bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape integration of North Patagonian mountain lakes: a first approach using characterization of dissolved organic matter
Authors: Garcia Patricia E. , Dieguez María C. , Queimaliños Claudia 
Published: March 2015

AbstractNorth‐western Patagonia contains a variety of glacially formed mountain lakes located at different positions from the treeline in the Andean Patagonian forest region. Water chemistry of six North Patagonian lakes located in an altitudinal gradient, above, at and below the treeline (~41°S) were analysed in this study. The relative importance of allochtonous to autochthonous carbon inputs along a marked catchment vegetation gradient encompassing altoandino vegetation and Nothofagus forests was addressed. The dissolved organic carbon (DOC) concentration varied among the study lakes, with the lakes located higher in the landscape exhibiting lower DOC concentrations (<1 mg L−1) than lakes located at or below the treeline (>2 mg L−1). Analysis of coloured and fluorescent dissolved organic matter (CDOM and FDOM, respectively) followed the DOC pattern, despite the contrasting catchments of the study lakes. The results indicated the CDOM in all the lakes had low molecular weight and low aromaticity. The excitation–emission matrices (EEMs) highlighted three distinctive fluorophores in the FDOM, including two humic‐like (peak A and peak C) revealing the presence of humic terrestrial material, and a protein‐like fluorophore (peak T) generally associated with autochthonous DOM. The increased intensities of the humic fluorophores in the lakes located below the treeline suggest higher allochtonous carbon inputs from their catchments. This evidence collectively suggests that mountain lakes exhibit some heterogeneity in terms of DOM, likely attributable to their position in relation to the treeline, which determines the contribution of the catchment. As remote lakes are extremely sensitive to changes in their catchments, these North Patagonian mountain lakes may accurately track the impact of climate and anthropogenic changes on the landscape.
The impact of Quaternary climate oscillations on divergence times and historical population sizes in Thylamys opossums from the Andes
Authors: Giarla Thomas C. , Jansa Sharon A. 
Published: March 2015

AbstractClimate oscillations during the Quaternary altered the distributions of terrestrial animals at a global scale. In mountainous regions, temperature fluctuations may have led to shifts in range size and population size as species tracked their shifting habitats upslope or downslope. This creates the potential for both allopatric speciation and population size fluctuations, as species are either constrained to smaller patches of habitat at higher elevations or able to expand into broader areas at higher latitudes. We considered the impact of climate oscillations on three pairs of marsupial species from the Andes (Thylamys opossums) by inferring divergence times and demographic changes. We compare four different divergence dating approaches, using anywhere from one to 26 loci. Each pair comprises a northern (tropical) lineage and a southern (subtropical to temperate) lineage. We predicted that divergences would have occurred during the last interglacial (LIG) period approximately 125 000 years ago and that population sizes for northern and southern lineages would either contract or expand, respectively. Our results suggest that all three north–south pairs diverged in the late Pleistocene during or slightly after the LIG. The three northern lineages showed no signs of population expansion, whereas two southern lineages exhibited dramatic, recent expansions. We attribute the difference in responses between tropical and subtropical lineages to the availability of ‘montane‐like’ habitats at lower elevations in regions at higher latitudes. We conclude that climate oscillations of the late Quaternary had a powerful impact on the evolutionary history of some of these species, both promoting speciation and leading to significant population size shifts.
The F‐box protein Fbp1 functions in the invasive growth and cell wall integrity mitogen‐activated protein kinase (MAPK) pathways in Fusarium oxysporum
Authors: Miguel‐Rojas Cristina , Hera Concepcion 
Published: March 2015

SummaryF‐box proteins determine substrate specificity of the ubiquitin–proteasome system. Previous work has demonstrated that the F‐box protein Fbp1, a component of the SCFFbp1 E3 ligase complex, is essential for invasive growth and virulence of the fungal plant pathogen Fusarium oxysporum. Here, we show that, in addition to invasive growth, Fbp1 also contributes to vegetative hyphal fusion and fungal adhesion to tomato roots. All of these functions have been shown previously to require the mitogen‐activated protein kinase (MAPK) Fmk1. We found that Fbp1 is required for full phosphorylation of Fmk1, indicating that Fbp1 regulates virulence and invasive growth via the Fmk1 pathway. Moreover, the Δfbp1 mutant is hypersensitive to sodium dodecylsulfate (SDS) and calcofluor white (CFW) and shows reduced phosphorylation levels of the cell wall integrity MAPK Mpk1 after SDS treatment. Collectively, these results suggest that Fbp1 contributes to both the invasive growth and cell wall integrity MAPK pathways of F. oxysporum.
Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries
Authors: Shafer K. M. , Janssen L. , Carrick‐Ranson G. , Rahmani S. , Palmer D. , Fujimoto N. , Livingston S. , Matulevicius S. A. , Forbess L. W. , Brickner B. , Levine B. D. 
Published: March 2015

Key Points
Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle.
Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat.
Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear.
We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment.
Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training.

AbstractWe aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high‐intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre‐ and post‐ training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high‐intensity intervals. Oxygen uptake (; Douglas bag technique), cardiac output (, foreign‐gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak , , and stroke volume (SV), a blunted / slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P < 0.001) compared with controls. After training, TGA patients increased peak by 6 ± 8.5%, similar to controls (interaction P = 0.24). The magnitude of SV reserve on initial testing correlated with training response (r = 0.58, P = 0.047), though overall, no change in peak was observed. High‐sensitivity troponin T (hs‐TnT) and N‐terminal prohormone of brain naturetic peptide (NT pro‐BNP) were low and did not change with acute exercise or after training. Our data show that TGA patients with SRVs in this study safely participated in exercise training and improved peak . Neither prolonged submaximal exercise, nor high‐intensity intervals, nor short‐term exercise training seem to injure the systemic right ventricle.
Type IV Pilus Secretins Have Extracellular C Termini
Authors: Lieberman Joshua A. , Petro Courtney D. , Thomas Stefani , Yang Austin , Donnenberg Michael S. 
Published: March 2015

ABSTRACTType IV pili (T4Ps) are surface appendages used by Gram-negative and Gram-positive pathogens for motility and attachment to epithelial surfaces. In Gram-negative bacteria, such as the important pediatric pathogen enteropathogenicEscherichia coli(EPEC), during extension and retraction, the pilus passes through an outer membrane (OM) pore formed by the multimeric secretin complex. The secretin is common to Gram-negative assemblies, including the related type 2 secretion (T2S) system and the type 3 secretion (T3S) system. The N termini of the secretin monomers are periplasmic and in some systems have been shown to mediate substrate specificity. In this study, we mapped the topology of BfpB, the T4P secretin from EPEC, using a combination of biochemical and biophysical techniques that allowed selective identification of periplasmic and extracellular residues. We applied rules based on solved atomic structures of outer membrane proteins (OMPs) to generate our topology model, combining the experimental results with secondary structure prediction algorithms and direct inspection of the primary sequence. Surprisingly, the C terminus of BfpB is extracellular, a result confirmed by flow cytometry for BfpB and a distantly related T4P secretin, PilQ, fromPseudomonas aeruginosa. Keeping with prior evidence, the C termini of two T2S secretins and one T3S secretin were not detected on the extracellular surface. On the basis of our data and structural constraints, we propose that BfpB forms a beta barrel with 16 transmembrane beta strands. We propose that the T4P secretins have a C-terminal segment that passes through the center of each monomer.IMPORTANCESecretins are multimeric proteins that allow the passage of secreted toxins and surface structures through the outer membranes (OMs) of Gram-negative bacteria. To date, there have been no atomic structures of the C-terminal region of a secretin, although electron microscopy (EM) structures of the complex are available. This work provides a detailed topology prediction of the membrane-spanning domain of a type IV pilus (T4P) secretin. Our study used innovative techniques to provide new and comprehensive information on secretin topology, highlighting similarities and differences among secretin subfamilies. Additionally, the techniques used in this study may prove useful for the study of other OM proteins.
Weekly variations of stroke occurrence: an observational cohort study based on the Kyoto Stroke Registry, Japan
Authors: Shigematsu Kazuo , Watanabe Yoshiyuki , Nakano Hiromi 
Published: March 2015

ObjectivesUnderstanding the temporal pattern of stroke onset and exploring the possible triggers are important strategies to reducing the incidence of stroke. If stroke occurs frequently on a specific day of the week, it is assumed that other factors, that is, ‘triggering factors’, induce stroke. The aim of the study is to investigate differences in the incidences of stroke among days of the week.DesignHospital-based registry stroke over an 11-year period.SettingKyoto Prefecture, Japan.ParticipantsA total of 13 788 patients with stroke identified from January 1999 to December 2009 inclusive in the entire Kyoto Prefecture and registered in the Kyoto Stroke Registry (KSR).Main outcome measuresPatients with stroke were classified into seven groups based on the day of the week on which stroke developed. We confirmed the differences in the incidence among days using the χ2test and then performed multinomial logistic analysis referring to the stroke incidence on Sunday to calculate the OR and 95% CI of the stroke occurrence on each day of the week.ResultsThe OR (95% CI) for stroke occurring on Monday, Tuesday, Wednesday, Thursday, Friday and Saturday was 1.157 (1.030 to 1.293), 1.101 (0.981 to 1.236), 1.059 (0.943 to 1.188), 1.091 (0.972 to 1.225), 1.053 (0.938 to 1.205) and 1.074 (0.956 to 1.205), respectively. After stratification by stroke subtypes, cerebral infarction occurred more frequently on Monday than on Sunday (OR and 95% CI were 1.189 and 1.034 to 1.366, p=0.014) independent of age and gender. There was no significant day of the week variation in cerebral haemorrhage or subarachnoid haemorrhage.ConclusionsSome factors that arise periodically appear to affect the incidence of cerebral infarction, which gradually develops over years, and this suggests an aetiological mechanism different from the conventional cumulative effect of risk factors due to long-term exposure. We propose a hypothesis that there is a ‘triggering factor’ for the development of cerebral infarction.
The CORE study protocol: a stepped wedge cluster randomised controlled trial to test a co-design technique to optimise psychosocial recovery outcomes for people affected by mental illness in the community mental health setting
Authors: Palmer Victoria J , Chondros Patty , Piper Donella , Callander Rosemary , Weavell Wayne , Godbee Kali , Potiriadis Maria , Richard Lauralie , Densely Konstancja , Herrman Helen , Furler John , Pierce David , Schuster Tibor , Iedema Rick , Gunn Jane 
Published: March 2015

IntroductionUser engagement in mental health service design is heralded as integral to health systems quality and performance, but does engagement improve health outcomes? This article describes the CORE study protocol, a novel stepped wedge cluster randomised controlled trial (SWCRCT) to improve psychosocial recovery outcomes for people with severe mental illness.MethodsAn SWCRCT with a nested process evaluation will be conducted over nearly 4 years in Victoria, Australia. 11 teams from four mental health service providers will be randomly allocated to one of three dates 9 months apart to start the intervention. The intervention, a modified version of Mental Health Experience Co-Design (MH ECO), will be delivered to 30 service users, 30 carers and 10 staff in each cluster. Outcome data will be collected at baseline (6 months) and at completion of each intervention wave. The primary outcome is improvement in recovery score using the 24-item Revised Recovery Assessment Scale for service users. Secondary outcomes are improvements to user and carer mental health and well-being using the shortened 8-item version of the WHOQOL Quality of Life scale (EUROHIS), changes to staff attitudes using the 19-item Staff Attitudes to Recovery Scale and recovery orientation of services using the 36-item Recovery Self Assessment Scale (provider version). Intervention and usual care periods will be compared using a linear mixed effects model for continuous outcomes and a generalised linear mixed effects model for binary outcomes. Participants will be analysed in the group that the cluster was assigned to at each time point.Ethics and disseminationThe University of Melbourne, Human Research Ethics Committee (1340299.3) and the Federal and State Departments of Health Committees (Project 20/2014) granted ethics approval. Baseline data results will be reported in 2015 and outcomes data in 2017.Trial registration numberAustralian and New Zealand Clinical Trials Registry ACTRN12614000457640.
Preventing Ischial Pressure Ulcers: III. Clinical Pilot Study of Chronic Neuromuscular Electrical Stimulation
Authors: Kaplan Hilton M. , Baker Lucinda L. , Rubayi Salah , Loeb Gerald E. 
Published: March 2015

Objective:BIONs™ (BIOnic Neurons) are injectable, wireless microstimulators that make chronic BION Active Seating (BAS) possible for pressure ulcer prevention (PUP). Neuromuscular electrical stimulation (NMES) produces skeletal motion and activates trophic factors, counteracting three major etiological mechanisms leading to pressure ulcers (PUs): immobility, soft-tissue atrophy, and ischemia. Companion papers I and II reviewed prior experience with NMES for PUP, and analyzed the biomechanical considerations, respectively. This paper presents a treatment strategy derived from this analysis, and the clinical results of the first three cases.Methods:Two BIONs implanted (one on inferior gluteal nerve to gluteus maximus (GM), and other on sciatic nerve to hamstrings (HS)), in 3 spinal cord injured (SCI) subjects already undergoing gluteal rotation flaps for PUs. BAS using HS when seated, and BION Conditioning (BC) via GM+HS when non-weightbearing. Follow-up: 1 yr, including 6 mo. treatment window (interface pressure mapping; muscle perfusion scans; MRI, X-ray volume assessments).Results:Successfully implanted and activated both desired muscle groups, selectively, in all. No PU recurrences or wound complications. Two subjects completed protocol. Mean results: Interface: contact pressure −10%; maximum pressure −20%; peak pressure area −15%. Vascularity: GM +20%, HS +110%. Perfusion: GM +70%, HS +440%. Muscle volume: GM +14%, HS +31%. Buttock soft-tissue padding: +49%. 1 BION failed; 1 BION rotated under GM.Conclusions:Promising proof-of-concept data supporting the feasibility of implanted microstimulators to achieve sufficiently strong and selective activation of target muscles for PUP. Ultimate goal is prophylactic deployment through bilateral, nonsurgical injection of BIONs in chronically immobile patients.
Preventing Ischial Pressure Ulcers: II. Biomechanics
Authors: Kaplan Hilton M. , Baker Lucinda L. , Davoodi Rahman , Wong Nga Ting , Loeb Gerald E. 
Published: March 2015

Background:Pressure ulcers (PUs) are common and debilitating wounds that arise when immobilized patients cannot shift their weight. Neuromuscular Electrical Stimulation (NMES) has been investigated for Pressure Ulcer Prevention (PUP) for over 20 years. Historically gluteus maximus (GM) has been considered an important actuator in attempting to redistribute seated pressures through NMES.Methods:Analysis of skeletal biomechanics to quantify the value of GM relative to hamstring hip extensors (HS), using muscle moment models based on torques and rigid body mass estimates from the literature. Surface stimulation experiments (n= 10 + 1,non-paralyzed) to validate model and identify promising stimulation sites and treatment strategies that would approximate healthy biomechanics.Results:Literature values and Rigid Body Analysis estimate: ~63 Nm extensor torque requirement calculated for complete ipsilateral unloading of the buttocks. Muscle Moment Analysis: GM can provide 70% of total hip extensor torque when walking vs. 18% when seated. HS can provide 100 Nm hip extension torque when seated, exceeding 63 Nm requirement. Surface Stimulation: ipsilateral seated interface pressure mean −26% during HS stimulation vs. +16% with GM; peak pressure area −94% HS vs. +213% GM.Conclusions:GM activation reduces disuse atrophy and improves circulation, but appears neither required, nor desired, for unloading when seated. HS stimulation alone should be capable of sufficient unloading. This new proposed approach is explored clinically in companion paper III.
Upregulation of MAPK Negative Feedback Regulators and RET in Mutant ALK Neuroblastoma: Implications for Targeted Treatment
Authors: Lambertz Irina , Kumps Candy , Claeys Shana , Lindner Sven , Beckers Anneleen , Janssens Els , Carter Daniel R. , Cazes Alex , Cheung Belamy B. , De Mariano Marilena , De Bondt An , De Brouwer Sara , Delattre Olivier , Gibbons Jay , Janoueix-Lerosey Isabelle , Laureys Geneviève , Liang Chris , Marchall Glenn M. , Porcu Michael , Takita Junko , Trujillo David Camacho , Van Den Wyngaert Ilse , Van Roy Nadine , Van Goethem Alan , Van Maerken Tom , Zabrocki Piotr , Cools Jan , Schulte Johannes H. , Vialard Jorge , Speleman Frank , De Preter Katleen 
Published: March 2015

Abstract
Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies.
Experimental Design: To achieve this goal, transcriptome profiling was performed in neuroblastoma cell lines with the ALKF1174L or ALKR1275Q hotspot mutations, ALK amplification, or wild-type ALK following pharmacologic inhibition of ALK using four different compounds. Next, we performed cross-species genomic analyses to identify commonly transcriptionally perturbed genes in MYCN/ALKF1174L double transgenic versus MYCN transgenic mouse tumors as compared with the mutant ALK-driven transcriptome in human neuroblastomas.
Results: A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALKF1174L and ALKR1275Q regulable overexpression constructs and in other ALKomas. In addition to the previously established PI3K/AKT/mTOR, MAPK/ERK, and MYC/MYCN signaling branches, we identified that mutant ALK drives a strong upregulation of MAPK negative feedback regulators and upregulates RET and RET-driven sympathetic neuronal markers of the cholinergic lineage.
Conclusions: We provide important novel insights into the transcriptional consequences and the complexity of mutant ALK signaling in this aggressive pediatric tumor. The negative feedback loop of MAPK pathway inhibitors may affect novel ALK inhibition therapies, whereas mutant ALK induced RET signaling can offer novel opportunities for testing ALK-RET oriented molecular combination therapies. Clin Cancer Res; 21(14); 3327–39. ©2015 AACR.
Effects of Metformin, Buformin, and Phenformin on the Post-Initiation Stage of Chemically Induced Mammary Carcinogenesis in the Rat
Authors: Zhu Zongjian , Jiang Weiqin , Thompson Matthew D. , Echeverria Dimas , McGinley John N. , Thompson Henry J. 
Published: March 2015

AbstractMetformin is a widely prescribed drug for the treatment of type II diabetes. Although epidemiologic data have provided a strong rationale for investigating the potential of this biguanide for use in cancer prevention and control, uncertainty exists whether metformin should be expected to have an impact in nondiabetic patients. Furthermore, little attention has been given to the possibility that other biguanides may have anticancer activity. In this study, the effects of clinically relevant doses of metformin (9.3 mmol/kg diet), buformin (7.6 mmol/kg diet), and phenformin (5.0 mmol/kg diet) were compared with rats fed control diet (AIN93-G) during the post-initiation stage of 1-methyl-1-nitrosourea-induced (50 mg/kg body weight) mammary carcinogenesis (n = 30/group). Plasma, liver, skeletal muscle, visceral fat, mammary gland, and mammary carcinoma concentrations of the biguanides were determined. In comparison with the control group, buformin decreased cancer incidence, multiplicity, and burden, whereas metformin and phenformin had no statistically significant effect on the carcinogenic process relative to the control group. Buformin did not alter fasting plasma glucose or insulin. Within mammary carcinomas, evidence was obtained that buformin treatment perturbed signaling pathways related to energy sensing. However, further investigation is needed to determine the relative contributions of host systemic and cell autonomous mechanisms to the anticancer activity of biguanides such as buformin. Cancer Prev Res; 8(6); 518–27. ©2015 AACR.