bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the Novel BKCa Channel Opener LDD175 on the Modulation of Corporal Smooth Muscle Tone
Authors: Sung Hyun Hwan , Choo Seol Ho , Han Deok Hyun , Chae Mee Ree , Kang Su Jeong , Park Chul-Seung , So Insuk , Park Jong Kwan , Lee Sung Won 
Published: November 2014

ABSTRACT

Introduction
The BKCa channel has been reported to play an important role in erectile function. Recently, novel BKCa channel activator, LDD175, was introduced.

Aim
This study aims to investigate whether LDD175 relaxes corporal smooth muscle (CSM) via BKCa channel activation.

Methods
After isolation of CSM strip from a male rabbit model, contraction studies using organ bath was performed. Isolating human tissue and cell cultures, electrophysiological studies were done via whole-cell patch-clamp recording.

Main Outcome Measures
Vasodilatory effects of LDD175 were evaluated by cumulative addition ranging from 10−7 to 10−4 M in corpus cavernosal strips after precontraction with 10−5 M phenylephrine via organ bath system. Using cultured human CSM cells, patch-clamp recording was performed. Erectile function was measured by in vivo rat cavernous nerve stimulation.

Results
LDD175 caused an endothelium-independent relaxation of corporal tissues, and this effect was abolished by pretreatment with iberiotoxin. The relaxation effect of 10−4 M LDD175 was greater than that of 10−6 M udenafil (54.0 ± 3.1% vs. 34.5 ± 3.9%, P &lt; 0.05); 10−5 M LDD175 with 10−6 M udenafil caused a greater relaxation effect on strips than 10−5 M LDD175 or 10−6 M udenafil alone (50.7%, 34.1%, vs. 20.7%, respectively, P &lt; 0.001). In patch-clamp recordings, LDD175 increased K+ currents in a dose-dependent manner, and washout of LDD175 or the addition of iberiotoxin fully reversed the increase. Intravenous LDD175 improved erectile function measured by area under the curve (AUC) of the intracavernosal pressure (ICP)/arterial blood pressure (ABP) ratio (1,612.1 ± 135.6 vs. 1,093.7 ± 123.1, P &lt; 0.05). There was no difference between 10 mg/kg LDD175 and 1 mg/kg udenafil regarding maximal ICP, maximal ICP/ABP ratio, and the AUC of the ICP/ABP ratio (P &gt; 0.05).

Conclusions
LDD175 leads to an endothelium-independent relaxation of erectile tissue, primarily through the opening of BKCa channels. The results suggest that LDD175 might be a new candidate treatment for erectile dysfunction.
Specific N‐terminal cleavage of ribosomal protein L27 in Staphylococcus aureus and related bacteria
Authors: Wall Erin A. , Caufield J. Harry , Lyons Charles E. , Manning Keith A. , Dokland Terje , Christie Gail E. 
Published: November 2014

SummaryRibosomal protein L27 is a component of the eubacterial large ribosomal subunit that has been shown to play a critical role in substrate stabilization during protein synthesis. This function is mediated by the L27 N‐terminus, which protrudes into the peptidyl transferase center. In this report, we demonstrate that L27 in Staphylococcus aureus and other Firmicutes is encoded with an N‐terminal extension that is not present in most Gram‐negative organisms and is absent from mature ribosomes. We have identified a cysteine protease, conserved among bacteria containing the L27 N‐terminal extension, which performs post‐translational cleavage of L27. Ribosomal biology in eubacteria has largely been studied in the Gram‐negative bacterium Escherichia coli; our findings indicate that there are aspects of the basic biology of the ribosome in S. aureus and other related bacteria that differ substantially from that of the E. coli ribosome. This research lays the foundation for the development of new therapeutic approaches that target this novel pathway.
VIII. CONCLUSIONS AND FUTURE DIRECTIONS OF THE RESEARCH ON PHYSICAL ACTIVITY AND CHILDHOOD COGNITIVE AND BRAIN HEALTH
Authors: Hillman Charles H. 
Published: November 2014

ABSTRACTThis chapter serves as a summary to the monograph. The main purpose is to concisely merge the individual chapters into a cohesive summary around markers of health behaviors and their relation to childhood cognition and brain health. In addition, future directions for research in this area are briefly discussed with the goal of shaping future research in several directions. Issues surrounding the need for causality and ethical considerations are also described. Finally, this chapter places the link between health behaviors and cognition within the greater context of the educational environment, lifelong health, and effective function.
The c‐di‐GMP phosphodiesterase BifA is involved in the virulence of bacteria from the Pseudomonas syringae complex
Authors: Aragón Isabel M. , Pérez‐Mendoza Daniel , Gallegos María‐Trinidad , Ramos Cayo 
Published: November 2014

SummaryIn a recent screen for novel virulence factors involved in the interaction between Pseudomonas savastanoi pv. savastanoi and the olive tree, a mutant was selected that contained a transposon insertion in a putative cyclic diguanylate (c‐di‐GMP) phosphodiesterase‐encoding gene. This gene displayed high similarity to bifA of Pseudomonas aeruginosa and Pseudomonas putida. Here, we examined the role of BifA in free‐living and virulence‐related phenotypes of two bacterial plant pathogens in the Pseudomonas syringae complex, the tumour‐inducing pathogen of woody hosts, P. savastanoi pv. savastanoi NCPPB 3335, and the pathogen of tomato and Arabidopsis, P. syringae pv. tomato DC3000. We showed that deletion of the bifA gene resulted in decreased swimming motility of both bacteria and inhibited swarming motility of DC3000. In contrast, overexpression of BifA in P. savastanoi pv. savastanoi had a positive impact on swimming motility and negatively affected biofilm formation. Deletion of bifA in NCPPB 3335 and DC3000 resulted in reduced fitness and virulence of the microbes in olive (NCPPB 3335) and tomato (DC3000) plants. In addition, real‐time monitoring of olive plants infected with green fluorescent protein (GFP)‐tagged P. savastanoi cells displayed an altered spatial distribution of mutant ΔbifA cells inside olive knots compared with the wild‐type strain. All free‐living phenotypes that were altered in both ΔbifA mutants, as well as the virulence of the NCPPB 3335 ΔbifA mutant in olive plants, were fully rescued by complementation with P. aeruginosa BifA, whose phosphodiesterase activity has been demonstrated. Thus, these results suggest that P. syringae and P. savastanoi BifA are also active phosphodiesterases. This first demonstration of the involvement of a putative phosphodiesterase in the virulence of the P. syringae complex provides confirmation of the role of c‐di‐GMP signalling in the virulence of this group of plant pathogens.
Double‐blinded, randomized controlled trial of N‐acetylcysteine for prevention of acute kidney injury in high risk patients undergoing off‐pump coronary artery bypass
Authors: Song Jong Wook , Shim Jae Kwang , Soh Sarah , Jang Jaewon , Kwak Young Lan 
Published: November 2014

AbstractAimThe aim of this study was to investigate the influence of perioperative N‐acetylcysteine (NAC) administration, a known antioxidant, on the incidence of acute kidney injury (AKI) after off‐pump coronary bypass surgery (OPCAB) in patients with known risk factors of AKI.MethodsOne hundred and seventeen patients with ≥1 of the following risk factors of AKI were randomized into either the control (n = 57) or the NAC (n = 60) group; (i) preoperative serum creatinine >1.4 mg/dL; (ii) left ventricular ejection fraction <35% or congestive heart failure (iii) age >70 years (iv) diabetes or (v) re‐operation. Patients in the NAC group received 150 mg/kg of NAC IV bolus at anaesthetic induction followed by a continuous infusion at 150 mg/kg per day for 24 h. AKI was diagnosed based on Acute Kidney Injury Network criteria during 48 h postoperatively.ResultsThe incidence of AKI was 32% (19/60) and 35% (20/57) in the control and the NAC group, respectively (P = 0.695). The serum concentrations of creatinine and cystatin C were similar between the groups throughout the study period. Fluid balance including the amount of blood loss and transfusion requirement were similar between the groups except the amount of postoperative urine output, which was higher in the control group compared with the NAC group (5528 ± 1247 mL vs. 4982 ± 1185 mL, control vs. NAC, P = 0.017).ConclusionPerioperative administration of NAC did not prevent the development of postoperative AKI after OPCAB in highly susceptible patients to AKI.
TAL effectors – pathogen strategies and plant resistance engineering
Authors: Boch Jens , Bonas Ulla , Lahaye Thomas 
Published: November 2014

SummaryTranscription activator‐like effectors (TALEs) from plant pathogenic Xanthomonas spp. and the related RipTALs from Ralstonia solanacearum are DNA‐binding proteins with a modular DNA‐binding domain. This domain is both predictable and programmable, which simplifies elucidation of TALE function in planta and facilitates generation of DNA‐binding modules with desired specificity for biotechnological approaches. Recently identified TALE host target genes that either promote or stop bacterial disease provide new insights into how expression of TALE genes affects the plant–pathogen interaction. Since its elucidation the TALE code has been continuously refined and now provides a mature tool that, in combination with transcriptome profiling, allows rapid isolation of novel TALE target genes. The TALE code is also the basis for synthetic promoter‐traps that mediate recognition of TALE or RipTAL proteins in engineered plants. In this review, we will summarize recent findings in plant‐focused TALE research. In addition, we will provide an outline of the newly established gene isolation approach for TALE or RipTAL host target genes with an emphasis on potential pitfalls.
Prior Authorization in the Treatment of Patients with pDPN and FM
Authors: Placzek Hilary E. D. , Masters Elizabeth T. , Gu Tao , Cappelleri Joseph C. , Wasser Thomas E. , Clair Andrew G. , Cook Joseph P. , Eisenberg Debra F. 
Published: November 2014

AbstractPurposeTo determine prior authorization (PA) impact on healthcare utilization, costs, and pharmacologic treatment patterns for painful diabetic peripheral neuropathy (pDPN) and fibromyalgia (FM).MethodsThis retrospective, observational, longitudinal cohort study used medical and pharmacy claims data. Newly diagnosed patients treated for FM or pDPN between 7/1/2007 and 12/31/2011 were included. PA and no PA groups were matched by propensity score 4:1. Medical resource utilization, direct medical and pharmacy costs, and treatment pattern differences were compared. Pre and postindex differences between PA and no PA cohorts were determined by difference in difference analysis.ResultsAnalysis of 2,315 FM patients (1,852 PA; 463 no PA) demonstrated greater increases in postindex all‐cause costs ($197; P = 0.6673) and disease‐related costs ($72; P = 0.4186) in the PA cohort. Analysis of 1,300 pDPN patients (1,040 PA; 260 no PA) demonstrated postindex all‐cause cost increases of $1,155 more in the no PA cohort (P = 0.6248); disease‐related costs decreased $2,809 more in the no PA cohort (P = 0.4312). Treatment patterns were similar between cohorts; opioid usage was higher in the FM PA cohort (P = 0.0082).ConclusionsThere was no evidence of statistically significant differences between PA and no PA cohorts in either FM or pDPN populations for total all‐cause or disease‐related costs.
Prevalence of insomnia and its clinical correlates in a general population in Turkey
Authors: Benbir Gulcin , Demir Ahmet Ugur , Aksu Murat , Ardic Sadik , Firat Hikmet , Itil Oya , Ozgen Fuat , Yılmaz Hikmet , Karadeniz Derya 
Published: November 2014

AimThe prevalence of insomnia is influenced by environmental factors. This study aimed to investigate the prevalence of insomnia and its sociodemographic and clinical correlates in a general population‐based survey in Turkey.MethodsThis population‐based study included 4758 subjects among 5021 who participated in the Turkish Adult Population Epidemiology of Sleep Disorders study. Questionnaire items evaluating insomnia were adapted from the International Classification of Sleep Disorders II and the DSM‐IV‐TR. Subjects with restless legs syndrome were excluded.ResultsInsomnia was found to be associated with older age (18–24 years, 9.8%; 25–44 years, 11.7%; 45–64 years, 13.8%; 65 years or older, 13.9%), lower income level (<500 USD, 16.5%), time spent watching TV (6–8 h or more, 18.4%), tea consumption in the evening (≥6 glasses, 14.5%) and smoking status (current and ex‐smoker, both 14.2%) in multiple logistic regression analysis. In respect to other medical disorders, insomnia was significantly associated with the presence of hypertension, diabetes and heart diseases after the adjustment for relevant risk factors for each disease, across all age and sex groups.ConclusionsInsomnia is a major health problem in our population, affecting subjects in the working age group and those of lower socioeconomic status. It should especially be screened in patients with chronic diseases. A relatively low proportion of insomnia diagnosed as a sleep disorder suggests that this condition and its clinical correlates are possibly under‐recognized.
High psychiatric comorbidity in adolescents with dissociative disorders
Authors: Bozkurt Hasan , Duzman Mutluer Tuba , Kose Cigdem , Zoroglu Salih 
Published: November 2014

AimThe aim of this study was to evaluate psychiatric comorbidity rates and patterns in a sample of clinically referred adolescents diagnosed with dissociative disorders (DD) by using a structured interview.MethodsAll participants completed a comprehensive test battery, which consisted of a questionnaire for sociodemographic data and clinical history, Child Posttraumatic Stress Reaction Index, Childhood Abuse and Neglect Questionnaire and the Adolescent Dissociative Experiences Scale. Diagnosis was made by the Structured Clinical Interview for DSM‐IV Dissociative Disorders. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version.ResultsA total of 25 adolescent subjects aged 12–18 years participated in the study. Ten adolescents were diagnosed as having dissociative identity disorder and 15 of them were diagnosed as having dissociative disorder–not otherwise specified based on the Structured Clinical Interview for DSM‐IV Dissociative Disorders findings. Adolescents with dissociative identity disorder were found to have higher scores on the Adolescent Dissociative Experiences Scale and Child Posttraumatic Stress Reaction Index than the dissociative disorder–not otherwise specified group. Sexual and physical abuses were also found to be among the main traumatic events. Incest was reported in six cases of the study sample. All subjects had at least one comorbid psychiatric disorder. The most common psychiatric diagnoses were major depressive disorder (n = 25; 100%) and post‐traumatic stress disorder (n = 22; 88%).ConclusionHigh psychiatric comorbidity rates were found in adolescents diagnosed with DD. A prevalent history of abuse and traumatic events was represented. Clinicians should be aware of the impacts of DD on adolescents' mental health.
Judicial enforcement deputies: Causes and effects ofChinese judges enforcing environmental administrative decisions
Authors: Zhang Xuehua 
Published: November 2014

AbstractThis paper explores how and whyChinese courts became involved in regulating pollution by aiding administrative agencies in executing sanction decisions and collecting pollution levies. It also studies the effects of their regulatory involvement, both in terms of deterrence inferred from available information, as well as the compliance behavior of regulated actors defined as payment of regulatory penalties. It finds that judicial involvement in regulatory enforcement proved to be short‐lived and depended on a particular context at a particular period of time when a regulatory need coincided with administrative and financial judicial needs and particular judges. The paper also finds that court involvement enhanced deterrence in terms of certainty of punishment and to some extent the severity of punishment; however that deterrent effect was undermined by the close relationship between the courts and the regulated entities as fines and levies were almost always negotiated. In effect, deterrence increased the number of compliers paying levies without increasing the depth of compliance in terms of their full payment.
Irish Existentials in Context
Authors: McCloskey James 
Published: November 2014

AbstractThis paper aims to contribute to the comparative typology of existential constructions by examining Irish existentials in detail. It goes on to engage some of the central theoretical issues raised in that investigation and provides support for the bifurcated analysis of the definiteness restriction proposed by McNally (1992). It identifies what is argued to be a true existential predicate and argues that there is no common syntactic form for existentials crosslinguistically; rather, the observed commonalities among existentials across languages reflect semantic primitives out of which they are constructed. Diversity in the expression of existential propositions principally reflects different patterns of lexicalization.
Th/Ex, Agreement, and Case in Expletive Sentences
Authors: Sobin Nicholas 
Published: November 2014

AbstractRecent accounts of existential sentences (ES) within the government‐and‐binding/Minimalist Program tradition (Chomsky 2000, 2001; Deal 2009) claim that nominative Case valuation and ϕ‐agreement take place inES(directly or indirectly) between T and the associateDP, essentially the same as between T and “subject” in non‐ES. However, the surface facts of Case and ϕ‐agreement inESrun contrary to such claims (e.g.,There is only me in that picture/*There am only I in that picture;There is/?*are a boy and a girl at the door). Furthermore, such accounts leave unexplained the short‐movement phenomenon (including Milsark's [1974] “LeftmostbeCondition”) found inES(e.g.,There is someone being arrested/* There is being someone arrestedorThere is a train arriving/*There is arriving a train). Following claims of Richards & Biberauer (2005) and Deal (2009) that merger ofthereinESis low, I explore the possibility that “short movement” inES, as well as the ban on multiple instances ofthere, is accounted for via Extended Projection Principle features of the relevant verbalizing functional heads that are articulated into their Agree and Merge components. Furthermore, an analysis of Case and ϕ‐agreement is presented that accounts directly for the broad range of ϕ‐agreement forms (including “frozen” forms and first‐conjunct agreement), the necessarily accusative Case form of pronominal associates allowableES, and the ban on ϕ‐agreement with pronominal associates inES.
Sudden death of a horse with supraventricular tachycardia following oral administration of flecainide acetate
Authors: Dembek Katarzyna A. , Hurcombe Samuel D.A. , Schober Karsten E. , Toribio Ramiro E. 
Published: November 2014

AbstractObjectiveTo describe a case of supraventricular tachycardia and sudden death in a horse following administration of flecainide acetate.Case SummaryAn 8‐year‐old Hanoverian warmblood gelding was treated for chronic, naturally occurring, supraventricular tachycardia with digoxin, procainamide hydrochloride, quinidine sulfate, and flecainide acetate. After oral administration of flecainide, polymorphic ventricular tachycardia (torsades de pointes) and ventricular fibrillation developed, leading to cardiovascular collapse and death.New or Unique Information ProvidedAtrial fibrillation is the most commonly diagnosed dysrhythmia associated with poor performance in horses, while atrial tachycardia is rarely documented. Here, we describe a case of sudden death in a horse with atrial tachycardia following the oral administration of flecainide acetate, after the lack of response to other antiarrhythmic drugs. Information provided in this case report is new and will make clinicians aware of the potential complications of flecainide alone or in combination with other drugs, in horses with cardiac dysrhythmias.
Selmer groups and class groups
Authors: Česnavičius Kęstutis 
Published: November 2014

AbstractLet $A$ be an abelian variety over a global field $K$ of characteristic $p\geqslant 0$. If $A$ has nontrivial (respectively full) $K$-rational $l$-torsion for a prime $l\neq p$, we exploit the fppf cohomological interpretation of the $l$-Selmer group $\text{Sel}_{l}\,A$ to bound $\#\text{Sel}_{l}\,A$ from below (respectively above) in terms of the cardinality of the $l$-torsion subgroup of the ideal class group of $K$. Applied over families of finite extensions of $K$, the bounds relate the growth of Selmer groups and class groups. For function fields, this technique proves the unboundedness of $l$-ranks of class groups of quadratic extensions of every $K$ containing a fixed finite field $\mathbb{F}_{p^{n}}$ (depending on $l$). For number fields, it suggests a new approach to the Iwasawa ${\it\mu}=0$ conjecture through inequalities, valid when $A(K)[l]\neq 0$, between Iwasawa invariants governing the growth of Selmer groups and class groups in a $\mathbb{Z}_{l}$-extension.
Developmentally regulated neurosteroid synthesis enhances GABAergic neurotransmission in mouse thalamocortical neurones
Authors: Brown Adam R. , Herd Murray B. , Belelli Delia , Lambert Jeremy J. 
Published: November 2014

Key points
During neuronal development synaptic events mediated by GABAA receptors are progressively reduced in their duration, allowing for rapid and precise network function.
Here we focused on ventrobasal thalamocortical neurones, which contribute to behaviourally relevant oscillations between thalamus and cortex.
We demonstrate that the developmental decrease in the duration of inhibitory phasic events results predominantly from a precisely timed loss of locally produced neurosteroids, which act as positive allosteric modulators of the GABAA receptor.
The mature thalamus retains the ability to synthesise neurosteroids, thus preserving the capacity to enhance both phasic and tonic inhibition, mediated by synaptic and extrasynaptic GABAA receptors, respectively, in physiological and pathophysiological scenarios associated with perturbed neurosteroid levels.
Our data establish a potent, endogenous mechanism to locally regulate the GABAA receptor function and thereby influence thalamocortical activity.
AbstractDuring brain development the duration of miniature inhibitory postsynaptic currents (mIPSCs) mediated by GABAA receptors (GABAARs) progressively reduces, to accommodate the temporal demands required for precise network activity. Conventionally, this synaptic plasticity results from GABAAR subunit reorganisation. In particular, in certain developing neurones synaptic α2‐GABAARs are replaced by α1‐GABAARs. However, in thalamocortical neurones of the mouse ventrobasal (VB) thalamus, the major alteration to mIPSC kinetics occurs on postnatal (P) day 10, some days prior to the GABAAR isoform change. Here, whole‐cell voltage‐clamp recordings from VB neurones of mouse thalamic slices revealed that early in postnatal development (P7–P8), the mIPSC duration is prolonged by local neurosteroids acting in a paracrine or autocrine manner to enhance GABAAR function. However, by P10, this neurosteroid ‘tone’ rapidly dissipates, thereby producing brief mIPSCs. This plasticity results from a lack of steroid substrate as pre‐treatment of mature thalamic slices (P20–24) with the GABAAR‐inactive precursor 5α‐dihydroprogesterone (5α‐DHP) resulted in markedly prolonged mIPSCs and a greatly enhanced tonic conductance, mediated by synaptic and extrasynaptic GABAARs, respectively. In summary, endogenous neurosteroids profoundly influence GABAergic neurotransmission in developing VB neurones and govern a transition from slow to fast phasic synaptic events. Furthermore, the retained capacity for steroidogenesis in the mature thalamus raises the prospect that certain physiological or pathophysiological conditions may trigger neurosteroid neosynthesis, thereby providing a local mechanism for fine‐tuning neuronal excitability.