grouper fish farms. Real-time qPCR also confirmed the copious content of NNV in grouper fin, similar to that in primary tissues; the result was verified by using
in situ
reverse transcription-PCR (RT-PCR). This indicated that grouper fin was a suitable sample for NNV detection, in a manner that could be relatively benign to the fish. The rapid spread of NNV infection to the entire population of affected farms was evident. The developed real-time qPCR method is rapid, highly sensitive, and applicable to routine high-throughput detection of large numbers of samples and has potential as a suitable tool for diagnostic, epidemiological, and genetic studies of grouper aquaculture.
Smad-Interacting Protein-1 and MicroRNA 200 Family Define a Nitric Oxide–Dependent Molecular Circuitry Involved in Embryonic Stem Cell Mesendoderm Differentiation
Authors: Rosati Jessica , Spallotta Francesco , Nanni Simona , Grasselli Annalisa , Antonini Annalisa , Vincenti Sara , Presutti Carlo , Colussi Claudia , D'Angelo Carmen , Biroccio Anna , Farsetti Antonella , Capogrossi Maurizio C. , Illi Barbara , Gaetano Carlo 
Published: January 2011

Objective—
Smad-interacting protein-1 (Sip1/ZEB2) is a transcriptional repressor of the telomerase reverse transcriptase catalytic subunit (Tert) and has recently been identified as a key regulator of embryonic cell fate with a phenotypic effect similar, in our opinion, to that reported for nitric oxide (NO). Remarkably, SIP1/ZEB2 is a known target of the microRNA 200 (miR-200) family. In this light, we postulated that Sip1/ZEB2 and the miR-200 family could play a role during the NO-dependent differentiation of mES.

Methods and Results—
The results of the present study show that Sip1/ZEB2 expression is downregulated during the NO-dependent expression of mesendoderm and early cardiovascular precursor markers, including Flk1 and CXCR4 in mES. Coincidently, members of the miR-200 family, namely miR-429, -200a, -200b, and -200c, were transcriptionally induced in parallel to mouse Tert. This regulation occurred at the level of chromatin. Remarkably, miR-429/miR-200a overexpression or Sip1/ZEB2 knockdown by short hairpin RNA interference elicited a gene expression pattern similar to that of NO regardless of the presence of leukemia inhibitory factor.

Conclusion—
These results are the first demonstrating that the miR-200 family and Sip1/ZEB2 transcription factor are regulated by NO, indicating an unprecedented molecular circuitry important for telomerase regulation and early differentiation of mES.
Disruption of the Apelin-APJ System Worsens Hypoxia-Induced Pulmonary Hypertension
Authors: Chandra Suparna M. , Razavi Hedi , Kim Jongmin , Agrawal Rani , Kundu Ramendra K. , de Jesus Perez Vinicio , Zamanian Roham T. , Quertermous Thomas , Chun Hyung J. 
Published: January 2011

Objective—
The G-protein–coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH).

Methods and Results—
We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Micro-computed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2 (KLF2), a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and KLF2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls.

Conclusion—
These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease.