bluuebunny/crossref_metadata_2025_split huggingface dataset:
α‐Synuclein forms non‐selective cation channels and stimulates ATP‐sensitive potassium channels in hippocampal neurons
Authors: Mironov Sergej L. 
Published: October 2014

Key points
In Parkinson's disease, the protein α‐synuclein (αS) is produced within neurons and also appears in the extracellular fluid.
In this study in hippocampal neurons, αS formed non‐selective cation channels with multiple levels of conductance and rectification depending on their insertion site.
αS channels induced local spontaneous increases in intracellular Na+ and Ca2+, depolarized neurons, augmented bursting activity and stimulated the opening of ATP‐sensitive K+ channels.
Non‐selective channels were also observed in neurons transfected with either wild‐type or mutant A53T αS, and after extracellular application of these proteins.
The properties of αS channels in neuronal membranes suggest that extracellular αS is more toxic than αS produced within neurons.
AbstractIn Parkinson's disease and several other neurodegenerative diseases, the protein α‐synuclein (αS) is produced within neurons and accumulates in the extracellular fluid. Several mechanisms of αS action are proposed, one of which is the formation of cation‐permeable pores that may mediate toxicity. αS induces non‐selective cation channels in lipid bilayers, but whether this occurs in living neurons and which properties the channels possess have not yet been examined. In this study the properties of αS channels in dissociated hippocampal neurons are documented. In cell‐attached recordings the incorporation of αS into membranes was driven by applied negative potentials. These channels exhibited multiple levels of conductance (30, 70 and 120 pS at −100 mV) and inward rectification. The persistent activity of αS channels induced local changes in intracellular Na+ and Ca2+, depolarized neurons and augmented bursting activity. αS channels formed by adding αS to the intracellular membrane in inside‐out patches exhibited outward rectification. αS channels were equally permeable to Na+, K+ and Ca2+. These channels were also observed in neurons transfected with wild‐type or mutant A53T αS, and after extracellular application of wild‐type or mutant A53T αS proteins. Opening of αS channels stimulated opening of ATP‐sensitive K+ (KATP ) channels and did not interfere with the activity of delayed rectifier K+ channels. The properties of αS channels in neuronal membranes suggest stronger toxicity of extracellularly applied αS than intracellular αS. Enhancement of neuronal excitability and distortions in ion homeostasis may underlie the toxic effects of αS that can be dampened by KATP channels.
Reporting Physical Activity: Perceptions and Practices of Australian Media Professionals
Authors: Smith Ben J. , Bonfiglioli Catriona M.F. 
Published: October 2014

Background:Advocacy informed by scientific evidence is necessary to influence policy and planning to address physical inactivity. The mass media is a key arena for this advocacy. This study investigated the perceptions and practices of news media professionals reporting physical activity and sedentariness to inform strategic communication about these issues.Methods:We interviewed media professionals working for major television, radio, newspaper and online news outlets in Australia. The interviews explored understandings of physical activity and sedentariness, attributions of causality, assignment of responsibility, and factors affecting news reporting on these topics. Data were thematically analyzed using NVivo.Results:Physical inactivity was recognized as pervasive and important, but tended to be seen as mundane and not newsworthy. Sedentariness was regarded as more novel than physical activity, and more likely to require organizational and environment action. Respondents identified that presenting these issues in visual and engaging ways was an ongoing challenge.Conclusions:Physical activity researchers and advocates need to take account of prevailing news values and media practices to improve engagement with the news media. These include understanding the importance of novelty, narratives, imagery, and practical messages, and how to use these to build support for environmental and policy action.
Activity Behaviors of University Staff in the Workplace: A Pilot Study
Authors: Bird Marie-Louise , Shing Cecilia , Mainsbridge Casey , Cooley Dean , Pedersen Scott 
Published: October 2014

Background:Sedentary behavior is related to metabolic syndrome and might have implications for the long-term health of workers in a low activity environment. The primary aim of this pilot study was to determine activity levels of adults working at a University during work hours. A secondary aim was to determine the relationship between actual and perceived activity levels.Methods:Activity levels of university staff (n = 15, male = 7, age = 53 ± 7 years, BMI = 26.5 ± 2.5kg·m2) were monitored over 5 consecutive workdays using SenseWear accelerometers, then participants completed a questionnaire of their perception of workplace sedentary time.Results:Each participant spent 71.5 ± 13.1% (358 ± 78 min) of their workday being sedentary (< 1.5 METs), 15.6 ± 9.0% involved in light activity (1.5–3 METs), 11.7 ± 10.0% in moderate activity (3–5 METs), and 1.1 ± 1.3% in vigorous activity (> 5 METs) (P < .0001). The mean difference between actual (SenseWear < 1.5 METs) and perceived sitting time was –2 ± 32%; however, perceived sedentary time was reported with a range of under-to-over estimation of –75% to 51%.Conclusion:This pilot study identifies long periods of low metabolic activity during the workday and poor perception of individual sedentary time. Interventions to reduce sedentary time in the workplace may be necessary to ensure that the work environment does not adversely affect long-term health.
Postprandial Metabolic Effects of Accelerometer Measured Spontaneous Low-Level Activity
Authors: Peddie Meredith C. , Cameron Claire , Rehrer Nancy , Perry Tracy 
Published: October 2014

Background:Interrupting sedentary time induces improvements in glucose metabolism; however, it is unclear how much activity is required to reduce the negative effects of prolonged sitting.Methods:Sixty-six participants sat continuously for 9 hours except for required bathroom breaks. Participants were fed meal replacement beverages at 60, 240 and 420 min. Blood samples were obtained hourly for 9 hours, with additional samples collected 30 and 45 min after each feeding. Responses were calculated as incremental area under the curve (iAUC) for plasma glucose, insulin and triglyceride. Participants wore a triaxial accelerometer and a heart rate monitor. Energy expenditure was estimated using indirect calorimetry.Results:After controlling for age, sex and BMI, every 100 count increase in accelerometer derived total movement was associated with a 0.06 mmol·L-1·9 hours decrease in glucose iAUC (95% CI 0.004–0.1; P = .035), but not associated with changes in insulin or triglyceride iAUC. Every 1 bpm increase in mean heart rate was associated with a 0.76 mmol·L-1·9 hours increase in triglyceride iAUC (95% CI 0.13–1.38).Conclusion:Accelerometer measured movement during periods of prolonged sitting can result in minor improvements in postprandial glucose metabolism, but not lipid metabolism.
An
In Planta
-Expressed Polyketide Synthase Produces (
R
)-Mellein in the Wheat Pathogen Parastagonospora nodorum
Authors: Chooi Yit-Heng , Krill Christian , Barrow Russell A. , Chen Shasha , Trengove Robert , Oliver Richard P. , Solomon Peter S. 
Published: October 2014

ABSTRACT

Parastagonospora nodorum
is a pathogen of wheat that affects yields globally. Previous transcriptional analysis identified a partially reducing polyketide synthase (PR-PKS) gene, SNOG_00477 (
SN477
), in
P. nodorum
that is highly upregulated during infection of wheat leaves. Disruption of the corresponding
SN477
gene resulted in the loss of production of two compounds, which we identified as (
R
)-mellein and (
R
)-
O
-methylmellein. Using a
Saccharomyces cerevisiae
yeast heterologous expression system, we successfully demonstrated that SN477 is the only enzyme required for the production of (
R
)-mellein. This is the first identification of a fungal PKS that is responsible for the synthesis of (
R
)-mellein. The
P. nodorum
Δ
SN477
mutant did not show any significant difference from the wild-type strain in its virulence against wheat. However, (
R
)-mellein at 200 μg/ml inhibited the germination of wheat (
Triticum aestivum
) and barrel medic (
Medicago truncatula
) seeds. Comparative sequence analysis identified the presence of mellein synthase (MLNS) homologues in several Dothideomycetes and two sodariomycete genera. Phylogenetic analysis suggests that the MLNSs in fungi and bacteria evolved convergently from fungal and bacterial 6-methylsalicylic acid synthases.
Enhancing Terpene Yield from Sugars via Novel Routes to 1-Deoxy-
d
-Xylulose 5-Phosphate
Authors: Kirby James , Nishimoto Minobu , Chow Ruthie W. N. , Baidoo Edward E. K. , Wang George , Martin Joel , Schackwitz Wendy , Chan Rossana , Fortman Jeffrey L. , Keasling Jay D. 
Published: October 2014

ABSTRACT

Terpene synthesis in the majority of bacterial species, together with plant plastids, takes place via the 1-deoxy-
d
-xylulose 5-phosphate (DXP) pathway. The first step of this pathway involves the condensation of pyruvate and glyceraldehyde 3-phosphate by DXP synthase (Dxs), with one-sixth of the carbon lost as CO
2
. A hypothetical novel route from a pentose phosphate to DXP (nDXP) could enable a more direct pathway from C
5
sugars to terpenes and also circumvent regulatory mechanisms that control Dxs, but there is no enzyme known that can convert a sugar into its 1-deoxy equivalent. Employing a selection for complementation of a
dxs
deletion in
Escherichia coli
grown on xylose as the sole carbon source, we uncovered two candidate nDXP genes. Complementation was achieved either via overexpression of the wild-type
E. coli
yajO
gene, annotated as a putative xylose reductase, or via various mutations in the native
ribB
gene.
In vitro
analysis performed with purified YajO and mutant RibB proteins revealed that DXP was synthesized in both cases from ribulose 5-phosphate (Ru5P). We demonstrate the utility of these genes for microbial terpene biosynthesis by engineering the DXP pathway in
E. coli
for production of the sesquiterpene bisabolene, a candidate biodiesel. To further improve flux into the pathway from Ru5P, nDXP enzymes were expressed as fusions to DXP reductase (Dxr), the second enzyme in the DXP pathway. Expression of a Dxr-RibB(G108S) fusion improved bisabolene titers more than 4-fold and alleviated accumulation of intracellular DXP.
Patients’ values and preferences of the expected efficacy of hip arthroscopy for osteoarthritis: a protocol for a multinational structured interview-based study combined with a randomised survey on the optimal amount of information to elicit preferences
Authors: Zhang Yuqing , Tikkinen Kari A O , Agoritsas Thomas , Ayeni Olufemi R , Alexander Paul , Imam Maha , Yoo Daniel , Tsalatsanis Athanasios , Djulbegovic Benjamin , Thabane Lehana , Schünemann Holger , Guyatt Gordon H 
Published: October 2014

IntroductionSymptomatic hip osteoarthritis (OA) is a disabling condition with up to a 25% cumulative lifetime risk. Total hip arthroplasty (THA) is effective in relieving patients’ symptoms and improving function. It is, however, associated with substantial risk of complications, pain and major functional limitation before patients can return to full function. In contrast, hip arthroscopy (HA) is less invasive and can postpone THA. However, there is no evidence regarding the delay in the need for THA that patients would find acceptable to undergoing HA. Knowing patients’ values and preferences (VP) on this expected delay is critical when making recommendations regarding the advisability of HA. Furthermore, little is known on the optimal amount of information regarding interventions and outcomes needed to present in order to optimally elicit patients’ VP.Methods and analysisWe will perform a multinational, structured interview-based survey of preference in delay time for THA among patients with non-advanced OA who failed to respond to conservative therapy. We will combine these interviews with a randomised trial addressing the optimal amount of information regarding the interventions and outcomes required to elicit preferences. Eligible patients will be randomly assigned (1 : 1) to either a short or a long format of health scenarios of THA and HA. We will determine each patient's VP using a trade-off and anticipated regret exercises. Our primary outcomes for the combined surveys will be: (1) the minimal delay time in the need for THA surgery that patients would find acceptable to undertaking HA, (2) patients’ satisfaction with the amount of information provided in the health scenarios used to elicit their VPs.Ethics and disseminationThe protocol has been approved by the Hamilton Integrated Research Ethics Board (HIREB13-506). We will disseminate our study findings through peer-reviewed publications and conference presentations, and make them available to guideline makers issuing recommendations addressing HA and THA.
Outcomes after endovascular treatment for anterior circulation stroke presenting as wake-up strokes are not different than those with witnessed onset beyond 8 hours
Authors: Aghaebrahim Amin , Leiva-Salinas Carlos , Jadhav Ashutosh P , Jankowitz Brian , Zaidi Syed , Jumaa Mouhammad , Urra Xabi , Amorim Edilberto , Zhu Guangming , Giurgiutiu Dan-Victor , Horev Anat , Reddy Vivek , Hammer Maxim , Wechsler Lawrence , Wintermark Max , Jovin Tudor 
Published: October 2014

ObjectivePrevious studies have suggested that patients with wake-up stroke (WUS) may have superior outcomes compared with patients with a witnessed late time of onset after revascularization. We sought to test this hypothesis in patients with anterior circulation large vessel occlusion stroke (ACLVOS) treated with endovascular therapy beyond 8 h from time last seen well (TLSW).MethodsA single center retrospective review of a prospectively acquired database of consecutive patients was performed to identify patients presenting beyond 8 h of TLSW with radiographic evidence of ACLVOS, small core, and large penumbra who subsequently underwent endovascular treatment.ResultsWe identified 206 patients. Patients were divided into two groups: (1) patients with WUS (38%, n=78) and (2) patients with witnessed onset beyond 8 h (62%, n=128). The groups were similar in age, baseline National Institutes of Health Stroke Scale score, TLSW to reperfusion, baseline infarct volume, and rate of successful recanalization. Rates of good outcome (modified Rankin Scale score of 0–2 at 90 days, 43% vs 50%, p=0.3), parenchymal hematoma (9% vs 5.5%, p=0.3), and final infarct volume (75.2 vs 61.4 mL, p=0.6) were comparable. Multivariate analysis identified age (OR=0.95, 95% CI 0.91 to 0.99, p<0.042), successful recanalization (OR 6.0, 95% CI 1.5 to 23.5, p=0.009), and final infarct volume (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) but not mode of presentation as predictors of favorable outcomes.ConclusionsRates of good outcomes, parenchymal hematoma, and final infarct volumes following endovascular treatment may not be different in patients with WUS compared with patients with witnessed onset of symptoms beyond 8 h.
Stochastic resonance of charge carrier diffusion in a nonhomogeneous medium in the presence of an harmonic external potential
Authors: Aragie Berhanu 
Published: October 2014

The dynamics of charge carriers (electrons) hopping through a nonhomogeneous medium in semiconductor layer is investigated by changing a thermal noise of strength D and an external harmonic potential V(x). The nonhomogeneous medium exhibits denser trap distribution around the center, which biases the electrons to therein concentrate. Applying also a monostable potential at the center further enhances the accumulation of electrons. However, by applying a nonhomogeneous hot temperature in the vicinity of the potential minimum forced the electrons to diffuse away from the center and redistribute around two points. Thermally activated rate of hopping and diffusion of electrons in a nonhomogeneous medium, as a function of model parameters, is also considered in the high barrier limit. Using two states approximation, I have also studied the stochastic resonance (SR) of the electrons dynamics in the presence of a time-varying signal. I found a strong spectral amplification η and lower temperature occurrence of its peak as compared to previous works [M. Asfaw, B. Aragie and M. Bekele, Eur. Phys. J. B 79, 371 (2011); B. Aragie, Y. B. Tateka and M. Bekele, Eur. Phys. J. B 87, 101 (2014)].
MMP-1 and Pro-MMP-10 as Potential Urinary Pharmacodynamic Biomarkers of FGFR3-Targeted Therapy in Patients with Bladder Cancer
Authors: Du Xiangnan , Lin Benjamin C. , Wang Qian-Rena , Li Hao , Ingalla Ellen , Tien Janet , Rooney Isabelle , Ashkenazi Avi , Penuel Elicia , Qing Jing 
Published: October 2014

AbstractPurpose: The aim of this study was to identify noninvasive pharmacodynamic biomarkers of FGFR3-targeted therapies in bladder cancer to facilitate the clinical development of experimental agent targeting FGFR3.Experimental Design: Potential soluble pharmacodynamic biomarkers of FGFR3 were identified using a combination of transcriptional profiling and biochemical analyses in preclinical models. Two matrix metalloproteinases (MMP), MMP-1 and MMP-10, were selected for further studies in human bladder cancer xenograft models treated with a specific anti-FGFR3 monoclonal antibody, R3Mab. Serum and urinary levels of MMP-1 and MMP-10 were determined in healthy donors and patients with bladder cancer. The modulation of MMP-1 and MMP-10 by R3Mab in patients with bladder cancer was further evaluated in a phase I dose-escalation study.Results: MMP-1 and MMP-10 mRNA and protein were downmodulated by FGFR3 shRNA and R3Mab in bladder cancer cell lines. FGFR3 signaling promoted the expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. In bladder cancer xenograft models, R3Mab substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, both MMP-1 and pro-MMP-10 were elevated in the urine of patients with advanced bladder cancer. In a phase I dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in patients with bladder cancer.Conclusion: These findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for R3Mab in patients with bladder cancer. Clin Cancer Res; 20(24); 6324–35. ©2014 AACR.
Response of a Simulated Hurricane to Misalignment Forcing Compared to the Predictions of a Simple Theory
Authors: Schecter David A. 
Published: October 2014

Abstract
This paper compares the tilt dynamics of a mature tropical cyclone simulated with a conventional cloud model to reduced modeling results and theoretical predictions. The primary experiment involves a tropical cyclone of hurricane strength on the f plane exposed to a finite period of idealized misalignment forcing. A complementary experiment shows how the vortex responds to the same forcing when moisture and symmetric secondary circulation (SSC) are removed from the initial condition. It is found that the applied forcing excites a much stronger tilt mode in the dry nonconvective vortex than in the moist convective hurricane. The evolution of tilt in both experiments agrees reasonably well with a simple linear response theory that neglects the SSC and assumes moisture merely reduces static stability in the vortex core. An additional experiment with suspended cloud water but no substantial SSC supports the theoretical notion that reduction of static stability is sufficient to inhibit the excitation of a tilt mode. However, there is some discrepancy between theory and details of asymmetric convection in the eyewall region of the simulated hurricane. Moreover, a final experiment without moisture but with an artificially maintained secondary circulation suggests that the SSC has a nonnegligible role in reducing tilt. Diagnosis of the primary hurricane simulation further illustrates how the SSC has discernible influence over misalignment at least in the eyewall. Sensitivity of tilt dynamics to the azimuthally averaged vortex structure is briefly addressed.
The Changing Relationship between Interannual Variations of the North Atlantic Oscillation and Northern Tropical Atlantic SST
Authors: Chen Shangfeng , Wu Renguang , Chen Wen 
Published: October 2014

Abstract
The relationship between interannual variations of boreal winter North Atlantic Oscillation (NAO) and northern tropical Atlantic (NTA) sea surface temperature (SST) experienced obvious interdecadal changes during 1870–2012. Similar interdecadal changes are observed in the amplitude of NTA SST anomalies. The mean NTA SST change may be a plausible reason for several changes in the NAO–NTA SST connection. Under a higher mean NTA SST, NTA SST anomalies induce larger wind anomalies over the North Atlantic that produce a tripole SST anomaly pattern and amplify NTA SST anomalies. Comparison of the evolution of anomalies between 1970–86 and 1996–2012 unravels changing roles of El Niño–Southern Oscillation (ENSO) and extratropical atmospheric disturbances in the formation of NTA SST anomalies. During 1970–86, ENSO events play a key role in initiating NTA SST anomalies in the preceding spring through atmospheric circulation changes. With the decay of ENSO, SST anomalies in the midlatitude North Atlantic weaken in the following summer, whereas NTA SST anomalies are maintained up to winter. This leads to a weak NAO–NTA SST connection in winter. During 1996–2012, the preceding spring atmospheric circulation disturbances over the midlatitude North Atlantic play a dominant role in the genesis of a North Atlantic horseshoe (NAH)-like SST anomaly pattern in the following summer and fall. This NAH-like SST anomaly pattern contributes to the development of the NAO in late fall and early winter. The atmospheric circulation anomaly, in turn, is conducive to the maintenance of NTA SST anomalies to winter via changing surface latent heat flux and shortwave radiation. This leads to a close NAO–NTA SST connection in winter.