bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Rare Disease-Associated Tyk2 Variants Are Catalytically Impaired but Signaling Competent
Authors: Li Zhi , Gakovic Milica , Ragimbeau Josiane , Eloranta Maija-Leena , Rönnblom Lars , Michel Frédérique , Pellegrini Sandra 
Published: January 2013

AbstractTyk2 belongs to the Janus protein tyrosine kinase family and is involved in signaling of immunoregulatory cytokines (type I and III IFNs, IL-6, IL-10, and IL-12 families) via its interaction with shared receptor subunits. Depending on the receptor complex, Tyk2 is coactivated with either Jak1 or Jak2, but a detailed molecular characterization of the interplay between the two enzymes is missing. In human populations, the Tyk2 gene presents high levels of genetic diversity with &gt;100 nonsynonymous variants being detected. In this study, we characterized two rare Tyk2 variants, I684S and P1104A, which have been associated with susceptibility to autoimmune disease. Specifically, we measured their in vitro catalytic activity and their ability to mediate Stat activation in fibroblasts and genotyped B cell lines. Both variants were found to be catalytically impaired but rescued signaling in response to IFN-α/β, IL-6, and IL-10. These data, coupled with functional study of an engineered Jak1 P1084A, support a model of nonhierarchical activation of Janus kinases in which one catalytically competent Jak is sufficient for signaling provided that its partner behaves as proper scaffold, even if inactive. Through the analysis of IFN-α and IFN-γ signaling in cells with different Jak1 P1084A levels, we also illustrate a context in which a hypomorphic Jak can hamper signaling in a cytokine-specific manner. Given the multitude of Tyk2-activating cytokines, the cell context–dependent requirement for Tyk2 and the catalytic defect of the two disease-associated variants studied in this paper, we predict that these alleles are functionally significant in complex immune disorders.
A Spectral Method for Second Order Volterra Integro-Differential Equation with Pantograph Delay
Authors: Zheng Weishan , Chen Yanping 
Published: January 2013

AbstractIn this paper, a Legendre-collocation spectral method is developed for the second order Volterra integro-differential equation with pantograph delay. We provide a rigorous error analysis for the proposed method. The spectral rate of convergence for the proposed method is established in both L2-norm and L∞-norm.
Spatial Mental Models: The Interaction of Presentation Format, Task Requirements and Availability of Working Memory Components
Authors: Picucci Luciana , Gyselinck Valérie , Piolino Pascale , Nicolas Serge , Bosco Andrea 
Published: January 2013

SummaryTwo experiments investigate how people create spatial mental models (SMMs) as a function of presentation format. Spatial representations following a route within a virtual environment (visual) and an auditory description (verbal) were compared. Moreover, a dual‐task procedure was adopted to depict the role of working memory (WM) components in such a task. Two testing formats were examined in both experiments: sentence verification (verbal) and sketch map (visual) tasks. This study shows that both presentations lead to adequate spatial representation. Nonetheless, SMMs are not presentation free. They are built by virtual presentation with a contribution of visuo‐spatial WM. An involvement of verbal WM emerged while encoding spatial information from both verbal and virtual presentation. Congruency between presentation and testing formats slightly reduces the gap between verbal and virtual presentation. SMMs appear to be affected by the interaction of presentation and testing format as well as by the WM availability. Copyright © 2013 John Wiley & Sons, Ltd.
Functionalized Fe‐Filled Multiwalled Carbon Nanotubes as Multifunctional Scaffolds for Magnetization of Cancer Cells
Authors: Marega Riccardo , De Leo Federica , Pineux Florent , Sgrignani Jacopo , Magistrato Alessandra , Naik Anil Damodar , Garcia Yann , Flamant Lionel , Michiels Carine , Bonifazi Davide 
Published: January 2013

AbstractWith the aim to design addressable magnetically‐active carbon nanotubes (CNTs) for cancer treatment, the use of Fe‐filled CNTs (Fe@MWCNTs) as multifunctional scaffolds is reported for exohedrally anchoring a monoclonal antibody (mAb) known to bind a plasma membrane receptor over‐expressed in several cancer cells (EGFR). Comprehensive microscopic (transmission electron microscopy, atomic force microscopy, and scanning electron microscopy) and spectroscopic (Raman, 57Fe Mossbauer, energy dispersive spectroscopy, X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction) characterizations reveal the efficient confinement of magnetically‐active Fe phases (α‐Fe and Fe3C), while compositional evaluations through XPS, thermogravimetric analysis and gel electrophoresis confirm that mAb immobilization onto Fe@MWCNTs occurs. Enzyme‐linked immunosorbent assay (ELISA), confocal microscopy imaging and western blotting confirm the targeting action toward EGFR‐overexpressing cell lines (EGFR+). In vitro magnetic filtration experiments demonstrate that a selective removal of EGFR+ cells from a mixed population of healthy cell lines could be obtained in very short times (≈10 min). Cytotoxicity evaluations by classic cell staining procedures after application of an electromagnetic radiation inducing magnetic fluid hyperthermia (MFH), show a selective suppression of the EGFR+ cell line. Molecular dynamics and docking simulations of the hybrid mAb/Fe@MWCNTs conjugates nicely show how the presence of the CNT framework does not sterically affect the conformational properties of the two antigen binding regions, further supporting the biochemical findings.
Palladium‐Catalyzed Oxidative Acylation of N‐Benzyltriflamides with Aldehydes via CH Bond Activation
Authors: Sharma Satyasheel , Park Jihye , Park Eonjeong , Kim Aejin , Kim Minyoung , Kwak Jong Hwan , Jung Young Hoon , Kim In Su 
Published: January 2013

AbstractA palladium‐catalyzed ortho‐acylation of N‐benzyltriflamides with aldehydes via direct sp2 CH bond activation is described. Benzylamines with a triflamide directing group in the presence of palladium acetate, acetic acid, and tert‐butyl hydroperoxide as an oxidant can be effectively coupled with aryl and alkyl aldehydes to provide ortho‐acyl‐N‐benzyltriflamides with a high regioselectivity.
Periosteal versus true cross‐sectional geometry: A comparison along humeral, femoral, and tibial diaphyses
Authors: Macintosh Alison A. , Davies Thomas G. , Ryan Timothy M. , Shaw Colin N. , Stock Jay T. 
Published: January 2013

AbstractCross‐sectional geometric (CSG) properties of human long bone diaphyses are typically calculated from both periosteal and endosteal contours. Though quantification of both is desirable, periosteal contours alone have provided accurate predictions of CSG properties at the midshaft in previous studies. The relationship between CSG properties calculated from external contours and “true” (endosteal and periosteal) CSG properties, however, has yet to be examined along the whole diaphysis. Cross‐sectional computed tomography scans were taken from 21 locations along humeral, femoral, and tibial diaphyses in 20 adults from a late prehistoric central Illinois Valley cemetery. Mechanical properties calculated from images with (a) artificially filled medullary cavities (“solid”) and (b) true unaltered cross‐sections were compared at each section location using least squares regression. Results indicate that, in this sample, polar second moments of area (J), polar section moduli (Zp), and cross‐sectional shape (Imax/Imin) calculated from periosteal contours correspond strongly with those calculated from cross‐sections that include the medullary cavity. Correlations are high throughout most of the humeral diaphysis and throughout large portions of femoral and tibial diaphyses (R2 = 0.855–0.998, all P < 0.001, %SEE ≤ 8.0, %PE ≤ 5.0), the major exception being the proximal quarter of the tibial diaphysis for J and Zp. The main source of error was identified as variation in %CA. Results reveal that CSG properties quantified from periosteal contours provide comparable results to (and are likely to detect the same differences among individuals as) true CSG properties along large portions of long bone diaphyses. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.
Genetic evidence for spatio‐temporal changes in the dispersal patterns of two sympatric African colobine monkeys
Authors: Minhós Tania , Nixon Elizabeth , Sousa Cláudia , Vicente Luis M. , da Silva Maria Ferreira , Sá Rui , Bruford Michael W. 
Published: January 2013

AbstractWestern black‐and‐white colobus and Temmink's red colobus are two forest‐dependent African primates with similar ecological requirements, often found in sympatry. Their most striking difference lies in their social system: black‐and‐white colobus live in small groups with mainly male‐mediated dispersal but where females can also disperse, whereas red colobus live in larger groups with males described as philopatric. To investigate whether genetic evidence supports the reported patterns of dispersal based on observational data, we examined eight black‐and‐white and six red colobus social groups from Cantanhez National Park, Guinea‐Bissau. Microsatellite markers revealed a lack of sex‐biased dispersal for black‐and‐white colobus. Gene flow, mainly mediated by females, better explained the genetic patterns found in red colobus, with some evidence for less extensive male dispersal. In contrast to the microsatellite data, low mitochondrial diversity for the black‐and‐white colobus suggests that historical and/or long‐range male‐mediated gene flow might have been favored. In red colobus, the co‐existence of three divergent mitochondrial haplogroups suggests that the Cantanhez population contains a secondary contact zone between divergent lineages that evolved in allopatry. Female‐biased dispersal in this species may be a major factor contributing to the colonization by such differentiated mitochondrial lineages in the region. Overall, we find evidence for a spatio‐temporal change in the dispersal patterns of the colobus monkeys of Cantanhez, with mitochondrial DNA indicating dispersal by mainly a single sex and microsatellite data suggesting that recently both sexes appear to be dispersing within the population. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.
Intrinsic connectivity network disruption in progressive supranuclear palsy
Authors: Gardner Raquel C. , Boxer Adam L. , Trujillo Andrew , Mirsky Jacob B. , Guo Christine C. , Gennatas Efstathios D. , Heuer Hilary W. , Fine Eric , Zhou Juan , Kramer Joel H. , Miller Bruce L. , Seeley William W. 
Published: January 2013

ObjectiveProgressive supranuclear palsy (PSP) has been conceptualized as a large‐scale network disruption, but the specific network targeted has not been fully characterized. We sought to delineate the affected network in patients with clinical PSP.MethodsUsing task‐free functional magnetic resonance imaging, we mapped intrinsic connectivity to the dorsal midbrain tegmentum (dMT), a region that shows focal atrophy in PSP. Two healthy control groups (1 young, 1 older) were used to define and replicate the normal connectivity pattern, and patients with PSP were compared to an independent matched healthy control group on measures of network connectivity.ResultsHealthy young and older subjects showed a convergent pattern of connectivity to the dMT, including brainstem, cerebellar, diencephalic, basal ganglia, and cortical regions involved in skeletomotor, oculomotor, and executive control. Patients with PSP showed significant connectivity disruptions within this network, particularly within corticosubcortical and cortico‐brainstem interactions. Patients with more severe functional impairment showed lower mean dMT network connectivity scores.InterpretationThis study defines a PSP‐related intrinsic connectivity network in the healthy brain and demonstrates the sensitivity of network‐based imaging methods to PSP‐related physiological and clinical changes. Ann Neurol 2013;73:603–616
Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12
Authors: Draaken Markus , Mughal Sadaf S. , Pennimpede Tracie , Wolter Stefanie , Wittler Lars , Ebert Anne‐Karoline , Rösch Wolfgang , Stein Raimund , Bartels Enrika , Schmidt Dominik , Boemers Thomas M. , Schmiedeke Eberhard , Hoffmann Per , Moebus Susanne , Herrmann Bernhard G. , Nöthen Markus M. , Reutter Heiko , Ludwig Michael 
Published: January 2013

AbstractBACKGROUNDThe exstrophy‐epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC.METHODS Array‐based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high‐penetrance mutations involving small sequence changes. RESULTS A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ. CONCLUSIONS The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples.19p13.12, microduplication, bladder exstrophy‐epispadias complex, array‐based molecular karyotyping, in situ hybridization analysis, copy number variations, WIZ Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.
Quality control of mitochondria during aging: Is there a good and a bad side of mitochondrial dynamics?
Authors: Figge Marc Thilo , Osiewacz Heinz D. , Reichert Andreas S. 
Published: January 2013

AbstractMaintenance of functional mitochondria is essential in order to prevent degenerative processes leading to disease and aging. Mitochondrial dynamics plays a crucial role in ensuring mitochondrial quality but may also generate and spread molecular damage through a population of mitochondria. Computational simulations suggest that this dynamics is advantageous when mitochondria are not or only marginally damaged. In contrast, at a higher degree of damage, mitochondrial dynamics may be disadvantageous. Deceleration of fusion‐fission cycles could be one way to adapt to this situation and to delay a further decline in mitochondrial quality. However, this adaptive response makes the mitochondrial network more vulnerable to additional molecular damage. The “mitochondrial infectious damage adaptation” (MIDA) model explains a number of inconsistent and counterintuitive data such as the “clonal expansion” of mutant mitochondrial DNA. We propose that mitochondrial dynamics is a double‐edged sword and suggest ways to test this experimentally.
Glycan Sequence‐Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library
Authors: Wang Ning , Huang Cheng‐yuan , Hasegawa Mizuho , Inohara Naohiro , Fujimoto Yukari , Fukase Koichi 
Published: January 2013

AbstractNucleotide oligomerization domain‐containing protein 2 (Nod2), an innate immune receptor, recognizes bacterial cell‐wall peptidoglycan (PGN), the minimum ligand of which is muramyl dipeptide (MDP). Enzymatic digestion of PGN appears to be important for Nod2 recognition. PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAcβ(1→4)MurNAc or MurNAcβ(1→4)GlcNAc. In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 (hNod2) were investigated. The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties. (MurNAcβ(1→4)GlcNAc)2‐containing structures exhibited stronger activity than those containing (GlcNAcβ(1→4)MurNAc)2. The results suggest that differences in the enzymatic degradation process affect the host's immunomodulation process.
Management of paravalvular regurgitation after Edwards SAPIEN transcatheter aortic valve replacement: Management of paravalvular regurgitation after TAVR
Authors: Martinez Claudia A. , Singh Vikas , O'Neill Brian P. , Alfonso Carlos E. , Bilsker Martin S. , Martinez Clark Pedro , Williams Donald , Cohen Mauricio G. , Heldman Alan W. , O'Neill William W. 
Published: January 2013

BackgroundWith the expansion in the use of transcatheter valve therapies for aortic stenosis, the incidence of hemodynamically significant paravalvular regurgitation (PVR) has become a clinical challenge.MethodsThe study population consisted of those patients with either acute significant PVR immediately post‐Edwards SAPIEN (ES) aortic valve implantation, requiring additional maneuvers during the index transcatheter aortic valve replacement (TAVR) or symptomatic PVR requiring treatment by transcatheter closure at a later date. All the patients were assessed within 24 hrs, 30 days, 3 months, 6 months and 12 months after the procedure.ResultsA total of 100 consecutive patients underwent ES TAVR (62% with 23 mm and 38% with 26 mm valve), of them 27% (27/100) were identified to have hemodynamically significant PVR requiring additional percutaneous interventions during or after the index procedure. Patient's mean age was 85 ± 12 years and 74% (20/27) were male. The mean Society of Thoracic Surgeon Score was 11.3% (range 4.6–17.6%), 59% had a 23 mm and 41% had a 26 mm ES valve. There was no difference in the occurrence of PVR between a) two valve sizes—23 mm (16/62) vs. 26 mm (11/38) (P = 0.817) and b) the two approaches—transfemoral (15/48) vs. transapical (TA) (12/52) (P = 0.37). A total of 32 procedures were performed on the 27 patients: one patient required four and two required two procedures each. There were 19 repeat ballooning, seven valve in valve and six transcatheter device closure procedures. The approach was retrograde in 66%, antegrade transeptal in 6% and antegrade TA in 28%. The procedural success rate was 90.6%, the total 30‐day, 3 months and 6 months mortality rate was 7.4, 18.5, and 22% respectively. At the time of final analysis a total of 56% (15/27) had completed a 12 month follow‐up.ConclusionThe management of PVR in the TAVR era is a technical challenge. We present our experience and propose a management approach. © 2013 Wiley Periodicals, Inc.
Staged total percutaneous treatment of aortic valve pathology and mitral regurgitation: Institutional experience
Authors: Kische Stephan , D'Ancona Giuseppe , Paranskaya Liliya , Schubert Jochen , Arsoy Nicole , Hauenstein Karl Heinz , Alozie Anthony , Jovanovich Bojan , Nienaber Christoph , Ince Hüseyin 
Published: January 2013

ObjectivesTo summarize our single Institution experience with staged total percutaneous management of aorto‐mitral pathology.BackgroundPercutaneous treatment of aortic valve stenosis (AVS) and mitral valve regurgitation (MVR) has been recently proposed for patients at high surgical risk.MethodsData concerning consecutive patients undergoing percutaneous transcatheter AV implantation (TAVI) followed by MV repair with MitraClip® were prospectively collected and analyzed.ResultsFrom January 2010 to February 2012 a total of 254 patients were referred to undergo TAVI in our Institution. Seventeen (6.7%) had preoperative severe MVR that remained unchanged after TAVI. Due to exacerbation of symptoms 12 patients were subsequently submitted to MV repair with the MitraClip® device. Mean age was 79 years (72–86 years), median Ambler score was 30.1 (17.2–42.6) and EuroSCORE 22.3 (10.2–48.6). Procedural success rate was 100%. Postprocedural hospitalization was 7.1 ± 2.7 and 4.6 ± 0.9 days after TAVI and MV repair, respectively. Six months follow‐up echocardiography confirms improvement in LV‐EF (37.2 ± 9.9 vs. 43.5 ± 10.7, P < 0.0001). No patient presents MVR exceeding grade I+ or prosthetic aortic insufficiency > I grade and all patients experienced an improvement in functional status.ConclusionsPercutaneous treatment of AVS and MVR is feasible and safe. A tailored approach should be considered to treat firstly the AVS and subsequently the MVR when severe MV dysfunction and symptoms persist. Short‐term durability of this combined percutaneous approach seems encouraging and justifies the economical burden to treat patients that have no other option. © 2013 Wiley Periodicals, Inc.
Impact of advanced age on the safety and effectiveness of paclitaxel‐eluting stent implantation in patients with ST‐segment elevation myocardial infarction undergoing primary angioplasty
Authors: Dudek Dariusz , Mehran Roxana , Dziewierz Artur , Witzenbichler Bernhard , Brodie Bruce R. , Kornowski Ran , Fahy Martin , Lansky Alexandra J. , Rakowski Tomasz , Legutko Jacek , Bryniarski Leszek , Stone Gregg W. 
Published: January 2013

ObjectivesTo assess the impact of age on safety and efficacy of paclitaxel‐eluting stent (PES) implantation during primary percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI).BackgroundThe benefits of paclitaxel‐eluting stent (PES) implantation during primary PCI were confirmed by the long‐term results of the HORIZONS‐AMI trial. Whether the effects of PES are independent of age has not been reported.MethodsData on 3,006 patients from the HORIZONS‐AMI study randomized in a 3:1 ratio to PES or bare‐metal stent (BMS) in whom at least one stent was implanted were assessed. There were 2,302 (76.6%) patients <70, and 704 patients ≥70 years of age.ResultsAt 3 years, among older patients a trend toward lower risk of major adverse cardiac events (MACE; death from any cause, stroke, reinfarction and unplanned revascularization for ischemia) related to PES use was observed (PES vs. BMS: 18.0% vs. 21.3%; P = 0.07). There was also a trend for reduction of MACE related to PES in older patients (26.4% vs. 33.1%; P = 0.09). Both, patients <70 and ≥70 years of age treated with PES were at lower risk for ischemic target vessel revascularization. However, a higher risk of major bleeding in elderly patients treated with PES was observed (P = 0.02 for interaction between age group and PES effects). No interaction between age and stent type in terms of the risk of other clinical end points, including all‐cause death, was confirmed.ConclusionsFor STEMI patients undergoing primary PCI, the implantation of PES as compared with BMS reduced ischemic TVR, and this effect was independent of age. [NCT00433966]. © 2013 Wiley Periodicals, Inc.