bluuebunny/crossref_metadata_2025 huggingface dataset:
Adult Motor Neuron Apoptosis Is Mediated by Nitric Oxide and Fas Death Receptor Linked by DNA Damage and p53 Activation
Authors: Martin Lee J. , Chen Kevin , Liu Zhiping
Published: July 2005

The mechanisms of injury- and disease-related degeneration of motor neurons (MNs) need clarification. Unilateral avulsion of the sciatic nerve in the mouse induces apoptosis of spinal MNs that is p53 and Bax dependent. We tested the hypothesis that MN apoptosis is Fas death receptor dependent and triggered by nitric oxide (NO)- and superoxide-mediated damage to DNA. MNs in mice lacking functional Fas receptor and Fas ligand were protected from apoptosis. Fas protein levels and cleaved caspase-8 increased in MNs after injury. Fas upregulation was p53 dependent. MNs in mice deficient in neuronal NO synthase (nNOS) and inducible NOS (iNOS) resisted apoptosis. After injury, MNs increased nNOS protein but decreased iNOS protein; however, iNOS contributed more than nNOS to basal and injury-induced levels of NADPH diaphorase activity in MNs. NO and peroxynitrite (ONOO-) fluorescence increased in injured MNs, as did nitrotyrosine staining of MNs. DNA damage, assessed as 8-hydroxy-2-deoxyguanosine and single-stranded DNA, accumulated within injured MNs and was attenuated by nNOS and iNOS deficiency. nNOS deficiency increased DNA repair protein oxoguanine DNA-glycosylase, whereas iNOS deficiency blocked diaphorase activity. MN apoptosis was blocked by the antioxidant Trolox and by overexpression of wild-type human superoxide dismutase-1 (SOD1). In contrast, injured MNs in mice harboring mutant human SOD1 had upregulated Fas and iNOS, escalated DNA damage, and accelerated and increased MN degeneration and underwent necrosis instead of apoptosis. Thus, adult spinal MN apoptosis is mediated by upstream NO and ONOO-genotoxicity and downstream p53 and Fas activation and is shifted to necrosis by mutant SOD1.
Olfactory Impairments in Patients with Unilateral Cerebellar Lesions Are Selective to Inputs from the Contralesional Nostril
Authors: Mainland Joel D. , Johnson Bradley N. , Khan Rehan , Ivry Richard B. , Sobel Noam
Published: July 2005

Functional imaging studies of olfaction have consistently reported odorant-induced activation of the cerebellum. However, the cerebellar role in olfaction remains unknown. We examined the olfactory and olfactomotor abilities of patients with unilateral cerebellar lesions, comparing performance within subjects across nostrils, as well as between subjects with age-matched and young controls. Regarding olfactory performance, initial testing revealed that patients had a contralesional impairment in olfactory identification but not olfactory detection threshold. However, when tested under conditions that prevented compensatory sniffing strategies, the patients also exhibited a contralesional olfactory detection impairment. Regarding olfactomotor function, a healthy olfactomotor system generates sniffs that are (1) sufficiently vigorous and (2) inversely proportional to odorant concentration in sniff mean airflow velocity, maximum airflow velocity, volume, and duration. Patients' sniffs were lower in overall airflow velocity and volume in comparison with control participants. Furthermore, reduced sniff velocity predicted poorer detection thresholds in patients. Finally, whereas young controls used concentration-dependent sniffs, there was a trend in that direction only for age-matched controls. Patients used sniffs that were concentration invariant. In conclusion, cerebellar lesions impacted olfactory and olfactomotor performance. These findings strongly implicate an olfactocerebellar pathway prominent in odor identification and detection that functionally connects each nostril primarily to the contralateral cerebellum.
On the Computations Analyzing Natural Optic Flow: Quantitative Model Analysis of the Blowfly Motion Vision Pathway
Authors: Lindemann J. P. , Kern R. , van Hateren J. H. , Ritter H. , Egelhaaf M.
Published: July 2005

For many animals, including humans, the optic flow generated on the eyes during locomotion is an important source of information about self-motion and the structure of the environment. The blowfly has been used frequently as a model system for experimental analysis of optic flow processing at the microcircuit level. Here, we describe a model of the computational mechanisms implemented by these circuits in the blowfly motion vision pathway. Although this model was originally proposed based on simple experimenter-designed stimuli, we show that it is also capable to quantitatively predict the responses to the complex dynamic stimuli a blowfly encounters in free flight. In particular, the model visual system exploits the active saccadic gaze and flight strategy of blowflies in a similar way, as does its neuronal counterpart. The model circuit extracts information about translation velocity in the intersaccadic intervals and thus, indirectly, about the three-dimensional layout of the environment. By stepwise dissection of the model circuit, we determine which of its components are essential for these remarkable features. When accounting for the responses to complex natural stimuli, the model is much more robust against parameter changes than when explaining the neuronal responses to simple experimenter-defined stimuli. In contrast to conclusions drawn from experiments with simple stimuli, optimization of the parameter set for different segments of natural optic flow stimuli do not indicate pronounced adaptational changes of these parameters during long-lasting stimulation.
Constitutively Active Cytoplasmic c-Jun N-Terminal Kinase 1 Is a Dominant Regulator of Dendritic Architecture: Role of Microtubule-Associated Protein 2 as an Effector
Authors: Björkblom Benny , Östman Nina , Hongisto Vesa , Komarovski Vladislav , Filén Jan-Jonas , Nyman Tuula A. , Kallunki Tuula , Courtney Michael J. , Coffey Eleanor T.
Published: July 2005

Normal functioning of the nervous system requires precise regulation of dendritic shape and synaptic connectivity. Here, we report a severe impairment of dendritic structures in the cerebellum and motor cortex of c-Jun N-terminal kinase 1 (JNK1)-deficient mice. Using an unbiased screen for candidate mediators, we identify the dendrite-specific high-molecular-weight microtubule-associated protein 2 (MAP2) as a JNK substrate in the brain. We subsequently show that MAP2 is phosphorylated by JNK in intact cells and that MAP2 proline-rich domain phosphorylation is decreased in JNK1-/- brain. We developed compartment-targeted JNK inhibitors to define whether a functional relationship exists between the physiologically active, cytosolic pool of JNK and dendritic architecture. Using these, we demonstrate that cytosolic, but not nuclear, JNK determines dendritic length and arbor complexity in cultured neurons. Moreover, we confirm that MAP2-dependent process elongation is enhanced after activation of JNK. Using JNK1-/- neurons, we reveal a dominant role for JNK1 over ERK in regulating dendritic arborization, whereas ERK only regulates dendrite shape under conditions in which JNK activity is low (JNK1-/- neurons). These results reveal a novel antagonism between JNK and ERK, potentially providing a mechanism for fine-tuning the dendritic arbor. Together, these data suggest that JNK phosphorylation of MAP2 plays an important role in defining dendritic architecture in the brain.
A Highly Specific Inhibitor of Matrix Metalloproteinase-9 Rescues Laminin from Proteolysis and Neurons from Apoptosis in Transient Focal Cerebral Ischemia
Authors: Gu Zezong , Cui Jiankun , Brown Stephen , Fridman Rafael , Mobashery Shahriar , Strongin Alex Y. , Lipton Stuart A.
Published: July 2005

Neuronal cell death occurs during many neurodegenerative disorders and stroke. The aberrant, excessive activity of matrix metalloproteinases (MMPs), especially MMP-9, contributes directly to neuron apoptosis and brain damage (Rosenberg et al., 1996; Asahi et al., 2001; Gu et al., 2002; Horstmann et al., 2003). We determined that MMP-9 degrades the extracellular matrix protein laminin and that this degradation induces neuronal apoptosis in a transient focal cerebral ischemia model in mice. We also determined that the highly specific thiirane gelatinase inhibitor SB-3CT blocks MMP-9 activity, including MMP-9-mediated laminin cleavage, thus rescuing neurons from apoptosis. We conclude that MMP-9 is a highly promising drug target and that SB-3CT derivatives have significant therapeutic potential in stroke patients.
Identification of Dopaminergic Neurons of Nigral and Ventral Tegmental Area Subtypes in Grafts of Fetal Ventral Mesencephalon Based on Cell Morphology, Protein Expression, and Efferent Projections
Authors: Thompson Lachlan , Barraud Perrine , Andersson Elin , Kirik Deniz , Björklund Anders
Published: July 2005

Transplants of fetal ventral mesencephalic tissue are known to contain a mixture of two major dopamine (DA) neuron types: the A9 neurons of the substantia nigra pars compacta (SNpc) and the A10 neurons of the ventral tegmental area (VTA). Previous studies have suggested that these two DA neuron types may differ in their growth characteristics, but, because of technical limitations, it has so far been difficult to identify the two subtypes in fetal ventral mesencephalon (VM) grafts and trace their axonal projections. Here, we have made use of a transgenic mouse expressing green fluorescent protein (GFP) under the tyrosine hydroxylase promoter. The expression of the GFP reporter allowed for visualization of the grafted DA neurons and their axonal projections within the host brain. We show that the SNpc and VTA neuron subtypes in VM grafts can be identified on the basis of their morphology and location within the graft, and their expression of a G-protein-gated inwardly rectifying K+channel subunit (Girk2) and calbindin, respectively, and also that the axonal projections of the two DA neuron types are markedly different. By retrograde axonal tracing, we show that dopaminergic innervation of the striatum is derived almost exclusively from the Girk2-positive SNpc cells, whereas the calbindin-positive VTA neurons project to the frontal cortex and probably also other forebrain areas. The results suggest the presence of axon guidance and target recognition mechanisms in the DA-denervated forebrain that can guide the growing axons to their appropriate targets and indicate that cell preparations used for cell replacement in Parkinson's disease will be therapeutically useful only if they contain cells capable of generating the correct nigral DA neuron phenotype.
Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway
Authors: Lotharius Julie , Falsig Jeppe , van Beek Johan , Payne Sarah , Dringen Ralf , Brundin Patrik , Leist Marcel
Published: July 2005

Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies. For validation of putative neuroprotectants, a model is desirable in which the events leading to neurodegeneration replicate those occurring in the disease. We developed a humanin vitromodel of PD based on the assumption that dysregulated cytoplasmic dopamine levels trigger cell loss in this disorder. Differentiated human mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to promote cytoplasmic dopamine accumulation. In the presence of elevated iron concentrations, as observed in PD, increased cytosolic dopamine led to oxidative stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration, and eventually apoptosis. We examined the role of the mixed-lineage kinases (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9-bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented FeCl2+/METH-induced JNK activation and apoptosis but also early events such as neurite degeneration and oxidative stress. This broad neuroprotective action of CEP1347 was associated with increased expression of an oxidative stress-response modulator, activating transcription factor 4. As a functional consequence, transcription of the cystine/glutamate and glycine transporters, cellular cystine uptake and intracellular levels of the redox buffer glutathione were augmented. In conclusion, this new human model of parkinsonian neurodegeneration has the potential to yield new insights into neurorestorative therapeutics and suggests that enhancement of cytoprotective mechanisms, in addition to blockade of apoptosis, may be essential for disease modulation.
Pathological Aggression in “Fierce” Mice Corrected by Human Nuclear Receptor 2E1
Authors: Abrahams Brett S. , Kwok Melvin C. H. , Trinh Eric , Budaghzadeh Saeed , Hossain Sazzad M. , Simpson Elizabeth M.
Published: July 2005

“Fierce” mice, homozygous for the deletion of nuclear receptor 2E1 (NR2E1), show abnormal brain-eye development and pathological aggression. To evaluate functional equivalency between mouse and humanNR2E1, we generated mice transgenic for a genomic clone spanning the humanNR2E1locus and bred these animals to fierce mice deleted for the corresponding mouse gene. In fierce mutants carrying humanNR2E1, structural brain defects were eliminated and eye abnormalities ameliorated. Excitingly, behavior in these “rescue” mice was indistinguishable from controls. Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the humanNR2E1clone are functional in mouse. Normal behavior in rescue animals suggests that mechanisms underlying the behavioral abnormalities in fierce mice may also be conserved in humans. Our data support the hypothesis that variation atNR2E1may contribute to human behavioral disorders. Use of this rescue paradigm with other genes will permit the direct evaluation of human genes hypothesized to play a causal role in psychiatric disease but for which evidence is lacking or equivocal.
Native American Popular Religion in New England’s Old Colony, 1670–1770
Authors: Winiarski Douglas L.
Published: July 2005

In recent years, historians have turned their attention to the continued presence of Native Americans living “behind the frontier” in eighteenth-century New England. Where a previous generation of scholars once wrangled over the benignity of seventeenth-century Puritan “praying towns” and equated conversion with cultural suicide, current studies of Native religion in the decades preceding the American Revolution suggest that Indians preserved traditional culture by grafting Christianity onto a preexisting grid of beliefs and practices. A case study based on the writings of a lay missionary and civil magistrate named Josiah Cotton, this essay contributes to revisionist scholarship by examining Native American spirituality under the broader and more inclusive category of popular religion. Most Wampanoag families in New England's “Old Colony” lived between cultures—neither fully integrated into English society nor fully traditional in their identities or worldview. The ambiguities of their colonial situation, in turn, facilitated the emergence of a diverse spectrum of religious beliefs and practices that, at times, transcended racial categories. English settlers consulted Native American shamans and cunning folk; rumors of witchcraft, ghosts, and spirits permeated all ranks of society; and Indians and their white neighbors shared a preoccupation with spiritual healing. A few core families aspired to all the trappings of English life; they internalized Puritan doctrine, engaged in sophisticated devotional routines, and joined local Indian churches. Others continued to live in traditional ways and simply ignored the pastoral labors of regional missionaries. But for the majority of Native Christians who lived and worked side-by-side with their English neighbors, religion remained an eclectic affair as they deployed a variety of spiritual resources to combat the vicissitudes and uncertainties of everyday life.
Sex in the City of God: Free Love and the American Millennium
Authors: Gutierrez Cathy
Published: July 2005

This article examines several millennialist claims made in speeches and writings by Victoria Woodhull, the alternately celebrated and scandalous proponent of Spiritualism, Free Love, and women's suffrage in the nineteenth century. It focuses particularly on a utopian vision detailed in a speech, “The Elixir of Life,” that Woodhull addressed to the tenth annual meeting of the American Association of Spiritualists, in which Woodhull predicted a swiftly arriving millennium that would unite heaven and earth, bringing eternal life to the living and restoring the dead to an earthly but perfect existence. This millennial vision centered on the perfectability of the human body at the intersection of the discourses of medicine, politics, and religion. This utopia would be ushered in by society's embracing of the principles of Free Love, the reform movement that espoused that emotional and physical romantic relations should be governed by mutual love alone without interference from legal or religious authority.

This speech is read against the backdrop of contemporaneous social movements in Spiritualism, Free Love, and alternative forms of medicine. The article argues that Woodhull defied both normative Christianity and the mainstream of Spiritualist believers by refusing to subordinate the body to the soul. The millennial impulse toward progress, seen so keenly in Spiritualist circles, was transformed here to refer to the individual rather than society at large. Social perfection would follow corporeal perfection. Arguing for a natural immortality of the body, Woodhull maintained an essential union and interreliance between the body and soul rather than a disjuncture between them.
The Beauty of the Lilies: Femininity, Innocence, and the Sweet Gospel of Uldine Utley
Authors: Du Mez Kristin Kobes
Published: July 2005

In the 1920s, a child evangelist by the name of Uldine Utley toured the United States, attracting large crowds and captivating the press. She enjoyed the support of ministers from a wide variety of denominations, though her most ardent proponent was the famous fundamentalist preacher John Roach Straton. In many ways, Utley's success seems to counter existing narratives of early-twentieth-century religious history. Her revivalist ministry developed in an era that saw the decline of revivalism, and she rose to prominence during the height of the fundamentalist-modernist controversy. Claiming to adhere to biblical “literalism,” she nonetheless affirmed the appropriateness of female preaching. And, in the wake of efforts to masculinize American Protestantism and rediscover a “muscular” Christianity, Utley was known and celebrated for her femininity and beauty.

Utley's femininity was, in fact, central to her appeal. She preached a “sweet and kindly gospel” and fashioned an elaborate feminine persona. Her diminutive size, her blond hair and blue eyes, and her white attire seemed to give her an “angelic” appearance, and her persistent association with flowers, both allegorical and real, further contributed to her aura of femininity. In the context of shifting gender arrangements and changing constructions of sexuality and morality in early-twentieth-century America, Utley's femininity and innocence provided a soothing alternative to the uncertain times. But the model of femininity Utley displayed was fraught with ambivalence and proved difficult to maintain as she matured from child to young woman. In addition to illuminating a frequently overlooked strand of conservative Protestantism during this time, attention to Utley's life and ministry also reveals a powerful yet ambivalent script that remains available to modern Protestant women to this day.
Impairment of Cytotype Regulation of P-Element Activity in Drosophila melanogaster by Mutations in the Su(var)205 Gene
Authors: Haley Kevin J , Stuart Jeremy R , Raymond John D , Niemi Jarad B , Simmons Michael J
Published: July 2005

Cytotype regulation of transposable P elements in the germ line of Drosophila melanogaster is associated with maternal transmission of P elements inserted at the left telomere of the X chromosome. This regulation is impaired in long-term stocks heterozygous for mutations in Suppressor of variegation 205 [Su(var)205], a gene implicated in the control of telomere length. Regulation by TP5, a structurally incomplete P element at the X telomere, is more profoundly impaired than regulation by TP6, a different incomplete P element inserted at the same site in a TAS repeat at the X telomere. Genetic analysis with the TP5 element indicates that its regulatory ability is not impaired in flies whose fathers came directly from a stock heterozygous for a Su(var)205 mutation, even when the flies themselves carry this mutation. However, it is impaired in flies whose grandfathers came from such a stock. Furthermore, this impairment occurs even when the Su(var)205 mutation is not present in the flies themselves or in their mothers. The impaired regulatory ability of TP5 persists for at least several generations after TP5 X chromosomes extracted from a long-term mutant Su(var)205 stock are made homozygous in the absence of the Su(var)205 mutation. Impairment of TP5-mediated regulation is therefore not directly dependent on the Su(var)205 mutation. However, it is characteristic of the six mutant Su(var)205 stocks that were tested and may be related to the elongated telomeres that develop in these stocks. Impairment of regulation by TP5 is also seen in a stock derived from Gaiano, a wild-type strain that has elongated telomeres due to a dominant mutation in the Telomere elongation (Tel) gene. Regulation by TP6 is not impaired in the Gaiano genetic background. The regulatory abilities of the TP5 and TP6 elements are therefore not equally susceptible to the effects of elongated telomeres in the mutant Su(var)205 and Gaiano stocks.
Extreme Population Structure and High Interspecific Divergence of the Silene Y Chromosome
Authors: Ironside Joseph E , Filatov Dmitry A
Published: July 2005

Previous studies have demonstrated that the diversity of Y-linked genes is substantially lower than that of their X-linked homologs in the plant Silene latifolia. This difference has been attributed to selective sweeps, Muller's ratchet, and background selection, processes that are predicted to severely affect the evolution of the nonrecombining Y chromosome. We studied the DNA diversity of a noncoding region of the homologous genes DD44Y and DD44X, sampling S. latifolia populations from a wide geographical area and also including the closely related species S. dioica, S. diclinis, and S. heuffelii. On the Y chromosome of S. latifolia, we found substantial DNA diversity. Geographical population structure was far higher than on the X chromosome and differentiation between the species was also higher for the Y than for the X chromosome. Our findings indicate that the loss of genetic diversity on the Y chromosome in Silene occurs within local populations rather than within entire species. These results are compatible with background selection, Muller's ratchet, and local selective sweeps, but not with species-wide selective sweeps. The higher interspecific divergence of DD44Y, compared to DD44X, supports the hypothesis that Y chromosome differentiation between incipient species precedes reproductive isolation of the entire genome, forming an early stage in the process of speciation.
Genomic Mutation in Lines ofArabidopsis thalianaExposed to Ultraviolet-B Radiation
Authors: MacKenzie Joanna L , Saadé Fabienne E , Le Quang Hien , Bureau Thomas E , Schoen Daniel J
Published: July 2005

Studies that have attempted to estimate the rate of deleterious mutation have typically been conducted under low levels of ultraviolet-B (UV-B) radiation, a naturally occurring mutagen. We conducted experiments to test whether the inclusion of natural levels of UV-B radiation in mutation-accumulation (MA) experiments influences the rate and effects of mildly deleterious mutation in the plant Arabidopsis thaliana. Ten generations of MA proved insufficient to observe significant changes in means or among-line variances in experimental lines maintained either with or without supplemental UV-B radiation. Maximum-likelihood estimates of mutation rate for total flower number revealed a small but significant rate of mutation for MA lines propagated under supplemental UV-B exposure, but not for those in which supplemental UV-B was omitted. A fraction of the flower number mutations under UV-B (∼25–30%) are estimated to increase flower number. Results from the application of transposon display to plant materials obtained after MA, in both the presence and absence of supplemental UV-B, suggest that the average rate of transposition for the class I and II transposable elements (TEs) surveyed was no more than 10−4. Overall, the estimates of mutation parameters are qualitatively similar to what has been observed in other MA experiments with this species in which supplemental UV-B levels have not been used. As well, it appears that naturally occurring levels of UV-B do not lead to detectable increases in levels of transposable element activity.
Recombination and the Properties of Tajima's D in the Context of Approximate-Likelihood Calculation
Authors: Thornton Kevin
Published: July 2005

I show that Tajima's D, a commonly used summary of the site-frequency spectrum for single-nucleotide polymorphism data, is a biased summary of the site-frequency spectrum. Under neutral models, this bias depends on the population recombination rate. This bias of D in summarizing the data makes inference of demographic parameters sensitive to assumptions about recombination rates.
Genetic Interactions Between Mediator and the Late G1-Specific Transcription Factor Swi6 in Saccharomyces cerevisiae
Authors: Li Lihong , Quinton Tina , Miles Shawna , Breeden Linda L
Published: July 2005

Swi6 associates with Swi4 to activate HO and many other late G1-specific transcripts in budding yeast. Genetic screens for suppressors of SWI6 mutants have been carried out. A total of 112 of these mutants have been identified and most fall into seven complementation groups. Six of these genes have been cloned and identified and they all encode subunits of the mediator complex. These mutants restore transcription to the HO-lacZ reporter in the absence of Swi6 and have variable effects on other Swi6 target genes. Deletions of other nonessential mediator components have been tested directly for suppression of, or genetic interaction with, swi6. Mutations in half of the known subunits of mediator show suppression and/or growth defects in combination with swi6. These phenotypes are highly variable and do not correlate with a specific module of the mediator. Mutations in tail module components sin4 and pgd1 showed both growth defects and suppression when combined with swi6, but a third tail component, gal11, showed neither. A truncated form of the essential Srb7 mediator subunit also suppresses swi6 mutations and shows a defect in recruitment of the tail module components Sin4, Pgd1, and Gal11 to the mediator complex.
Reevaluation of the Role of the med-1 and med-2 Genes in Specifying the Caenorhabditis elegans Endoderm
Authors: Goszczynski Barbara , McGhee James D
Published: July 2005

The med-1 and med-2 genes encode a pair of essentially identical GATA factor-related transcription factors that have been proposed to be necessary for specification of the C. elegans endoderm (intestine or E lineage) as well as part of the C. elegans mesoderm. med-1 and med-2 are proposed to be the direct downstream targets and the principal effectors of the maternally provided SKN-1 transcription factor; med-1 and med-2 would thus occupy the pivotal interface between maternal and zygotic control of gene expression. The conclusion that med-1 and med-2 are necessary for C. elegans endoderm specification was based on a partially penetrant (∼50%) loss of endoderm markers produced by RNA-mediated interference (RNAi). To determine whether this partial penetrance reflects: (i) inefficient RNAi against early zygotic transcripts, (ii) experimental uncertainty in the expected level of endoderm loss in skn-1 nulls, or (iii) additional redundancy in the pathway of endoderm specification, we constructed worm strains that segregate embryos lacking both the med-1 gene (because of a gene-specific deletion) and the med-2 gene (using either of two chromosomal deficiencies). Contrary to expectations, we observe that only ∼3–20% of med-2(−); med-1(−) embryos do not express markers of endoderm differentiation. Furthermore, we found no evidence for a maternal contribution of the med genes to endoderm specification. We conclude that the major pathway(s) for endoderm specification in C. elegans must be independent of the med-1 and med-2 genes.
Mutational Hypersensitivity of a Gene Regulatory Protein: Saccharomyces cerevisiae Gal80p
Authors: Melcher Karsten
Published: July 2005

The inhibitor of galactose catabolic (GAL) gene expression in Saccharomyces cerevisiae, Gal80p, interacts with the activator Gal4p and the signal transducer Gal3p and self-associates. Selection for loss of Gal80p inhibitor function yielded gal80 mutants at an extremely high rate. Out of these, 21 nonoverlapping point mutants were identified; each were due to a single-amino-acid exchange in conserved residues. Semiquantitative biochemical analysis of the corresponding mutant proteins revealed that each of the 21 amino acid alterations caused simultaneous defects in every single protein-protein interaction and in Gal80's structural integrity. Thus, Gal80 provides an unprecedented example for a protein's structural sensitivity to minimal sequence alterations.
Two Quantitative Trait Loci for Prepulse Inhibition of Startle Identified on Mouse Chromosome 16 Using Chromosome Substitution Strains
Authors: Petryshen Tracey L , Kirby Andrew , Hammer Ronald P , Purcell Shaun , O'Leary Sinead B , Singer Jonathan B , Hill Annie E , Nadeau Joseph H , Daly Mark J , Sklar Pamela
Published: July 2005

Prepulse inhibition (PPI) of acoustic startle is a genetically complex quantitative phenotype of considerable medical interest due to its impairment in psychiatric disorders such as schizophrenia. To identify quantitative trait loci (QTL) involved in mouse PPI, we studied mouse chromosome substitution strains (CSS) that each carry a homologous chromosome pair from the A/J inbred strain on a host C57BL/6J inbred strain background. We determined that the chromosome 16 substitution strain has elevated PPI compared to C57BL/6J (P = 1.6 × 10−11), indicating that chromosome 16 carries one or more PPI genes. QTL mapping using 87 F2 intercross progeny identified two significant chromosome 16 loci with LODs of 3.9 and 4.7 (significance threshold LOD is 2.3). The QTL were each highly significant independently and do not appear to interact. Sequence variation between B6 and A/J was used to identify strong candidate genes in the QTL regions, some of which have known neuronal functions. In conclusion, we used mouse CSS to rapidly and efficiently identify two significant QTL for PPI on mouse chromosome 16. The regions contain a limited number of strong biological candidate genes that are potential risk genes for psychiatric disorders in which patients have PPI impairments.
Genome-Wide Synthetic Lethal Screens Identify an Interaction Between the Nuclear Envelope Protein, Apq12p, and the Kinetochore in Saccharomyces cerevisiae
Authors: Montpetit Ben , Thorne Ken , Barrett Irene , Andrews Kim , Jadusingh Ravi , Hieter Phil , Measday Vivien
Published: July 2005

The maintenance of genome stability is a fundamental requirement for normal cell cycle progression. The budding yeast Saccharomyces cerevisiae is an excellent model to study chromosome maintenance due to its well-defined centromere and kinetochore, the region of the chromosome and associated protein complex, respectively, that link chromosomes to microtubules. To identify genes that are linked to chromosome stability, we performed genome-wide synthetic lethal screens using a series of novel temperature-sensitive mutations in genes encoding a central and outer kinetochore protein. By performing the screens using different mutant alleles of each gene, we aimed to identify genetic interactions that revealed diverse pathways affecting chromosome stability. Our study, which is the first example of genome-wide synthetic lethal screening with multiple alleles of a single gene, demonstrates that functionally distinct mutants uncover different cellular processes required for chromosome maintenance. Two of our screens identified APQ12, which encodes a nuclear envelope protein that is required for proper nucleocytoplasmic transport of mRNA. We find that apq12 mutants are delayed in anaphase, rereplicate their DNA, and rebud prior to completion of cytokinesis, suggesting a defect in controlling mitotic progression. Our analysis reveals a novel relationship between nucleocytoplasmic transport and chromosome stability.
Yellow Perch Length–Fecundity and Length–Egg Size Relationships in Indiana Waters of Lake Michigan
Authors: Lauer Thomas E. , Shroyer Steven M. , Kilpatrick John M. , McComish Thomas S. , Allen Paul J.
Published: July 2005

This study was undertaken to quantify the length–fecundity and length–egg size relationships for yellow perch Perca flavescens in the Indiana waters of Lake Michigan. Data were pooled from gill-net collections made in 1985, 1986, and 1999, resulting in a wide length range of mature female yellow perch (172–332 mm total length (TL)). The length–fecundity relationship was log10  F = −3.220 + 3.223·log10TL (r2 = 0.89), where F is fecundity. The mean preserved egg volume (V; mL) increased with yellow perch TL and was represented by the following equation: log10  V = −2.06 + 1.10·log10TL (r2 = 0.48). These results reveal that larger females produced both more and larger eggs than did smaller females. Therefore, the intense harvest targeting large yellow perch (primarily females) in the 1980s and 1990s may have had an effect on the quantity and quality of eggs spawned by the population, possibly resulting in reduced recruitment.
Agricultural Dust Production in Standard and Conservation Tillage Systems in the San Joaquin Valley
Authors: Baker J. B. , Southard R. J. , Mitchell J. P.
Published: July 2005

The negative health effects of repeated dust exposure have been well documented. In California's San Joaquin Valley, agricultural operations may contribute substantially to airborne particulates. We evaluated four management systems to assess impacts on dust production and soil properties for a cotton (Gossypium hirsutum L.)–tomato (Lycopersicon esculentum Mill.) rotation: standard tillage with (STCC) and without (STNO) cover crop, and conservation tillage with (CTCC) and without (CTNO) cover crop. Gravimetric analysis of total dust (TD, <100‐μm aerodynamic diameter) and respirable dust (RD, 4‐μm aerodynamic diameter) samples collected in the plume generated by field implements showed that dust concentrations for CTNO treatments were about one‐third of their STNO counterparts for both cumulative TD and RD measured throughout the two‐year rotation, primarily due to fewer in‐field operations. The TD and RD production for STNO and STCC was comparable, whereas the CTCC system produced about twice as much TD and RD as CTNO. Energy dispersive spectroscopy (EDS) analyses showed absolute increases of 8 and 39% organic fragments in STCC and CTCC over STNO and CTNO, respectively, while organic fragments in the TD increased by 6% in both cover crop treatments. Soil C content was positively correlated with clay content and increased by an average of 0.12 and 0.07% in the cover crop and non‐cover crop treatments, respectively, although soil C for each treatment showed a distinct response to a field texture gradient. While dust emissions show an immediate decrease due to fewer field operations for the conservation tillage treatments, long‐term sampling is necessary to determine the effects that increased aggregation through organic matter additions may have on dust production.
Fertilizer, Tillage, and Dairy Manure Contributions to Nitrate and Herbicide Leaching
Authors: Stoddard C. S. , Grove J. H. , Coyne M. S. , Thom W. O.
Published: July 2005

Few studies have examined the water quality impact of manure use in no‐tillage systems. A lysimeter study in continuous corn (Zea maysL.) was performed on Maury silt loam (fine, mixed, semiactive, mesic Typic Paleudalf) to evaluate the effect(s) of tillage (no‐till [NT] and chisel‐disk [CD]), nitrogen fertilizer rate (0 and 168 kg N ha−1), and dairy manure application timing (none, spring, fall, or fall plus spring) on NO3–N, atrazine (2‐chloro‐4‐ethylamino‐6‐isopropylamino‐s‐triazine), and alachlor [2‐chloro‐2′‐6′‐diethyl‐N‐(methoxymethyl)acetanilide] concentrations in leachate collected at a 90‐cm depth. Herbicides were highest immediately after application, declining to less than 4 μg L−1in about two months. Manure and manure timing by tillage interactions had little effect on leachate herbicides; rather, the data suggest that macropores rapidly transmitted atrazine and alachlor through the soil. Tillage usually did not significantly affect leachate NO3–N, but no‐tillage tended to cause higher NO3–N. Manuring caused higher NO3–N concentrations; spring manuring had more impact than fall, but fall manure contained about 78% of the N found in spring manure. Nitrate under spring “only fertilizer” treatment exceeded 10 mg L−138% of the time, compared with 15% for spring only manure treatment. After three years, manured soil leachate NO3–N exceeded that for soil receiving only N fertilizer. Soil profile (90 cm) NO3–N after corn harvest exceeding 22 kg N ha−1was associated with winter leachate NO3–N greater than 10 mg N L−1Manure can be used effectively in conservation tillage systems on this and similar soils. Accounting for all N inputs, including previous manure applications, will be important.
Physicochemical Characteristics of Animal and Municipal Wastes Decomposed in Arid Soils
Authors: Fares Farouk , Albalkhi Akram , Dec Jerzy , Bruns Mary Ann , Bollag Jean‐Marc
Published: July 2005

The application of anaerobically processed animal manure to maintain adequate levels of organic matter in arid soils is becoming a common practice. The purpose of this study was to characterize two farm manure products as compared with municipal waste compost (MWC). The anaerobic processing to obtain a biogas manure (BM) product was much faster (25 d) than the aerobic composting of farmyard manure (FYM) (90 d). Drying by three different methods (solar‐drying, vacuum‐drying at 45°C, and freeze‐drying) did not affect the quality of BM. Based on the chemical characteristics, FYM and BM products were comparable, and, containing less ash (30%) and heavy metals (50 mg Pb kg−1), seemed superior to MWC that contained 65% ash and 108 mg Pb kg−1On the other hand, MWC had higher C content (69.9%), lower acidity (15.04 mol kg−1), and higher exothermic peaks (300–460°C) than BM and FYM (50% C, 20 mol kg−1, and 275–450°C, respectively), thus showing a greater extent of humification. Also, when the organic materials were incubated with arid soils and monitored for mean residence times (MRT), MWC was slightly more resistant to decomposition (MRT 175–180 d) than BM or FYM (MRT 161–166 d). The observed differences, however, were too small to dismiss any of the products as a valuable material for land applications to improve soil quality. In view of the results obtained, MWC may be considered an adequate substitute for BM or FYM, whenever the latter are in short supply.
Surface Runoff and Transport of Sulfonamide Antibiotics and Tracers on Manured Grassland
Authors: Burkhardt Michael , Stamm Christian , Waul Christopher , Singer Heinz , Müller Stephan
Published: July 2005

Despite their common use in animal production the environmental fate of the veterinary sulfonamide antibiotics after excretion is only poorly understood. We performed irrigation experiments to investigate the transport of these substances with surface runoff on grassland. Liquid manure from pigs treated with sulfadimidine was spiked with sulfadiazine, sulfathiazole, the herbicide atrazine (2‐chloro‐4‐ethylamino‐6‐isopropylamino‐1,3,5‐triazine), and the conservative tracer bromide and spread onto eight plots. Four plots received the same amounts of the spiked substances in aqueous solution (controls). Apart from the application matrix we varied the time between application and irrigation. Manure increased the runoff volume up to six times compared with the controls. It seemed that manure enhanced the runoff by sealing the soil surface. On manured plots the relative antibiotic concentrations in runoff were higher than on the controls, reaching an average of 0.3% (sulfadiazine), 0.8% (sulfathiazole), and 1.4% (sulfadimidine) of the input concentrations after a 1‐d contact time. The corresponding values on the controls were 0.16% for sulfadiazine and 0.08% for sulfathiazole. After 3 d, the maximum values on the manured plots were even higher, whereas they had fallen below the limit of quantification on the controls. As a consequence, the sulfonamide losses were 10 to 40 times larger on the manured plots. The relative mobility of the sulfonamides on the control plots followed the trend expected from their chromatographic separation but the opposite was found on the manured plots. Hence it is important to consider explicitly the physical and chemical effects of manure when assessing the environmental fate of sulfonamides.
Quantification of Intrinsic Water Use Efficiency along a Moisture Gradient in Northeastern China
Authors: Yu Mei , Xie Yichun , Zhang Xinshi
Published: July 2005

Water use efficiency (WUE) is an important ecophysiological characteristic of plants, especially in semiarid and arid regions. At the scale of community or ecosystem, WUE is difficult to quantify because the amount of water used per unit dry mass production is a function of microclimatic variables and species composition. In this study, we analyzed corrected intrinsic water use efficiency (IWUEs) of grass and shrub species along the western segment of the Northeast China Transect (NECT) and the relationship between IWUEs and mean annual rainfall, habitat degradation status, vegetation type, and plant functional type (C3 versus C4) at 22 survey sites. Site intrinsic water use efficiency (IWUEv) and its relationship with the aforementioned site variables were analyzed based on species frequencies at each site. First, it was concluded that photosynthetic pathway played a very important role in determining species IWUEs Mean IWUEs for C4 species was approximately double that of C3 species. Second, mean annual rainfall, vegetation type, and site degradation status significantly affected IWUEs (p < 0.01). Mean IWUEs at degraded sites was twice as high as that at nondegraded sites. The mean IWUEs for meadows was significantly higher than those for other vegetation types (p < 0.05). Third, the frequency of occurrence of C4 plants explained 36% of the variance in IWUEv across the survey sites. The mean frequency of C4 occurrence at degraded sites was more than double that at nondegraded sites. Consequently, mean IWUEv at degraded sites was more than double that at nondegraded sites. Dominant C4 species in saline–alkaline areas tended to have higher intrinsic WUE than dominant C4 species in sandy shrub communities.
Visible‐Near Infrared Reflectance Spectroscopy for Rapid, Nondestructive Assessment of Wetland Soil Quality
Authors: Cohen Matthew J. , Prenger Joseph P. , DeBusk William F.
Published: July 2005

Recent evidence supports using visible‐near infrared reflectance spectroscopy (VNIRS) for sensing soil quality; advantages include low‐cost, nondestructive, rapid analysis that retains high analytical accuracy for numerous soil performance measures. Research has primarily targeted agricultural applications (precision agriculture, performance diagnostics), but implications for assessing ecological systems are equally significant. Our objective was to extend chemometrics for sensing soil quality to wetlands. Hydric soils posed two challenges. First, wetland soils exhibit a wider range of organic matter concentrations, particularly in riparian areas where levels range from <1% in sedimentation zones to >90% in backwater floodplains; this may mute spectral responses from other soil fractions. Second, spectral inference of cation concentrations in terrestrial soils is for oxidized species; under reducing conditions in wetlands, oxidation state variability is observed, which strongly affects chroma. Riparian soils (n = 273) from western Florida exhibiting substantial target parameter variability were compiled. After minimal pre‐processing, soils were scanned under artificial illumination using a laboratory spectrometer. A multivariate data mining technique (regression trees) was used to relate post‐processed reflectance spectra to laboratory observations (pH, organic content, cation concentrations, total N, C, and P, extracellular enzyme activity). High validation accuracy was generally observed (r2validation > 0.8, RPD > 2.0, where RPD is the ratio of the standard deviation of an attribute to the observed standard error of validation); where accuracy was lower, categorical models (classification trees) successfully screened samples based on diagnostic functional thresholds (validation odds ratio > 10). Graphical models verified significant association between predictions and observations for all parameters, conditioning on biogeochemical covariates. Visible‐near infrared reflectance spectroscopy offers both cost and statistical power advantages; hydric conditions do not appear to constrain application.
Phosphorus Leaching in Sandy Outwash Soils following Potato‐Processing Wastewater Application
Authors: Zvomuya Francis , Gupta Satish C. , Rosen Carl J.
Published: July 2005

Land application of wastewater presents potential for ground water pollution if not properly managed. In situ breakthrough tests were conducted using potato (Solanum tuberosum L.)–processing wastewater and a Br tracer to characterize P leaching in seasonally frozen sandy outwash soils. In the first test, P and Br breakthrough were measured in a 7‐m deep well following wastewater [2.94 mg L−1 total P (TP); 280 mg L−1 Br] application at the site that had 13.1 mg water‐extractable P (WEP) kg−1and 94.4 mg Bray‐1 P kg−1 Bromide was detected in the well after ∼0.4 pore volumes, but there was no P break‐through after 7 pore volumes. In the second breakthrough test, wastewater containing 3.6 mg L−1 TP and 259 mg L−1 Br was applied on 1.5‐m deep lysimeters at low (0.8 mg WEP kg−1; 12.1 mg Bray‐1 P kg−1) and high soil test P sites (104 mg WEP kg−1; 585 mg Bray‐1 P kg−1). Leachate TP concentration during the test remained constant (0.04 mg L−1) at the low P sites but increased from ∼3.5 to 5.6 mg L−1 at the high P sites. These results indicate no P leaching in low P soils, but leaching in high P soils, thus suggesting that most of the P leached at the high P sites was mainly due to desorption and dissolution of weakly adsorbed P from prior P applications. This was consistent with P transport simulations using the convective–dispersive equation. We conclude that P concentration in land‐applied wastewater should be regulated based on soil test‐P level plus wastewater P loading.