bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angelman syndrome: Mutations influence features in early childhood
Authors: Tan Wen‐Hann , Bacino Carlos A. , Skinner Steven A. , Anselm Irina , Barbieri‐Welge Rene , Bauer‐Carlin Astrid , Beaudet Arthur L. , Bichell Terry Jo , Gentile Jennifer K. , Glaze Daniel G. , Horowitz Lucia T. , Kothare Sanjeev V. , Lee Hye‐Seung , Nespeca Mark P. , Peters Sarika U. , Sahoo Trilochan , Sarco Dean , Waisbren Susan E. , Bird Lynne M. 
Published: December 2010

AbstractAngelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternal copy of UBE3A. Although the “classic” features of AS are well described, few large‐scale studies have delineated the clinical features in AS. We present baseline data from 92 children with a molecular diagnosis of AS between 5 and 60 months old who are enrolled in the National Institutes of Health Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study from January 2006 to March 2008. Seventy‐four percent of participants had deletions, 14% had either uniparental disomy (UPD) or imprinting defects, and 12% had UBE3A mutations. Participants with UPD/imprinting defects were heavier (P = 0.0002), while those with deletions were lighter, than the general population (P < 0.0001). Twenty out of 92 participants were underweight, all of whom had deletions or UBE3A mutations. Eight out of 92 participants (6/13 (46%) with UPD/imprinting defects and 2/11 (18%) with UBE3A mutations) were obese. Seventy‐four out of 92 participants (80%) had absolute or relative microcephaly. No participant was macrocephalic. The most common behavioral findings were mouthing behavior (95%), short attention span (92%), ataxic or broad‐based gait (88%), history of sleep difficulties (80%), and fascination with water (75%). Frequent, easily provoked laughter was observed in 60%. Clinical seizures were reported in 65% of participants but all electroencephalograms (EEGs) were abnormal. We conclude that the most characteristic feature of AS is the neurobehavioral phenotype, but specific EEG findings are highly sensitive for AS. Obesity is common among those with UPD/imprinting defects. © 2010 Wiley‐Liss, Inc.
A novel homozygous COL11A2 deletion causes a C‐terminal protein truncation with incomplete mRNA decay in a Turkish patient
Authors: Kayserili Hülya , Wollnik Bernd , Güven Gamze , Emiroğlu Melike Ulubil , Başerer Nermin , Uyguner Z. Oya 
Published: December 2010

AbstractRecessive mutations in COL11A2 (collagen, type XI, alpha 2), are responsible for otospondylomegaepiphyseal dysplasia (OSMED) and non‐syndromic hearing loss while dominant mutations are associated with Stickler type III, isolated cleft palate, Robin sequence, non‐ophthalmic Stickler syndrome, early onset osteoarthritis and autosomal dominant hearing loss. We describe here the clinical findings of two Turkish cousins with OSMED carrying a novel homozygous truncating mutation in exon 38 of COL11A2 gene, c.2763delT, identified on cDNA and confirmed at gDNA. This mutation is located on triple helix repeat domain of the collagen alpha‐2(XI) chain, where the majority of the previously identified mutations are located. Real‐time RT‐PCR experiment provided that mutated transcript does not decay completely. Although our analysis displays the partial survival of the mutant transcript from blood tissue, not from cartilage, we propose that this mechanism may play an important role on the variable expressivity of the heterozygous COL11A2 gene mutations. © 2010 Wiley‐Liss, Inc.
Genotype–phenotype analysis of the branchio‐oculo‐facial syndrome
Authors: Milunsky Jeff M. , Maher Tom M. , Zhao Geping , Wang Zhenyuan , Mulliken John B. , Chitayat David , Clemens Michele , Stalker Heather J. , Bauer Mislen , Burch Michele , Chénier Sébastien , Cunningham Michael L. , Drack Arlene V. , Janssens Sandra , Karlea Audrey , Klatt Regan , Kini Usha , Klein Ophir , Lachmeijer Augusta M. , Megarbane Andre , Mendelsohn Nancy J. , Meschino Wendy S. , Mortier Geert R. , Parkash Sandhya , Ray C. Renai , Roberts Angharad , Roberts Amy , Reardon Willie , Schnur Rhonda E. , Smith Rosemarie , Splitt Miranda , Tezcan Kamer , Whiteford Margo L. , Wong Derek A. , Zori Roberto , Lin Angela E. 
Published: December 2010

AbstractBranchio‐oculo‐facial syndrome (BOFS; OMIM#113620) is a rare autosomal dominant craniofacial disorder with variable expression. Major features include cutaneous and ocular abnormalities, characteristic facies, renal, ectodermal, and temporal bone anomalies. Having determined that mutations involving TFAP2A result in BOFS, we studied a total of 30 families (41 affected individuals); 26/30 (87%) fulfilled our cardinal diagnostic criteria. The original family with the 3.2 Mb deletion including the TFAP2A gene remains the only BOFS family without the typical CL/P and the only family with a deletion. We have identified a hotspot region in the highly conserved exons 4 and 5 of TFAP2A that harbors missense mutations in 27/30 (90%) families. Several of these mutations are recurrent. Mosaicism was detected in one family. To date, genetic heterogeneity has not been observed. Although the cardinal criteria for BOFS have been based on the presence of each of the core defects, an affected family member or thymic remnant, we documented TFAP2A mutations in three (10%) probands in our series without a classic cervical cutaneous defect or ectopic thymus. Temporal bone anomalies were identified in 3/5 patients investigated. The occurrence of CL/P, premature graying, coloboma, heterochromia irides, and ectopic thymus, are evidence for BOFS as a neurocristopathy. Intrafamilial clinical variability can be marked. Although there does not appear to be mutation‐specific genotype–phenotype correlations at this time, more patients need to be studied. Clinical testing for TFAP2A mutations is now available and will assist geneticists in confirming the typical cases or excluding the diagnosis in atypical cases. © 2010 Wiley‐Liss, Inc.
ARX polyalanine expansions are highly implicated in familial cases of mental retardation with infantile epilepsy and/or hand dystonia
Authors: Cossée Mireille , Faivre Laurence , Philippe Christophe , Hichri Heifa , de Saint‐Martin Anne , Laugel Vincent , Bahi‐Buisson Nadia , Lemaitre Jean‐François , Leheup Bruno , Delobel Bruno , Demeer Bénédicte , Poirier Karine , Biancalana Valérie , Pinoit Jean‐Michel , Julia Sophie , Chelly Jamel , Devys Didier , Mandel Jean‐Louis 
Published: December 2010

AbstractMutations in the ARX gene cause both nonsyndromic and several forms of syndromic mental retardation (MR). Two polyalanine (polyA) expansions of ARX are recurrent mutations. The most common one, the c.428_451dup, is associated with a wide spectrum of phenotypes, ranging from the most severe West syndrome to Partington syndrome (MR and hand dystonia), and even nonsyndromic X‐linked mental retardation (NS‐XLMR). Studies of patients not selected for specific clinical signs showed that the c.428_451dup is relatively frequent in families harboring X‐linked MR (7.5%), but less common in familial cases compatible with X‐linked NR (1%), and very rare in sporadic cases (0.1%). The c.333_334ins(GCG)7 expansion is less frequent and mainly associated with West syndrome. We screened for both ARX polyA expansions in 98 unrelated patients selected for the presence of NR associated with different types of epilepsy and/or with hand dystonia. We also studied two families with an initial diagnosis of NS‐XLMR, one of which was identified as showing linkage to the ARX locus. The c.428_451dup was identified in three patients and the c.333_334ins(GCG)7 in one; all of the patients were from families with two affected brothers. We also found the c.428_451dup in the family linked to ARX, and clinical re‐evaluation showed subtle, previously undetected signs. Our study illustrates that ARX polyA expansions are primarily associated with syndromic MR and shows a higher yield (18% in our cohort) when these mutations are screened in familial cases of MR with epilepsy and/or dystonia. © 2010 Wiley‐Liss, Inc.
Monosomy 21q22.11‐q22.13 presenting as a Fanconi anemia phenotype
Authors: Byrd Robert S. , Zwerdling Theodore , Moghaddam Billur , Pinter Joseph D. , Steinfeld Mary Beth 
Published: December 2010

AbstractWe report on a 5‐year‐old Caucasian female with multiple anomalies whose deletion, 46,XX,del(21)(q22.11q22.13), was determined by a 105K oligonucleotide‐based microarray. This case is a unique deletion that mimicked Fanconi anemia (combination of thrombocytopenia, thumb anomalies, congenital heart defects, borderline small head circumference, strabismus, hydronephrosis, and significant developmental delay) but testing for Fanconi anemia was negative, as was testing for a wide array of genetic/metabolic conditions. Microarray testing done at 5 months failed to demonstrate the interstitial deletion that was found on a newer generation microarray test performed after 3 years of age. When compared to other reported cases of partial monosomy 21q, the unique features of this case include: (1) cleft palate, although high palate is reported in other cases; (2) neonatal thrombocytopenia requiring platelet transfusion; (3) a platelet function defect, reported previously as platelet storage pool defect as part of a familial platelet disorder; and (4) an immune function defect. Similar to other reported patients with terminal 21q deletion, this child had significant developmental delay, and feeding and growth problems. This case also highlights the ability for newer technology microarrays to identify small interstitial deletions previously missed by an earlier version microarray. The advances in the microarray technologies are allowing us to better define new phenotypes and leading to the identification of a diagnosis for many patients who have been previously undiagnosed. Review of the genes involved in these novel deletions allows the caring physician to design surveillance strategies that are custom‐designed for these unique patients. © 2010 Wiley‐Liss, Inc.
White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: A diffusion‐tensor imaging and voxel‐based morphometry study
Authors: Scherfler Christoph , Frauscher Birgit , Schocke Michael , Iranzo Alex , Gschliesser Viola , Seppi Klaus , Santamaria Joan , Tolosa Eduardo , Högl Birgit , Poewe Werner ,   for the SINBAR (Sleep Innsbruck Barcelona) Group
Published: December 2010

AbstractObjectiveWe applied diffusion‐tensor imaging (DTI) including measurements of mean diffusivity (MD), a parameter of brain tissue integrity, fractional anisotropy (FA), a parameter of neuronal fiber integrity, as well as voxel‐based morphometry (VBM), a measure of gray and white matter volume, to detect brain tissue changes in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD).MethodsMagnetic resonance imaging (MRI) was performed in 26 patients with iRBD (mean disease duration, 9.2 ± 6.4 years) and 14 age‐matched healthy control subjects. Statistical parametric mapping (SPM) was applied to objectively identify focal changes of MRI parameters throughout the entire brain volume.ResultsSPM localized significant decreases of FA in the tegmentum of the midbrain and rostral pons and increases of MD within the pontine reticular formation overlapping with a cluster of decreased FA in the midbrain (p < 0.001). VBM revealed increases of gray matter densities in both hippocampi of iRBD patients (p < 0.001).InterpretationThe observed changes in the pontomesencephalic brainstem localized 2 areas harboring key neuronal circuits believed to be involved in the regulation of REM sleep and overlap with areas of structural brainstem damage causing symptomatic RBD in humans. Bilateral increases in gray matter density of the hippocampus suggest functional neuronal reorganization in this brain area in iRBD. This study indicates that DTI detects distinct structural brainstem tissue abnormalities in iRBD in the regions where REM is modulated. Further studies should explore the relationship between MRI pathology and the risk of patients with iRBD of developing alpha‐synuclein–related neurodegenerative diseases like Parkinson disease. Ann Neurol 2011.
Surface Chemistry of Metal–Organic Frameworks at the Liquid–Solid Interface
Authors: Zacher Denise , Schmid Rochus , Wöll Christof , Fischer Roland A. 
Published: December 2010

AbstractMetal–organic frameworks (MOFs) are a fascinating class of novel inorganic–organic hybrid materials. They are essentially based on classic coordination chemistry and hold much promise for unique applications ranging from gas storage and separation to chemical sensing, catalysis, and drug release. The evolution of the full innovative potential of MOFs, in particular for nanotechnology and device integration, however requires a fundamental understanding of the formation process of MOFs. Also necessary is the ability to control the growth of thin MOF films and the positioning of size‐ and shape‐selected crystals as well as MOF heterostructures on a given surface in a well‐defined and oriented fashion. MOFs are solid‐state materials typically formed by solvothermal reactions and their crystallization from the liquid phase involves the surface chemistry of their building blocks. This Review brings together various key aspects of the surface chemistry of MOFs.
Nanogel‐based scaffold delivery of prostaglandin E2 receptor–specific agonist in combination with a low dose of growth factor heals critical‐size bone defects in mice
Authors: Kamolratanakul Paksinee , Hayata Tadayoshi , Ezura Yoichi , Kawamata Aya , Hayashi Chikako , Yamamoto Yuka , Hemmi Hiroaki , Nagao Masashi , Hanyu Ryo , Notomi Takuya , Nakamoto Tetsuya , Amagasa Teruo , Akiyoshi Kazunari , Noda Masaki 
Published: December 2010

AbstractObjectiveRegeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low‐dose bone morphogenetic protein 2 (BMP‐2).MethodsCombined delivery of EP4A and BMP‐2 was carried out with a nanogel‐based scaffold in the shape of a disc, to repair critical‐size circle‐shaped bone defects in calvariae that otherwise did not heal spontaneously.ResultsCombination treatment with EP4A and low‐dose BMP‐2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low‐dose BMP‐2–induced cell differentiation and activation of transcription events in osteoblasts.ConclusionThese data indicate that combined delivery of EP4A and low‐dose BMP‐2 via nanogel‐based hydrogel provides a new system for bone repair.
Toll‐like receptor 2 induces Th17 myeloperoxidase autoimmunity while Toll‐like receptor 9 drives Th1 autoimmunity in murine vasculitis
Authors: Summers Shaun A. , Steinmetz Oliver M. , Gan Poh‐Yi , Ooi Joshua D. , Odobasic Dragana , Kitching A. Richard , Holdsworth Stephen R. 
Published: December 2010

AbstractObjectiveAutoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody–associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll‐like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to investigate the role of TLR ligation on cellular and humoral autoimmunity and glomerular injury in experimental myeloperoxidase (MPO)–induced AAV.MethodsWe analyzed autoimmune responses in wild‐type mice immunized with MPO alone or coimmunized with MPO and a TLR‐2 or TLR‐9 ligand. The major vascular injury found in human disease, glomerulonephritis with focal necrosis, was triggered by administering a subnephritogenic dose of nephrotoxic serum.ResultsMPO alone induced low‐titer antineutrophil cytoplasmic antibodies (ANCAs) without delayed‐type hypersensitivity or CD4 cytokine responses. However, when MPO was given with either TLR ligand, cellular and humoral autoimmunity was enhanced, but with distinctly different CD4 subsets and IgG ANCA isotypes. TLR‐2 ligand induced Th17 autoimmunity, with retinoic acid receptor–related orphan nuclear receptor γt–dependent interleukin‐17A (IL‐17A) production. TLR‐9 ligand promoted Th1 autoimmunity, with enhanced production of interferon‐γ (IFNγ) and Th1‐associated IgG subclasses. Glomerular vasculitis developed only after the administration of nephrotoxic serum in mice immunized with either TLR ligand and MPO. Glomerulonephritis directed by MPO and TLR‐2 ligation was attenuated when IL‐17A was neutralized, while glomerulonephritis induced by MPO and TLR‐9 ligation was attenuated when IFNγ was neutralized.ConclusionOur findings indicate a pathogenic role of TLRs in initiating autoimmune AAV. TLR‐2 induces Th17 CD4 cells while TLR‐9 can also direct vasculitis, by directing Th1 autoimmunity.
Heparin exerts a dual effect on murine lupus nephritis by enhancing enzymatic chromatin degradation and preventing chromatin binding in glomerular membranes
Authors: Hedberg Annica , Fismen Silje , Fenton Kristin A. , Fenton Chris , ØSterud Bjarne , Mortensen Elin S. , Rekvig Ole Petter 
Published: December 2010

AbstractObjectiveAssociation of nucleosome–IgG immune complexes with glomerular basement membranes (GBMs) is an important event in the development of lupus nephritis. Preventing this binding and/or increasing nuclease sensitivity of nucleosomes may be viable strategies for the prevention of the disease. Theoretically, heparin may alter nucleosomal structure and increase sensitivity to proteinases and nucleases, and may also inhibit binding of nucleosomes and nucleosome–IgG complexes to basement membrane structures. The aim of this study was to investigate whether and eventually how heparin prevents murine lupus nephritis.MethodsSurface plasmon resonance was used to analyze if heparin inhibits binding of nucleosomes to laminin and collagen. The effect of heparin on nuclease‐ and proteinase‐mediated degradation of nucleosomes was analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and agarose gel electrophoresis. In vitro results were compared with analyses in vivo in heparin‐treated (NZB × NZW)F1 mice. Anti–double‐stranded DNA antibody production, deposition of nucleosome–IgG complexes in GBMs, and development of proteinuria were monitored, and circulating chromatin fragments were quantified using quantitative polymerase chain reaction.ResultsIn vitro studies demonstrated that heparin increased enzymatic degradation of nucleosomes and almost completely inhibited binding of nucleosomes to laminin and collagen. (NZB × NZW)F1 mice treated with heparin demonstrated delayed or no antibody production and higher variation of circulating chromatin levels compared with untreated control mice. This effect was accompanied by highly reduced nucleosome–IgG complexes in GBMs and delayed development of nephritis.ConclusionIncreasing the degradation of nucleosomes, reducing their immunogenicity, and preventing binding of nucleosome–IgG complexes in glomeruli together provide an alternative basis for the treatment of lupus nephritis.
Score tests for inverse Gaussian mixtures
Authors: Desmond A. F. , Yang Z. L. 
Published: December 2010

The mixed inverse Gaussian given by Whitmore (biScand. J. Statist.,13, 1986, 211–220) provides a convenient way for testing the goodness‐of‐fit of a pure inverse Gaussian distribution. The test is a one‐sided score test with the null hypothesis being the pure inverse Gaussian (i.e. the mixing parameter is zero) and the alternative a mixture. We devise a simple score test and study its finite sample properties. Monte Carlo results show that it compares favourably with the smooth test of Ducharme (Test,10, 2001, 271‐290).In practical applications, when the pure inverse Gaussian distribution is rejected, one is interested in making inference about the general values of the mixing parameter. However, as it is well known that the inverse Gaussian mixture is a defective distribution; hence, the standard likelihood inference cannot be applied. We propose several alternatives and provide score tests for the mixing parameter. Finite sample properties of these tests are examined by Monte Carlo simulation. Copyright © 2010 John Wiley & Sons, Ltd.
Nutzer‐ und klimaangepasstes Bauen — Leitbild und Chance für die globale Verbreitung von nachhaltigen Gebäudelösungen
Authors: Wallbaum Holger , Ostermeyer York , Goto Yutaka 
Published: December 2010

AbstractDer Artikel gibt einen Überblick über Hintergründe und Ausblicke einer nachhaltigen Entwicklung als Leitbild im Bausektor. Im Fokus steht hierbei die Notwendigkeit der Anpassung bei der Übertragung bereits generierter Erfahrungswerte in andere Klimazonen und Kulturen. Gerade in diesem Sektor liegt enormes Potential in Bezug auf eine Lösung der globalen Probleme wie Klimaerwärmung und die Endlichkeit vieler Ressourcen. Erfahrungen mit analysierten Projekten zeigen jedoch, dass häufig Technologien nicht auf regionale Bedingungen angepasst werden, um schadensfreie und gesunde Gebäude zu erstellen.Am Beispiel eines Projektes der Eidgenössischen Mess‐ und Prüfanstalt (EMPA) und der Eidgenössischen Technischen Hochschule Zürich (ETHZ), in dem eine klimaangepasste Gebäudehülle für zentraljapanische Wohngebäude entwickelt wurde, wird aufgezeigt, warum gerade im Bereich der Bauphysik die Anpassung von Konzepten zwingend ist, um Bauschäden zu vermeiden und nachhaltige Gebäude zu ermöglichen.Daneben soll durch ein Aufzeigen der Wechselwirkungen und Abhängigkeiten der entwickelten Hülle mit verschiedenen Rahmenbedingungen, wie beispielsweise der regionalen Ressourcenverfügbarkeit, gezeigt werden, welche Herausforderungen ein solches Vorhaben mit sich bringt und welche Aspekte beachtet werden sollen, um Probleme möglichst vollumfänglich und regionalspezifisch zu lösen.User‐ and Climate‐tailored Design — a vision and chance for global acceptance of sustainable building solutions. The paper gives an overview on background and outlook on sustainable development as a trend and vision in the building sector. Focus is on the necessity to adapt existing experience values and concepts in when transferring them to other climate zones and cultures than they originate from. This approach shows a great potential in regards to a solution of problems like global warming and limited resources. Experiences with analyzed projects show however, that, despite the goal to create working and healthy homes, technologies and concepts often are not tailored to local conditions.Using the example of a cooperation project of the Swiss Federal Institute of Technology Zürich (ETH Zürich) and the Swiss Federal Laboratories for Materials Science and Technology (EMPA) in which a climate adapted building envelope was developed the paper shows what modifications have to be made. This is especially relevant in the field of building physics in order to increase efficiency and avoid damages to the building and inhabitants and create sustainable homes.Besides this the interchange of the developed envelope, associated production methods and other relevant frame conditions, like local resource availability, is used to demonstrate what barriers and potential synergies can emerge in the course of such a project.