bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Changes in Frontoparietal Activity after Repetitive Transcranial Magnetic Stimulation over the Dorsolateral Prefrontal Cortex in a Cued Reaction Time Task
Authors: Rounis Elisabeth , Stephan Klaas E. , Lee Lucy , Siebner Hartwig R. , Pesenti A. , Friston Karl J. , Rothwell John C. , Frackowiak Richard S. J.
Published: September 2006

Lesion and functional imaging studies in humans have suggested that the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and intraparietal sulcus (IPS) are involved in orienting attention. A functional magnetic resonance imaging study supplemented by a behavioral experiment examined the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) conditioning to the right and left DLPFC on reaction times and synaptic activity as indexed by changes in the blood oxygenation level-dependent (BOLD) signal during a cued choice reaction time task. Orienting precues were either correct (valid) or incorrect (invalid) with respect to the subsequent move cue. The effects of real and sham rTMS were compared for each site of stimulation. Invalid trials showed a significant increase in response times and increases in the BOLD signal in right frontal and parietal regions when compared with valid trials. Conditioning left DLPFC with rTMS led to decreased BOLD signal during performance of this reorienting task in areas including left VLPFC and left IPS. Comparing invalid to valid trials after right DLPFC conditioning revealed decreased BOLD signal in right VLPFC. Data from the behavioral study showed that right DLPFC rTMS selectively increases response times in invalid trials. This effect was only present in the first 10 min after rTMS conditioning. No effect was found in either validly or invalidly cued trials with left DLPFC conditioning. These results suggest that 5 Hz rTMS over right DLPFC exerts remote effects on the activity of areas that functionally interact with the DLPFC during attentional processes, particularly when the reorienting of attention is more demanding as in invalid trials.
A Specific Survival Response in Dopamine Neurons at Most Risk in Parkinson's Disease
Authors: Murase Sachiko , McKay Ronald D.
Published: September 2006

The specific expression of fibroblast growth factor 20 (FGF-20) in the adult substantia nigra and the association between FGF-20 mutations and Parkinson's disease provoked exploration of the function of this growth factor. We show by gain- and loss-of-functionin vitroexperiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine hydroxylase in calbindin-negative neurons. In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1). These data show that FGF signals to elevate DA levels and protect the specific midbrain neuron type at most risk in Parkinson's patients.
A Deletion at the MouseXistGene ExposesTrans-effects That Alter the Heterochromatin of the Inactive X Chromosome and the Replication Time and DNA Stability of Both X Chromosomes
Authors: Diaz-Perez Silvia V , Ferguson David O , Wang Chen , Csankovszki Gyorgyi , Wang Chengming , Tsai Shih-Chang , Dutta Devkanya , Perez Vanessa , Kim SunMin , Eller C Daniel , Salstrom Jennifer , Ouyang Yan , Teitell Michael A , Kaltenboeck Bernhard , Chess Andrew , Huang Sui , Marahrens York
Published: September 2006

The inactive X chromosome of female mammals displays several properties of heterochromatin including late replication, histone H4 hypoacetylation, histone H3 hypomethylation at lysine-4, and methylated CpG islands. We show that cre-Lox-mediated excision of 21 kb from both Xist alleles in female mouse fibroblasts led to the appearance of two histone modifications throughout the inactive X chromosome usually associated with euchromatin: histone H4 acetylation and histone H3 lysine-4 methylation. Despite these euchromatic properties, the inactive X chromosome was replicated even later in S phase than in wild-type female cells. Homozygosity for the deletion also caused regions of the active X chromosome that are associated with very high concentrations of LINE-1 elements to be replicated very late in S phase. Extreme late replication is a property of fragile sites and the 21-kb deletions destabilized the DNA of both X chromosomes, leading to deletions and translocations. This was accompanied by the phosphorylation of p53 at serine-15, an event that occurs in response to DNA damage, and the accumulation of γ-H2AX, a histone involved in DNA repair, on the X chromosome. The Xist locus therefore maintains the DNA stability of both X chromosomes.
Test of Association Between Haplotypes and Phenotypes in Case–Control Studies: Examination of Validity of the Application of an Algorithm for Samples From Cohort or Clinical Trials to Case–Control Samples Using Simulated and Real Data
Authors: Furihata Shiori , Ito Toshikazu , Kamatani Naoyuki
Published: September 2006

The use of haplotype information in case–control studies is an area of focus for the research on the association between phenotypes and genetic polymorphisms. We examined the validity of the application of the likelihood-based algorithm, which was originally developed to analyze the data from cohort studies or clinical trials, to the data from case–control studies. This algorithm was implemented in a computer program called PENHAPLO. In this program, haplotype frequencies and penetrances are estimated using the expectation-maximization algorithm, and the haplotype–phenotype association is tested using the generalized likelihood ratio. We show that this algorithm was useful not only for cohort studies but also for case–control studies. Simulations under the null hypothesis (no association between haplotypes and phenotypes) have shown that the type I error rates were accurately estimated. The simulations under alternative hypotheses showed that PENHAPLO is a robust method for the analysis of the data from case–control studies even when the haplotypes were not in HWE, although real penetrances cannot be estimated. The power of PENHAPLO was higher than that of other methods using the likelihood-ratio test for the comparison of haplotype frequencies. Results of the analysis of real data indicated that a significant association between haplotypes in the SAA1 gene and AA-amyloidosis phenotype was observed in patients with rheumatoid arthritis, thereby suggesting the validity of the application of PENHAPLO for case–control data.
The Large Isoform of Drosophila melanogaster Heterochromatin Protein 2 Plays a Critical Role in Gene Silencing and Chromosome Structure
Authors: Shaffer Christopher D , Cenci Giovanni , Thompson Brandi , Stephens Gena E , Slawson Elizabeth E , Adu-Wusu Kwame , Gatti Maurizio , Elgin Sarah C R
Published: September 2006

Drosophila melanogaster heterochromatin protein 2 (HP2) interacts with heterochromatin protein 1 (HP1). In polytene chromosomes, HP2 and HP1 colocalize at the chromocenter, telomeres, and the small fourth chromosome. We show here that HP2 is present in the arms as well as the centromeric regions of mitotic chromosomes. We also demonstrate that Su(var)2-HP2 exhibits a dosage-dependent modification of variegation of a yellow reporter transgene, indicating a structural role in heterochromatin formation. We have isolated and characterized 14 new mutations in the Su(var)2-HP2 gene. Using wm4h, many (but not all) mutant alleles show dominant Su(var) activity. Su(var)2-HP2 mutant larvae show a wide variety of mitotic abnormalities, but not the telomere fusion seen in larvae deficient for HP1. The Su(var)2-HP2 gene codes for two isoforms: HP2-L (∼365 kDa) and HP2-S (∼175 kDa), lacking exons 5 and 6. In general, mutations that affect only the larger isoform result in more pronounced defects than do mutations common to both isoforms. This suggests that an imbalance between large and small isoforms is particularly deleterious. These results indicate a role for HP2 in the structural organization of chromosomes and in heterochromatin-induced gene silencing and show that the larger isoform plays a critical role in these processes.
Identification of a Novel Gene Family Involved in Osmotic Stress Response inCaenorhabditis elegans
Authors: Wheeler Jeanna M , Thomas James H
Published: September 2006

Organisms exposed to the damaging effects of high osmolarity accumulate solutes to increase cytoplasmic osmolarity. Yeast accumulates glycerol in response to osmotic stress, activated primarily by MAP kinase Hog1 signaling. A pathway regulated by protein kinase C (PKC1) also responds to changes in osmolarity and cell wall integrity. C. elegans accumulates glycerol when exposed to high osmolarity, but the molecular pathways responsible for this are not well understood. We report the identification of two genes, osm-7 and osm-11, which are related members of a novel gene family. Mutations in either gene lead to high internal levels of glycerol and cause an osmotic resistance phenotype (Osr). These mutants also have an altered defecation rhythm (Dec). Mutations in cuticle collagen genes dpy-2, dpy-7, and dpy-10 cause a similar Osr Dec phenotype. osm-7 is expressed in the hypodermis and may be secreted. We hypothesize that osm-7 and osm-11 interact with the cuticle, and disruption of the cuticle causes activation of signaling pathways that increase glycerol production. The phenotypes of osm-7 are not suppressed by mutations in MAP kinase or PKC pathways, suggesting that C. elegans uses signaling pathways different from yeast to mount a response to osmotic stress.
The Meiotic Bouquet Promotes Homolog Interactions and Restricts Ectopic Recombination inSchizosaccharomyces pombe
Authors: Davis Luther , Smith Gerald R
Published: September 2006

Chromosome architecture undergoes extensive, programmed changes as cells enter meiosis. A highly conserved change is the clustering of telomeres at the nuclear periphery to form the “bouquet” configuration. In the fission yeast Schizosaccharomyces pombe the bouquet and associated nuclear movement facilitate initial interactions between homologs. We show that Bqt2, a meiosis-specific protein required for bouquet formation, is required for wild-type levels of homolog pairing and meiotic allelic recombination. Both gene conversion and crossing over are reduced and exhibit negative interference in bqt2Δ mutants, reflecting reduced homolog pairing. While both the bouquet and nuclear movement promote pairing, only the bouquet restricts ectopic recombination (that between dispersed repetitive DNA). We discuss mechanisms by which the bouquet may prevent deleterious translocations by restricting ectopic recombination.
Nonneutral Evolution of Organelle Genes in Silene vulgaris
Authors: Houliston Gary J , Olson Matthew S
Published: September 2006

Knowledge of mitochondrial gene evolution in angiosperms has taken a dramatic shift within the past decade, from universal slow rates of nucleotide change to a growing realization of high variation in rates among lineages. Additionally, evidence of paternal inheritance of plant mitochondria and recombination among mitochondrial genomes within heteroplasmic individuals has led to speculation about the potential for independent evolution of organellar genes. We report intraspecific mitochondrial and chloroplast sequence variation in a cosmopolitan sample of 42 Silene vulgaris individuals. There was remarkably high variation in two mitochondrial genes (atp1, atp9) and additional variation within a third gene (cob). Tests for patterns of nonneutral evolution were significant for atp1 and atp9, indicative of the maintenance of balanced polymorphisms. Two chloroplast genes (matK, ndhF) possessed less, but still high, variation and no divergence from neutral expectations. Phylogenetic patterns of organelle genes in both the chloroplast and mitochondria were incongruent, indicating the potential for independent evolutionary trajectories. Evidence indicated reassociation among cytoplasmic genomes and recombination between mitochondrial genes and within atp1, implying transient heteroplasmy in ancestral lineages. Although the mechanisms for long-term maintenance of mitochondrial polymorphism are currently unknown, frequency-dependent selection on linked cytoplasmic male sterility genes is a potential candidate.
A Thurstonian Model for Quantitative Genetic Analysis of Ranks: A Bayesian Approach
Authors: Gianola Daniel , Simianer Henner
Published: September 2006

A fully Bayesian method for quantitative genetic analysis of data consisting of ranks of, e.g., genotypes, scored at a series of events or experiments is presented. The model postulates a latent structure, with an underlying variable realized for each genotype or individual involved in the event. The rank observed is assumed to reflect the order of the values of the unobserved variables, i.e., the classical Thurstonian model of psychometrics. Parameters driving the Bayesian hierarchical model include effects of covariates, additive genetic effects, permanent environmental deviations, and components of variance. A Markov chain Monte Carlo implementation based on the Gibbs sampler is described, and procedures for inferring the probability of yet to be observed future rankings are outlined. Part of the model is rendered nonparametric by introducing a Dirichlet process prior for the distribution of permanent environmental effects. This can lead to potential identification of clusters of such effects, which, in some competitions such as horse races, may reflect forms of undeclared preferential treatment.
Estimating Recombination Rates From Single-Nucleotide Polymorphisms Using Summary Statistics
Authors: Padhukasahasram Badri , Wall Jeffrey D , Marjoram Paul , Nordborg Magnus
Published: September 2006

We describe a novel method for jointly estimating crossing-over and gene-conversion rates from population genetic data using summary statistics. The performance of our method was tested on simulated data sets and compared with the composite-likelihood method of R. R. Hudson. For several realistic parameter values, the new method performed similarly to the composite-likelihood approach for estimating crossing-over rates and better when estimating gene-conversion rates. We used our method to analyze a human data set recently genotyped by Perlegen Sciences.
A Gain-of-Function Screen Identifying Genes Required for Vein Formation in the Drosophila melanogaster Wing
Authors: Molnar Cristina , López-Varea Ana , Hernández Rosario , de Celis Jose F
Published: September 2006

The formation of the Drosophila wing involves developmental processes such as cell proliferation, pattern formation, and cell differentiation that are common to all multicellular organisms. The genes controlling these cellular behaviors are conserved throughout the animal kingdom, and the genetic analysis of wing development has been instrumental in their identification and functional characterization. The wing is a postembryonic structure, and most loss-of-function mutations are lethal in homozygous flies before metamorphosis. In this manner, loss-of-function genetic screens aiming to identify genes affecting wing formation have not been systematically utilized. As an alternative, a number of genetic searches have utilized the phenotypic consequences of gene gain-of-expression, as a method more efficient to search for genes required during imaginal development. Here we present the results of a gain-of-function screen designed to identify genes involved in the formation of the wing veins. We generated 13,000 P-GS insertions of a P element containing UAS sequences (P-GS) and combined them with a Gal4 driver expressed mainly in the developing pupal veins. We selected 500 P-GSs that, in combination with the Gal4 driver, result in modifications of the veins, changes in the morphology of the wing, or defects in the differentiation of the trichomes. The P-element insertion sites were mapped to the genomic sequence, identifying 373 gene candidates to participate in wing morphogenesis and vein formation.
Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans
Authors: Mendenhall Alexander R , LaRue Bobby , Padilla Pamela A
Published: September 2006

Oxygen deprivation has a role in the pathology of many human diseases. Thus it is of interest in understanding the genetic and cellular responses to hypoxia or anoxia in oxygen-deprivation-tolerant organisms such as Caenorhabditis elegans. In C. elegans the DAF-2/DAF-16 pathway, an IGF-1/insulin-like signaling pathway, is involved with dauer formation, longevity, and stress resistance. In this report we compared the response of wild-type and daf-2(e1370) animals to anoxia. Unlike wild-type animals, the daf-2(e1370) animals have an enhanced anoxia-survival phenotype in that they survive long-term anoxia and high-temperature anoxia, do not accumulate significant tissue damage in either of these conditions, and are motile after 24 hr of anoxia. RNA interference was used to screen DAF-16-regulated genes that suppress the daf-2(e1370)-enhanced anoxia-survival phenotype. We identified gpd-2 and gpd-3, two nearly identical genes in an operon that encode the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. We found that not only is the daf-2(e1370)-enhanced anoxia phenotype dependent upon gpd-2 and gpd-3, but also the motility of animals exposed to brief periods of anoxia is prematurely arrested in gpd-2/3(RNAi) and daf-2(e1370);gpd-2/3(RNAi) animals. These data suggest that gpd-2 and gpd-3 may serve a protective role in tissue exposed to oxygen deprivation.
Large-Scale Gene Expression Differences Across Brain Regions and Inbred Strains Correlate With a Behavioral Phenotype
Authors: Nadler Jessica J , Zou Fei , Huang Hanwen , Moy Sheryl S , Lauder Jean , Crawley Jacqueline N , Threadgill David W , Wright Fred A , Magnuson Terry R
Published: September 2006

Behaviors are often highly heritable, polygenic traits. To investigate molecular mediators of behavior, we analyzed gene expression patterns across seven brain regions (amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus, cingulate cortex, and olfactory bulb) of 10 different inbred mouse strains (129S1/SvImJ, A/J, AKR/J, BALB/cByJ, BTBR T+ tf/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and FVB/NJ). Extensive variation was observed across both strain and brain region. These data provide potential transcriptional intermediates linking polygenic variation to differences in behavior. For example, mice from different strains had variable performance on the rotarod task, which correlated with the expression of >2000 transcripts in the cerebellum. Correlation with this task was also found in the amygdala and hippocampus, but not in other regions examined, indicating the potential complexity of motor coordination. Thus we can begin to identify expression profiles contributing to behavioral phenotypes through variation in gene expression.
The WTM Genes in Budding Yeast Amplify Expression of the Stress-Inducible Gene RNR3
Authors: Tringe Susannah Green , Willis Jason , Liberatore Katie L , Ruby Stephanie W
Published: September 2006

Cellular responses to DNA damage and inhibited replication are evolutionarily conserved sets of pathways that are critical to preserving genome stability. To identify new participants in these responses, we undertook a screen for regulators that, when present on a high-copy vector, alter expression of a DNA damage-inducible RNR3-lacZ reporter construct in Saccharomyces cerevisiae. From this screen we isolated a plasmid encoding two closely related paralogs, WTM1 and WTM2, that greatly increases constitutive expression of RNR3-lacZ. Moderate overexpression of both genes together, or high-level expression of WTM2 alone from a constitutive promoter, upregulates RNR3-lacZ in the absence of DNA damage. Overexpressed, tagged Wtm2p is associated with the RNR3 promoter, indicating that this effect is likely direct. Further investigation reveals that Wtm2p and Wtm1p, previously described as regulators of meiotic gene expression and transcriptional silencing, amplify transcriptional induction of RNR3 in response to replication stress and modulate expression of genes encoding other RNR subunits.
Molecular-Genetic Biodiversity in a Natural Population of the YeastSaccharomyces cerevisiaeFrom “Evolution Canyon”: Microsatellite Polymorphism, Ploidy and Controversial Sexual Status
Authors: Ezov T Katz , Boger-Nadjar E , Frenkel Z , Katsperovski I , Kemeny S , Nevo E , Korol A , Kashi Y
Published: September 2006

The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, “Evolution Canyon” at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.
TheAspergillus nidulans rcoAGene Is Required forveA-Dependent Sexual Development
Authors: Todd Richard B , Hynes Michael J , Andrianopoulos Alex
Published: September 2006

The Aspergillus nidulans rcoAΔ mutant exhibits growth and developmental defects. We show that the rcoAΔ mutant lacks cleistothecia and is self-sterile. In crosses with wild-type strains, rcoAΔ nuclei do not contribute to the cleistothecial walls. Furthermore, sexual development resulting from veA overexpression is rcoA dependent, indicating that rcoA lies downstream of veA in the sexual development pathway.
SWAN-1, a Caenorhabditis elegans WD Repeat Protein of the AN11 Family, Is a Negative Regulator of Rac GTPase Function
Authors: Yang Yieyie , Lu Jiamiao , Rovnak Joel , Quackenbush Sandra L , Lundquist Erik A
Published: September 2006

Rac GTPases are key regulators of cell shape and cytoskeletal organization. While some regulators of Rac activity are known, such as GTPase-activating proteins (GAPs) that repress Rac activity, other Rac regulators remain to be identified. The novel Caenorhabditis elegans WD-repeat protein SWAN-1 was identified in a yeast two-hybrid screen with the LIM domains of the Rac effector UNC-115/abLIM. SWAN-1 was found to also associate physically with Rac GTPases. The swan-1(ok267) loss-of-function mutation suppressed defects caused by the hypomorphic ced-10(n1993) allele and enhanced ectopic lamellipodia and filopodia formation induced by constitutively active Rac in C. elegans neurons. Furthermore, SWAN-1(+) transgenic expression suppressed the effects of overactive Rac, including ectopic lamellipodia and filopodia formation in C. elegans neurons, ectopic lamellipodia formation in cultured mammalian fibroblasts, and cell polarity and actin cytoskeleton defects in yeast. These studies indicate that SWAN-1 is an inhibitor of Rac GTPase function in cellular morphogenesis and cytoskeletal organization. While broadly conserved across species, SWAN-1 family members show no sequence similarity to previously known Rac inhibitors.
Drosophila Model of Human Inherited Triosephosphate Isomerase Deficiency Glycolytic Enzymopathy
Authors: Celotto Alicia M , Frank Adam C , Seigle Jacquelyn L , Palladino Michael J
Published: September 2006

Heritable mutations, known as inborn errors of metabolism, cause numerous devastating human diseases, typically as a result of a deficiency in essential metabolic products or the accumulation of toxic intermediates. We have isolated a missense mutation in the Drosophila sugarkill (sgk) gene that causes phenotypes analogous to symptoms of triosephosphate isomerase (TPI) deficiency, a human familial disease, characterized by anaerobic metabolic dysfunction resulting from pathological missense mutations affecting the encoded TPI protein. In Drosophila, the sgk gene encodes the glycolytic enzyme TPI. Our analysis of sgk mutants revealed TPI impairment associated with reduced longevity, progressive locomotor deficiency, and neural degeneration. Biochemical studies demonstrate that mutation of this glycolytic enzyme gene does not result in a bioenergetic deficit, suggesting an alternate cause of enzymopathy associated with TPI impairment.
Differential Requirement of DNA Replication Factors for Subtelomeric ARS Consensus Sequence Protosilencers in Saccharomyces cerevisiae
Authors: Rehman Muhammad Attiq , Fourel Genevieve , Mathews Amit , Ramdin Danielle , Espinosa Maria , Gilson Eric , Yankulov Krassimir
Published: September 2006

The establishment of silent chromatin requires passage through S-phase, but not DNA replication per se. Nevertheless, many proteins that affect silencing are bona fide DNA replication factors. It is not clear if mutations in these replication factors affect silencing directly or indirectly via deregulation of S-phase or DNA replication. Consequently, the relationship between DNA replication and silencing remains an issue of debate. Here we analyze the effect of mutations in DNA replication factors (mcm5-461, mcm5-1, orc2-1, orc5-1, cdc45-1, cdc6-1, and cdc7-1) on the silencing of a group of reporter constructs, which contain different combinations of “natural” subtelomeric elements. We show that the mcm5-461, mcm5-1, and orc2-1 mutations affect silencing through subtelomeric ARS  consensus sequences (ACS), while cdc6-1 affects silencing independently of ACS. orc5-1, cdc45-1, and cdc7-1 affect silencing through ACS, but also show ACS-independent effects. We also demonstrate that isolated nontelomeric ACS do not recapitulate the same effects when inserted in the telomere. We propose a model that defines the modes of action of MCM5 and CDC6 in silencing.
The Caenorhabditis elegans rhy-1 Gene Inhibits HIF-1 Hypoxia-Inducible Factor Activity in a Negative Feedback Loop That Does Not Include vhl-1
Authors: Shen Chuan , Shao Zhiyong , Powell-Coffman Jo Anne
Published: September 2006

Hypoxia-inducible factor (HIF) transcription factors implement essential changes in gene expression that enable animals to adapt to low oxygen (hypoxia). The stability of the C. elegans HIF-1 protein is controlled by the evolutionarily conserved EGL-9/VHL-1 pathway for oxygen-dependent degradation. Here, we describe vhl-1-independent pathways that attenuate HIF-1 transcriptional activity in C. elegans. First, the expression of HIF-1 target genes is markedly higher in egl-9 mutants than in vhl-1 mutants. We show that HIF-1 protein levels are similar in animals carrying strong loss-of-function mutations in either egl-9 or vhl-1. We conclude that EGL-9 inhibits HIF-1 activity, as well as HIF-1 stability. Second, we identify the rhy-1 gene and show that it acts in a novel negative feedback loop to inhibit expression of HIF-1 target genes. rhy-1 encodes a multi-pass transmembrane protein. Although loss-of-function mutations in rhy-1 cause relatively modest increases in hif-1 mRNA and HIF-1 protein expression, some HIF-1 target genes are expressed at higher levels in rhy-1 mutants than in vhl-1 mutants. Animals lacking both vhl-1 and rhy-1 function have a more severe phenotype than either single mutant. Collectively, these data support models in which RHY-1 and EGL-9 function in VHL-1-independent pathway(s) to repress HIF-1 transcriptional activity.
Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe
Authors: Wells Jennifer L , Pryce David W , Estreicher Anna , Loidl Josef , McFarlane Ramsay J
Published: September 2006

Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms. Previous studies have led to the suggestion that axial structures are essential to mediate meiotic recombination. Rec10 protein is a major component of S. pombe LinEs and is required for their development. In this report we study recombination in a number of rec10 mutants, one of which (rec10-155) does not form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has levels of crossing over and gene conversion substantially higher than a rec10 null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative of meiotic recombination intermediates. These data demonstrate that while Rec10 is required for meiotic recombination, substantial meiotic recombination can occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are not essential for all meiotic recombination.
sli-3 Negatively Regulates the LET-23/Epidermal Growth Factor Receptor-Mediated Vulval Induction Pathway in Caenorhabditis elegans
Authors: Gupta Bhagwati P , Liu Jing , Hwang Byung J , Moghal Nadeem , Sternberg Paul W
Published: September 2006

The LIN-3–LET-23-mediated inductive signaling pathway plays a major role during vulval development in C. elegans. Studies on the components of this pathway have revealed positive as well as negative regulators that function to modulate the strength and specificity of the signal transduction cascade. We have carried out genetic screens to identify new regulators of this pathway by screening for suppressors of lin-3 vulvaless phenotype. The screens recovered three loci including alleles of gap-1 and a new gene represented by sli-3. Our genetic epistasis experiments suggest that sli-3 functions either downstream or in parallel to nuclear factors lin-1 and sur-2. sli-3 synergistically interacts with the previously identified negative regulators of the let-23 signaling pathway and causes excessive cell proliferation. However, in the absence of any other mutation sli-3 mutant animals display wild-type vulval induction and morphology. We propose that sli-3 functions as a negative regulator of vulval induction and defines a branch of the inductive signaling pathway. We provide evidence that sli-3 interacts with the EGF signaling pathway components during vulval induction but not during viability and ovulation processes. Thus, sli-3 helps define specificity of the EGF signaling to induce the vulva.
Molecular Assembly of Meiotic Proteins Asy1 and Zyp1 and Pairing Promiscuity in Rye (Secale cereale L.) and Its Synaptic Mutant sy10
Authors: Mikhailova E I , Phillips D , Sosnikhina S P , Lovtsyus A V , Jones R N , Jenkins G
Published: September 2006

Assembly of two orthologous proteins associated with meiotic chromosome axes in Arabidopsis thaliana (Asy1 and Zyp1) was studied immunologically at meiotic prophase of meiosis of wild-type rye (Secale cereale) and its synaptic mutant sy10, using antibodies derived from A. thaliana. The temporal and spatial expression of the two proteins were similar in wild-type rye, but with one notable difference. Unlike A. thaliana, in which foci of the transverse filament protein Zyp1 appear to linearize commensurately with synapsis, linear tracts of Asy1 and Zyp1 protein form independently at leptotene and early zygotene of rye and coalign into triple structures resembling synaptonemal complexes (SCs) only at later stages of synapsis. The sy10 mutant used in this study also forms spatially separate linear tracts of Asy1 and Zyp1 proteins at leptotene and early zygotene, and these coalign but do not form regular triple structures at midprophase. Electron microscopy of spread axial elements reveals extensive asynapsis with some exchanges of pairing partners. Indiscriminate SCs support nonhomologous chiasma formation at metaphase I, as revealed by multi-color fluorescence in situ hybridization enabling reliable identification of all the chromosomes of the complement. Scrutiny of chiasmate associations of chromosomes at this stage revealed some specificity in the associations of homologous and nonhomologous chromosomes. Inferences about the nature of synapsis in this mutant were drawn from such observations.
Genetic Evidence for Phospholipid-Mediated Regulation of the Rab GDP-Dissociation Inhibitor in Fission Yeast
Authors: Ma Yan , Kuno Takayoshi , Kita Ayako , Nabata Toshiya , Uno Satoshi , Sugiura Reiko
Published: September 2006

We have previously identified mutant alleles of genes encoding two Rab proteins, Ypt3 and Ryh1, through a genetic screen using the immunosuppressant drug FK506 in fission yeast. In the same screen, we isolated gdi1-i11, a mutant allele of the essential gdi1+ gene encoding Rab GDP-dissociation inhibitor. In gdi1-i11, a conserved Gly267 was substituted by Asp. The Gdi1G267D protein failed to extract Rabs from membrane and Rabs were depleted from the cytosolic fraction in the gdi1-i11 mutant cells. Consistently, the Gdi1G267D protein was found mostly in the membrane fraction, whereas wild-type Gdi1 was found in both the cytosolic and the membrane fraction. Notably, overexpression of spo20+, encoding a phosphatidylcholine/phosphatidylinositol transfer protein, rescued gdi1-i11 mutation, but not ypt3-i5 or ryh1-i6. The gdi1-i11 and spo20-KC104 mutations are synthetically lethal, and the wild-type Gdi1 failed to extract Rabs from the membrane in the spo20-KC104 mutant. The phosphatidylinositol-transfer activity of Spo20 is dispensable for the suppression of the gdi1-i11 mutation, suggesting that the phosphatidylcholine-transfer activity is important for the suppression. Furthermore, knockout of the pct1+ gene encoding a choline phosphate cytidyltransferase rescued the gdi1-i11 mutation. Together, our findings suggest that Spo20 modulates Gdi1 function via regulation of phospholipid metabolism of the membranes.
Response of Five Summer-Squash (Cucurbita pepo) Cultivars to Halosulfuron
Authors: Starke Keith D. , Monks David W. , Mitchem Wayne E. , Macrae Andrew W.
Published: September 2006

Response of ‘Dixie’, ‘Lemondrop’, ‘Multipik’, ‘Superpik’, and ‘Seneca Prolific’ summer squash to halosulfuron PRE or POST at 0.036, 0.053, and 0.072 kg ai/ha, or halosulfuron PRE fb halosulfuron POST at 0.018 fb 0.018, 0.027 fb 0.027, and 0.036 fb 0.036 kg/ha was field evaluated in 1997 and 1998. All halosulfuron treatments and rates reduced the height of cultivars 17–19% at 6 WAP (weeks after planting) and summer-squash injury (chlorosis and necrosis of crop foliage) was 6, 14, and 11% from halosulfuron PRE, POST, and PRE fb POST, respectively. Early summer-squash flowering was reduced 32–82% by halosulfuron, resulting in reduced early yields. Dixie was the cultivar most tolerant to halosulfuron. Early flowering of Dixie was reduced 32–36% compared to 32–82% for the other cultivars. Marketable yield of summer squash was reduced 20–30% by all rates of halosulfuron when averaged over all application timings. Marketable yield of Seneca Prolific, Superpik, Dixie, Multipik, and Lemondrop was reduced 0–17% by halosulfuron PRE. Halosulfuron POST or PRE fb POST reduced marketable yield of all summer-squash cultivars by 25–46%. Thus, summer squash was not tolerant of POST halosulfuron; however, Dixie, Multipik, Seneca Prolific, and Superpik exhibited tolerance to halosulfuron PRE.
Weed Control in Glyphosate-Resistant Corn as Affected by Preemergence Herbicide and Timing of Postemergence Herbicide Application
Authors: Parker Robert G. , York Alan C. , Jordan David L.
Published: September 2006

Field studies were conducted at three locations during both 2002 and 2003 to evaluate weed control and response of glyphosate-resistant (GR) corn to glyphosate or nicosulfuron plus atrazine applied POST at three application timings with and without alachlor plus atrazine applied PRE. The POST herbicides were applied timely (5- to 9-cm weeds) or applications were delayed 1 or 2 wk. All treatments, except the weedy check, were followed by glyphosate postemergence-directed (PDIR) 4 wk after the timely POST application. Common lambsquarters, common ragweed, Palmer amaranth, prickly sida, and smooth pigweed were controlled at least 94% regardless of PRE or POST treatments. Large crabgrass and fall panicum were controlled at least 96% by glyphosate regardless of PRE herbicide or POST application timing. In contrast, control by nicosulfuron plus atrazine POST in the absence of PRE herbicide decreased as application was delayed. Sicklepod was controlled at least 94% when POST herbicides were applied timely, but control by both POST herbicide treatments decreased with delayed application regardless of PRE herbicide. Tall morningglory was controlled 93% or greater by POST herbicides applied timely. Control by both POST herbicide treatments decreased as application was delayed, with glyphosate being affected more by timing than nicosulfuron plus atrazine. Corn grain yield was similar with glyphosate and nicosulfuron plus atrazine. Yield was unaffected by POST application timing when PRE herbicides were included. Without PRE herbicide, grain yield decreased as POST herbicide application was delayed.
Burning Nettle, Common Purslane, and Rye Response to a Clove Oil Herbicide
Authors: Boyd Nathan S. , Brennan Eric B.
Published: September 2006

Weed management is often difficult and expensive in organic production systems. Clove oil is an essential oil that functions as a contact herbicide and may provide an additional weed management tool for use on organic farms. Burning nettle, purslane, and rye responses to 5, 10, 20, 40, and 80% v/v clove oil mixture applied in spray volumes of 281 and 468 L/ha were examined. Log-logistic curves were fitted to the nettle and purslane data to determine the herbicide dose required to reduce plant dry weight 50% (GR50) and 90% (GR90). A three-parameter Gaussian curve was fitted to the rye data. The GR50 and GR90 were largely unaffected by spray volume. Nettle dry weight was reduced by 90% with 12 to 61 L clove oil/ha, whereas 21 to 38 L clove oil/ha were required to reduce purslane biomass to the same level. Rye was not effectively controlled by clove oil. Clove oil controls broadleaf weeds at high concentrations, but its cost makes broadcast applications prohibitive, even in high-value vegetable production systems.
Catalytic Wet Oxidation of 2,4‐Dichlorophenol Solutions: Activity of the Manganese–Cerium Composite Catalyst and Biodegradability of the Effluent Stream
Authors: Lee Bing‐Nan , Lou Jie‐Chung , Yen Po‐Chung
Published: September 2006

Aqueous solutions containing 100 to 1000 mg/L of 2,4‐dichlorophenol (2,4‐DCP) were oxidized in an upflowing fixed‐bed reactor in this study of manganese–cerium composite catalysts, which were prepared by the coprecipitation of both manganese nitrate and ceric nitrate at various molar concentrations. Results showed that 2,4‐DCP conversion by wet oxidation in the presence of the manganese–cerium composite catalysts was a function of the molar ratio of the manganese–cerium catalyst. The kinetic behavior of 2,4‐DCP oxidation with catalysis could be explained by using a zero‐order rate expression. Total organic carbon (TOC) removal by wet oxidation in the absence of any catalyst was nil, while approximately 68% TOC reduction was achieved during wet oxidation over a manganese–cerium (7:3 mol/mol) catalyst at 160 °C and an oxygen partial pressure of 1.0 MPa. Moreover, the 5‐day biochemical oxygen demand/chemical oxygen demand ratios of all the effluent streams were determined to be greater than 0.45 as the wet catalytic processes were carried out at a liquid hourly space velocity less than 24 h−1, indicating that they could be made more amenable to further biological treatment.
The Role of Poly‐hydroxy‐alkanoate Form in Determining the Response of Enhanced Biological Phosphorus Removal Biomass to Volatile Fatty Acids
Authors: Liu Yan‐Hua , Geiger Cherie , Randall Andrew Amis
Published: September 2006

Anaerobic–aerobic batch experiments indicated that poly‐hydroxy‐alkanoate (PHA) form was important in determining the net phosphorus removal resulting from different volatile fatty acids (VFAs). Poly‐3‐hydroxy‐butyrate (3HB) content was found to correlate fairly well with higher observed aerobic phosphorus uptake per unit PHA carbon degraded. Poly‐3‐hydroxy‐valerate (3HV) correlated with lower aerobic phosphorus uptakes per unit PHA carbon degraded. These experiments, conducted with synthetic wastewater, imply that VFA speciation might have a significant effect on aerobic phosphorus uptakes and net phosphorus removal. In addition, the model parameter ƒP,UPT (Barker and Dold, 1997) could vary with the proportion of acetic to propionic acid received (i.e., the acetic/propionic acid ratio may be an important parameter for these systems). Carbohydrate data implied that the lower aerobic phosphorus uptake resulting from 3HV might have been caused by a greater fraction of PHA carbon shunting to carbohydrate biosynthesis during aerobiosis.
Attenuation of Methyl tert‐Butyl Ether in Water Using Sunlight and a Photocatalyst
Authors: Sahle‐Demessie E. , Enriquez J. , Gupta G.
Published: September 2006

The use of methyl tert‐butyl ether (MTBE) as a gasoline additive has resulted in increasing pollution of groundwater. Most of the conventional treatment technologies are inefficient or costly when the initial concentration of MTBE is low (< 200 μg/L). To find an ecology friendly and inexpensive method for MTBE remediation, we used solar radiation with titanium dioxide (TiO2) as a photocatalyst. For synthetic samples, almost complete degradation (99+%) of MTBE was observed at the end of 5‐hour test run with 0.05 g/L of slurry TiO2. Intermediate products detected were tertiary butyl formate, tertiary butyl alcohol, and trace amounts of acetone. Studies conducted using contaminated groundwater samples with TiO2 and sunlight showed that aromatic organic species benzene, toluene, ethylbenzene, and xylenes (BTEX) were degraded up to a factor of 10 times faster than MTBE. However, dissolved metals (Fe2+) and chloride ions in contaminated waters decreased the photo‐activity of TiO2 for the degradation of MTBE. Reducing the pH of the groundwater samples increased the MTBE degradation rate threefold. Photocatalysis accelerates the solar degradation of MTBE and reduces its half‐life by more than 3 orders of magnitude. The study indicated that solar degradation is a low‐cost and effective alternative to attenuate MTBE in drinking water supplies.
Occurrence and Distribution of Ammonium in Iowa Groundwater
Authors: Schilling Keith E.
Published: September 2006

Excess ammonium in groundwater may lead to nitrification or loss of chlorine residuals in public drinking water supplies. In Iowa, where groundwater supplies nearly 75% of all drinking water used in the state, naturally occurring ammonium is found in all major aquifers, including two unconsolidated units and five bedrock aquifers. An evaluation of ammonium concentrations in 841 municipal water supply wells indicated highest concentrations were found most often in Quaternary wells. More than one‐half of all Quaternary wells sampled in Iowa showed ammonium concentrations greater than 2 mg/L, and more than 5% had concentrations greater than 5 mg/L. Nearly 5% of all bedrock wells used in this study showed ammonium concentrations greater than 2 mg/L. Aquifers overlain by carbon‐rich Pennsylvanian strata or glacial drift seemed most vulnerable to elevated ammonium. Alluvial aquifers were least vulnerable to elevated ammonium concentrations in Iowa municipal water supplies. Ammonium concentrations tended to be higher in wells that screened groundwater containing more dissolved solids, including sulfate, chloride and iron.
The Effectiveness of Bioaugmentation in Nitrifying Systems Stressed by a Washout Condition and Cold Temperature
Authors: Abeysinghe Dilrika H. , De Silva D.G. Viraj , Stahl David A. , Rittmann Bruce E.
Published: September 2006

Bioaugmentation consists of adding selected strains of microorganisms with known capabilities to a biological process to improve performance. In this study, laboratory‐scale completely stirred tank reactors were bioaugmented with nitrifying bacteria while operated under high‐stress conditions for the nitrifiers: a 2‐day solids retention time (SRT) at 22 °C or a 5‐day SRT at 4 °C. Intensive sampling was carried out to document the effects of the bioaugmentation. To quantitatively interpret the effects of biomass addition on process performance, mathematical modeling was carried out. Experimental and modeling results indicate that the maximum effect of a one‐time bioaugmentation depend on the dose and decays as bioaugmented nitrifiers are washed out. Daily maintenance dosing results in long‐term good performance, provided that the dose is large enough. For severe stress, almost all of the biomass in the system must be added by bioaugmentation.
Empirical Equations for the Limiting Solids Flux of Final Clarifiers
Authors: Ah Yuen Weng
Published: September 2006

Using the solids flux theory, two quantities (i.e., the dimensionless limiting solids flux [G = kGL/υo] and the dimensionless underflow velocity [U = FR/(Aυo)] are introduced for a final clarifier based on the Vesilind equation of sludge zone‐settling velocity (υ = υoexp[−kX], where X is the suspended solids concentration, υo and k are empirical coefficients, and GL, FR, and A are the limiting solids flux, recycle flowrate, and surface area of the settling tank, respectively). In this paper, the dimensionless limiting solids flux is shown to be a function of the dimensionless underflow velocity only and is accurately represented by empirical equations. The limiting solids flux can, thus, be easily calculated by using the empirical equations without resorting to tedious numerical procedures. Furthermore, using the dimensionless quantities (G and U), two final clarifier equations that express the relationship among suspended solids concentration, surface area of the clarifier, recycle flowrate, and wastewater flowrate are derived. Their applications to final clarifier analysis and to determining required surface area of final clarifier are illustrated.
Evaluation of Three Models for Predicting Newly Determined Octanol–Water Partition Coefficients and Mechanisms for Substituted Aromatic Compounds
Authors: Wu Chunde , Wei Dongbin , Liu Xinhui , Lin Zhifen , Wang Liansheng
Published: September 2006

Octanol‐water partition coefficients (Kow) of 27 substituted aromatic compounds, including polyhalogenated aromatics, were determined. A molecular connectivity index (MCI), a theoretical linear solvation energy relationship, and a quantum chemical method were applied to model the property and study the partition mechanism. The multiple correction coefficients (r2adj) (≥0.870) and the standard errors (≤0.33) for log Kow indicated that the models were successful. Comparing the three models, the MCI method (including the nondisperse force factor) was the most satisfactory. However, the quantum chemical model based on the potential of the negative atomic charge, total energy, and molecular weight revealed that the molecular bulk properties and electrostatic interaction were the most important factors influencing the partition process.