bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunpathogenetische Subtypisierung der Multiplen Sklerose / Immunopathogenetic subtyping of multiple sclerosis
Authors: Berger Thomas , Reindl Markus
Published: October 2004

Zusammenfassung Multiple Sklerose ist keine einheitliche Erkrankung, sondern ein Formenkreis unterschiedlicher entzündlichdemyelinisierender ZNS-Erkrankungen. Die Variabilität des klinischen Verlaufs, verbunden mit fehlenden individuellen prognostischen Parametern, führt vor allem zu einem unterschiedlichen, letztlich nicht voraussagbaren Ansprechen auf therapeutische Interventionen. Daraus ergibt sich die Forderung nach einer differenzierten Subtypisierung der Patienten nach genetischen, klinischen, neuroradiologischen, neuropathologischen und neuroimmunologischen Gesichtspunkten. Damit wäre es erstmals möglich, Patienten nach einem differentialtherapeutischen Konzept spezifisch für eine individuelle Therapie zu stratifizieren und den Erfolg bisheriger Therapiestrategien zu steigern.
Anti-Glykolipid-Antikörper in der Diagnostik von Immunneuropathien / Anti-glycolipid antibodies in the diagnosis of immunoneuropathies
Authors: Wanschitz Julia , Deisenhammer Florian
Published: October 2004

Zusammenfassung Unter den nicht hereditären Formen von Neuropathien (NP) stellen die Immunneuropathien insofern eine Sonderform dar, als sie meistens einer kausalen Therapie zugeführt werden können. Die Diagnose stützt sich wie bei anderen Formen auf die klinische Untersuchung und den elektrophysiologischen Befund. Manche Immunneuropathien sind durch spezifische Antikörper gegen Nervenmembranbestandteile charakterisiert. Dazu zählen verschiedene Ganglioside, das Myelin-assoziierte Glykoprotein und Sulfatide. Zwar sind Immunneuropathien selten, es können aber bei bestimmten Formen in bis zu annähernd 100% der Fälle solche Antikörper nachgewiesen werden. Am häufigsten wird eine direkte ELISA-Methode angewandt, wobei insbesondere bei IgM-Antikörpern beachtet werden muss, dass solche wegen ihrer Kreuzreaktivität in niedrigen Titern auch bei der gesunden Bevölkerung mit hoher Frequenz vorkommen.

In dieser Arbeit werden die wichtigsten Typen von Immunneuropathien und die dazu gehörigen charakteristischen Laborbefunde beschrieben.
Joint Mapping of Quantitative Trait Loci for Multiple Binary Characters
Authors: Xu Chenwu , Li Zhikang , Xu Shizhong
Published: October 2004

Joint mapping for multiple quantitative traits has shed new light on genetic mapping by pinpointing pleiotropic effects and close linkage. Joint mapping also can improve statistical power of QTL detection. However, such a joint mapping procedure has not been available for discrete traits. Most disease resistance traits are measured as one or more discrete characters. These discrete characters are often correlated. Joint mapping for multiple binary disease traits may provide an opportunity to explore pleiotropic effects and increase the statistical power of detecting disease loci. We develop a maximum-likelihood method for mapping multiple binary traits. We postulate a set of multivariate normal disease liabilities, each contributing to the phenotypic variance of one disease trait. The underlying liabilities are linked to the binary phenotypes through some underlying thresholds. The new method actually maps loci for the variation of multivariate normal liabilities. As a result, we are able to take advantage of existing methods of joint mapping for quantitative traits. We treat the multivariate liabilities as missing values so that an expectation-maximization (EM) algorithm can be applied here. We also extend the method to joint mapping for both discrete and continuous traits. Efficiency of the method is demonstrated using simulated data. We also apply the new method to a set of real data and detect several loci responsible for blast resistance in rice.
Using Molecular Sizes of Simple Sequence Repeats vs. Discrete Binned Data in Assessing Probability of Ancestry
Authors: Berry Donald A , Wright Deanne , Xie Chongqing , Seltzer Jon D , Smith J Stephen C
Published: October 2004

Most inferential methods for profiling genotypes based upon the use of DNA fragments use molecular-size data transcribed into discrete bins, which are intervals of DNA fragment sizes. Categorizing into bins is labor intensive with inevitable arbitrariness that may vary between laboratories. We describe and evaluate an algorithm for determining probabilities of parentage based on raw molecular-size data without establishing bins. We determine the standard deviation of DNA fragment size and assess the association of standard deviation with fragment size. We consider a pool of potential ancestors for an index line that is a hybrid with unknown pedigree. We evaluate the identification of inbred parents of maize hybrids with simple sequence repeat data in the form of actual molecular sizes received from two laboratories. We find the standard deviation to be essentially constant over the molecular weight. We compare these results with those of parallel analyses based on these same data that had been transcribed into discrete bins by the respective laboratories. The conclusions were quite similar in the two cases, with excellent performance using either binned or molecular-size data. We demonstrate the algorithm's utility and robustness through simulations of levels of missing and misscored molecular-size data.
On the Meaning and Existence of an Effective Population Size
Authors: Sjödin P , Kaj I , Krone S , Lascoux M , Nordborg M
Published: October 2004

We investigate conditions under which a model with stochastic demography or population structure converges to the coalescent with a linear change in timescale. We argue that this is a necessary condition for the existence of a meaningful effective population size. We find that such a linear timescale change is obtained when demographic fluctuations and coalescence events occur on different timescales. Simple models of population structure and randomly fluctuating population size are used to exemplify the ideas and provide an intuitive feel for the meaning of the conditions.
The LF1 Gene of Chlamydomonas reinhardtii Encodes a Novel Protein Required for Flagellar Length Control
Authors: Nguyen Rachel L , Tam Lai-Wa , Lefebvre Paul A
Published: October 2004

Flagellar length is tightly regulated in the biflagellate alga Chlamydomonas reinhardtii. Several genes required for control of flagellar length have been identified, including LF1, a gene required to assemble normal-length flagella. The lf1 mutation causes cells to assemble extra-long flagella and to regenerate flagella very slowly after amputation. Here we describe the positional cloning and molecular characterization of the LF1 gene using a bacterial artificial chromosome (BAC) library. LF1 encodes a protein of 804 amino acids with no obvious sequence homologs in other organisms. The single LF1 mutant allele is caused by a transversion that produces an amber stop at codon 87. Rescue of the lf1 phenotype upon transformation was obtained with clones containing the complete LF1 gene as well as clones that lack the last two exons of the gene, indicating that only the amino-terminal portion of the LF1 gene product (LF1p) is required for function. Although LF1 helps regulate flagellar length, the LF1p localizes almost exclusively in the cell body, with <1% of total cellular LF1p localizing to the flagella.
The Amplification Model for Adaptive Mutation
Authors: Pettersson Mats E , Andersson Dan I , Roth John R , Berg Otto G
Published: October 2004

It has been proposed that the lac revertants arising under selective conditions in the Cairns experiment do not arise by stress-induced mutagenesis of stationary phase cells as has been previously assumed. Instead, these revertants may arise within growing clones initiated by cells with a preexisting duplication of the weakly functional lac allele used in this experiment. It is proposed that spontaneous stepwise increases in lac copy number (amplification) allow a progressive improvement in growth. Reversion is made more likely primarily by the resultant increase in the number of mutational targets—more cells with more lac copies. The gene amplification model requires no stress-induced variation in the rate or target specificity of mutation and thus does not violate neo-Darwinian theory. However, it does require that a multistep process of amplification, reversion, and amplification segregation be completed within ∼20 generations of growth. This work examines the proposed amplification model from a theoretical point of view, formalizing it into a mathematical framework and using this to determine what would be required for the process to occur within the specified period. The analysis assumes no stress-induced change in mutation rate and describes only the growth improvement occurring during the process of amplification and subsequent elimination of excess mutant lac copies. The dynamics of the system are described using Monte Carlo simulations and numerical integration of the deterministic equations governing the system. The results imply that the amplification model can account for the behavior of the system using biologically reasonable parameter values and thus can, in principle, explain Cairnsian adaptive mutation.
Ccr4-Not Complex mRNA Deadenylase Activity Contributes to DNA Damage Responses in Saccharomyces cerevisiae
Authors: Traven Ana , Hammet Andrew , Tenis Nora , Denis Clyde L , Heierhorst Jörg
Published: October 2004

DNA damage checkpoints regulate gene expression at the transcriptional and post-transcriptional level. Some components of the yeast Ccr4-Not complex, which regulates transcription as well as transcript turnover, have previously been linked to DNA damage responses, but it is unclear if this involves transcriptional or post-transcriptional functions. Here we show that CCR4 and CAF1, which together encode the major cytoplasmic mRNA deadenylase complex, have complex genetic interactions with the checkpoint genes DUN1, MRC1, RAD9, and RAD17 in response to DNA-damaging agents hydroxyurea (HU) and methylmethane sulfonate (MMS). The exonuclease-inactivating ccr4-1 point mutation mimics ccr4Δ phenotypes, including synthetic HU hypersensitivity with dun1Δ, demonstrating that Ccr4-Not mRNA deadenylase activity is required for DNA damage responses. However, ccr4Δ and caf1Δ DNA damage phenotypes and genetic interactions with checkpoint genes are not identical, and deletions of some Not components that are believed to predominantly function at the transcriptional level rather than mRNA turnover, e.g., not5Δ, also lead to increased DNA damage sensitivity and synthetic HU hypersensitivity with dun1Δ. Taken together, our data thus suggest that both transcriptional and post-transcriptional functions of the Ccr4-Not complex contribute to the DNA damage response affecting gene expression in a complex manner.
Convergent, RIC-8-Dependent Gα Signaling Pathways in the Caenorhabditis elegans Synaptic Signaling Network
Authors: Reynolds Nicole K , Schade Michael A , Miller Kenneth G
Published: October 2004

We used gain-of-function and null synaptic signaling network mutants to investigate the relationship of the Gαq and Gαs pathways to synaptic vesicle priming and to each other. Genetic epistasis studies using Gαq gain-of-function and null mutations, along with a mutation that blocks synaptic vesicle priming and the synaptic vesicle priming stimulator phorbol ester, suggest that the Gαq pathway generates the core, obligatory signals for synaptic vesicle priming. In contrast, the Gαs pathway is not required for the core priming function, because steady-state levels of neurotransmitter release are not significantly altered in animals lacking a neuronal Gαs pathway, even though these animals are strongly paralyzed as a result of functional (nondevelopmental) defects. However, our genetic analysis indicates that these two functionally distinct pathways converge and that they do so downstream of DAG production. Further linking the two pathways, our epistasis analysis of a ric-8 null mutant suggests that RIC-8 (a receptor-independent Gα guanine nucleotide exchange factor) is required to maintain both the Gαq vesicle priming pathway and the neuronal Gαs pathway in a functional state. We propose that the neuronal Gαs pathway transduces critical positional information onto the core Gαq pathway to stabilize the priming of selected synapses that are optimal for locomotion.
The Dlx Gene Complement of the Leopard Shark, Triakis semifasciata, Resembles That of MammalsSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY738118, AY738119, AY738120, AY738121, AY738122, AY738123.
Authors: Stock David W
Published: October 2004

Extensive gene duplication is thought to have occurred in the vertebrate lineage after it diverged from cephalochordates and before the divergence of lobe- and ray-finned fishes, but the exact timing remains obscure. This timing was investigated by analysis of the Dlx gene family of a representative cartilaginous fish, the leopard shark, Triakis semifasciata. Dlx genes encode homeodomain transcription factors and are arranged in mammals as three convergently transcribed bigene clusters. Six Dlx genes were cloned from Triakis and shown to be orthologous to single mammalian Dlx genes. At least four of these are arranged in bigene clusters. Phylogenetic analyses of Dlx genes were used to propose an evolutionary scenario in which two genome duplications led to four Dlx bigene clusters in a common ancestor of jawed vertebrates, one of which was lost prior to the diversification of the group. Dlx genes are known to be involved in jaw development, and changes in Dlx gene number are mapped to the same branch of the vertebrate tree as the origin of jaws.
Suppression of Histone H1 Genes in Arabidopsis Results in Heritable Developmental Defects and Stochastic Changes in DNA Methylation
Authors: Wierzbicki Andrzej T , Jerzmanowski Andrzej
Published: October 2004

Histone H1 is an abundant component of eukaryotic chromatin that is thought to stabilize higher-order chromatin structures. However, the complete knock-out of H1 genes in several lower eukaryotes has no discernible effect on their appearance or viability. In higher eukaryotes, the presence of many mutually compensating isoforms of this protein has made assessment of the global function of H1 more difficult. We have used double-stranded RNA (dsRNA) silencing to suppress all the H1 genes of Arabidopsis thaliana. Plants with a >90% reduction in H1 expression exhibited a spectrum of aberrant developmental phenotypes, some of them resembling those observed in DNA hypomethylation mutants. In subsequent generations these defects segregated independently of the anti-H1 dsRNA construct. Downregulation of H1 genes did not cause substantial genome-wide DNA hypo- or hypermethylation. However, it was correlated with minor but statistically significant changes in the methylation patterns of repetitive and single-copy sequences, occurring in a stochastic manner. These findings reveal an important and previously unrecognized link between linker histones and specific patterns of DNA methylation.
The Dynamics of Transposable Elements in Structured Populations
Authors: Deceliere Grégory , Charles Sandrine , Biémont Christian
Published: October 2004

We analyzed the dynamics of transposable elements (TEs) according to Wright's island and continent-island models, assuming that selection tends to counter the deleterious effects of TEs. We showed that migration between host populations has no impact on either the existence or the stability of the TE copy number equilibrium points obtained in the absence of migration. However, if the migration rate is slower than the transposition rate or if selection is weak, then the TE copy numbers in all the populations can be expected to slowly become homogeneous, whereas a heterogeneous TE copy number distribution between populations is maintained if TEs are mobilized in some populations. The mean TE copy number is highly sensitive to the population size, but as a result of migration between populations, it decreases as the sum of the population sizes increases and tends to reach the same value in these populations. We have demonstrated the existence of repulsion between TE insertion sites, which is established by selection and amplified by drift. This repulsion is reduced as much as the migration rate is higher than the recombination rate between the TE insertion sites. Migration and demographic history are therefore strong forces in determining the dynamics of TEs within the genomes and the populations of a species.
The Influence of Genes on the Aging Process of Mice
Authors: de Magalhães João Pedro , Cabral José A S , Magalhães Domingos
Published: October 2004

Genetic interventions that accelerate or retard aging in mice are crucial in advancing our knowledge over mammalian aging. Yet determining if a given intervention affects the aging process is not straightforward since, for instance, many disease-causing mutations may decrease life span without affecting aging. In this work, we employed the Gompertz model to determine whether several published interventions previously claimed to affect aging in mice do indeed alter the aging process. First, we constructed age-specific mortality tables for a number of mouse cohorts used in longevity experiments and calculated the rate at which mortality increases with age. Estimates of age-independent mortality were also calculated. We found no statistical evidence that GHRHR, IGF1R, INSR, PROP1, or TRX delay or that ATM + TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN + TERC, or TOP3B accelerate mouse aging. Often, changes in the expression of these genes affected age-independent mortality and so they may prove useful to other aspects of medicine. We found statistical evidence that C/EBP, MSRA, SHC1, growth hormone, GHR, PIT1, and PolgA may influence aging in mice. These results were interpreted together with age-related physiological and pathological changes and provide novel insights regarding the role of several genes in the mammalian aging process.
Mutations That Rescue the Paralysis of Caenorhabditis elegans ric-8 (Synembryn) Mutants Activate the Gαs Pathway and Define a Third Major Branch of the Synaptic Signaling Network
Authors: Schade Michael A , Reynolds Nicole K , Dollins Claudia M , Miller Kenneth G
Published: October 2004

To identify hypothesized missing components of the synaptic Gαo-Gαq signaling network, which tightly regulates neurotransmitter release, we undertook two large forward genetic screens in the model organism C. elegans and focused first on mutations that strongly rescue the paralysis of ric-8(md303) reduction-of-function mutants, previously shown to be defective in Gαq pathway activation. Through high-resolution mapping followed by sequence analysis, we show that these mutations affect four genes. Two activate the Gαq pathway through gain-of-function mutations in Gαq; however, all of the remaining mutations activate components of the Gαs pathway, including Gαs, adenylyl cyclase, and protein kinase A. Pharmacological assays suggest that the Gαs pathway-activating mutations increase steady-state neurotransmitter release, and the strongly impaired neurotransmitter release of ric-8(md303) mutants is rescued to greater than wild-type levels by the strongest Gαs pathway activating mutations. Using transgene induction studies, we show that activating the Gαs pathway in adult animals rapidly induces hyperactive locomotion and rapidly rescues the paralysis of the ric-8 mutant. Using cell-specific promoters we show that neuronal, but not muscle, Gαs pathway activation is sufficient to rescue ric-8(md303)'s paralysis. Our results appear to link RIC-8 (synembryn) and a third major Gα pathway, the Gαs pathway, with the previously discovered Gαo and Gαq pathways of the synaptic signaling network.
Characterization of AFLP Sequences From Regions of Maize B Chromosome Defined by 12 B-10L TranslocationsSequence data from this article have been deposited with the GenBank Data Libraries under accession nos. CL603055, CL603056, CL603057, CL603058, CL603059, CL603060, CL603061, CL603062, CL603063, CL603064, CL603065, CL603066, CL603067, CL603068, CL603069, CL603070.
Authors: Peng Shu-Fen , Lin Yao-Pin , Lin Bor-yaw
Published: October 2004

Maize B chromosome sequences have been previously cloned by microdissection, and all are proven to be highly repetitive, to be homologous to the normal complement, and to show no similarity to any published gene other than mobile elements. In this study, we isolated sequences from defined B regions. The strategy involved identification and then mapping of AFLP-derived B fragments before cloning. Of 14 B AFLPs, 13 were mapped by 12 B-10L translocations: 3 around the centromeric knob region, 3 in the proximal euchromatic, 1 around the border of proximal euchromatic and distal heterochromatic, and 6 in the distal heterochromatic region of the B long arm. The AFLP fragments were cloned and sequenced. Analogous to the microdissected sequences, all sequences were repetitive, and all but two were highly homologous to the A chromosomes. FISH signals of all but three clones appeared in pachytene B as well as in somatic A and B chromosomes. None of these clones exhibits identity to any published gene. Six clones displayed homology to two centromeric BACs, four to sequences of chromosomes 3, 4, 7, and 10, four to retrotransposons, and three to no sequence deposited in GenBank. Furthermore, flanking regions of two highly B-specific clones were characterized, showing extension of a B-exclusive nature. The possibility of the presence of novel B repeat(s) is discussed.
High-Resolution Mapping of the Drosophila Fourth Chromosome Using Site-Directed Terminal Deficiencies
Authors: Sousa-Neves Rui , Lukacsovich Tamas , Mizutani Claudia Mieko , Locke John , Podemski Lynn , Marsh J Lawrence
Published: October 2004

For more than 80 years, the euchromatic right arm of the Drosophila fourth chromosome (101F-102F) has been one of the least genetically accessible regions of the fly genome despite the fact that many important genes reside there. To improve the mapping of genes on the fourth chromosome, we describe a strategy to generate targeted deficiencies and we describe 13 deficiencies that subdivide the 300 kb between the cytological coordinates 102A6 and 102C1 into five discrete regions plus a 200-kb region from 102C1 to 102D6. Together these deficiencies substantially improve the mapping capabilities for mutant loci on the fourth chromosome.
Sperm Competitive Ability in Drosophila melanogaster Associated With Variation in Male Reproductive Proteins
Authors: Fiumera Anthony C , Dumont Bethany L , Clark Andrew G
Published: October 2004

Multiple mating by females establishes the opportunity for postcopulatory sexual selection favoring males whose sperm is preferentially employed in fertilizations. Here we use natural variation in a wild population of Drosophila melanogaster to investigate the genetic basis of sperm competitive ability. Approximately 101 chromosome 2 substitution lines were scored for components of sperm competitive ability (P1′, P2′, fecundity, remating rate, and refractoriness), genotyped at 70 polymorphic markers in 10 male reproductive genes, and measured for transcript abundance of those genes. Permutation tests were applied to quantify the statistical significance of associations between genotype and phenotype. Nine significant associations were identified between polymorphisms in the male reproductive genes and sperm competitive ability and 13 were identified between genotype and transcript abundance, but no significant associations were found between transcript abundance and sperm competitive ability. Pleiotropy was evident in two genes: a polymorphism in Acp33A associated with both P1′ and P2′ and a polymorphism in CG17331 associated with both elevated P2′ and reduced refractoriness. The latter case is consistent with antagonistic pleiotropy and may serve as a mechanism maintaining genetic variation.
Nonadditive Gene Expression in Diploid and Triploid Hybrids of Maize
Authors: Auger Donald L , Gray Anjali Dogra , Ream Thomas S , Kato Akio , Coe Edward H , Birchler James A
Published: October 2004

The molecular basis of hybrid vigor (heterosis) has remained unknown despite the importance of this phenomenon in evolution and in practical breeding programs. To formulate a molecular basis of heterosis, an understanding of gene expression in inbred and hybrid states is needed. In this study, we examined the amount of various transcripts in hybrid and inbred individuals (B73 and Mo17) to determine whether the quantities of specific messenger RNAs were additive or nonadditive in the hybrids. Further, we examined the levels of the same transcripts in hybrid triploid individuals that had received unequal genomic contributions, one haploid genome from one parent and two from the other. If allelic expression were merely the additive value in hybrids from the two parents, the midparent values would be observed. Our study revealed that a substantial number of genes do not exhibit the midparent value of expression in hybrids. Instead, transcript levels in the diploid hybrids correlate negatively with the levels in diploid inbreds. Although transcript levels were clearly nonadditive, transcript levels in triploid hybrids were affected by genomic dosage.
A Mutation With Major Effects on Drosophila melanogaster Sex Pheromones
Authors: Marcillac Fabrice , Bousquet François , Alabouvette Josiane , Savarit Fabrice , Ferveur Jean-François
Published: October 2004

Sex pheromones are intraspecific chemical signals that are crucial for mate attraction and discrimination. In Drosophila melanogaster, the predominant hydrocarbons on the cuticle of mature female and male flies are radically different and tend to stimulate or inhibit male courtship, respectively. This sexual difference depends largely upon the number of double bonds (one in males and two in females) added by desaturase enzymes. A mutation was caused by a PGal4 transposon inserted in the desat1 gene that codes for the desaturase crucial for setting these double bonds. Homozygous mutant flies produced 70–90% fewer sex pheromones than control flies, and the pheromonal difference between the sexes was almost abolished. A total of 134 excision alleles were induced by pulling out all or a part of the transposon. The pheromonal profile was generally rescued in excision alleles with a completely or largely removed transposon whereas it remained mutant in alleles with a larger piece of the transposon. Five desat1 transcripts were detected during larval-to-adult development. Their levels were precisely quantified in 24-hr-old adults, a critical period for the production of sex pheromones. Three transcripts significantly varied between control females and males; however, the predominant transcript showed no difference. In mutant flies, the predominant transcript was highly decreased with the two sexually dimorphic transcripts.These two transcripts were also absent in the sibling species D. simulans, which shows no sexually dimorphic hydrocarbons. We also induced a larval-lethal allele that lacked all transcripts and failed to complement the defective hydrocarbon phenotype of mutant alleles.
The Meiotic Recombination Hot Spot ura4A in Schizosaccharomyces pombe
Authors: Baur Michel , Hartsuiker Edgar , Lehmann Elisabeth , Ludin Katja , Munz Peter , Kohli Juerg
Published: October 2004

The meiotic recombination hot spot ura4A (formerly ura4-aim) of Schizosaccharomyces pombe was observed at the insertion of the ura4+ gene 15 kb centromere-proximal to ade6 on chromosome III. Crosses heterozygous for the insertion showed frequent conversion at the heterology with preferential loss of the insertion. This report concerns the characterization of 12 spontaneous ura4A mutants. A gradient of conversion ranging from 18% at the 5′ end to 6% at the 3′ end was detected. A novel phenomenon also was discovered: a mating-type-related bias of conversion. The allele entering with the h+ parent acts preferentially as the acceptor for conversion (ratio of 3:2). Tetrad analysis of two-factor crosses showed that heteroduplex DNA is predominantly asymmetrical, enters from the 5′ end, and more often than not covers the entire gene. Restoration repair of markers at the 5′ end was inferred. Random spore analyses of two-factor crosses and normalization of prototroph-recombinant frequencies to physical distance led to the demonstration of map expansion: Crosses involving distant markers yielded recombinant frequencies higher than the sum of the frequencies measured in the subintervals. Finally, marker effects on recombination were defined for two of the ura4A mutations.
Mss11p Is a Central Element of the Regulatory Network That Controls FLO11 Expression and Invasive Growth in Saccharomyces cerevisiae
Authors: van Dyk Dewald , Pretorius Isak S , Bauer Florian F
Published: October 2004

The invasive and filamentous growth forms of Saccharomyces cerevisiae are adaptations to specific environmental conditions, under particular conditions of limited nutrient availability. Both growth forms are dependent on the expression of the FLO11 gene, which encodes a cell-wall-associated glycoprotein involved in cellular adhesion. A complex regulatory network consisting of signaling pathways and transcription factors has been associated with the regulation of FLO11. Mss11p has been identified as a transcriptional activator of this gene, and here we present an extensive genetic analysis to identify functional relationships between Mss11p and other FLO11 regulators. The data show that Mss11p is absolutely required for the activation of FLO11 by most proteins that have previously been shown to affect FLO11 expression, including the signaling proteins Ras2p, Kss1p, and Tpk2p, the activators Tec1p, Flo8p, and Phd1p, and the repressors Nrg1p, Nrg2p, Sok2p, and Sfl1p. The genetic evidence furthermore suggests that Mss11p activity is not dependent on the presence of any of the above-mentioned factors and that the protein also regulates other genes involved in cellular adhesion phenotypes. Taken together, the data strongly suggest a central role for Mss11p in the regulatory network controlling FLO11 expression, invasive growth, and pseudohyphal differentiation.
Genetic Evidence for a Regulatory Pathway Controlling Alternative Oxidase Production in Neurospora crassa
Authors: Descheneau Andrea T , Cleary Ian A , Nargang Frank E
Published: October 2004

When the cytochrome-mediated mitochondrial electron transport chain of Neurospora crassa is disrupted, an alternative oxidase encoded by the nuclear aod-1 gene is induced. The alternative oxidase donates electrons directly to oxygen from the ubiquininol pool and is insensitive to chemicals such as antimycin A and KCN that affect the standard electron transport chain. To facilitate isolation of mutants affecting regulation of aod-1, a reporter system containing the region upstream of the aod-1 coding sequence fused to the coding sequence of the N. crassa tyrosinase gene (T) was transformed into a strain carrying a null allele of the endogenous T gene. In the resulting reporter strain, growth in the presence of chloramphenicol, an inhibitor of mitochondrial translation whose action decreases the level of mitochondrial translation products resulting in impaired cytochrome-mediated respiration, caused induction of both alternative oxidase and tyrosinase. Conidia from the reporter strain were mutagenized, plated on medium containing chloramphenicol, and colonies that did not express tyrosinase were identified as potential regulatory mutants. After further characterization, 15 strains were found that were unable to induce both the reporter and the alternative oxidase. Complementation analysis revealed that four novel loci involved in aod-1 regulation had been isolated. The discovery that several genes are required for regulation of aod-1 suggests the existence of a complex pathway for signaling from the mitochondria to the nucleus and/or for expression of the gene.
Mapping a Syntenic Modifier on Mouse Chromosome 1 Influencing the Expressivity of the Compact Phenotype in the Myostatin Mutant (MstnCmpt-dl1Abc) Compact Mouse
Authors: Varga László , Pinke Orsolya , Müller Géza , Kovács Balázs , Korom Edit , Szabó Gyula , Soller Morris
Published: October 2004

A novel method for mapping a modifier gene that is syntenic to its major gene was used to map a male-sex-limited modifier of the expressivity of the Compact phenotype in the myostatin mutant (MstnCmpt-dl1Abc) Compact mouse. The modifier was mapped to the general region of D1Mit262, 40 cM distal to Mstn on chromosome 1. Myogenin, a postulated downstream target of myostatin, maps to the same region.
A Screen for Schizosaccharomyces pombe Mutants Defective in Rereplication Identifies New Alleles of rad4+, cut9+ and psf2+
Authors: Gómez Eliana B , Angeles Vanessa T , Forsburg Susan L
Published: October 2004

Fission yeast mutants defective in DNA replication have widely varying morphological phenotypes. We designed a screen for temperature-sensitive mutants defective in the process of replication regardless of morphology by isolating strains unable to rereplicate their DNA in the absence of cyclin B (Cdc13). Of the 42 rereplication-defective mutants analyzed, we were able to clone complementing plasmids for 10. This screen identified new alleles of the APC subunit cut9+, the initiation/checkpoint factor rad4+/cut5+, and the first mutant allele of psf2+, a subunit of the novel GINS replication complex. Other genes identified are likely to play general roles in gene expression and protein localization.
How the Rgt1 Transcription Factor of Saccharomyces cerevisiae Is Regulated by Glucose
Authors: Polish Jeffrey A , Kim Jeong-Ho , Johnston Mark
Published: October 2004

Rgt1 is a transcription factor that regulates expression of HXT genes encoding glucose transporters in the yeast Saccharomyces cerevisiae. Rgt1 represses HXT gene expression in the absence of glucose; high levels of glucose cause Rgt1 to activate expression of HXT1. We identified four functional domains of Rgt1. A domain required for transcriptional repression (amino acids 210–250) is required for interaction of Rgt1 with the Ssn6 corepressor. Another region of Rgt1 (320–380) is required for normal transcriptional activation, and sequences flanking this region (310–320 and 400–410) regulate this function. A central region (520–830) and a short sequence adjacent to the zinc cluster DNA-binding domain (80–90) inhibit transcriptional repression when glucose is present. We found that this middle region of Rgt1 physically interacts with the N-terminal portion of the protein that includes the DNA-binding domain. This interaction is inhibited by the Rgt1 regulator Mth1, which binds to Rgt1. Our results suggest that Mth1 promotes transcriptional repression by Rgt1 by binding to it and preventing the intramolecular interaction, probably by preventing phosphorylation of Rgt1, thereby enabling Rgt1 to bind to DNA. Glucose induces HXT1 gene expression by causing Mth1 degradation, allowing Rgt1 phosphorylation, and leading to the intramolecular interaction that inhibits DNA binding of Rgt1.
Structure and Evolution of the r/b Chromosomal Regions in Rice, Maize and SorghumSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY542311, AF466202, AF466203, and AY542310.
Authors: Swigoňová Zuzana , Bennetzen Jeffrey L , Messing Joachim
Published: October 2004

The r1 and b1 genes of maize, each derived from the chromosomes of two progenitors that hybridized >4.8 million years ago (MYA), have been a rich source for studying transposition, recombination, genomic imprinting, and paramutation. To provide a phylogenetic context to the genetic studies, we sequenced orthologous regions from maize and sorghum (>600 kb) surrounding these genes and compared them with the rice genome. This comparison showed that the homeologous regions underwent complete or partial gene deletions, selective retention of orthologous genes, and insertion of nonorthologous genes. Phylogenetic analyses of the r/b genes revealed that the ancestral gene was amplified independently in different grass lineages, that rice experienced an intragenomic gene movement and parallel duplication, that the maize r1 and b1 genes are descendants of two divergent progenitors, and that the two paralogous r genes of sorghum are almost as old as the sorghum lineage. Such sequence mobility also extends to linked genes. The cisZOG genes are characterized by gene amplification in an ancestral grass, parallel duplications and deletions in different grass lineages, and movement to a nonorthologous position in maize. In addition to gene mobility, both maize and rice regions experienced recent transposition (<3 MYA).
A Genetic Linkage Map of the Mimetic ButterflyHeliconius melpomene
Authors: Jiggins Chris D , Mavarez Jesus , Beltrán Margarita , McMillan W Owen , Johnston J Spencer , Bermingham Eldredge
Published: October 2004

Heliconius melpomene is a mimetic butterfly that exhibits great geographic variation in color pattern. We present here a genetic linkage map based on analysis of genetic markers in 73 individuals from a single F2 family, offspring of a cross between H. m. cythera from western Ecuador and H. m. melpomene from French Guiana. A novel “three-step method” is described for the analysis of dominant markers in an F2 cross, using outbred parental strains and taking advantage of the lack of crossing over in female Lepidoptera. This method is likely to prove useful for future mapping studies in outbred species with crossing over restricted to one sex, such as the Lepidoptera and Drosophila. The resulting linkage map has 21 linkage groups corresponding to the 21 chromosomes of H. melpomene and includes 219 AFLP markers, 23 microsatellites, 19 single-copy nuclear genes, and the color pattern switch genes Yb and Sb. The marker density is high, averaging >1/7 cM. The total map length is 1616 cM and the average chromosome length is 77 cM. The genome size of H. melpomene was estimated to be 292 Mb, giving a relationship of physical-to-map distance of 180 kb/cM. This map forms the basis for future comparative linkage analysis of color pattern evolution in Heliconius.
On the Evolution of Codon Volatility
Authors: Zhang Jianzhi
Published: October 2004

Volatility of a codon is defined as the probability that a random point mutation in the codon generates a nonsynonymous change. It has been proposed that higher-than-expected mean codon volatility of a gene indicates that positive selection for nonsynonymous changes has acted on the gene in the recent past. I show that strong frequency-dependent selection (minority advantage) in large populations can increase codon volatility slightly, whereas directional positive selection has no effect on volatility. Factors unrelated to positive selection, such as expression-related or GC-content-related codon usage bias, also affect volatility. These and other considerations suggest that codon volatility has only limited utility for detecting positive selection at the DNA sequence level.
Mutation of l7Rn3 Shows That Odz4 Is Required for Mouse Gastrulation
Authors: Lossie Amy C , Nakamura Hisashi , Thomas Sharon E , Justice Monica J
Published: October 2004

A mouse homolog of the Drosophila pair-rule gene Odd Oz (Odz4) maps to the critical region of the l7Rn3 locus on mouse chromosome 7. Here we show that Odz4 is an excellent candidate for this allelic series because (1) it spans the entire critical region, (2) the phenotypes correlate with embryonic expression, (3) the complex genetic inheritance of the alleles is consistent with complex transcriptional regulation, and (4) one allele has a mutation in a conserved amino acid. Odz4 uses five alternate promoters that encode both secreted and membrane-bound proteins. Intragenic complementation of the l7Rn3 alleles is consistent with these multiple-protein isoforms. Further, the allelic series shows that Odz4 is required to establish the anterior-posterior axis of the gastrulating mouse embryo and is necessary later for mesoderm-derived tissues such as somites, heart, and skeleton. Sequencing of RT-PCR products from five of the six alleles reveals a nonconservative amino acid change in the l7Rn3m4 allele. This amino acid is important evolutionarily, as it is conserved to Drosophila. Together, our data indicate that Odz4 is mutated in the l7Rn3 allele series and performs roles in the mouse brain, heart, and embryonic patterning similar to those of its Drosophila counterpart.
Regulation of Leucine Uptake by tor1+ in Schizosaccharomyces pombe Is Sensitive to Rapamycin
Authors: Weisman Ronit , Roitburg Irina , Nahari Tal , Kupiec Martin
Published: October 2004

TOR protein kinases are key regulators of cell growth in eukaryotes. TOR is also known as the target protein for the immunosuppressive and potentially anticancer drug rapamycin. The fission yeast Schizosaccharomyces pombe has two TOR homologs. tor1+ is required under starvation and a variety of stresses, while tor2+ is an essential gene. Surprisingly, to date no rapamycin-sensitive TOR-dependent function has been identified in S. pombe. Herein, we show that S. pombe auxotrophs, in particular leucine auxotrophs, are sensitive to rapamycin. This sensitivity is suppressed by deletion of the S. pombe FKBP12 or by introducing a rapamycin-binding defective tor1 allele, suggesting that rapamycin inhibits a tor1p-dependent function. Sensitivity of leucine auxotrophs to rapamycin is observed when ammonia is used as the nitrogen source and can be suppressed by its replacement with proline. Consistently, using radioactive labeled leucine, we show that cells treated with rapamycin or disrupted for tor1+ are defective in leucine uptake when the nitrogen source is ammonia but not proline. Recently, it has been reported that tsc1+ and tsc2+, the S. pombe homologs for the mammalian TSC1 and TSC2, are also defective in leucine uptake. TSC1 and TSC2 may antagonize TOR signaling in mammalian cells and Drosophila. We show that reduction of leucine uptake in tor1 mutants is correlated with decreased expression of three putative amino acid permeases that are also downregulated in tsc1 or tsc2. These findings suggest a possible mechanism for regulation of leucine uptake by tor1p and indicate that tor1p, as well as tsc1p and tsc2p, positively regulates leucine uptake in S. pombe.
Long-Term Experimental Evolution in Escherichia coli. XII. DNA Topology as a Key Target of Selection
Authors: Crozat Estelle , Philippe Nadège , Lenski Richard E , Geiselmann Johannes , Schneider Dominique
Published: October 2004

The genetic bases of adaptation are being investigated in 12 populations of Escherichia coli, founded from a common ancestor and serially propagated for 20,000 generations, during which time they achieved substantial fitness gains. Each day, populations alternated between active growth and nutrient exhaustion. DNA supercoiling in bacteria is influenced by nutritional state, and DNA topology helps coordinate the overall pattern of gene expression in response to environmental changes. We therefore examined whether the genetic controls over supercoiling might have changed during the evolution experiment. Parallel changes in topology occurred in most populations, with the level of DNA supercoiling increasing, usually in the first 2000 generations. Two mutations in the topA and fis genes that control supercoiling were discovered in a population that served as the focus for further investigation. Moving the mutations, alone and in combination, into the ancestral background had an additive effect on supercoiling, and together they reproduced the net change in DNA topology observed in this population. Moreover, both mutations were beneficial in competition experiments. Clonal interference involving other beneficial DNA topology mutations was also detected. These findings define a new class of fitness-enhancing mutations and indicate that the control of DNA supercoiling can be a key target of selection in evolving bacterial populations.
Genome-Wide Screen for Genes With Effects on Distinct Iron Uptake Activities in Saccharomyces cerevisiae
Authors: Lesuisse Emmanuel , Knight Simon A B , Courel Maïté , Santos Renata , Camadro Jean-Michel , Dancis Andrew
Published: October 2004

We screened a collection of 4847 haploid knockout strains (EUROSCARF collection) of Saccharomyces cerevisiae for iron uptake from the siderophore ferrioxamine B (FOB). A large number of mutants showed altered uptake activities, and a few turned yellow when grown on agar plates with added FOB, indicating increased intracellular accumulation of undissociated siderophores. A subset consisting of 197 knockouts with altered uptake was examined further for regulated activities that mediate cellular uptake of iron from other siderophores or from iron salts. Hierarchical clustering analysis grouped the data according to iron sources and according to mutant categories. In the first analysis, siderophores grouped together with the exception of enterobactin, which grouped with iron salts, suggesting a reductive pathway of iron uptake for this siderophore. Mutant groupings included three categories: (i) high-FOB uptake, high reductase, low-ferrous transport; (ii) isolated high- or low-FOB transport; and (iii) induction of all activities. Mutants with statistically altered uptake activities included genes encoding proteins with predominant localization in the secretory pathway, nucleus, and mitochondria. Measurements of different iron-uptake activities in the yeast knockout collection make possible distinctions between genes with general effects on iron metabolism and those with pathway-specific effects.
Chromosome Identification and Nomenclature of Sorghum bicolor
Authors: Kim Jeong-Soon , Klein Patricia E , Klein Robert R , Price H James , Mullet John E , Stelly David M
Published: October 2004

Linkage group identities and homologies were determined for metaphase chromosomes of Sorghum bicolor (2n = 20) by FISH of landed BACs. Relative lengths of chromosomes in FISH-karyotyped metaphase spreads of the elite inbred BTx623 were used to estimate the molecular size of each chromosome and to establish a size-based nomenclature for sorghum chromosomes (SBI-01–SBI-10) and linkage groups (LG-01 to LG-10). Lengths of arms were determined to orient linkage groups relative to a standard karyotypic layout (short arms at top). The size-based nomenclature for BTx623 represents a reasonable choice as the standard for a unified chromosome nomenclature for use by the sorghum research community.
The Role of Information Technology in Older Adult Learning
Authors: Timmermann Sandra
Published: October 2004

Many seniors have entered the information age through the use of computers.
This discussion focuses on probabilities, limitations, and challenges of
technology for older adult education.
Intranets for Learning and Performance Support
Authors: Gilbert Linda S.
Published: October 2004

The use of Internet technologies on internal organizational networks provides
new opportunities for training and human resource development. This
review of research outlines resources, methods, and concerns.
Adult Learning and the Internet: Themes and Things to Come
Authors: Cahoon Brad
Published: October 2004

Common themes emerging from previous chapters are summarized, and
possible effects of emerging technology on adult learning are discussed.
Work and Family Issues: Their Impact on Women's Career Development
Authors: Wentling Rose Mary
Published: October 2004

The author explores the challenges of managing work and family and suggests
responses that employers can make to ease the tension.
Women's Career Development in Midlife and Beyond
Authors: Mott Vivian W.
Published: October 2004

The emergence of women working in middle and later life is considered,
with attention to how women's careers in later life present challenges and
opportunities for career development.
Mentoring and Women's Career Development
Authors: Hansman Catherine A.
Published: October 2004

This chapter explores the human resource development strategy of mentoring
and its implications for women's career development.