bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organic Phenolic Configurationally Locked Polyene Single Crystals for Electro‐optic and Terahertz Wave Applications
Authors: Kwon O‐Pil , Kwon Seong‐Ji , Jazbinsek Mojca , Brunner Fabian D. J. , Seo Jung‐In , Hunziker Christoph , Schneider Arno , Yun Hoseop , Lee Yoon‐Sup , Günter Peter 
Published: September 2008

AbstractWe investigate a configurationally locked polyene (CLP) crystal 2‐(3‐(4‐hydroxystyryl)‐5,5‐dimethylcyclohex‐2‐enylidene)malononitrile (OH1) containing a phenolic electron donor, which also acts as a hydrogen bond donor. The OH1 crystals with orthorhombic space group Pna21 (point group mm2) exhibit large second‐order nonlinear optical figures of merit, high thermal stability and very favorable crystal growth characteristics. Higher solubility in methanol and a larger temperature difference between the melting temperature and the decomposition temperature of OH1 compared to analogous CLP crystals, are of advantage for solution and melt crystal growth, respectively. Acentric bulk OH1 crystals of large sizes with side lengths of up to 1 cm with excellent optical quality have been successfully grown from methanol solution. The microscopic and macroscopic nonlinearities of the OH1 crystals are investigated theoretically and experimentally. The OH1 crystals exhibit a large macroscopic nonlinearity with four times larger powder second harmonic generation efficiency than that of analogous CLP crystals containing dimethylamino electron donor. A very high potential of OH1 crystals for broadband THz wave emitters in the full frequency range of 0.1–3 THz by optical rectification of 160 fs pulses has been demonstrated.
Enhanced circadian phase resetting in R192Q Cav2.1 calcium channel migraine mice
Authors: van Oosterhout Floor , Michel Stephan , Deboer Tom , Houben Thijs , van de Ven Rob C. G. , Albus Henk , Westerhout Joost , Vansteensel Mariska J. , Ferrari Michel D. , van den Maagdenberg Arn M. J. M. , Meijer Johanna H. 
Published: September 2008

AbstractObjectiveMammalian circadian rhythms are driven by the circadian pacemaker of the suprachiasmatic nucleus (SCN) and are synchronized to the external 24‐hour light/dark cycle. After advance time zone transitions (eastbound jet lag), overt circadian rhythms require several days to adjust. The retarded adaptation may protect against acute imbalance of different brain systems. Abrupt circadian rhythm changes may trigger migraine attacks, possibly because migraineurs have an inadequate adaptation mechanism. The novel R192Q knock‐in migraine mouse model carries mutated Cav2.1 calcium channels, causing increased presynaptic calcium influx and neurotransmitter release. We investigated whether these mice have an abnormal adjustment to phase advance shifts.MethodsWe examined phase resetting to 6‐hour advance shifts of the light/dark cycle with behavioral and electroencephalographic recordings in R192Q and wild‐type mice. We recorded excitatory postsynaptic currents in the SCN, and electrical impulse frequency in vitro and in vivo.ResultsR192Q mice showed a more than twofold enhanced adjustment of behavioral wheel‐running activity and electroencephalographic patterns, as well as enhanced shifts of electrical activity of SCN neurons in vivo. No differences were found for in vitro recordings of the electrical impulse frequency in SCN slices.InterpretationR192Q migraine mice lack the physiological retardation in circadian adaptation to phase advance shifts. The opposite findings in vivo and in vitro exclude involvement of the retinal input pathway or the phase‐shifting capacity of the SCN. Thus, the physiological inhibitory process appears to be mediated by Cav2.1 channel–dependent afferent signaling from extra‐SCN brain areas to the SCN. Ann Neurol 2008;64:315–324
Collagen VI glycine mutations: Perturbed assembly and a spectrum of clinical severity
Authors: Pace Rishika A. , Peat Rachel A. , Baker Naomi L. , Zamurs Laura , Mörgelin Matthias , Irving Melita , Adams Naomi E. , Bateman John F. , Mowat David , Smith Nicholas J. C. , Lamont Phillipa J. , Moore Steven A. , Mathews Katherine D. , North Kathryn N. , Lamandé Shireen R. 
Published: September 2008

AbstractObjectiveThe collagen VI muscular dystrophies, Bethlem myopathy and Ullrich congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes.MethodsWe studied eight new patients who presented with a spectrum of clinical severity, screened the three collagen VI messenger RNA for mutations, and examined collagen VI biosynthesis and the assembly pathway.ResultsAll eight patients had heterozygous glycine mutations toward the N‐terminal end of the triple helix. The mutations produced two assembly phenotypes. In the first patient group, collagen VI dimers accumulated in the cell but not the medium, microfibril formation in the medium was moderately reduced, and the amount of collagen VI in the extracellular matrix was not significantly altered. The second group had more severe assembly defects: some secreted collagen VI tetramers were not disulfide bonded, microfibril formation in the medium was severely compromised, and collagen VI in the extracellular matrix was reduced.InterpretationThese data indicate that collagen VI glycine mutations impair the assembly pathway in different ways and disease severity correlates with the assembly abnormality. In mildly affected patients, normal amounts of collagen VI were deposited in the fibroblast matrix, whereas in patients with moderate‐to‐severe disability, assembly defects led to a reduced collagen VI fibroblast matrix. This study thus provides an explanation for how different glycine mutations produce a spectrum of clinical severity. Ann Neurol 2008
Developmental impact of a familial GABAA receptor epilepsy mutation
Authors: Chiu Cindy , Reid Christopher A. , Tan Heneu O. , Davies Philip J. , Single Frank N. , Koukoulas Irene , Berkovic Samuel F. , Tan Seong‐Seng , Sprengel Rolf , Jones Mathew V. , Petrou Steven 
Published: September 2008

AbstractObjectiveA major goal of epilepsy research is to understand the molecular and functional basis of seizure genesis. A human GABAA γ2 gene mutation (R43Q) is associated with generalized epilepsy. Introduction of this mutation into a mouse by gene targeting recapitulates the human phenotype demonstrating a strong genotype to phenotype link. GABAA receptors play a role in the moment‐to‐moment control of brain function and also on the long‐term wiring of the brain by directing neuronal development. Our objective was to determine whether developmental expression of the mutation alters seizure susceptibility later in life.MethodsA tetracycline‐based conditional model for activation of a hypomorphic Q43 disease allele was created and validated. Seizure susceptibility was assessed using the subcutaneous pentylenetetrazole model.ResultsSeizure susceptibility was significantly reduced in mice where the Q43 allele was suppressed during development.InterpretationThese results demonstrate that a human epilepsy‐causing mutation impacts network stability during a critical developmental period. These data suggest that identification of presymptomatic children may provide a window for therapeutic intervention before overt symptoms are observed, potentially altering the course of epileptogenesis. Ann Neurol 2008
Human parechovirus causes encephalitis with white matter injury in neonates
Authors: Verboon‐Maciolek Malgorzata A. , Groenendaal Floris , Hahn Cecil D. , Hellmann Jonathan , van Loon Anton M. , Boivin Guy , de Vries Linda S. 
Published: September 2008

AbstractObjectiveTo assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs.MethodsClinical presentation, cranial ultrasonography, magnetic resonance imaging (MRI) findings, and neurodevelopmental outcome of 10 infants admitted to a neonatal intensive care unit and diagnosed with encephalitis caused by HPeVs are reported.ResultsNine of 10 infants, with a gestational age of 29 to 41 weeks, presented at 36 to 41 weeks postmenstrual age with clinical seizures. Seven had a fever and six had a rash. Clinical presentation was similar to that of infants with enterovirus infection. Cranial ultrasonography showed increased echogenicity in the periventricular white matter in all infants. Neonatal MRI confirmed white matter changes in nine infants, which changed to gliosis on later MRI. Outcome was variable with cerebral palsy in one, a suspect outcome at 18 months in one, learning disabilities at 7 years of age in one, epilepsy in one, and normal neurodevelopmental outcome in five children. Follow‐up of one infant was only 9 months.InterpretationHPeVs should be added to the list of neurotropic viruses that may cause severe central nervous system infection in the neonatal period. White matter injury can be visualized with cranial ultrasonography, but more detailed information is obtained with MRI and especially diffusion‐weighted imaging. Because clinical presentation of HPeV encephalitis is similar to that of enterovirus, real‐time polymerase chain reaction for both viruses should be performed in atypical presentation of neonatal seizures. Ann Neurol 2008
Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase
Authors: Hadjivassiliou Marios , Aeschlimann Pascale , Strigun Alexander , Sanders David S. , Woodroofe Nicola , Aeschlimann Daniel 
Published: September 2008

AbstractObjectiveGluten sensitivity typically presents as celiac disease, a chronic, autoimmune‐mediated, small‐intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.MethodsUsing recombinant human transglutaminases, we developed enzyme‐linked immunosorbent assays and inhibition assays to analyze serum samples of patients with gluten‐sensitive gastrointestinal and neurological disorders, and various control groups including unrelated inherited or immune conditions for the presence and specificity of autoantibodies.ResultsWhereas the development of anti‐transglutaminase 2 IgA is linked with gastrointestinal disease, an anti‐transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6.InterpretationAntibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti‐gliadin and anti‐transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease. Ann Neurol 2008;64:332–343
“High‐Tech”‐Anwendungen von supramolekularen nanostrukturierten Gelmaterialien – von der regenerativen Medizin bis hin zu elektronischen Bauelementen
Authors: Hirst Andrew R. , Escuder Beatriu , Miravet Juan F. , Smith David K. 
Published: September 2008

AbstractDie Nanofabrikation wird sehr wahrscheinlich Teil vieler Technologien im 21. Jahrhundert sein. Dabei bietet die chemische Synthese einen effizienten Ansatz zur Herstellung von molekularen Strukturen, die sich zu funktionellen Nanoarchitekturen organisieren. Ein starkes Interesse an selbstorganisierenden niedermolekularen Gelbildnern führte zu Kenntnissen über nichtkovalente Wechselwirkungen und Packungsparameter bei der Gelbildung. Die Moleküle bauen hierarchische supramolekulare Strukturen auf, was sich makroskopisch in der Bildung eines Gels ausdrückt. Eine Variation der Molekülstruktur kann die Organisation der Nanostrukturen bestimmen und dadurch spezifische Materialeigenschaften hervorbringen. Durch eine Kombination von supramolekularer Chemie, Materialwissenschaft und Biomedizin konnten anwendungsspezifische Materialien entwickelt werden. Auf dem Gebiet von regenerativer Medizin und Gewebezüchtung waren molekulare Gele als nanostrukturierte Gerüste zur Nachzüchtung von Nervenzellen in vivo erfolgreich, und die Aussicht auf den Einsatz von selbstorganisierten Fasern als eindimensionale Leiter in Gelmaterialien hat großes Interesse an der Nanoelektronik hervorgerufen.
High‐Tech Applications of Self‐Assembling Supramolecular Nanostructured Gel‐Phase Materials: From Regenerative Medicine to Electronic Devices
Authors: Hirst Andrew R. , Escuder Beatriu , Miravet Juan F. , Smith David K. 
Published: September 2008

AbstractIt is likely that nanofabrication will underpin many technologies in the 21st century. Synthetic chemistry is a powerful approach to generate molecular structures that are capable of assembling into functional nanoscale architectures. There has been intense interest in self‐assembling low‐molecular‐weight gelators, which has led to a general understanding of gelation based on the self‐assembly of molecular‐scale building blocks in terms of non‐covalent interactions and packing parameters. The gelator molecules generate hierarchical, supramolecular structures that are macroscopically expressed in gel formation. Molecular modification can therefore control nanoscale assembly, a process that ultimately endows specific material function. The combination of supramolecular chemistry, materials science, and biomedicine allows application‐based materials to be developed. Regenerative medicine and tissue engineering using molecular gels as nanostructured scaffolds for the regrowth of nerve cells has been demonstrated in vivo, and the prospect of using self‐assembled fibers as one‐dimensional conductors in gel materials has captured much interest in the field of nanoelectronics.
High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging
Authors: Werner Eric J. , Datta Ankona , Jocher Christoph J. , Raymond Kenneth N. 
Published: September 2008

AbstractThe desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues, such as solubility and in vivo toxicity, must also be addressed, making the attainment of safe, high‐relaxivity agents a challenging goal. This Minireview presents recent advances in the field, with an emphasis on gadolinium(III) hydroxypyridinone chelate complexes.
Proteomic characterization of mouse cartilage degradation in vitro
Authors: Wilson Richard , Belluoccio Daniele , Little Christopher B. , Fosang Amanda J. , Bateman John F. 
Published: September 2008

AbstractObjectiveTo develop proteomics to analyze mouse cartilage degradation and correlate transcriptional and translational responses to catabolic stimuli.MethodsProteomic techniques were used to analyze catabolism in mouse femoral head cartilage. Using specific methods to prepare cartilage extracts and conditioned media for 2‐dimensional polyacrylamide gel electrophoresis and subsequent tandem mass spectrometry, we identified novel proteins and fragments released into the media of control, interleukin‐1α (IL‐1α)–treated, and all‐trans‐retinoic acid (RetA)–treated explants. Fluorescence 2‐dimensional difference gel electrophoresis was used to quantify protein expression changes. We also measured changes in messenger RNA (mRNA) expression to distinguish transcriptional and posttranslational regulation of released proteins.ResultsDifferentially abundant proteins in the media of control and treated explants included fragments of thrombospondin 1 and connective tissue growth factor. IL‐1α stimulated release of the cartilage degeneration marker matrix metalloproteinase 3, as well as proteins with uncharacterized roles in cartilage pathology, such as neutrophil gelatinase–associated lipocalin. RetA stimulated release of the extracellular matrix proteins cartilage oligomeric matrix protein, link protein, and matrilin‐3 into the media, which was accompanied by a dramatic reduction in the corresponding mRNA transcript levels. Gelsolin, which has been implicated in cytoskeletal reorganization in arthritis synovial fibroblasts but has not been previously associated with cartilage pathology, was regulated by IL‐1α and RetA.ConclusionIn this first analysis of mouse cartilage degradation and protein release using proteomics, we identified proteins and fragments, some of which represent novel candidate biomarkers for cartilage degradation. Applying these proteomic techniques to wild‐type and genetically modified mouse cartilage will provide insights into the mechanisms of cartilage degeneration.
Modulation of peripheral B cell tolerance by CD72 in a murine model
Authors: Li Daniel Hsieh‐Hsin , Winslow Monte M. , Cao Thai M. , Chen Albert H. , Davis Corrine R. , Mellins Elizabeth D. , Utz Paul J. , Crabtree Gerald R. , Parnes Jane R. 
Published: September 2008

AbstractObjectiveB cells play a dominant role in the pathogenesis of several autoimmune diseases, including systemic lupus erythematosus. It is not well understood how B cell signaling contributes to autoantibody production. The goal of this study was to elucidate the role of CD72 in modulating B cell receptor (BCR)–mediated tolerogenic signaling and peripheral B cell tolerance.MethodsA mouse model utilizing hen egg lysozyme (HEL) “anergic” B cells was studied. CD72‐deficient mice carrying the BCR‐specific IgHEL and/or soluble HEL (sHEL) transgenes were generated by breeding IgHEL‐transgenic MD4 mice and/or sHEL‐transgenic ML5 mice with congenic, CD72‐deficient C57BL/6J mice. Normal and anergic B cells were isolated for analyses of B cell signaling. Aged wild‐type and CD72‐deficient mice were also examined for autoimmune phenomena.ResultsIn the absence of CD72, anergic B cells inappropriately proliferated and survived in response to stimulation with self antigen. Biochemical analyses indicated that in anergic B cells, CD72 dominantly down‐regulated BCR signaling to limit the antigen‐induced elevation in [Ca2+]i and the activation of NFATc1, NF‐κB, MAPK, and Akt. Mechanistically, CD72 was associated with, and regulated, the molecular adaptor Cbl‐b in anergic B cells, suggesting that Cbl‐b may play a role in mediating the negative effects of CD72 on BCR signaling. Moreover, in aged CD72‐deficient mice, spontaneous production of antinuclear and anti–double‐stranded DNA autoantibodies and features of lupus‐like autoimmune disease were observed.ConclusionCD72 is required to maintain B cell anergy and functions as a regulator of peripheral B cell tolerance. Thus, altered CD72 expression may play a role during the development of systemic lupus erythematosus.
Polymorphisms in the interleukin‐1 receptor antagonist and interleukin‐6 genes affect risk of osteolysis in patients with total hip arthroplasty
Authors: Gordon Andrew , Kiss‐Toth E. , Stockley Ian , Eastell Richard , Wilkinson J. Mark 
Published: September 2008

AbstractObjectiveTo determine whether osteolysis after total hip arthroplasty (THA) is associated with common polymorphisms within the genes encoding the interleukin‐1 (IL‐1) family and IL‐6, and to determine whether polymorphisms that are associated with osteolysis affect in vitro messenger RNA (mRNA) expression in human peripheral blood mononuclear cells (PBMCs) in response to wear particles.MethodsUnrelated white subjects of North European descent (n = 612) were recruited a mean of 11 years after cemented THA for primary osteoarthritis. Of these subjects, 272 had previous osteolysis and 340 had no radiographic evidence of osteolysis (control group). Genomic DNA was genotyped for the following single‐nucleotide polymorphisms (SNPs): IL1A +4845, IL1B +3954, IL1B –3737, IL1B –511, IL1RA +2018, IL6 –174, IL6 –572, and IL6 –597. In a subset of 60 subjects, PBMCs were extracted and stimulated with titanium particles and/or endotoxin, and cytokine mRNA expression was measured using quantitative real‐time reverse transcriptase–polymerase chain reaction.ResultsThe odds ratio (OR) for osteolysis associated with carriage of the IL1RA +2018C allele was 0.66 (95% confidence interval [95% CI] 0.48–0.91) (P = 0.012). The remaining SNPs were not individually associated with osteolysis. The uncommon IL6 haplotype −174G/−572G/−597A (osteolysis group frequency 2.4%, control group frequency 0.8%) was associated with osteolysis (P = 0.02, calculated using Haploview software). The IL1RA +2018CC genotype was associated with increased mRNA expression compared with the +2018TT genotype in both unstimulated and stimulated PBMCs (P = 0.01 by analysis of variance, after Bonferroni correction).ConclusionThe IL1RA +2018C allele is associated with a decreased risk of osteolysis after THA and with increased IL‐1 receptor antagonist mRNA expression in vitro. An uncommon haplotype within the promoter region of the gene for IL‐6 is positively associated with osteolysis.
Spinal interleukin‐1β in a mouse model of arthritis and joint pain
Authors: Fiorentino Paolo M. , Tallents Ross H. , Miller Jen‐Nie H. , Brouxhon Sabine M. , O'Banion M. Kerry , Puzas J. Edward , Kyrkanides Stephanos 
Published: September 2008

AbstractObjectivePain from arthritis has been associated with peripheral sensitization of primary sensory afferents and the development of inflammation at the dorsal horns. This study was undertaken to determine whether the role of spinal interleukin‐1β (IL‐1β) in central processing of pain is important in the development of arthritis.MethodsCol1‐IL‐1βXATmice and GFAP‐IL‐1βXATmice were injected with the feline immunodeficiency virus (FIV) (Cre) vector in the right and left temporomandibular joints (TMJs), or in the cisterna magna, respectively, to induce IL‐1β expression in the dorsal horns of the spinal horn. To inhibit intrathecal IL‐1 receptor type I (IL‐1RI) signaling, FIV(IL‐1Ra) vector was injected into the cisterna magna of Col1‐IL‐1βXATmice. The effects of IL‐1RI receptor inhibition in GFAP‐IL‐1βXATmice were studied in the GFAP‐IL‐1βXAT–IL‐1RI−/−compound mouse model. Neuroinflammatory, sensory, and behavioral changes were evaluated in conjunction with arthritic changes in the TMJ, assessed by histopathologic and immunohistochemical analyses.ResultsInduction of an osteoarthritis‐like condition in the TMJ in the Col1‐IL‐1βXATmouse model resulted in up‐regulation of murine IL‐1β at the dorsal horns. Moreover, intrathecal inhibition of IL‐1RI in Col1‐IL‐1βXATmice with arthritis led to amelioration of joint pathology and attenuation of the attendant joint pain. Overexpression of spinal IL‐1β in the recently developed GFAP‐IL‐1βXATsomatic mosaic model of neuroinflammation led to development of arthritis‐like pathology accompanied by increased pain‐like behavior.ConclusionOur results indicate that joint pathology and pain are dependent on spinal IL‐1β, and suggest the presence of a bidirectional central nervous system–peripheral joints crosstalk that may contribute to the development, expansion, and exacerbation of arthritis.