bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetrabutylammonium Decatungstate (Chemo)selective Photocatalyzed, Radical CH Functionalization in Amides
Authors: Angioni Simone , Ravelli Davide , Emma Daniele , Dondi Daniele , Fagnoni Maurizio , Albini Angelo 
Published: September 2008

AbstractPhotoamidation of electron‐poor olefins has been achieved by means of a radical‐induced CH functionalization in amides. Tetrabutylammonium decatungstate was used as photocatalyst of the reaction and allowed the smooth generation of different carbon‐centered radicals depending on the amide structure.
Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine
Authors: Morrell Martha J. , Hayes Frances J. , Sluss Patrick M. , Adams Judith M. , Bhatt Mohit , Ozkara Cigdem , Warnock M.S. Clay R. , Isojärvi Jouko 
Published: September 2008

AbstractObjectiveTo evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.MethodsFemale individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3‐month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty.ResultsMore women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine).InterpretationDevelopment of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years. Ann Neurol 2008;64:200–211
An idiopathic epilepsy syndrome linked to 3q13.3‐q21 and missense mutations in the extracellular calcium sensing receptor gene
Authors: Kapoor Ashish , Satishchandra Parthasarathy , Ratnapriya Rinki , Reddy Ramesh , Kadandale Jayaram , Shankar Susarla K. , Anand Anuranjan 
Published: September 2008

AbstractObjectiveTo identify the disease locus in a three‐generation south Indian family having several of its members affected with idiopathic epilepsy.MethodsGenome‐wide parametric linkage analysis was performed with 382 autosomal markers. Mutational analysis of the positional candidate genes in linked interval was performed by direct sequencing of genomic DNA from the proband in the family. Expression analysis in human adult brain was performed by Western blotting.ResultsA novel epilepsy genetic locus on chromosome 3q13.3‐q21 was identified by linkage analysis. This locus comprises about 12 megabases of the genomic interval, with its proximal and distal genetic boundaries defined by microsatellite markers, D3S3675 and D3S1551, respectively. In this interval, we found a novel, patient‐specific, missense variant, Arg898Gln, at the extracellular calcium sensing receptor (CASR), a gene belonging to the G‐protein–coupled receptor family. CASR expression was detected in the temporal lobe, frontal lobe, parietal lobe, cerebellum, and hippocampus. Four additional, potentially pathogenic, missense CASR variants, Glu354Ala, Ile686Val, Ala988Val, and Ala988Gly, were observed in five individuals affected with idiopathic generalized epilepsy.InterpretationA novel idiopathic epilepsy locus has been mapped on chromosome 3q13.3‐q21, as evident by presence of significant genetic linkage. Identification of novel, rare missense CASR variants at evolutionary‐conserved residues in epilepsy patients and CASR expression in various subregions of human brain raises an interesting possibility of involvement of CASR in pathophysiology of epileptic disorders. Ann Neurol 2008;64:158–167
The continuing problem of human African trypanosomiasis (sleeping sickness)
Authors: Kennedy Peter G. E. 
Published: September 2008

AbstractHuman African trypanosomiasis, also known as sleeping sickness, is a neglected disease, and it continues to pose a major threat to 60 million people in 36 countries in sub‐Saharan Africa. Transmitted by the bite of the tsetse fly, the disease is caused by protozoan parasites of the genus Trypanosoma and comes in two types: East African human African trypanosomiasis caused by Trypanosoma brucei rhodesiense and the West African form caused by Trypanosoma brucei gambiense. There is an early or hemolymphatic stage and a late or encephalitic stage, when the parasites cross the blood–brain barrier to invade the central nervous system. Two critical current issues are disease staging and drug therapy, especially for late‐stage disease. Lumbar puncture to analyze cerebrospinal fluid will remain the only method of disease staging until reliable noninvasive methods are developed, but there is no widespread consensus as to what exactly defines biologically central nervous system disease or what specific cerebrospinal fluid findings should justify drug therapy for late‐stage involvement. All four main drugs used for human African trypanosomiasis are toxic, and melarsoprol, the only drug that is effective for both types of central nervous system disease, is so toxic that it kills 5% of patients who receive it. Eflornithine, alone or combined with nifurtimox, is being used increasingly as first‐line therapy for gambiense disease. There is a pressing need for an effective, safe oral drug for both stages of the disease, but this will require a significant increase in investment for new drug discovery from Western governments and the pharmaceutical industry. Ann Neurol 2008;64:116–126
Computerized grading of anatomy laboratory practical examinations
Authors: Krippendorf Beth B. , Bolender David L. , Kolesari Gary L. 
Published: September 2008

AbstractAt the Medical College of Wisconsin, a procedure was developed to allow computerized grading and grade reporting of laboratory practical examinations in the Clinical Human Anatomy course. At the start of the course, first year medical students were given four Lists of Structures. On these lists, numbered items were arranged alphabetically; the items were anatomical structures that could be tagged on a given lab practical examination. Each lab exam featured an anatomy laboratory component and a computer laboratory component. For the anatomy lab component, students moved from one question station to another at timed intervals and identified tagged anatomical structures. As students identified a tagged structure, they referred to a copy of the list (provided with their answer sheet) and wrote the number corresponding to the structure on their answer sheet. Immediately after the anatomy lab component, students were escorted to a computer instruction laboratory where they typed their answer numbers into a secured testing component of a learning management system that recorded their answers for automatic grading. After a brief review of examination scores and item analysis by faculty, exam scores were reported to students electronically. Adding this brief computer component to each lab exam greatly reduced faculty grading time, reduced grading errors and provided faster performance feedback for students without changing overall student performance. Anat Sci Ed 1:220–223, 2008. © 2008 American Association of Anatomists.
Accelerated embryonic development associated with increased risk of neural tube defects induced by maternal diet in offspring of SELH/Bc mice
Authors: Stoate Katharine L. , Harris Muriel J. , Juriloff Diana M. 
Published: September 2008

AbstractBACKGROUND: The SELH/Bc mouse strain has a high risk of the NTD, exencephaly, caused by multifactorial genetics. All SELH/Bc embryos have delayed elevation of neural folds; some never elevate (future exencephalics). Maternal diets affect SELH/Bc exencephaly rates: 25–35% on Purina Diet 5015 versus 5–10% on Purina Diet 5001. We hypothesized that in SELH/Bc, the diets affect maternal blood glucose and embryonic developmental rate. METHODS: We compared mice fed the two diets. On GD 9.4 we tested maternal blood glucose and examined embryos for developmental age (somite count) and cranial neural fold morphology. We observed GD 14 exencephaly rates. RESULTS: Diet 5015 caused fivefold more exencephaly (40 vs. 7% on GD 14), significantly higher mean maternal blood glucose in replicate experiments (6.3 vs. 5.5, p < .05; 6.3 vs. 5.3 mmol/L, p < .05), and significantly higher mean litter somite count on GD 9.4 (18.4 vs. 15.0, p < .05; 16.7 vs. 14.4 somites, p < .05). Among midrange embryos (15–16 somites), embryos from Diet 5015 were significantly shifted to earlier stages of midbrain fold morphology and had significantly more distance between the tips of the folds (p < .05). CONCLUSIONS: In SELH/Bc mice, the 5015 diet causes higher maternal blood glucose, a faster overall embryonic developmental rate during neural tube closure, and delayed midbrain fold elevation relative to overall development. This pattern suggests that maternal dietary effects that modestly increase embryonic growth rate may exacerbate a lack of coordination between genetically delayed neural folds and normally developing underlying tissues, increasing risk of NTD. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.
Profilin, a multi‐modal regulator of neuronal plasticity
Authors: Birbach Andreas 
Published: September 2008

AbstractThirty years after its initial characterization and more than 1000 publications listed in PubMed describing its properties, the small (ca15 kDa) protein profilin continues to surprise us with new, recently discovered functions. Originally described as an actin‐binding protein, profilin has now been shown to interact with more than a dozen proteins in mammalian cells. Some of the more recently described and intriguing interactions are within neurons involving a neuronal profilin family member. Profilin is now regarded as a regulator of various cellular processes such as cytoskeletal dynamics, membrane trafficking and nuclear transport. Profilin is a necessary element in key steps of neuronal differentiation and synaptic plasticity, and embodies properties postulated for a synaptic tag. These findings identify profilin as an important factor linking cellular and behavioural plasticity in neural circuits. BioEssays 30:994–1002, 2008. © 2008 Wiley Periodicals, Inc.
Shaping segments: Hox gene function in the genomic age
Authors: Hueber Stefanie D. , Lohmann Ingrid 
Published: September 2008

AbstractDespite decades of research, morphogenesis along the various body axes remains one of the major mysteries in developmental biology. A milestone in the field was the realisation that a set of closely related regulators, called Hox genes, specifies the identity of body segments along the anterior–posterior (AP) axis in most animals. Hox genes have been highly conserved throughout metazoan evolution and code for homeodomain‐containing transcription factors. Thus, they exert their function mainly through activation or repression of downstream genes. However, while much is known about Hox gene structure and molecular function, only a few target genes have been identified and studied in detail. Our knowledge of Hox downstream genes is therefore far from complete and consequently Hox‐controlled morphogenesis is still poorly understood. Genome‐wide approaches have facilitated the identification of large numbers of Hox downstream genes both in Drosophila and vertebrates, and represent a crucial step towards a comprehensive understanding of how Hox proteins drive morphological diversification. In this review, we focus on the role of Hox genes in shaping segmental morphologies along the AP axis in Drosophila, discuss some of the conclusions drawn from analyses of large target gene sets and highlight methods that could be used to gain a more thorough understanding of Hox molecular function. In addition, the mechanisms of Hox target gene regulation are considered with special emphasis on recent findings and their implications for Hox protein specificity in the context of the whole organism. BioEssays 30:965–979, 2008. © 2008 Wiley Periodicals, Inc.
Nonsense‐mediated decay: paving the road for genome diversification
Authors: Sánchez‐Sánchez Francisco , Mittnacht Sibylle 
Published: September 2008

AbstractThe expression of protein‐encoding genes is a complex process culminating in the production of mature mRNA and its translation by the ribosomes. The production of a mature mRNA involves an intricate series of processing steps. The majority of eukaryotic protein‐encoding genes contain intron sequences that disrupt the protein‐encoding frame, and hence have to be removed from immature mRNA prior to translation into protein. The mechanism involved in the selection of correct splice sites is incompletely understood. A considerable body of evidence suggests that the splicing machinery has suboptimal efficiency and fidelity leading to substantial processing inaccuracy. Here we discuss a recently published article1 that extends observations that cells rely on nonsense‐mediated mRNA decay (NMD) to compensate for such suboptimal processing accuracy. Intriguingly these authors provide evidence for a strong selective pressure in favour of premature termination of mRNA translation in the event of intron retention. The analysis presented implies a positive role of NMD in transcript diversification through alternative splicing and suggest that this ancient surveillance mechanism may have co‐evolved with intron acquisition born from the need for quality control of splicing patterns. BioEssays 30:926–928, 2008. © 2008 Wiley Periodicals, Inc.
Luminescent properties of a novel fluorene organic material
Authors: Lou Shuangling , Yu Junsheng , Qian Jincheng , Jiang Yadong , Zhang Qing , Xu Hongjie , Sun Limei 
Published: September 2008

AbstractThe photo‐physical properties of 6,6′‐(9H‐fluoren‐9,9‐diyl)bis(2,3‐bis(9,9‐dihexyl‐9H‐fluoren‐2‐yl)quinoxaline) (BFLBBFLYQ) and its blend doped withN′‐biphenyl‐N,N′‐bis‐(3‐methylphenyl)‐1,1′‐biphenyl‐4,4′‐diamine (TPD) were investigated. The absorption, photoluminescence (PL) and electroluminescence (EL) properties of pristine BFLBBFLYQ and blend in solution and spin‐coated film are outlined, including a discussion of charge‐transfer (CT) exciplex emission of BFLBBFLYQ:TPD blend in the solid state. The luminescent properties of BFLBBFLYQ films using different deposition processes were studied. It was found that the low‐energy emission bands at 530–570 nm appeared in the PL spectra of BFLBBFLYQ evaporated films in ultra‐high vacuum. Also, the low‐energy band was the exclusive emission in the EL spectra of BFLBBFLYQ films. Copyright © 2008 John Wiley & Sons, Ltd.
Engineering cell lines for production of replication defective HSV‐1 gene therapy vectors
Authors: Grant Kyle G. , Krisky David M. , Ataai Mohammed M. , Glorioso Joseph C. 
Published: September 2008

AbstractHerpes simplex virus type 1 (HSV‐1) represents an attractive vehicle for a variety of gene therapy applications. To render this virus safe for clinical use, its cytotoxic genes must be removed without losing its ability to express transgenes efficiently. Our vectors are deleted for the essential immediate early genes ICP4 and ICP27. These genes are controlled by unique promoters having enhancer elements responsive to a viral structural protein VP16. The expression of these genes occurs prior to the activation of all other lytic functions and is thus required to initiate and complete the virus replication cycle. For large scale manufacture of clinical grade vectors, efficient cell lines must be generated that express the essential viral gene products in trans during vector propagation. Here we describe methods for engineering HSV‐1 production cell lines that improve vector growth by altering the kinetics of complementing gene expression. We examined the ability of Vero cells independently transduced with ICP4 and ICP27 under transcriptional control of their respective promoters to support the growth of a replication defective vector (JDTOZHE), deleted for ICP4, ICP27 and approximately 20 kb of internal elements that are not required for virus growth in Vero cells. Vector yield on this cell line was 3 logs lower than wild‐type virus grown on Vero cells. To understand the mechanism underlying poor vector yield, we examined the expression of ICP4 and ICP27 during virus complementation. While ICP27 was expressed immediately on vector infection, the expression of ICP4 was considerably delayed by 8–10 h, suggesting that the ICP4 promoter was not adequately activated by VP16 delivered by the infectious vector particle. Use of the ICP0 promoter to express ICP4 from the cellular genome resulted in higher induction levels and faster kinetics of ICP4 expression and a 10‐fold improvement in vector yield. This study suggests that vector complementation is highly dependent on the kinetics of complementing gene expression and can lead to large differences in vector yield. Biotechnol. Bioeng. 2009;102: 1087–1097. © 2008 Wiley Periodicals, Inc.
A clone screening method using mRNA levels to determine specific productivity and product quality for monoclonal antibodies
Authors: Lee Christina J. , Seth Gargi , Tsukuda Joni , Hamilton Robert W. 
Published: September 2008

AbstractTo meet increasing demands for efficient and streamlined production processes of therapeutic antibodies, improved methods of screening clones are required. In this article, we examined the potential of using antibody transcript levels as criteria for clone screening. We evaluated the QuantiGene Plex, a commercially available, high‐throughput assay for simultaneously measuring multiple transcripts from cell lysate. Using the development of stable Chinese hamster ovary cell lines as examples, we investigated the relationship between transcript and antibody levels through several rounds of screening. First, we observed that measured heavy chain transcript levels are generally correlated with specific productivity, enabling the identification of high‐producing clones from mRNA. Second, we observed that low ratios (<1.5) of light to heavy chain transcript levels may be indicative of high antibody aggregation levels, allowing for the rapid identification and elimination of clones of questionable product quality. Therefore, an efficient process of identifying high‐producing clones of desirable product quality is possible by using QuantiGene Plex assay to measure antibody transcript levels. Biotechnol. Bioeng. 2009;102: 1107–1118. © 2008 Wiley Periodicals, Inc.
Determination of a novel epothilone D analog (AV‐EPO‐106) in human plasma using ultra‐performance liquid chromatography–tandem mass spectrometry
Authors: Zhang Shuang‐Qing , Vinnakota Harsha , Jung Jae‐Chul , Carvalho Paulo , Chittiboyina Amar G. , Avery Mitchell A. , Avery Bonnie A. 
Published: September 2008

AbstractA novel ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS‐MS) method has been established for the determination of a newly synthesized epothilone D analog (AV‐EPO‐106) in human plasma. The plasma samples were prepared by liquid–liquid extraction with cold tert‐butyl methyl ether. The chromatographic separation was achieved within 5 min on a C18 column with water–methanol (10:90, v/v) as mobile phase at a flow‐rate of 0.8 mL/min. Mass transition of m/z 568.2 to 386.1 was measured for AV‐EPO‐106 in positive atmospheric pressure chemical ionization mode. A detailed validation of the method was performed as per the USFDA guidelines. For AV‐EPO‐106 at the concentrations of 1.0, 5.0 and 10.0 µg/mL in human plasma, the absolute extraction recoveries were 86.17, 85.24 and 85.69%, respectively. The linear quantification range of the method was 0.10–20.0 µg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra‐day and inter‐day accuracy for AV‐EPO‐106 at the levels of 1.0, 5.0 and 10.0 µg/mL in human plasma fell in the ranges of 98.25–100.47 and 94.19–97.25%, and the intra‐ and inter‐day precision were in the ranges of 4.75–6.30% and 8.89–10.45%, respectively. The method was successfully applied to quantify AV‐EPO‐106 in human plasma to determine the half‐life of this compound in human plasma. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of chemically bonded stationary phases and mobile phase composition on β‐blockers retention in RP‐HPLC
Authors: Buszewski Boguslaw , Welerowicz Tomasz , Kowalkowski Tomasz 
Published: September 2008

AbstractThe effects of stationary and mobile phase on retention of 18 β‐adrenolytic drugs (β‐blockers) have been studied. Four ‘deactivated surface’ stationary phases (polar‐embedded or end‐capped) were examined. Special attention was drawn to the cholesterolic (SG‐CHOL) and alkylamide (SG‐AP) stationary phases, and their application for analysis of the compounds. The retention of analyzed substances was also examined in terms of mobile phase composition. Sixteen different configurations of mobile phases were prepared, all based on methanol and acetonitrile with ammonium acetate and ammonium formate. The difference in retention between ammonium formate and acetate water solutions, and peak shape changes related to the addition of triethylamine (TEA), were investigated. Principal component analysis was used to find the similarities between stationary phases. Polar‐embedded phases synthesized on the same sorbent possess very similar properties. All phases based on silica gel compared with the monolithic column also showed similarities in retention of β‐blockers. The addition of TEA to the mobile phase did not influence strongly the retention, and analysis of asymmetry factors showed only a little peak broadening for a few compounds on the monolithic column. Copyright © 2008 John Wiley & Sons, Ltd.
Determination of 3′,4′,5′,5,7‐pentamethoxyflavone in the plasma and intestinal mucosa of mice by HPLC with UV detection
Authors: Cai Hong , Brown Karen , Steward William P. , Gescher Andreas J. 
Published: September 2008

AbstractIn a preliminary experiment 3′,4′,5′,5,7‐pentamethoxyflavone (PMF) inhibited adenoma development in ApcMin mice, a model of the human heritable condition familial adenomatous polyposis. An HPLC method for tricin was modified and validated to permit measurement of PMF in mouse plasma and intestinal mucosa. HPLC analysis was carried out on a Hypersil‐BDS C18 column with detection at 324 nm and tricin as internal standard. The assay was linear in the range of 100–2000 ng/mL plasma and 1.0–40 µg/mL mucosa. PMF in plasma was efficiently extracted using solid‐phase columns. In the case of mucosa organic solvent protein precipitation displayed satisfactory accuracy and precision. The assay recovery at low, medium and high concentrations was between 85 and 103% for both biomatrices, with a relative standard deviation of <15%. The lower limits of quantitation for plasma and mucosa were 100 ng/mL and 1.0 µg/mL, respectively. This method allowed measurement of PMF steady‐state median concentrations in plasma (1.08 nmol/mL, n = 11; 10th and 90th percentiles: 0.633 and 2.385 nmol/mL) and mucosa (108.5 nmol/g, n = 9; 10th and 90th percentiles: 38.9 and 164.4 nmol/g) in mice which had received PMF (0.2%, w/w) with their diet. Copyright © 2008 John Wiley & Sons, Ltd.