bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular cloning, epigenetic regulation, and functional characterization of Prkd1 gene promoter in dopaminergic cell culture models of Parkinson's disease
Authors: Ay Muhammet , Jin Huajun , Harischandra Dilshan S. , Asaithambi Arunkumar , Kanthasamy Arthi , Anantharam Vellareddy , Kanthasamy Anumantha G. 
Published: July 2015

AbstractWe recently identified a compensatory survival role for protein kinase D1 (PKD1) in protecting dopaminergic neurons from oxidative insult. To investigate the molecular mechanism of Prkd1 gene expression, we cloned the 5′‐flanking region (1620‐bp) of the mouse Prkd1 gene. Deletion analyses revealed that the −250/+113 promoter region contains full promoter activity in MN9D dopaminergic neuronal cells. In silico analysis of the Prkd1 promoter uncovered binding sites for key redox transcription factors including Sp1 and NF‐κB. Over‐expression of Sp1, Sp3, and NF‐κB‐p65 proteins stimulated Prkd1 promoter activity. Binding of Sp3 and NF‐κB‐p65 to the Prkd1 promoter was confirmed using chromatin immunoprecipitation. Treatment with the Sp inhibitor mithramycin A significantly attenuated Prkd1 promoter activity and PKD1 mRNA and protein expression. Further mechanistic studies revealed that inhibition of histone deacetylation and DNA methylation up‐regulated PKD1 mRNA expression. Importantly, negative modulation of PKD1 signaling by pharmacological inhibition or shRNA knockdown increased dopaminergic neuronal sensitivity to oxidative damage in a human mesencephalic neuronal cell model. Collectively, our findings demonstrate that Sp1, Sp3, and NF‐κB‐p65 can transactivate the mouse Prkd1 promoter and that epigenetic mechanisms, such as DNA methylation and histone modification, are key regulatory events controlling the expression of pro‐survival kinase PKD1 in dopaminergic neuronal cells.
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Previously, we demonstrated that protein kinase D1 (PKD1) plays a survival role during the early stage of oxidative stress in dopaminergic neuronal cells. Here, we cloned and characterized the mouse Prkd1 gene promoter. Our results suggest that Sp1, Sp3, and NF‐κB‐p65 transactivate the mouse Prkd1 promoter and that histone acetylation and DNA methylation play important roles in regulating Prkd1 expression in neuronal cells.
Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy
Authors: Zschüntzsch Jana , Zhang Yaxin , Klinker Florian , Makosch Gregor , Klinge Lars , Malzahn Dörthe , Brinkmeier Heinrich , Liebetanz David , Schmidt Jens 
Published: July 2015

AbstractDuchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD.
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Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11‐week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre‐clinical long‐term studies should be helpful.
Inhibiting amyloid β‐protein assembly: Size–activity relationships among grape seed‐derived polyphenols
Authors: Hayden Eric Y. , Yamin Ghiam , Beroukhim Shiela , Chen Benson , Kibalchenko Mikhail , Jiang Lin , Ho Lap , Wang Jun , Pasinetti Giulio M. , Teplow David B. 
Published: July 2015

AbstractEpidemiological evidence that red wine consumption negatively correlates with risk of Alzheimer's disease has led to experimental studies demonstrating that grape seed extracts inhibit the aggregation and oligomerization of Aβ in vitro and ameliorate neuropathology and behavioral deficits in a mouse model of Alzheimer's disease. The active agent in the extracts is a mixed population of polyphenolic compounds. To evaluate the relative potency of each of these compounds, HPLC was used to fractionate the mixture into monomers, dimers, and oligomers. Each fraction was analyzed for its effect on Aβ conformational dynamics (circular dichroism), oligomerization (zero‐length photochemical cross‐linking), aggregation kinetics (Thioflavin T fluorescence), and morphology (electron microscopy). The relative activities of each fraction were determined on the basis of molar concentration (mol/L) or mass concentration (g/L). When molar concentration, the number concentration of each polyphenolic compound, was considered, the oligomer fraction was the most potent inhibitor of Aβ oligomerization and aggregation. However, when mass concentration, the number concentration of phenolic groups, was considered, monomers were the most potent inhibitors. To understand these ostensibly contradictory results, a model of polyphenol:Aβ complexation was developed. This model, which was found to be consistent with published X‐ray crystallographic studies, offers an explanation for the effects of functional group polyvalency on inhibitor activity. Our data emphasize the importance of an in‐depth understanding of the mechanism(s) underlying ‘concentration dependence’ in inhibitor systems involving polyfunctional agents.
imageGrape seed polyphenolic extracts have been shown to inhibit the aggregation of Aβ in vitro and to ameliorate neuropathology and behavioral deficits in a mouse model of AD. The active agent in the extracts is a mixed population of polyphenolic compounds, including monomers, dimers, and oligomers. We found that monomers were the most potent inhibitors, when the number concentration of phenolic groups was considered. We developed a model of polyphenol:Aβ complexation that offers an explanation for the effects of functional group polyvalency on inhibitor activity. Our data emphasize the importance of an in‐depth understanding of the mechanism(s) underlying ‘concentration dependence’ in inhibitor systems involving polyfunctional agents.
Adult Patients’ Experiences of Nursing Care Dependence
Authors: Piredda Michela , Matarese Maria , Mastroianni Chiara , D'Angelo Daniela , Hammer Marilyn J. , De Marinis Maria Grazia 
Published: July 2015

AbstractPurposeCare dependence can be associated with suffering and humiliation. Nurses’ awareness of patients’ perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients’ experience of nursing care dependence.MethodA metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients’ experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings.FindingsThe experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient’ suffering.ConclusionsCare dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse–patient relationship is important to the dependent patients’ experience.Clinical RelevanceA greater understanding of patients’ experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering.
Stenting and Adjunctive Delivery of Paclitaxel Via Balloon Coating Versus Durable Polymeric Matrix for De Novo Coronary Lesions: Clinical and Angiographic Results from the Prospective Randomized Trial
Authors: Żurakowski Aleksander , Buszman Piotr P. , Milewski Krzysztof P. , Janas Adam , Gorycki Bogdan , Kondys Marek , Gąsior Paweł , Michalak Magdalena , Boxberger Michael , Peppas Athanasios , Granada Juan F. , Buszman Paweł E. 
Published: July 2015

BackgroundThere is limited comparative clinical data regarding the safety and efficacy profile of paclitaxel delivery via balloon versus stent‐polymer matrix. In this study, we aimed to compare the clinical and angiographic results of two different methods of paclitaxel delivery among patients undergoing percutaneous coronary intervention (PCI) for single de novo coronary lesions.MethodsA total of 202 patients undergoing PCI due to symptomatic heart disease and at least one significant coronary artery lesion were prospectively enrolled in a multicenter non‐inferiority trial. Eligible patients were randomized to a revascularization with either a paclitaxel eluting stent (PES = Coroflex Please, B.Braun) or a bare metal stent (BMS) followed by a paclitaxel coated balloon (PCB) dilation (BMS = Coroflex + PCB = Sequent Please, B.Braun). Clinical follow‐up was obtained at 9 months in all patients, whereas angiographic in a subset of 94 (46.5%) patients.ResultsThe baseline characteristics were well balanced between groups. At 9 months, the primary endpoint of in‐stent late lumen loss in BMS + PCB was comparable and non‐inferior to PES (0.21 ± 0.5 vs. 0.30 ± 0.7 mm, respectively. Pnon‐inf < 0.05). At 9 months, the incidence of MACE (7.0 vs. 6.9%, HR = 1, 95%CI: 0.3–2.8; P = 0.99), comprising the occurrence of myocardial infarction (4.9 vs. 3.0%, HR = 1.62, 95%CI: 0.4–6.5; P = 0.32), target lesion revascularization (6.9 vs. 5.0%, HR = 1.42, 95%CI: 0.4–4.4; p = 0.54) and stent thrombosis (4.9 vs. 3.0%, HR = 2.01, 95%CI: 0.5–7.4; P = 0.74) was comparable between BMS + PCB and PES, respectively. In the BMS + PCB group, thrombosis tended to occur within 30 days (3.9 vs. 1.0%; P = 0.38).ConclusionsPaclitaxel delivery via drug coated balloon or polymer‐stent matrix achieved comparable angiographic and clinical results among patients with de novo coronary lesions. BMS + PCB revascularization was associated with a higher rate of stent thrombosis when compared to newer generation drug eluting stents, therefore, should be recommended as a bail‐out for PCB alone angioplasty.
Latté Art Influences both the Expected and Rated Value of Milk‐Based Coffee Drinks
Authors: van Doorn George , Colonna‐Dashwood Maxwell , Hudd‐Baillie Reuben , Spence Charles 
Published: July 2015

AbstractThe present study investigated whether consumers’ expectations and perceptions concerning milk‐based coffee drinks would be influenced by: (1) the presence/absence of latté art on the froth of the coffee, and (2) shape‐taste symbolism (i.e., angular versus rounded shapes presented on the froth). An online survey conducted using photographs of cups of coffee revealed that the presence of latté art did indeed influence people's expectations concerning the value of the drink. Follow‐up research revealed that people were willing to pay more for a milk‐based coffee drink that had latté art as compared to a similar drink served without art. In a third experiment, an online survey revealed that an angular shape, relative to a more rounded shape, influenced people's expectations concerning the likability, bitterness and quality of the drink. A final experiment (Experiment 4) revealed that shape influenced people's perception of the quality and estimated price of the coffee. Taken together, the various results reported here demonstrate that the presence of latté art influences how much people expect, and are willing, to pay for a café latté. As such, adding art to, and the type of visual design on, a customer's drink should be considered by those serving café latté as an effective means of increasing value.Practical ApplicationsThe addition of latté art to milk‐based coffees is an interesting, and somewhat recent, phenomenon. The inclusion of latté art can help baristas differentiate their product from those of others. The results reported here suggest that the addition of latté art influences how much people expect, and are willing to pay for milk‐based coffees. As such, for the cafe owner thinking about how to increase profits, the experiments reported here suggest that people are willing to pay between 11–13% more for coffee with latté art than for those without it.
Development of a new benazepril hydrochloride chewable tablet and evaluation of its bioequivalence for treatment of heart failure in dogs
Authors: Qian M. , Chen T. , Zhou D. , Zhang Z. , Zhang Q. , Tang S. , Xiao X. 
Published: July 2015

The aim of the study was to develop a new chewable benazepril hydrochloride(BH) tablet, investigate its physical properties, and evaluate its bioequivalence with the branded formulation (Fortekor®). A corrective agent was included in the formula to improve its palatability and convenience for administration to dogs. The tablet remained stable in light, heat, and humidity tests, and its physical properties such as hardness, uniformity of content, and dissolution rate were highly consistent with the technical standards. After single and repeated administrations to eight beagles and single dose to 14 mongrel dogs (0.5 mg/kg p.o.), plasma BH and its active metabolite, benazeprilat (BZ), were detected. There was no significant difference in the major pharmacokinetic parameters (Cmax, Tmax, and AUC0–24) between the two formulations. The 90% confidence intervals calculated for the ratios of area under the time–concentration curve (AUC0–24) were 92.4–116.3% for BH and 89.9–102.3% for BZ, within the accepted range for bioequivalence of 80–125%. The results showed our new chewable tablet is bioequivalent to the commercial product and suitable for addition to the benazepril product family for the treatment of heart failure in dogs.
Pharmacokinetics studies of enrofloxacin injectable in situ forming gel in dogs
Authors: Li H.‐M. , Tian J. , Zhang Z.‐R. , Luo X.‐Q. , Yu Z.‐G. 
Published: July 2015

The objective of this study was to evaluate the pharmacokinetic characteristics of enrofloxacin (ENR) injectable in situ gel we developed in dogs following a single intramuscular (i.m.) administration. Twelve healthy dogs were randomly divided into two groups (six dogs per group), then administrated a single 20 mg/kg body weight (b.w.) ENR injectable in situ gel and a single 5 mg/kg b.w. ENR conventional injection, respectively. High‐performance liquid chromatography (HPLC) was used to determine ENR plasma concentrations. The pharmacokinetic parameters of ENR injectable in situ gel and conventional injection in dogs are as follows: MRT (mean residence time) (45.59 ± 14.05) h verse (11.40 ± 1.64) h, AUC (area under the blood concentration vs. time curve) (28.66 ± 15.41) μg·h/mL verse (11.06 ± 3.90) μg·h/mL, cmax (maximal concentration) (1.59 ± 0.35) μg/mL verse (1.46 ± 0.07) μg/mL, tmax (time needed to reach cmax) (1.25 ± 1.37) h verse (1.40 ± 0.55) h, t1/2λz (terminal elimination half‐life) (40.27 ± 17.79) h verse (10.32 ± 0.97) h. The results demonstrated that the in situ forming gel system could increase dosing interval of ENR and thus reduced dosing frequency during long‐term treatment. Therefore, the ENR injectable in situ gel seems to be worth popularizing in veterinary clinical application.
Evaluation of tizanidine as a marker of canine CYP1A2 activity
Authors: Locuson C. W. , Williams P. , Adcock J. M. , Daniels J. S. 
Published: July 2015

The dog CYP1A2 enzyme is likely an important contributor to the metabolism of veterinary drugs. Dog CYP1A2 is expressed in liver, plus it is inducible and polymorphic, creating the potential for intersubject differences in pharmacokinetics. Hence, the ability to probe dog CYP1A2 activity and inhibition is relevant toward veterinary drug development and drug–drug interaction assessment. Previous studies have relied on human probes with questionable specificity for CYP1A2, so it was hypothesized that recombinant CYP1A2 could be used to find a specific CYP1A2 substrate. Intrinsic clearance experiments demonstrated that tizanidine was a substrate of CYP1A2. Profiling of tizanidine metabolites generated by CYP1A2 identified the imidazole metabolite that was detectable in dog plasma. The imidazole metabolite was subsequently used to evaluate tizanidine as a CYP1A2 probe. Co‐administration of the CYP1A inhibitor enrofloxacin with tizanidine significantly decreased (30%; n = 3) the formation of the imidazole metabolite vs. control experiments. As enrofloxacin is a weak inhibitor, further studies are required to confirm the sensitivity of tizanidine as an in vivo probe. However, tizanidine may be a more selective CYP1A2 probe than phenacetin when conducting in vitro studies due to the presence of other phenacetin‐metabolizing enzymes in dog liver microsomes.
Introgression between invasive and native blue mussels (genus Mytilus) in the central California hybrid zone
Authors: Saarman Norah P. , Pogson Grant H. 
Published: July 2015

AbstractThe ecological and genetic factors determining the extent of introgression between species in secondary contact zones remain poorly understood. Here, we investigate the relative importance of isolating barriers and the demographic expansion of invasive Mytilus galloprovincialis on the magnitude and the direction of introgression with the native Mytilus trossulus in a hybrid zone in central California. We use double‐digest restriction‐site‐associated DNA sequencing (ddRADseq) to genotype 1337 randomly selected single nucleotide polymorphisms and accurately distinguish early and advanced generation hybrids for the first time in the central California Mytilus spp. hybrid zone. Weak levels of introgression were observed in both directions but were slightly more prevalent from the native M. trossulus into the invasive M. galloprovincialis. Few early and advanced backcrossed individuals were observed across the hybrid zone confirming the presence of strong barriers to interbreeding. Heterogeneous patterns of admixture across the zone of contact were consistent with the colonization history of M. galloprovincialis with more extensive introgression in northern localities furthest away from the putative site of introduction in southern California. These observations reinforce the importance of dynamic spatial and demographic expansions in determining patterns of introgression between close congeners, even in those with high dispersal potential and well‐developed reproductive barriers. Our results suggest that the threat posed by invasive M. galloprovincialis is more ecological than genetic as it has displaced, and continues to displace the native M. trossulus from much of central and southern California.
Identifying and integrating consumer perspectives in clinical practice guidelines on autosomal‐dominant polycystic kidney disease
Authors: Tong Allison , Tunnicliffe David J. , Lopez‐Vargas Pamela , Mallett Andrew , Patel Chirag , Savige Judy , Campbell Katrina , Patel Manish , Tchan Michel C. , Alexander Stephen I , Lee Vincent , Craig Jonathan C. , Fassett Robert , Rangan Gopala K. 
Published: July 2015

AbstractAimThis study aimed to identify consumer perspectives on topics and outcomes to integrate in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA‐CARI) clinical practice guidelines on autosomal‐dominant polycystic kidney disease (ADPKD).MethodsA workshop involving three concurrent focus groups with 18 consumers (patients with ADPKD (n = 15), caregivers (n = 3)) was convened. Guideline topics, interventions and outcomes were identified, and integrated into guideline development. Thematic analysis was used to analyse the reasons for their choices.ResultsTwenty‐two priority topics were identified, with most focussed on non‐pharmacological management (diet, fluid intake, physical activity, complementary medicine), pain management and psychosocial care (mental health, counselling, cognitive and behavioural training, education, support groups). They also identified 26 outcomes including quality of life (QoL), progression of kidney disease, kidney function, cyst growth and nephrotoxity. Almost all topics and outcomes suggested were identified by health professionals with the exception of five topics/outcomes. Six themes reflected reasons for their choices: clarifying ambiguities, resolving debilitating pain, concern for family, preparedness for the future, taking control and significance of impact.ConclusionAlthough there was considerable concordance between the priority topics and outcomes of health professionals and consumers for guidelines of ADPKD, there was also important discordance with consumers focused on fewer issues, but particularly on lifestyle, psychosocial support, pain, and QoL and renal outcomes. Active consumer engagement in guidelines development can help to ensure the inclusion of patient‐centred recommendations, which may lead to better management of disease progression, symptoms, complications, and psychosocial impact.
Using modern plant trait relationships between observed and theoretical maximum stomatal conductance and vein density to examine patterns of plant macroevolution
Authors: McElwain Jennifer C. , Yiotis Charilaos , Lawson Tracy 
Published: July 2015

Summary

Understanding the drivers of geological‐scale patterns in plant macroevolution is limited by a hesitancy to use measurable traits of fossils to infer palaeoecophysiological function.

Here, scaling relationships between morphological traits including maximum theoretical stomatal conductance (gmax) and leaf vein density (Dv) and physiological measurements including operational stomatal conductance (gop), saturated (Asat) and maximum (Amax) assimilation rates were investigated for 18 extant taxa in order to improve understanding of angiosperm diversification in the Cretaceous.

Our study demonstrated significant relationships between gop, gmax and Dv that together can be used to estimate gas exchange and the photosynthetic capacities of fossils. We showed that acquisition of high gmax in angiosperms conferred a competitive advantage over gymnosperms by increasing the dynamic range (plasticity) of their gas exchange and expanding their ecophysiological niche space. We suggest that species with a high gmax (> 1400 mmol m−2 s−1) would have been capable of maintaining a high Amax as the atmospheric CO2 declined through the Cretaceous, whereas gymnosperms with a low gmax would experience severe photosynthetic penalty.

Expansion of the ecophysiological niche space in angiosperms, afforded by coordinated evolution of high gmax, Dv and increased plasticity in gop, adds further functional insights into the mechanisms driving angiosperm speciation.