bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretion and properties of a hybrid Kluyveromyces lactis-Aspergillus niger β-galactosidase
Authors: Rodríguez Ángel Pereira , Leiro Rafael Fernández , Trillo M Cristina , Cerdán M Esperanza , Siso M Isabel González , Becerra Manuel
Published: December 2006

Background

The β-galactosidase from Kluyveromyces lactis is a protein of outstanding biotechnological interest in the food industry and milk whey reutilization. However, due to its intracellular nature, its industrial production is limited by the high cost associated to extraction and downstream processing.

The yeast-system is an attractive method for producing many heterologous proteins. The addition of a secretory signal in the recombinant protein is the method of choice to sort it out of the cell, although biotechnological success is not guaranteed. The cell wall acting as a molecular sieve to large molecules, culture conditions and structural determinants present in the protein, all have a decisive role in the overall process.

Protein engineering, combining domains of related proteins, is an alternative to take into account when the task is difficult. In this work, we have constructed and analyzed two hybrid proteins from the β-galactosidase of K. lactis, intracellular, and its Aspergillus niger homologue that is extracellular. In both, a heterologous signal peptide for secretion was also included at the N-terminus of the recombinant proteins. One of the hybrid proteins obtained has interesting properties for its biotechnological utilization.

Results

The highest levels of intracellular and extracellular β-galactosidase were obtained when the segment corresponding to the five domain of K. lactis β-galactosidase was replaced by the corresponding five domain of the A. niger β-galactosidase. Taking into account that this replacement may affect other parameters related to the activity or the stability of the hybrid protein, a thoroughly study was performed. Both pH (6.5) and temperature (40°C) for optimum activity differ from values obtained with the native proteins. The stability was higher than the corresponding to the β-galactosidase of K. lactis and, unlike this, the activity of the hybrid protein was increased by the presence of Ni2+. The affinity for synthetic (ONPG) or natural (lactose) substrates was higher in the hybrid than in the native K. lactis β-galactosidase. Finally, a structural-model of the hybrid protein was obtained by homology modelling and the experimentally determined properties of the protein were discussed in relation to it.

Conclusion

A hybrid protein between K. lactis and A. niger β-galactosidases was constructed that increases the yield of the protein released to the growth medium. Modifications introduced in the construction, besides to improve secretion, conferred to the protein biochemical characteristics of biotechnological interest.
Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma
Authors: Ch'ng Sydney , Sullivan Michael , Yuan Lan , Davis Paul , Tan Swee T
Published: December 2006

Background

Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear.

Aim

This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1) and human glossal squamous cell carcinoma cell line (SCC25).

Methods

HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25.

Results

HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p < 0.001), and dysregulation of genes TRAIL, BIRC4, CDK6, Cyclin G2 and CDC6 in SCC25.

Conclusion

We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.
IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae species identification, Mopti and Savanna rDNA types, and resistance to dieldrin in Anopheles arabiensis
Authors: Wilkins Elien E , Howell Paul I , Benedict Mark Q
Published: December 2006

Background

Polymerase chain reactions to distinguish single-nucleotide polymorphisms are commonly used for mosquito identification and identifying insecticide resistance alleles. However, the existing methods used for primer design often result in analyses that are not robust or require additional steps.

Methods

Utilizing oligonucleotides that are unique in having an intentional mismatch to both templates three bases from the SNP at the 3-prime end, three new PCR assays that distinguish SNP targets using standard gel electrophoresis of undigested DNA fragments were developed and tested. These were applied to: (1) an alternative ribosomal DNA PCR assay to distinguish five members of the Anopheles gambiae complex; (2) detection of the Mopti and Savanna rDNA types; and (3) an assay to distinguish resistance to dieldrin (Rdl) alleles in Anopheles arabiensis.

Results

Reproducible specific amplification of the target alleles was observed in all three assays. The results were consistent with existing analyses but proved simpler and the results more distinct in our hands.

Conclusion

The simplicity and effectiveness of the method should be utilized in these and other PCR analyses to increase their specificity and simplicity. These results have the potential to be extended not only to mosquito analyses but also to parasite and human polymorphisms.
Race-specific geography of prostate cancer incidence
Authors: DeChello Laurie M , Gregorio David I , Samociuk Holly
Published: December 2006

Background

This study evaluated geographic distribution of race-specific prostate cancer incidence in Connecticut and Massachusetts. This cross-sectional analysis of census and cancer registry data included records of 29,040 Whites and 1,647 African Americans diagnosed with incident prostate cancer between 1994 and 1998. A spatial scan statistic was used to detect and test significance of the geographic variation in race-specific incidence rates within the two-state area.

Results

Significant geographic variation in age-adjusted incidence rates among both White and African American men was observed, with little overlap noted between distributions. Identified locations reflected patterns of residential segregation and socio-economic conditions. Among Whites, places with higher than expected incidence had higher socioeconomic status than places with lower than expected incidence. No discernable relationship between social indicators and rate variation among African Americans was evident.

Conclusion

Differences in race-specific geographic distribution of prostate cancer incidence do not suggest a shared environmental etiology. Furtherstudyof genetic, behavioral and health carefactors affecting the occurrence and/or reporting of the disease is warranted. This study highlights the need for race- and geographic-specific interventions to better control disease within at-risk communities and for on-going analysis into social and contextual factors that contribute to observed disparities between African Americans and Whites in the occurrence of cancer.
Analytical and preparative applications of magnetic split-flow thin fractionation on several ion-labeled red blood cells
Authors: Tsai Hweiyan , Fang Ying S , Fuh C Bor
Published: December 2006

Background

Magnetic Split-flow thin (SPLITT) fractionation is a newly developed technique for separating magnetically susceptible particles. Particles with different field-induced velocities can be separated into two fractions by adjusting applied magnetic forces and flow-rates at inlets and outlets.

Methods

Magnetic particles, Dynabeads, were used to test this new approach of field-induced velocity for susceptibility determination using magnetic SF at different magnetic field intensities. Reference measurements of magnetic susceptibility were made using a superconducting quantum interference device (SQUID) magnetometer. Various ion-labeled red blood cells (RBC) were used to study susceptibility determination and throughput parameters for analytical and preparative applications of magnetic SPLITT fractionation (SF), respectively. Throughputs were studied at different sample concentrations, magnetic field intensities, and channel flow-rates.

Results

The susceptibilities of Dynabeads determined by SPLITT fractionation (SF) were consistent with those of reference measurement using a superconducting quantum interference device (SQUID) magnetometer. Determined susceptibilities of ion-labeled RBC were consistent within 9.6% variations at two magnetic intensities and different flow-rates. The determined susceptibilities differed by 10% from referenced measurements. The minimum difference in magnetic susceptibility required for complete separation was about 5.0 × 10-6 [cgs]. Sample recoveries were higher than 92%. The throughput of magnetic SF was approximately 1.8 g/h using our experimental setup.

Conclusion

Magnetic SF can provide simple and economical determination of particle susceptibility. This technique also has great potential for cell separation and related analysis. Continuous separations of ion-labeled RBC using magnetic SF were successful over 4 hours. The throughput was increased by 18 folds versus early study. Sample recoveries were 93.1 ± 1.8% in triplicate experiments.
Psychogenic or neurogenic origin of agrammatism and foreign accent syndrome in a bipolar patient: a case report
Authors: Poulin Stéphane , Macoir Joël , Paquet Nancy , Fossard Marion , Gagnon Louis
Published: January 2007

Background

Foreign accent syndrome (FAS) is a rare speech disorder characterized by the appearance of a new accent, different from the speaker's native language and perceived as foreign by the speaker and the listener. In most of the reported cases, FAS follows stroke but has also been found following traumatic brain injury, cerebral haemorrhage and multiple sclerosis. In very few cases, FAS was reported in patients presenting with psychiatric disorders but the link between this condition and FAS was confirmed in only one case.

Case presentation

In this report, we present the case of FG, a bipolar patient presenting with language disorders characterized by a foreign accent and agrammatism, initially categorized as being of psychogenic origin. The patient had an extensive neuropsychological and language evaluation as well as brain imaging exams. In addition to FAS and agrammatism, FG also showed a working memory deficit and executive dysfunction. Moreover, these clinical signs were related to altered cerebral activity on an FDG-PET scan that showed diffuse hypometabolism in the frontal, parietal and temporal lobes bilaterally as well as a focal deficit in the area of the anterior left temporal lobe. When compared to the MRI, these deficits were related to asymmetric atrophy, which was retrospectively seen in the left temporal and frontal opercular/insular region without a focal lesion.

Discussion

To our knowledge, FG is the first case of FAS imaged with an 18F-FDG-PET scan. The nature and type of neuropsychological and linguistic deficits, supported by neuroimaging data, exclude a neurotoxic or neurodegenerative origin for this patient's clinical manifestations. For similar reasons, a psychogenic etiology is also highly improbable.

Conclusion

To account for the FAS and agrammatism in FG, various explanations have been ruled out. Because of the focal deficit seen on the brain imaging, involving the left insular and anterior temporal cortex, two brain regions frequently involved in aphasic syndrome but also in FAS, a cerebrovascular origin must be considered the best explanation to account for FG's language deficits.
Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cell
Authors: Yang Ke , Hitomi Masahiro , Stacey Dennis W
Published: December 2006

We present evidence that variations in cyclin D1 levels through the cell cycle are essential for continuing proliferation. Cyclin D1 levels must be high during G1 phase for a cell to initiate DNA synthesis, but then must be suppressed to low levels during S phase to allow for efficient DNA synthesis. This suppression during S phase is apparently regulated by cell cycle position alone and occurs automatically during each cell cycle. If the cell is to continue proliferating, cyclin D1 levels must be induced once again during G2 phase. This induction depends upon the activity of proliferative signaling molecules, and ensures that the extracellular environment continues to be conducive for growth. We propose that the suppression of cyclin D1 levels during each S phase ensures that the subsequent induction during G2 phase, and the resulting commitment to continuing proliferation, is closely linked to the cellular growth environment.
Evidence of a linkage between matrilin-1 gene (MATN1) and idiopathic scoliosis
Authors: Montanaro Lucio , Parisini Patrizio , Greggi Tiziana , Di Silvestre Mario , Campoccia Davide , Rizzi Simona , Arciola Carla Renata
Published: December 2006

Background

In a previous study, a number of genes, associated with spine musculoskeletal deformity phenotypes in mouse and in synteny between mouse and man, were identified as candidate genes for IS. Among these genes, MATN 1, which carries a polymorphic microsatellite marker within its sequence, was selected for a linkage analysis. MATN1 is localised at 1p35 and is mainly expressed in cartilage. The objective of this study was to assess a linkage disequilibrium between the matrilin-1 (MATN 1) gene and the idiopathic scoliosis (IS).

Methods

The genetic study was conducted on a population of 81 trios, each consistent of a daughter/son affected by idiopathic scoliosis (IS) and both parents. In all trios components, the region of MATN1 gene containing the microsatellite marker was amplified by a polymerase chain reaction. The amplicons were analysed by a DNA sequencer-genotyper. The statistical linkage analysis was performed using the extended transmission/disequilibrium test.

Results

Three microsatellite polymorphisms, respectively consisting of 103 bp, 101 bp and 99 bp, were identified. ETDT evidenced a significant preferential transmission for the 103 bp allele (Chi-square = 5.058, df = 1, P = 0.024)

Conclusion

The results suggest that the familial idiopathic scoliosis is associated to the MATN1 gene.
Dofequidar Fumarate (MS-209) in Combination With Cyclophosphamide, Doxorubicin, and Fluorouracil for Patients With Advanced or Recurrent Breast Cancer
Authors: Saeki Toshiaki , Nomizu Tadashi , Toi Masakazu , Ito Yoshinori , Noguchi Shinzaburo , Kobayashi Tadashi , Asaga Taro , Minami Hironobu , Yamamoto Naohito , Aogi Kenjiro , Ikeda Tadashi , Ohashi Yasuo , Sato Wakao , Tsuruo Takashi
Published: December 2006

Purpose

To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a novel, orally active quinoline derivative that reverses multidrug resistance.

Patients and Methods

In this randomized, double-blind, placebo-controlled trial, patients were treated with six cycles of CAF therapy: 28 days/cycle, with doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8 and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14. Patients received dofequidar (900 mg PO) 30 minutes before each dose of doxorubicin. Primary end point was overall response rate (ORR; partial or complete response). In total, 221 patients were assessable.

Results

ORR was 42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative improvement and 10.5% absolute increase (P = .077). There was a trend for prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal, had no prior therapy, and were stage IV at diagnosis with an intact primary tumor. Except for neutropenia and leukopenia, there was no statistically significant excess of grade 3/4 adverse events compared with CAF. Treatment with dofequidar did not affect the plasma concentration of doxorubicin.

Conclusion

Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy.
Rapid purification of RNAs using fast performance liquid chromatography (FPLC)
Authors: Kim Insil , McKenna Sean A. , Viani Puglisi Elisabetta , Puglisi Joseph D.
Published: December 2006

We present here an improved RNA purification method using fast performance liquid chromatography (FPLC) size-exclusion chromatography in place of denaturing polyacrylamide gel electrophoresis (PAGE). The method allows preparation of milligram quantities of pure RNA in a single day. As RNA oligonucleotides behave differently from globular proteins in the size-exclusion column, we present standard curves for RNA oligonucleotides of different lengths on both the Superdex 75 column and the Superdex 200 size-exclusion column. Using this approach, we can separate monomer from multimeric RNA species, purify the desired RNA product from hammerhead ribozyme reactions, and isolate refolded RNA that has aggregated after long-term storage. This methodology allows simple and rapid purification of RNA oligonucleotides for structural and biophysical studies.
Anthropology, History, and American Indians: Essays in Honor of William Curtis Sturtevant
Authors: DARNELL REGNA
Published: December 2006

Anthropology, History, and American Indians: Essays in Honor of William Curtis Sturtevant. WILLIAM L.MERRILL and IVES GODDARDS, Editors Washington D.C.: Smithsonian Institution Press. 2002. Pp. + 357.
Eskimo Drawings
Authors: KAPLAN SUSAN A.
Published: December 2006

Eskimo Drawings. SUZIJONES, editor. Anchorage, Alaska: Anchorage Museum of History and Art in association with Anchorage Museum Association. 2003. 208 pages, 182 illustrations, endnotes, bibliography, notes on contributors, and index. Paper, $24.95.
Who Owns Native Culture?
Authors: WHEELER GARY
Published: December 2006

Who Owns Native Culture? MICAHEL F.BROWN. Cambridge: Harvard University Press, 2003, 315 pp. Illustrations and index.
Weaving a Legacy: Indian Baskets and the People of Owens Valley, California
Authors: FOWLER CATHERINE S.
Published: December 2006

Weaving a Legacy:Indian Baskets and the People of Owens Valley, California. Sharon E. Dean, Peggy S. Ratcheson, Judith W. Finger, and Ellen F. Davis, with Craig D. Bates. Salt Lake City: University of Utah Press, 2004. 182 pp.
Liberating Culture: Cross‐Cultural Perspectives on Museums, Curation and Heritage Preservation
Authors: BROWN MICHAEL F.
Published: December 2006

Liberating Culture: C ross‐Cultural Perspectives on Museums, Curation and Heritage Preservation. Christina F. Kreps. London: Routledge, 2003. 185 pp.
Heritage, Museums and Galleries: An Introductory Reader
Authors: CHAMBERS ERVE
Published: December 2006

Heritage, Museums and Galleries: An Introductory Reader. Gerard Corsane, ed. London: Routledge, 2005. 392 pp.
Whadoo tehmi: Long‐Ago People's Packsack: Dene Babiche Bags: Tradition and Revival
Authors: RIDINGTON ROBIN
Published: December 2006

Whadoo tehmi: Long‐Ago People's Packsack: Dene Babiche Bags:Tradition and Revival. Suzan Marie and Judy Thompson. Canadian Museum of Civilization, Mercury Series Ethnology Paper 141. Ottawa: Canadian Museum of Civilization, 2004. 47 pp.
Small Spirits: Native American Dolls from the National Museum of the American Indian
Authors: SMETZER MEGAN A.
Published: December 2006

Small Spirits: Native American Dolls from the National Museum of the American Indian. Mary Jane Lenz. Washington, DC: National Museum of the American Indian, Smithsonian Institution, 2004. 176 pp. (Co‐published with the University of Washington Press.)
Medicine Man: The Forgotten Museum of Henry Wellcome
Authors: KUKLICK HENRIKA
Published: December 2006

Medicine Man: The Forgotten Museum of Henry Wellcome. Ken Arnold and Danielle Olsen, eds. London: The British Museum Press, 2003. 416 pp.
Islamic Art and Geometric Design: Activities for Learning
Authors: CROWE DONALD
Published: December 2006

Islamic Art and Geometric Design: Activities for Learning. [Teaching Resource] New York: Metropolitan Museum of Art, 2004.
Archaeological Theory and the Politics of Cultural Heritage
Authors: FINE‐DARE KATHLEEN S.
Published: December 2006

Archaeological Theory and the Politics of Cultural Heritage. Laurajane Smith. New York: Routledge, 2004. 260 pp.
Materiality
Authors: CATTELINO JESSICA
Published: December 2006

Materiality. Daniel Miller, ed. Durham, NC: Duke University Press, 2005. 295 pp.
G72/G30 Genes and Schizophrenia: A Systematic Meta-analysis of Association Studies
Authors: Li Dawei , He Lin
Published: December 2006

Schizophrenia may result from a neurotransmission hypofunction of glutamatergic and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has identified several promising and novel positional candidates, including the G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive association report, many subsequent studies have attempted to replicate the association but the results have been mixed. To try to resolve this inconsistency and to elucidate the relationship between the important glutamate-related genes and schizophrenia, the current meta-analysis has combined samples involving 16 polymorphisms covering all published case-control and family-based association studies up to October 2005. The results suggest that there is weak evidence of association between the G72/G30 genes and schizophrenia.
Identifying Quantitative Trait Locus by Genetic Background Interactions in Association Studies
Authors: Jannink Jean-Luc
Published: December 2006

Association studies are designed to identify main effects of alleles across a potentially wide range of genetic backgrounds. To control for spurious associations, effects of the genetic background itself are often incorporated into the linear model, either in the form of subpopulation effects in the case of structure or in the form of genetic relationship matrices in the case of complex pedigrees. In this context epistatic interactions between loci can be captured as an interaction effect between the associated locus and the genetic background. In this study I developed genetic and statistical models to tie the locus by genetic background interaction idea back to more standard concepts of epistasis when genetic background is modeled using an additive relationship matrix. I also simulated epistatic interactions in four-generation randomly mating pedigrees and evaluated the ability of the statistical models to identify when a biallelic associated locus was epistatic to other loci. Under additive-by-additive epistasis, when interaction effects of the associated locus were quite large (explaining 20% of the phenotypic variance), epistasis was detected in 79% of pedigrees containing 320 individuals. The epistatic model also predicted the genotypic value of progeny better than a standard additive model in 78% of simulations. When interaction effects were smaller (although still fairly large, explaining 5% of the phenotypic variance), epistasis was detected in only 9% of pedigrees containing 320 individuals and the epistatic and additive models were equally effective at predicting the genotypic values of progeny. Epistasis was detected with the same power whether the overall epistatic effect was the result of a single pairwise interaction or the sum of nine pairwise interactions, each generating one ninth of the epistatic variance. The power to detect epistasis was highest (94%) at low QTL minor allele frequency, fell to a minimum (60%) at minor allele frequency of about 0.2, and then plateaued at about 80% as alleles reached intermediate frequencies. The power to detect epistasis declined when the linkage disequilibrium between the DNA marker and the functional polymorphism was not complete.
Estimation of Population Heterozygosity and Library Construction-Induced Mutation Rate From Expressed Sequence Tag Collections
Authors: Long A D , Beldade P , Macdonald S J
Published: December 2006

Unigene alignments obtained from cDNA libraries made using multiple individuals are not currently used to estimate population heterozygosity, as they are known to harbor mutations created during library construction. We describe an estimator of population heterozygosity that utilizes only SNPs unlikely to be library construction artifacts.
Evaluation of the Genomic Extent of Effects of Fixed Inversion Differences on Intraspecific Variation and Interspecific Gene Flow in Drosophila pseudoobscura and D. persimilis
Authors: Machado Carlos A , Haselkorn Tamara S , Noor Mohamed A F
Published: December 2006

There is increasing evidence that chromosomal inversions may facilitate the formation or persistence of new species by allowing genetic factors conferring species-specific adaptations or reproductive isolation to be inherited together and by reducing or eliminating introgression. However, the genomic domain of influence of the inverted regions on introgression has not been carefully studied. Here, we present a detailed study on the consequences that distance from inversion breakpoints has had on the inferred level of gene flow and divergence between Drosophila pseudoobscura and D. persimilis. We identified the locations of the inversion breakpoints distinguishing D. pseudoobscura and D. persimilis in chromosomes 2, XR, and XL. Population genetic data were collected at specific distances from the inversion breakpoints of the second chromosome and at two loci inside the XR and XL inverted regions. For loci outside the inverted regions, we found that distance from the nearest inversion breakpoint had a significant effect on several measures of divergence and gene flow between D. pseudoobscura and D. persimilis. The data fitted a logarithmic relationship, showing that the suppression of crossovers in inversion heterozygotes also extends to loci located outside the inversion but close to it (within 1–2 Mb). Further, we detected a significant reduction in nucleotide variation inside the inverted second chromosome region of D. persimilis and near one breakpoint, consistent with a scenario in which this inversion arose and was fixed in this species by natural selection.
Global eQTL Mapping Reveals the Complex Genetic Architecture of Transcript-Level Variation in Arabidopsis
Authors: West Marilyn A L , Kim Kyunga , Kliebenstein Daniel J , van Leeuwen Hans , Michelmore Richard W , Doerge R W , St. Clair Dina A
Published: December 2006

The genetic architecture of transcript-level variation is largely unknown. The genetic determinants of transcript-level variation were characterized in a recombinant inbred line (RIL) population (n = 211) of Arabidopsis thaliana using whole-genome microarray analysis and expression quantitative trait loci (eQTL) mapping of transcript levels as expression traits (e-traits). Genetic control of transcription was highly complex: one-third of the quantitatively controlled transcripts/e-traits were regulated by cis-eQTL, and many trans-eQTL mapped to hotspots that regulated hundreds to thousands of e-traits. Several thousand eQTL of large phenotypic effect were detected, but almost all (93%) of the 36,871 eQTL were associated with small phenotypic effects (R2 < 0.3). Many transcripts/e-traits were controlled by multiple eQTL with opposite allelic effects and exhibited higher heritability in the RILs than their parents, suggesting nonadditive genetic variation. To our knowledge, this is the first large-scale global eQTL study in a relatively large plant mapping population. It reveals that the genetic control of transcript level is highly variable and multifaceted and that this complexity may be a general characteristic of eukaryotes.
Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans
Authors: Liégeois Samuel , Benedetto Alexandre , Michaux Grégoire , Belliard Guillaume , Labouesse Michel
Published: December 2006

Few studies have investigated whether or not there is an interdependence between osmoregulation and vesicular trafficking. We previously showed that in Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion, and sensory organ development. We report the identification of seven lethal mutations displaying che-14-like phenotypes, which define four new genes, rdy-1–rdy-4 (rod-like larval lethality and dye-filling defective). rdy-1, rdy-2, and rdy-4 mutations affect excretory canal function and cuticle formation. Moreover, rdy-1 and rdy-2 mutations reduce the amount of matrix material normally secreted by sheath cells in the amphid channel. In contrast, rdy-3 mutants have short cystic excretory canals, suggesting that it acts in a different process. rdy-1 encodes the vacuolar H+-ATPase a-subunit VHA-5, whereas rdy-2 encodes a new tetraspan protein. We suggest that RDY-1/VHA-5 acts upstream of RDY-2 and CHE-14 in some tissues, since it is required for their delivery to the epidermal, but not the amphid sheath, apical plasma membrane. Hence, the RDY-1/VHA-5 trafficking function appears essential in some cells and its proton pump function essential in others. Finally, we show that RDY-1/VHA-5 distribution changes prior to molting in parallel with that of actin microfilaments and propose a model for molting whereby actin provides a spatial cue for secretion.
Functional Deficiency in IL-7 Caused by an N-Ethyl-N-nitrosourea-Induced Point Mutation
Authors: Feng Jianxun , Wang Hongsheng , Morse Herbert C
Published: December 2006

N-ethyl-N-nitrosourea (ENU)-induced mutagenesis provides a powerful approach for identifying genes involved in immune regulation and diseases. Here we describe a new mutant strain, HLB368, with hereditary leukopenia. At necropsy, the mutant mice had very small thymuses and spleens. All but the inguinal nodes were absent and there were no Peyer's patches. By flow cytometry, the ratios of T-cell subsets were normal, but B-cell development was blocked at the pre-pro-B-cell stage. The development of B1 and marginal zone B cells was relatively normal. The mutation was mapped to chromosome 3 between D3Mit221 and D3Mit224, a region that contains the Il7 gene. cDNA and genomic DNA sequences of Il7 revealed a T-to-C missense transition resulting in a change of Leu to Pro within the leader peptide that would be predicted to inhibit secretion. In keeping with this concept, we found that in vitro treatment of B-cell progenitors from mutant mice with IL-7 induced them to differentiate into pre-BII cells. Phenotypic comparisons of HLB368 with genetically targeted Il7 null mice showed many similarities along with a few differences, indicating that this ENU-induced mutant carries a novel allele. This new strain thus provides a new model for studying the functions of IL-7 on a pure C57BL/6 background.
Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled
Authors: Chisa Jennifer L , Burke David T
Published: December 2006

Post-transcriptional RNA processing is an important regulatory control mechanism for determining the phenotype of eukaryotic cells. The processing of a transcribed RNA species into alternative splice isoforms yields products that can perform different functions. Each type of cell in a multi-cellular organism is presumed to actively control the relative quantities of alternative splice isoforms. In this study, the alternatively spliced isoforms of five mRNA transcription units were examined by quantitative reverse transcription–PCR amplification. We show that interindividual variation in splice-isoform selection is very highly constrained when measured in a large population of genetically diverse mice (i.e., full siblings; N = 150). Remarkably, splice-isoform ratios are among the most invariant phenotypes measured in this population and are confirmed in a second, genetically distinct population. In addition, the patterns of splice-isoform selection show tissue-specific and age-related changes. We propose that splice-isoform selection is exceptionally robust to genetic and environmental variability and may provide a control point for cellular homeostasis. As a consequence, splice-isoform ratios may be useful as a practical quantitative measure of the physiological status of cells and tissues.
Development of a Near-Isogenic Line Population ofArabidopsis thalianaand Comparison of Mapping Power With a Recombinant Inbred Line Population
Authors: Keurentjes Joost J B , Bentsink Leónie , Alonso-Blanco Carlos , Hanhart Corrie J , Blankestijn-De Vries Hetty , Effgen Sigi , Vreugdenhil Dick , Koornneef Maarten
Published: December 2006

In Arabidopsis recombinant inbred line (RIL) populations are widely used for quantitative trait locus (QTL) analyses. However, mapping analyses with this type of population can be limited because of the masking effects of major QTL and epistatic interactions of multiple QTL. An alternative type of immortal experimental population commonly used in plant species are sets of introgression lines. Here we introduce the development of a genomewide coverage near-isogenic line (NIL) population of Arabidopsis thaliana, by introgressing genomic regions from the Cape Verde Islands (Cvi) accession into the Landsberg erecta (Ler) genetic background. We have empirically compared the QTL mapping power of this new population with an already existing RIL population derived from the same parents. For that, we analyzed and mapped QTL affecting six developmental traits with different heritability. Overall, in the NIL population smaller-effect QTL than in the RIL population could be detected although the localization resolution was lower. Furthermore, we estimated the effect of population size and of the number of replicates on the detection power of QTL affecting the developmental traits. In general, population size is more important than the number of replicates to increase the mapping power of RILs, whereas for NILs several replicates are absolutely required. These analyses are expected to facilitate experimental design for QTL mapping using these two common types of segregating populations.
Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1
Authors: Chung Henry , Bogwitz Michael R , McCart Caroline , Andrianopoulos Alex , ffrench-Constant Richard H , Batterham Philip , Daborn Phillip J
Published: December 2006

Transposable elements are a major mutation source and powerful agents of adaptive change. Some transposable element insertions in genomes increase to a high frequency because of the selective advantage the mutant phenotype provides. Cyp6g1-mediated insecticide resistance in Drosophila melanogaster is due to the upregulation of the cytochrome P450 gene Cyp6g1, leading to the resistance to a variety of insecticide classes. The upregulation of Cyp6g1 is correlated with the presence of the long terminal repeat (LTR) of an Accord retrotransposon inserted 291bp upstream of the Cyp6g1 transcription start site. This resistant allele (DDT-R) is currently at a high frequency in D. melanogaster populations around the world. Here, we characterize the spatial expression of Cyp6g1 in insecticide-resistant and -susceptible strains. We show that the Accord LTR insertion is indeed the resistance-associated mutation and demonstrate that the Accord LTR carries regulatory sequences that increase the expression of Cyp6g1 in tissues important for detoxification, the midgut, Malpighian tubules, and the fat body. This study provides a significant example of how changes in tissue-specific gene expression caused by transposable-element insertions can contribute to adaptation.
Deterministic and Stochastic Regimes of Asexual Evolution on Rugged Fitness Landscapes
Authors: Jain Kavita , Krug Joachim
Published: December 2006

We study the adaptation dynamics of an initially maladapted asexual population with genotypes represented by binary sequences of length L. The population evolves in a maximally rugged fitness landscape with a large number of local optima. We find that whether the evolutionary trajectory is deterministic or stochastic depends on the effective mutational distance deff up to which the population can spread in genotype space. For deff = L, the deterministic quasi-species theory operates while for deff < 1, the evolution is completely stochastic. Between these two limiting cases, the dynamics are described by a local quasi-species theory below a crossover time T× while above T× the population gets trapped at a local fitness peak and manages to find a better peak via either stochastic tunneling or double mutations. In the stochastic regime deff < 1, we identify two subregimes associated with clonal interference and uphill adaptive walks, respectively. We argue that our findings are relevant to the interpretation of evolution experiments with microbial populations.
Evolutionary Conservation of the FLOWERING LOCUS C-Mediated Vernalization Response: Evidence From the Sugar Beet (Beta vulgaris)
Authors: Reeves Patrick A , He Yuehui , Schmitz Robert J , Amasino Richard M , Panella Lee W , Richards Christopher M
Published: December 2006

In many plant species, exposure to a prolonged period of cold during the winter promotes flowering in the spring, a process termed vernalization. In Arabidopsis thaliana, the vernalization requirement of winter-annual ecotypes is caused by the MADS-box gene FLOWERING LOCUS C (FLC), which is a repressor of flowering. During the vernalization process, FLC is downregulated by alteration of its chromatin structure, thereby permitting flowering to occur. In wheat, a vernalization requirement is imposed by a different repressor of flowering, suggesting that some components of the regulatory network controlling the vernalization response differ between monocots and dicots. The extent to which the molecular mechanisms underlying vernalization have been conserved during the diversification of the angiosperms is not well understood. Using phylogenetic analysis, we identified homologs of FLC in species representing the three major eudicot lineages. FLC homologs have not previously been documented outside the plant family Brassicaceae. We show that the sugar beet FLC homolog BvFL1 functions as a repressor of flowering in transgenic Arabidopsis and is downregulated in response to cold in sugar beet. Cold-induced downregulation of an FLC-like floral repressor may be a central feature of the vernalization response in at least half of eudicot species.
Adverse Events Associated With Pediatric Spinal Manipulation: A Systematic Review
Authors: Vohra Sunita , Johnston Bradley C. , Cramer Kristie , Humphreys Kim
Published: December 2006

BACKGROUND. Spinal manipulation is a noninvasive manual procedure applied to specific body tissues with therapeutic intent. Although spinal manipulation is commonly used in children, there is limited understanding of the pediatric risk estimates.

OBJECTIVE. Our goal was to systematically identify and synthesize available data on adverse events associated with pediatric spinal manipulation.

METHODS. A comprehensive search was performed of 8 major electronic databases (eg, Medline, AMED, MANTIS) from inception to June 2004 irrespective of language. Reports were included if they (1) were a primary investigation of spinal manipulation (eg, observation studies, controlled trials, surveys), (2) included a study population of children who were aged 18 years or younger, and (3) reported data on adverse events. Data were summarized to demonstrate the nature and severity of adverse events that may result rather than their incidence.

RESULTS. Thirteen studies (2 randomized trials, 11 observational reports) were identified for inclusion. We identified 14 cases of direct adverse events involving neurologic or musculoskeletal events. Nine cases involved serious adverse events (eg, subarachnoidal hemorrhage, paraplegia), 2 involved moderately adverse events that required medical attention (eg, severe headache), and 3 involved minor adverse events (eg, midback soreness). Another 20 cases of indirect adverse events involved delayed diagnosis (eg, diabetes, neuroblastoma) and/or inappropriate provision of spinal manipulation for serious medical conditions (ie, meningitis, rhabdomyosarcoma).

CONCLUSIONS. Serious adverse events may be associated with pediatric spinal manipulation; neither causation nor incidence rates can be inferred from observational data. Conduct of a prospective population-based active surveillance study is required to properly assess the possibility of rare, yet serious, adverse events as a result of spinal manipulation on pediatric patients.
Successful Field Pilot of In-Depth Colloidal Dispersion Gel (CDG) Technology in Daqing Oil Field
Authors: Chang Harry L. , Sui Xingguang , Xiao Long , Guo Zhidong , Yao Yuming , Xiao Yuguo , Chen Gang , Song Kaoping , Mack James C.
Published: December 2006

The first large-scale colloidal dispersion gel (CDG) pilot test was conducted in the largest oil field in China, Daqing oil field. The project was initiated in May 1999, and injection of chemical slugs was completed in May 2003.

This paper provides detailed descriptions of the gel-system characterization, chemical-slug optimization, project execution, performance analysis, injection facility design, and economics. The improvements of permeability variation and sweep efficiency were demonstrated by lower water cut, higher oil rate, improved injection profiles, and the increase of the total dissolved solids (TDS) in production wells.

The ultimate incremental oil recovery (defined as the amount of oil recovered above the projected waterflood recovery at 98% water cut) in the pilot area would be approximately 15% of the original oil in place (OOIP). The economic analysis showed that the chemical costs were approximately U.S. $2.72 per barrel of incremental oil recovered. Results are presented in 15 tables and 8 figures.
Winds and Air Movement
Authors: Kraght Peter E.
Published: December 2006

Specific Winds and Wind‐Related Terms
Oral Antidiabetic Drugs
Authors: Bischoff Hilmar
Published: December 2006

The article contains sections titled:

1.Introduction2.Stimulators of Insulin Secretion2.1.Sulfonylureas and Related Compounds2.2.Benzoic Acid Derivatives2.3.Amino Acid Derivatives2.4.Mode of Action2.5.New Insulinotropic Mechanisms2.5.1.Dipeptidyl Peptidase IV Inhibition2.5.2.Dipeptidyl Peptidase IV Inhibitors in Clinical Development3.Biguanides4.Inhibitors of Intestinal Carbohydrate Digestion4.1.α‐Glucosidase Inhibitors4.1.1.Mode of Action4.1.2.Pharmacology4.1.3.Individual Compounds4.2.Plant Fibers5.Enhancers of Insulin Action5.1.Mode of Action5.2.Pharmacology of PPARγ agonists5.3.Thiazolidine‐2,4‐Dione Derivatives (Glitazones)

The review describes all oral drugs used for the treatment of type 2 diabetes mellitus which are marketed or in late clinical development. Stimulators of insulin secretion are the most prescribed class of antidiabetic drugs. These compounds increase insulin secretion from pancreatic β‐cells via the closure of the ATP‐sensitive K+channel. Sulfonylurea (SU) derivatives bind to the SU receptor on a regulatory protein of the ATP‐sensitive K+channel. Since various binding sites exist, also other compounds like benzoic acid or amino acid derivatives are able to bind and to stimulate insulin secretion via the closure of the ATP‐sensitive K+ channel. Very new mechanisms, not yet approved and still in late clinical development, prevent the degradation of glucagons‐like‐peptide‐1 (GLP‐1), an intestinal hormone, which stimulates insulin secretion by increasing intracellular cAMP levels of β‐cells. Those compounds, which inhibit the GLP‐1 degrading enzyme dipeptidyl peptidase IV (DPP IV), sustain the insulinotropic effect of GLP‐1. The antidiabetic action of biguanides, only metformin is marketed today, is still not fully understood. Metformin improves insulin sensitivity probably by an increase in peripheral glucose utilization and additionally metformin reduces hepatic gluconeogenesis. Alpha‐glucosidase inhibitors are enzyme inhibitors of small intestinal carbohydrate digesting glucosidases. They display their antidiabetic effect by delaying the postprandial (pp) carbohydrate absorption resulting in reduced pp hyperglycemia and ‐insulinemia, which finally improves insulin sensitivity. Enhancers of insulin action are ligands of the peroxisome proliferator activated receptor γ (PPARγ). PPARs belong to the nuclear receptor family of ligand‐activated transcription factors. The major antidiabetic and blood glucose lowering effect of the PPARγ agonists is the improvement of insulin sensitivity, however, the mechanism is not fully elucidated yet.
Artists' Colors
Authors: Müller Hugo , Müller Wolfgang , Wehner Manfred , Liewald Heike
Published: December 2006

The article contains sections titled:

1.

Introduction

2.

Organic Pigments

3.

Inorganic Pigments

3.1.

White Inorganic Pigments

3.2.

Colored Inorganic Pigments

3.3.

Black Pigments

3.4.

Fillers

4.

Dyes for Silk Painting

5.

Binders

6.

Quality Factors

7.

Commercially Available Artists' Colors and Materials

7.1.

Oil Colors

7.2.

Acrylic Paints

7.3.

Watercolor (Aquarell)

7.4.

Pastels

7.5.

Gouache and Distemper (Tempera)

7.6.

Powdered Pigments

7.7.

Silk Paints

7.8.

Paints for Graphic Techniques

7.9.

Other Artists' Materials

Artists'; colors represent just a small sector of the paint industry, the total invoiced sales in Europe were about 222.7 × 10
6
 € in 2004, the production of artists' colors in Germany amounted to about 4180 t with a value of 67.1 × 10
6
 € in 2004. Artists' colors are mixtures of three major components: pigments, binders, and fillers.

Pigments determine the hue, hiding power, and tinting strength of artists' colors. Binders enable the pigments to adhere to the substrate. Fillers can influence optical properties such as whiteness and hiding power, rheological behavior, mechanical properties, and resistance to weathering and chemicals.

The commercially available artists' colors and materials are the following types: oil colors, acrylic paints, watercolors, pastels, gouache and tempera, powdered pigments, silk paints, paints for graphic techniques, and others artists' materials such as primers and varnishes.