bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures
Authors: Nakayama Junko , Fu Ying‐Hui , Clark Anna M. , Nakahara Satoko , Hamano Kenzo , Iwasaki Nobuaki , Matsui Akira , Arinami Tadao , Ptác̆ek Louis J. 
Published: October 2002

AbstractA naturally occurring mutation of the mass1 (monogenic audiogenic seizure‐susceptible) gene recently has been reported in the Frings mouse strain, which is prone to audiogenic seizures. The human orthologous gene, MASS1, was mapped to chromosome 5q14, for which we previously have reported significant evidence of linkage to febrile seizures (FEB4). We screened for MASS1 mutations in individuals from 48 families with familial febrile seizures and found 25 DNA alterations. None of nine missense polymorphic alleles was significantly associated with febrile seizures; however, a nonsense mutation (S2652X) causing a deletion of the C‐terminal 126 amino acid residues was identified in one family with febrile and afebrile seizures. Our results suggest that a loss‐of‐function mutation in MASS1 might be responsible for the seizure phenotypes, though it is not likely that MASS1 contributed to the cause of febrile seizures in most of our families.
Abnormal asymmetry in language association cortex in autism
Authors: Herbert Martha R. , Harris Gordon J. , Adrien Kristen T. , Ziegler David A. , Makris Nikos , Kennedy Dave N. , Lange Nicholas T. , Chabris Chris F. , Bakardjiev Anna , Hodgson James , Takeoka Masanori , Tager‐Flusberg Helen , Caviness Verne S. 
Published: October 2002

AbstractAutism is a neurodevelopmental disorder affecting cognitive, language, and social functioning. Although language and social communication abnormalities are characteristic, prior structural imaging studies have not examined language‐related cortex in autistic and control subjects. Subjects included 16 boys with autism (aged 7–11 years), with nonverbal IQ greater than 80, and 15 age‐ and handedness‐matched controls. Magnetic resonance brain images were segmented into gray and white matter; cerebral cortex was parcellated into 48 gyral‐based divisions per hemisphere. Asymmetry was assessed a priori in language‐related inferior lateral frontal and posterior superior temporal regions and assessed post hoc in all regions to determine specificity of asymmetry abnormalities. Boys with autism had significant asymmetry reversal in frontal language‐related cortex: 27% larger on the right in autism and 17% larger on the left in controls. Only one additional region had significant asymmetry differences on post hoc analysis: posterior temporal fusiform gyrus (more left‐sided in autism), whereas adjacent fusiform gyrus and temporooccipital inferior temporal gyrus both approached significance (more right‐sided in autism). These inferior temporal regions are involved in visual face processing. In boys with autism, language and social/face processing–related regions displayed abnormal asymmetry. These structural abnormalities may relate to language and social disturbances observed in autism.
p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism
Authors: Duan Wenzhen , Zhu Xiaoxiang , Ladenheim Bruce , Yu Qian‐Sheng , Guo Zhihong , Oyler Jon , Cutler Roy G. , Cadet Jean Lud , Greig Nigel H. , Mattson Mark P. 
Published: October 2002

AbstractDrugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial impairment and oxidative stress. We report that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin‐α (PFT‐α) and Z‐1‐117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease. Mice given intraperitoneal injections of PFT‐α or Z‐1‐117 exhibited improved motor function, reduced damage to nigrostriatal dopaminergic neurons and reduced depletion of dopamine and its metabolites after exposure to the toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). MPTP caused an increase in the level of the proapoptotic protein Bax, which was prevented by giving mice PFT‐α and Z‐1‐117. PFT‐α and Z‐1‐117 also suppressed Bax production and apoptosis in cultured dopaminergic cells exposed to MPP+. Our findings demonstrate a pivotal role for p53 in experimental parkinsonism and identify a novel class of synthetic p53 inhibitors with clinical potential.
Oligodendrocytic polyglutamine pathology in dentatorubral‐pallidoluysian atrophy
Authors: Yamada Mitsunori , Sato Toshiya , Tsuji Shoji , Takahashi Hitoshi 
Published: October 2002

AbstractWhite matter degeneration is one of the pathological conditions of dentatorubral‐pallidoluysian atrophy. Autopsy brains exhibited a reduced number of glial cells in the lesions and an involvement of oligodendrocytes in nuclear inclusion formation, which previously has been recognized only as a pathological hallmark in neurons. Dentatorubral‐pallidoluysian atrophy transgenic mice showed an increased number of affected glias with increasing age and with larger expansions of CAG repeats. These findings suggest that glial cells in dentatorubral‐pallidoluysian atrophy also are involved in the polyglutamine pathogenesis.
Intravenous TAT–Bcl‐Xl is protective after middle cerebral artery occlusion in mice
Authors: Kilic Ertugrul , Dietz Gunnar P. H. , Hermann Dirk M. , Bähr Mathias 
Published: October 2002

AbstractThe delivery of proteins across the blood–brain barrier is severely limited by the proteins' size and biochemical properties. Eleven–amino acid human immunodeficiency virus TAT protein is able to cross cell membranes even when coupled with larger peptides. We evaluated whether TAT–Bcl‐XL fusion protein is protective in focal ischemia. Mice underwent 30 or 90 minutes of intraluminal middle cerebral artery thread occlusion. TAT–Bcl‐XL, TAT–β‐galactosidase, or TAT‐GFP (0.6nmol each) were applied intravenously over 10 minutes either 1 hour before or immediately after ischemia. Additional animals received no TAT protein infusions. We show that the brain tissue is progressively transduced with TAT proteins within 3 to 4 hours after intravenous delivery. We provide evidence that TAT–Bcl‐XL treatment reduces infarct volume and neurological deficits after long ischemic insults lasting 90 minutes, when applied both before and after ischemia. After short insults, lasting only 30 minutes, TAT–Bcl‐XL further diminishes the number of caspase‐3–reactive and DNA fragmented cells and increases the number of viable neurons in the striatum. Our results indicate that TAT fusion proteins are elegant and powerful tools that might be of clinical interest for stroke treatment, because factors may be intravenously applied. Thus, fusion proteins may open fascinating perspectives for future research.
Neuronal and glial metabolite content of the epileptogenic human hippocampus
Authors: Petroff Ognen A. C. , Errante Laura D. , Rothman Douglas L. , Kim Jung H. , Spencer Dennis D. 
Published: October 2002

AbstractMesial temporal lobe epilepsy is characterized by hippocampal atrophy, hypometabolism, and decreased N‐acetylaspartate, often attributed to neuron loss and gliosis. Twenty hippocampal specimens were obtained during temporal lobectomy and frozen quickly. Perchloric acid extracts of the small metabolites were analyzed by proton magnetic resonance spectroscopy. There were no significant associations between hippocampal neuron loss and the cellular content of N‐acetylaspartate, glutamate, GABA, glutamine, or aspartate. The mean metabolite content of hippocampi with less than 30% of neurons remaining was the same as those with greater than 65% of neurons surviving. Mean N‐acetylaspartate levels were below those reported by in vivo studies of control subjects. The highest and the lowest glutamate concentrations were seen in specimens with the worst neuron loss. A highly significant association between hippocampal N‐acetylaspartate and glutamate content was seen with weak associations between N‐acetylaspartate and aspartate and glutamate and aspartate. The hippocampal content of N‐acetylaspartate, glutamate, GABA, glutamine, and aspartate is altered minimally by severe neuron loss in mesial temporal lobe epilepsy. The epileptic human hippocampus has increased intracellular glutamate content that may contribute to the epileptogenic nature of hippocampal sclerosis.
Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia
Authors: Kure Shigeo , Kojima Kanako , Ichinohe Akiko , Maeda Tomoki , Kalmanchey Rozalia , Fekete György , Berg Suzan Z. , Filiano Jim , Aoki Yoko , Suzuki Yoichi , Izumi Tatsuro , Matsubara Yoichi 
Published: October 2002

AbstractTransient neonatal hyperglycinemia is clinically or biochemically indistinguishable from nonketotic hyperglycinemia at onset. In the case of transient neonatal hyperglycinemia, the elevated plasma and cerebrospinal fluid glycine levels are normalized within 2 to 8 weeks. To elucidate the pathogenesis of transient neonatal hyperglycinemia, we studied three patients by screening mutations in the genes that encode three components of the glycine cleavage system. Heterozygous mutations were identified in all of the three patients, suggesting that transient neonatal hyperglycinemia develops in some heterozygous carriers for nonketotic hyperglycinemia.
Nonresonant Raman imaging of protein distribution in single human cells
Authors: Uzunbajakava N. , Lenferink A. , Kraan Y. , Willekens B. , Vrensen G. , Greve J. , Otto C. 
Published: October 2002

AbstractA confocal Raman microscope is used to study the protein distribution inside biological cells. It is shown that high quality Raman imaging of the protein distribution can be obtained using confocal nonresonant Raman imaging (λexc = 647.1 nm). The results are shown for two different human cell types. Perpheral blood lymphocytes are used as an example of the fully maturated cells with a low level of nuclear transcription. Human eye lens epithelial cells are used as an example of cells with a high level of nuclear activity. The protein distribution in both cell types is completely different. The nuclear distribution of the protein largely varies in the peripheral blood lymphocyte cells, while proteins are more homogenously distributed over the nuclear space in the eye lens epithelial cells. The imaging time is ∼20 min for a field of view of 10 × 10 μm2. The size of the sampling volume is 1.4 fL using a full width at half‐maximum criterion along the z axis and a 1/e2 criterion in the xy plane. The results presented here indicate that Raman imaging is particularly of interest in the study of cellular processes, like phagocytosis, apoptosis, chromatin compaction, and cellular differentiation, which are accompanied by relatively large‐scale redistributions of the materials. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 1–9, 2003
Unfolding and pH studies on manganese peroxidase: Role of heme and calcium on secondary structure stability
Authors: Banci Lucia , Bartalesi Ilaria , Ciofi‐Baffoni Simone , Tien Ming 
Published: October 2002

AbstractThe present study characterizes the unfolding and folding processes of recombinant manganese peroxidase. This enzyme contains five disulfide bonds, two calcium ions, and one heme prosthetic group. Circular dichroism in the far UV was used to monitor global changes of the protein secondary structure, whereas UV–visible spectroscopy of the Soret band provided information about local changes in the heme cavity. The effects of reducing agents, oxidizing agents, and denaturants on this process were investigated. In addition to affecting the secondary structure content, these factors also affect the binding of the heme and the calcium ions, both of which have a significant effect on the folding process. Our results also show that denaturants induce irreversible changes, which are most likely due to the inability of the denatured protein to rebind either calcium or the heme. Breaking of disulfide bonds by 30 mM dithiothreitol causes complete unfolding of recombinant manganese peroxidase. The unfolding process was also studied at low and high pH, where the protein reaches the final unfolded state through two different intermediate states. The data also indicate that only the acidic folding–unfolding process is reversible. Our results indicate a complex synergistic relationship between the secondary structure content, the tertiary structure arrangement, and the binding of the heme and the calcium ions and disulfide bridge formation. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 38–47, 2003
Analysis of the role of GADD153 in the control of apoptosis in NS0 myeloma cells
Authors: Lengwehasatit Idsada , Dickson Alan J. 
Published: October 2002

AbstractApoptosis can limit the maximum production of recombinant protein expression from cultured mammalian cells. This article focuses on the links between nutrient deprivation, ER perturbation, the regulation of (growth arrest and DNA damage inducible gene 153) GADD153 expression and apoptosis. During batch culture, decreases in glucose and glutamine correlated with an increase in apoptotic cells. This event was paralleled by a simultaneous increase in GADD153 expression. The expression of GADD153 in batch culture was suppressed by the addition of nutrients and with fed‐batch culture the onset of apoptosis was delayed but not completely prevented. In defined stress conditions, glucose deprivation had the greatest effect on cell death when compared to glutamine deprivation or the addition of tunicamycin (an inhibitor of glycosylation), added to generate endoplasmic reticulum stress. However, the contribution of apoptosis to overall cell death (as judged by morphology) was smaller in conditions of glucose deprivation than in glutamine deprivation or tunicamycin treatment. Transient activation of GADD153 expression was found to occur in response to all stresses and occurred prior to detection of the onset of cell death. These results imply that GADD153 expression is either a trigger for apoptosis or offers a valid indicator of the likelihood of cell death arising from stresses of relevance to the bioreactor environment. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 719–730, 2002.
Cumulative bondomers: A new concept in flux analysis from 2D [13C,1H] COSY NMR data
Authors: van Winden Wouter A. , Heijnen Joseph J. , Verheijen Peter J.T. 
Published: October 2002

AbstractA well‐established way of determining metabolic fluxes is to measure 2D [13C,1H] COSY NMR spectra of components of biomass grown on uniformly 13C‐labeled carbon sources. When using the entire set of measured data to simultaneously determine all fluxes in a proposed metabolic network model, the 13C‐labeling distribution in all measured compounds has to be simulated. This requires very large sets of isotopomer or cumomer balances. This article introduces the new concept of bondomers; entities that only vary in the numbers and positions of C–C bonds that have remained intact since the medium substrate molecule entered the metabolism. Bondomers are shown to have many analogies to isotopomers. One of these is that bondomers can be transformed to cumulative bondomers, just like isotopomers can be transformed to cumomers. Similarly to cumomers, cumulative bondomers allow an analytical solution of the entire set of balances describing a metabolic network. The main difference is that cumulative bondomer models are considerably smaller than corresponding cumomer models. This saves computational time, allows easier identifiability analysis, and yields new insights in the information content of 2D [13C,1H] COSY NMR data. We illustrate the theoretical concepts by means of a realistic example of the glycolytic and pentose phosphate pathways. The combinations of 2D [13C,1H] COSY NMR data that allow identification of all metabolic fluxes in these pathways are analyzed, and it is found that the NMR data contain less information than was previously expected. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 731–745, 2002.
Hydrogen production by cyanobacteria in an automated outdoor photobioreactor under aerobic conditions
Authors: Tsygankov A. A. , Fedorov A. S. , Kosourov S. N. , Rao K. K. 
Published: October 2002

AbstractThe possibility of hydrogen production by a hydrogenase impaired mutant strain of Anabaena variabilis in outdoor culture was studied. A computer‐controlled rooftop (outdoor) tubular photobioreactor (4.35 L) was assembled. H2 production rates by A. variabilis PK84 grown in CO2 + air in the photobioreactor were measured together with other parameters such as temperature, irradiance, pH, dry biomass weight, and pO2, and Chl a concentrations during summer months of 1998 and 1999. Efficiencies of light energy bioconversion to H2 energy and energy accumulated in biomass were calculated. The influence of irradiance, temperature, and mode of cultivation on H2 production and efficiency of light energy bioconversion were evaluated. The culture produced up to 1.1 L H2 day−1 PhBR−1. The efficiency of light energy to H2 energy bioconversion on some days was 0.094%. However, the conditions for maximum H2 photoproduction and for maximum efficiency of light energy to H2 energy bioconversion were not the same. A. variabilis PK84 could produce hydrogen for prolonged periods (up to 40 days) without injection of fresh inoculum. During this period photobioreactor produced 24.5 L of H2. Possibilities for increasing the efficiency of light energy conversion are discussed. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 777–783, 2002.
Characterization of electrostatic binding sites of extracellular polymers by linear programming analysis of titration data
Authors: Liu Hong , Fang Herbert H. P. 
Published: October 2002

AbstractElectrostatic binding sites of extracellular polymeric substances (EPS) were characterized from titration data using linear programming analysis. Test results for three synthetic solutions of given solutes comprising amino, carboxyl, and phenolic groups indicated that this method was able to identify the electrostatic binding sites. For the six sites with pKa between 3 and 10, the estimated pKa deviated 0.11 ± 0.09 from the theoretical values, and the estimated concentrations deviated 3.0% ± 0.9% from the actual concentrations. Two EPS samples were then extracted from a hydrogen‐producing sludge (HPS) and a sulfate‐reducing biofilm (SRB). Analysis of charge excess data in titration from pH 3 to 11 indicated that the EPS of HPS comprised of five electrostatic binding sites with pKa ranging from 3 to 11. The pKa values of these binding sites and the possible corresponding functional groups were pKa 4.8 (carboxyl), pKa 6.0 (carboxyl/phosphoric), pKa 7.0 (phosphoric), pKa 9.8 (amine/phenolic), and pKa 11.0 (hydroxyl). EPS of the SRB comprised five of similar binding sites (with corresponding pKa values of 4.4, 6.0, 7.4, 9.4, and 11.0), plus one extra site at pKa 8.2, which was likely corresponding to the sulfhydryl group. The total electrostatic binding site concentration of EPS extracted from HPS were 10.88 mmol/g‐EPS, of which the highest concentration was from the site of pKa 11.0. The corresponding values for the EPS extracted from SRB were 16.44 mmol/g‐EPS and pKa 4.4. The total concentrations of electrostatic binding sites found in this study were 20‐ to 30‐fold of those reported for bacterial cell surface, implying that EPS might be more crucial in biosorption of metals than bacterial cell surface in wastewater treatment and in bioremediation. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 806–811, 2002.
Effect of rate of chemical or thermal renaturation on refolding and aggregation of a simple lattice protein
Authors: Nguyen Hung D. , Hall Carol K. 
Published: October 2002

AbstractWe used dynamic Monte Carlo simulation to investigate how changing the rate of chemical or thermal renaturation affects the folding and aggregation behavior of a system of simple, two‐dimensional lattice protein molecules. Four renaturation methods were simulated: infinitely slow cooling; slow but finite cooling; quenching; and pulse renaturation. The infinitely slow cooling method, which is equivalent to dialysis or diafiltration, provides refolding yields that are relatively high and aggregates that are relatively small (mostly dimers or trimers). The slow but finite cooling method, which is equivalent to multiple‐step dilution, provides refolding yields that are almost as high as those observed in the infinitely slow cooling case, but in a relatively short period of time. Quenching, which is equivalent to one‐step dilution or quick quenching, is extremely slow and has low re‐ folding yields. A maximum appears in the refolding yield as a function of denaturant concentration in the simulation but disappears after a very long duration. Finally, the pulse renaturation method provides refolding yields that are substantially higher than those observed in the other three methods, even at high packing fractions. As in the early stages of quenching, there is a maximum in the refolding yield as a function of denaturant concentration when relatively large numbers of denatured chains are added to the refolding solution at each step. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 823–834, 2002.
A fast computational method for computer‐generated Fourier hologram using patch model
Authors: Sakamoto Yuji , Nagao Tomohiro 
Published: October 2002

AbstractComputer‐generated holography is a technique for displaying a three‐dimensional image from a virtual object inside the computer. It has drawn attention as a display format to satisfy three‐dimensional visual characteristics. However, one problem of the method is the enormous amount of time for calculation of light propagation needed in the generation of holograms. In this paper, as a method of modeling objects, a patch model that defines an object in terms of basic drawings is used. A method is proposed to calculate holograms at high speed from these models. Further, the algorithm is verified by computer simulation. The results of an optical experiment with the hologram fabricated by this proposed method are also reported. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 85(11): 16–24, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10051