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Sample records for agrb null mutants

  1. Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Signore, M.; Simeone, A.

    2001-01-01

    We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

  2. Procyclin Null Mutants of Trypanosoma brucei Express Free Glycosylphosphatidylinositols on Their Surface

    PubMed Central

    Vassella, Erik; Bütikofer, Peter; Engstler, Markus; Jelk, Jennifer; Roditi, Isabel

    2003-01-01

    Procyclins are abundant, glycosylphosphatidylinositol (GPI)-anchored proteins on the surface of procyclic (insect) form trypanosomes. To investigate whether trypanosomes are able to survive without a procyclin coat, all four procyclin genes were deleted sequentially. Bloodstream forms of the null mutant exhibited no detectable phenotype and were able to differentiate to procyclic forms. Initially, differentiated null mutant cells were barely able to grow, but after an adaptation period of 2 mo in culture they proliferated at the same rate as wild-type trypanosomes. Analysis of these culture-adapted null mutants revealed that they were covered by free GPIs. These were closely related to the mature procyclin anchor in structure and were expressed on the surface in numbers comparable with that of procyclin in wild-type cells. However, free GPIs were smaller than the procyclin anchor, indicative of a lower number of poly-N-acetyllactosamine repeats, and a proportion contained diacylphosphatidic acid. Free GPIs are also expressed by wild-type cells, although to a lesser extent. These have been overlooked in the past because they partition in a solvent fraction (chloroform/water/methanol) that is normally discarded when GPI-anchored proteins are purified. PMID:12686589

  3. Amphetamine-elicited striatal Fos expression is attenuated in neurotensin null mutant mice.

    PubMed

    Fadel, Jim; Dobner, Paul R; Deutch, Ariel Y

    2006-07-10

    Neurotensin (NT) has been suggested to interact with dopamine systems in different forebrain sites to exert both antipsychotic- and psychostimulant-like effects. We previously found that genetic or pharmacological manipulations that disrupt endogenous NT signaling attenuate antipsychotic drug-induced Fos expression in the dorsolateral and central striatum but not other striatal regions. To assess the role of NT in psychostimulant responses, we examined the ability of d-amphetamine (AMP) to induce Fos in wild-type and NT null mutant mice. AMP-elicited Fos expression was significantly attenuated in the medial striatum of NT null mutant mice, but was unaffected in other striatal territories. Similar results were obtained in rats and mice pretreated with the high affinity neurotensin receptor (NTR1) antagonist SR 48692. The effect of the NTR1 antagonist was particularly apparent in the striatal patch (striosome) compartment, as defined by mu-opioid receptor immunoreactivity. These data suggest that NT is required for the full activation by AMP of medial striatal neurons.

  4. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice.

    PubMed

    Yang, Mu; Bozdagi, Ozlem; Scattoni, Maria Luisa; Wöhr, Markus; Roullet, Florence I; Katz, Adam M; Abrams, Danielle N; Kalikhman, David; Simon, Harrison; Woldeyohannes, Leuk; Zhang, James Y; Harris, Mark J; Saxena, Roheeni; Silverman, Jill L; Buxbaum, Joseph D; Crawley, Jacqueline N

    2012-05-09

    Mutations in the synaptic scaffolding protein gene SHANK3 are strongly implicated in autism and Phelan-McDermid 22q13 deletion syndrome. The precise location of the mutation within the Shank3 gene is key to its phenotypic outcomes. Here, we report the physiological and behavioral consequences of null and heterozygous mutations in the ankyrin repeat domain in Shank3 mice. Both homozygous and heterozygous mice showed reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in the homozygous mice. Three independent cohorts were evaluated for magnitude and replicability of behavioral endophenotypes relevant to autism and Phelan-McDermid syndrome. Mild social impairments were detected, primarily in juveniles during reciprocal interactions, while all genotypes displayed normal adult sociability on the three-chambered task. Impaired novel object recognition and rotarod performance were consistent across cohorts of null mutants. Repetitive self-grooming, reduced ultrasonic vocalizations, and deficits in reversal of water maze learning were detected only in some cohorts, emphasizing the importance of replication analyses. These results demonstrate the exquisite specificity of deletions in discrete domains within the Shank3 gene in determining severity of symptoms.

  5. Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi▿

    PubMed Central

    Zago, M. Paola; Barrio, Alejandra B.; Cardozo, Rubén M.; Duffy, Tomás; Schijman, Alejandro G.; Basombrío, Miguel A.

    2008-01-01

    Trypanosoma cruzi infection of host cells is a complex process in which many proteins participate but only a few of these proteins have been identified experimentally. One parasite factor likely to be involved is the protein product of LYT1, a single-copy gene cloned, sequenced, and characterized by Manning-Cela et al. (Infect. Immun. 69:3916-3923, 2001). This gene was potentially associated with infectivity, since the deletion of both LYT1 alleles in the CL Brenner strain (the wild type [WT]) resulted in a null mutant T. cruzi clone (L16) that shows an attenuated phenotype in cell culture models. The aim of this work was to characterize the infective behavior of L16 in the insect vector and murine models. The infection of adult Swiss mice with 103 trypomastigotes of both clones revealed a significant reduction in infective behavior of L16, as shown by direct parasitemia, spleen index, and quantitation of tissue parasite burden, suggesting the loss of virulence in the null mutant clone. Although L16 blood counts were almost undetectable, blood-based PCRs indicated the presence of latent and persistent infection during all of the study period and epimastigotes were reisolated from hemocultures until 12 months postinfection. Nevertheless, virulence was not restored in L16 by serial passages in mice, and reisolated parasites lacking the LYT1 gene and bearing the antibiotic resistance genes revealed the stability of the genetic manipulation. Histopathological studies showed a strong diminution in the muscle inflammatory response triggered by L16 compared to that triggered by the WT group, consistent with a lower tissue parasite load. A strong protection against a virulent challenge in both L16- and WT-infected mice was observed; however, the immunizing infection by the genetically modified parasite was highly attenuated. PMID:17938222

  6. Kinetics of NH(4) Assimilation in Zea mays: Preliminary Studies with a Glutamate Dehydrogenase (GDH1) Null Mutant.

    PubMed

    Magalhães, J R; Ju, G C; Rich, P J; Rhodes, D

    1990-10-01

    In higher plants it is now generally considered that glutamate dehydrogenase (GDH) plays only a small or negligible role in ammonia assimilation. To test this specific point, comparative studies of (15)NH(4) (+) assimilation were undertaken with a GDH1-null mutant of Zea mays and a related (but not strictly isogenic) GDH1-positive wild type from which this mutant was derived. The kinetics of (15)NH(4) (+) assimilation into free amino acids and total reduced nitrogen were monitored in both roots and shoots of 2-week-old seedlings supplied with 5 millimolar 99% ((15)NH(4))(2)SO(4) via the aerated root medium in hydroponic culture over a 24-h period. The GDH1-null mutant, with a 10- to 15-fold lower total root GDH activity in comparison to the wild type, was found to exhibit a 40 to 50% lower rate of (15)NH(4) (+) assimilation into total reduced nitrogen. Observed rates of root ammonium assimilation were 5.9 and 3.1 micromoles per hour per gram fresh weight for the wild type and mutant, respectively. The lower rate of (15)NH(4) (+) assimilation in the mutant was associated with lower rates of labeling of several free amino acids (including glutamate, glutamine-amino N, aspartate, asparagine-amino N, and alanine) in both roots and shoots of the mutant in comparison to the wild type. Qualitatively, these labeling kinetics appear consistent with a reduced flux of (15)N via glutamate in the GDH1-null mutant. However, the responses of the two genotypes to the potent inhibitor of glutamine synthetase, methionine sulfoximine, and differences in morphology of the two genotypes (particularly a lower shoot:root ratio in the GDH1-null mutant) urge caution in concluding that GDH1 is solely responsible for these differences in ammonia assimilation rate.

  7. Reduction of germ cells in the Odysseus null mutant causes male fertility defect in Drosophila melanogaster.

    PubMed

    Cheng, Ya-Jen; Fang, Shu; Tsaur, Shun-Chern; Chen, Yi-Ling; Fu, Hua-Wen; Patel, Nipam H; Ting, Chau-Ti

    2012-01-01

    Odysseus (OdsH) has been identified as a hybrid male sterility gene between Drosophila mauritiana and D. simulans with accelerated evolutionary rate in both expression and DNA sequence. Loss of a testis-specific expression of OdsH causes male fertility defect in D. melanogaster. Yet, the underlying mechanisms at the cellular level are unknown. In an attempt to identify the possible mechanisms and functional roles of OdsH in spermatogenesis, the cell numbers at different developmental stages during spermatogenesis between the OdsH null mutant and wild-type flies were compared. The results showed that the early developing germ cells, including spermatogonia and spermatocytes, were reduced in the OdsH mutant males. In addition, the number of germline stem cells in aged males was also reduced, presumably due to the disruption of germline stem cell maintenance, which resulted in more severe fertility defect. These results suggest that the function of the enhancement of sperm production by OdsH acted across males of all ages.

  8. Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population.

    PubMed

    Coffee, Erin M; Yerkes, Laura; Ewen, Elizabeth P; Zee, Tiffany; Tolan, Dean R

    2010-02-01

    Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Delta4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance.

  9. Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population

    PubMed Central

    Coffee, Erin M.; Yerkes, Laura; Ewen, Elizabeth P.; Zee, Tiffany

    2010-01-01

    Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Δ4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Δ4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance. PMID:20033295

  10. Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant

    PubMed Central

    Rank, Gerhard; Sutton, Rosemary; Marshall, Vikki; Lundie, Rachel J.; Caddy, Jacinta; Romeo, Tony; Fernandez, Kate; McCormack, Matthew P.; Cooke, Brian M.; Foote, Simon J.; Crabb, Brendan S.; Curtis, David J.; Hilton, Douglas J.; Kile, Benjamin T.

    2009-01-01

    Insights into the role of ankyrin-1 (ANK-1) in the formation and stabilization of the red cell cytoskeleton have come from studies on the nb/nb mice, which carry hypomorphic alleles of Ank-1. Here, we revise several paradigms established in the nb/nb mice through analysis of an N-ethyl-N-nitrosourea (ENU)–induced Ank-1–null mouse. Mice homozygous for the Ank-1 mutation are profoundly anemic in utero and most die perinatally, indicating that Ank-1 plays a nonredundant role in erythroid development. The surviving pups exhibit features of severe hereditary spherocytosis (HS), with marked hemolysis, jaundice, compensatory extramedullary erythropoiesis, and tissue iron overload. Red cell membrane analysis reveals a complete loss of ANK-1 protein and a marked reduction in β-spectrin. As a consequence, the red cells exhibit total disruption of cytoskeletal architecture and severely altered hemorheologic properties. Heterozygous mutant mice, which have wild-type levels of ANK-1 and spectrin in their RBC membranes and normal red cell survival and ultrastructure, exhibit profound resistance to malaria, which is not due to impaired parasite entry into RBC. These findings provide novel insights into the role of Ank-1, and define an ideal model for the study of HS and malarial resistance. PMID:19179303

  11. Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism.

    PubMed

    Ju, Anes; Hammerschmidt, Kurt; Tantra, Martesa; Krueger, Dilja; Brose, Nils; Ehrenreich, Hannelore

    2014-08-15

    Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Loss-of-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism. Adult Nlgn4 null mutant (Nlgn4(-/-)) mice are a construct valid model of human autism, with both genders displaying a remarkable autistic phenotype, including deficits in social interaction and communication as well as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonatal and juvenile Nlgn4(-/-) mice have not been reported yet. The present study has been designed to systematically investigate in male and female Nlgn4(-/-) pups versus wildtype littermates (WT, Nlgn4(+/+)) developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development, followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexes and neuromotor coordination, did not yield any differences between Nlgn4(-/-) and their WT littermates. USV in pups (PND8-9) in response to brief separation from their mothers revealed remarkable gender effects, and a genotype influence in females regarding latency to first call. In juveniles (PND22-23), USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotype effect with reduced USV in Nlgn4(-/-) mice, and again a more prominent phenotype in females. Together, these data support an early manifestation of communication deficits in Nlgn4(-/-) mice that appear more pronounced in immature females with their overall stronger USV as compared to males.

  12. Cognition and Mood-Related Behaviors in L3mbtl1 Null Mutant Mice

    PubMed Central

    Shen, Erica Y.; Jiang, Yan; Mao, Wenjie; Futai, Kensuke; Hock, Hanno; Akbarian, Schahram

    2015-01-01

    Alterations in histone lysine methylation and epigenetic regulators of gene expression could play a role in the neurobiology and treatment of patients diagnosed with mood spectrum disorder, including depression and anxiety. Mutations and altered expression of various lysine methyltransferases (KMTs) and demethylases (KDMs) have been linked to changes in motivational and emotional behaviors in preclinical model systems. However, it is not known whether regulators operating downstream of histone lysine methylation could affect mood-related behavior. Malignant Brain Tumor (MBT) domain ‘chromatin reader’ proteins bind to methylated histone lysine residues and associate with chromatin remodeling complexes to facilitate or repress gene expression. MBT proteins, including the founding member, L3mbtl1, maintain high levels of expression in neurons of the mature brain. Here, we exposed L3mbtl1 null mutant mice to a wide range of tests exploring cognition and mood-relevant behaviors at baseline and in the context of social isolation, as a stressor to elicit depression-related behavior in susceptible mice. L3mbtl1 loss-of-function was associated with significant decreases in depression and and anxiety in some of the behavioral paradigms. This was not associated with a more generalized neurological dysfunction because cognition and memory remained unaltered in comparison to controls. These findings warrant further investigations on the role of MBT chromatin reader proteins in the context of emotional and affective behaviors. PMID:25849281

  13. Metabolic and Phenotypic Differences between Mice Producing a Werner Syndrome Helicase Mutant Protein and Wrn Null Mice

    PubMed Central

    Aumailley, Lucie; Garand, Chantal; Dubois, Marie Julie; Johnson, F. Brad; Marette, André; Lebel, Michel

    2015-01-01

    Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter mean life span. In contrast, mice lacking the entire Wrn protein (i.e. Wrn null mice) do not exhibit a premature aging phenotype. In this study, we used a targeted mass spectrometry-based metabolomic approach to identify serum metabolites that are differentially altered in young Wrn helicase mutant and Wrn null mice. An antibody-based quantification of 43 serum cytokines and markers of cardiovascular disease risk complemented this study. We found that Wrn helicase mutants exhibited elevated and decreased levels, respectively, of the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IL-18. Wrn helicase mutants also exhibited an increase in serum hydroxyproline and plasminogen activator inhibitor-1, markers of extracellular matrix remodeling of the vascular system and inflammation in aging. We also observed an abnormal increase in the ratio of very long chain to short chain lysophosphatidylcholines in the Wrn helicase mutants underlying a peroxisome perturbation in these mice. Remarkably, the Wrn mutant helicase protein was mislocalized to the endoplasmic reticulum and the peroxisomal fractions in liver tissues. Additional analyses with mouse embryonic fibroblasts indicated a severe defect of the autophagy flux in cells derived from Wrn helicase mutants compared to wild type and Wrn null animals. These results indicate that the deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles. PMID:26447695

  14. Toll-Like Receptor 4 Mutant and Null Mice Retain Morphine-Induced Tolerance, Hyperalgesia, and Physical Dependence

    PubMed Central

    Mattioli, Theresa Alexandra; Leduc-Pessah, Heather; Skelhorne-Gross, Graham; Nicol, Christopher J. B.; Milne, Brian; Trang, Tuan; Cahill, Catherine M.

    2014-01-01

    The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4). Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal) were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (−) naloxone, an opioid receptor antagonist, and (+) naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence. PMID:24824631

  15. The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats

    PubMed Central

    Garcia, J. P.; Beingesser, J.; Fisher, D. J.; Sayeed, S.; McClane, B. A.; Posthaus, H.; Uzal, F. A.

    2012-01-01

    Clostridium perfringens type C is an important cause of enteritis and/or enterocolitis in several animal species, including pigs, sheep, goats, horses and humans. The disease is a classic enterotoxemia and the enteric lesions and associated systemic effects are thought to be caused primarily by beta toxin (CPB), one of two typing toxins produced by C. perfringens type C. This has been demonstrated recently by fulfilling molecular Koch’s postulates in rabbits and mice. We present here an experimental study to fulfill these postulates in goats, a natural host of C. perfringens type C disease. Nine healthy male or female Anglo Nubian goat kids were inoculated with the virulent C. perfringens type C wild-type strain CN3685, an isogenic CPB null mutant or a strain where the cpb null mutation had been reversed. Three goats inoculated with the wild-type strain presented abdominal pain, hemorrhagic diarrhea, necrotizing enterocolitis, pulmonary edema, hydropericardium and death within 24 h of inoculation. Two goats inoculated with the CPB null mutant and two goats inoculated with sterile culture media (negative controls) remained clinically healthy during 24 h after inoculation and no gross or histological abnormalities were observed in the tissues of any of them. Reversal of the null mutation to partially restore CPB production also increased virulence; 2 goats inoculated with this reversed mutant presented clinical and pathological changes similar to those observed in goats inoculated with the wild-type strain, except that spontaneous death was not observed. These results indicate that CPB is required for C. perfringens type C to induce disease in goats, supporting a key role for this toxin in natural C. perfringens type C disease pathogenesis. PMID:22296994

  16. The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats.

    PubMed

    Garcia, J P; Beingesser, J; Fisher, D J; Sayeed, S; McClane, B A; Posthaus, H; Uzal, F A

    2012-06-15

    Clostridium perfringens type C is an important cause of enteritis and/or enterocolitis in several animal species, including pigs, sheep, goats, horses and humans. The disease is a classic enterotoxemia and the enteric lesions and associated systemic effects are thought to be caused primarily by beta toxin (CPB), one of two typing toxins produced by C. perfringens type C. This has been demonstrated recently by fulfilling molecular Koch's postulates in rabbits and mice. We present here an experimental study to fulfill these postulates in goats, a natural host of C. perfringens type C disease. Nine healthy male or female Anglo Nubian goat kids were inoculated with the virulent C. perfringens type C wild-type strain CN3685, an isogenic CPB null mutant or a strain where the cpb null mutation had been reversed. Three goats inoculated with the wild-type strain presented abdominal pain, hemorrhagic diarrhea, necrotizing enterocolitis, pulmonary edema, hydropericardium and death within 24h of inoculation. Two goats inoculated with the CPB null mutant and two goats inoculated with sterile culture media (negative controls) remained clinically healthy during 24h after inoculation and no gross or histological abnormalities were observed in the tissues of any of them. Reversal of the null mutation to partially restore CPB production also increased virulence; 2 goats inoculated with this reversed mutant presented clinical and pathological changes similar to those observed in goats inoculated with the wild-type strain, except that spontaneous death was not observed. These results indicate that CPB is required for C. perfringens type C to induce disease in goats, supporting a key role for this toxin in natural C. perfringens type C disease pathogenesis.

  17. Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null mutant of Drosophila melanogaster

    SciTech Connect

    Reveillaud, I.; Kongpachith, A.; Fleming, J.E.

    1994-02-01

    Null mutants for Cu/Zn superoxide dismutase (CuZnSOD) in Drosophila melanogaster are male sterile, have a greatly reduced adult life span, and are hypersensitive to paraquat. We have introduced a synthetic bovine CuZnSOD transgene under the transcriptional control of the D. melanogaster 5C actin promoter into a CuZnSOD-null mutant of D. melanogaster. This was carried out by P-element-mediated transformation of the Drosophila-bovine CuZnSOD transgene into a CuZnSOD{sup +} recipient strain followed by genetic crossing of the transgene into a strain carrying the CuZnSOD-null mutation, cSOD{sup n108}. The resulting transformants express bovine CuZnSOD exclusively to about 30% of normal Drosophila CuZnSOD levels. Expression of the Drosophila-bovine CuZnSOD transgene in the CuZnSOD-null mutant rescues male fertility and resistance to paraquat to apparently normal levels. However, adult life span is restored to only 30% of normal, and resistance to hyperoxia is 90% of that found in control flies. This striking differential restoration of pleiotropic phenotypes could be the result of a threshold of CuZnSOD expression necessary for normal male fertility and resistance to the toxicity of paraquat or hyperoxia which is lower than the threshold required to sustain a normal adult life span. Alternatively, the differential rescue of fertility, resistance to active oxygen, and life span might indicate different cell-specific transcriptional requirements for these functions which are normally provided by the control elements of the native CuZnSOD gene but are only partly compensated for by the transcriptional control elements of the actin 5C promoter. 29 refs., 5 figs., 1 tab.

  18. A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice.

    PubMed

    Tanimoto, Keiji; Kanafusa, Sumiyo; Ushiki, Aki; Matsuzaki, Hitomi; Ishida, Junji; Sugiyama, Fumihiro; Fukamizu, Akiyoshi

    2014-10-01

    Renin is predominantly expressed in juxtaglomerular cells in the kidney and regulates blood pressure homeostasis. To examine possible in vivo functions of a mouse distal enhancer (mdE), we generated transgenic mice (TgM) carrying either wild-type or mdE-deficient renin BACs (bacterial artificial chromosome), integrated at the identical chromosomal site. In the kidneys of the TgM, the mdE contributed 80% to basal renin promoter activity. To test for possible physiological roles for the mdE, renin BAC transgenes were used to rescue the hypotensive renin-null mice. Interestingly, renal renin expression in the Tg(BAC):renin-null compound mice was indistinguishable between the wild-type and mutant BAC carriers. Surprisingly, however, the plasma renin activity and angiotensin I concentration in the mdE compound mutant mice were significantly lower than the same parameters in the control mice, and the mutants were consistently hypotensive, demonstrating that blood pressure homeostasis is regulated through transcriptional cis elements controlling renin activity.

  19. Epidermal growth factor impairs palatal shelf adhesion and fusion in the Tgf-β 3 null mutant.

    PubMed

    Barrio, M Carmen; Del Río, Aurora; Murillo, Jorge; Maldonado, Estela; López-Gordillo, Yamila; Paradas-Lara, Irene; Hernandes, Luzmarina; Catón, Javier; Martínez-Álvarez, Concepción

    2014-01-01

    The cleft palate presented by transforming growth factor-β3 (Tgf-β3) null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 (Tgf-β1) and muscle segment homeobox-1 (Msx-1) is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in Tgf-β3 knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, Tgf-β1 and Msx-1 in Tgf-β3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal mesenchyme. Inhibition of TGF-β1 does not affect either EGF or Msx-1 expression.

  20. Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

    PubMed Central

    2011-01-01

    Background Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy. Results In this study, we tested the ability of a Leishmania infantum deletion mutant, lacking both HSP70-II alleles (ΔHSP70-II), to provide protection against Leishmania infection in the L. major-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-Leishmania IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (Mesocricetus auratus), infected with mutant parasites did not develop any sign of pathology. Conclusions The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis. PMID:21794145

  1. Ku70 and ku80 null mutants improve the gene targeting frequency in Monascus ruber M7.

    PubMed

    He, Yi; Liu, Qingpei; Shao, Yanchun; Chen, Fusheng

    2013-06-01

    Normally, gene targeting by homologous recombination occurs rarely during a transformation process since non-homologous recombination is predominant in filamentous fungi. In our previous researches, the average gene replacement frequency (GRF) in Monascus ruber M7 was as low as 15 %. To develop a highly efficient gene targeting system for M. ruber M7, two M. ruber M7 null mutants of ku70 (MrΔku70) and ku80 (MrΔku80) were constructed which had no apparent defects in the development including vegetative growth, colony phenotype, microscopic morphology and spore yield compared with M. ruber M7. In addition, the production of some significant secondary metabolites such as pigments and citrinin had no differences between the two disruptants and the wild-type strain. Further results revealed that the GRFs of triA (encoding a putative acetyltransferase) were 42.2 % and 61.5 % in the MrΔku70 and MrΔku80 strains, respectively, while it was only about 20 % in M. ruber M7. Furthermore, GRFs of these two disruptants at other loci (the pigE, fmdS genes in MrΔku70 and the ku70 gene in MrΔku80) were investigated, and the results indicated that GRFs in the MrΔku70 strain and the MrΔku80 strain were doubled and tripled compared with that in M. ruber M7, respectively. Therefore, the ku70 and ku80 null mutants of M. ruber M7, especially the ku80-deleted strain, will be excellent hosts for efficient gene targeting.

  2. Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice

    PubMed Central

    Nassar, Mohammed A; Baker, Mark D; Levato, Alessandra; Ingram, Rachel; Mallucci, Giovanna; McMahon, Stephen B; Wood, John N

    2006-01-01

    Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Nav1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Nav1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Nav1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Nav1.3 mutant mouse lines. We used Nav1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Nav1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Nav1.3 in global knock-out mice. Our data demonstrate that Nav1.3 is neither necessary nor sufficient for the development of nerve-injury related pain. PMID:17052333

  3. Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant

    PubMed Central

    Boominathan, Amutha; Vanhoozer, Shon; Basisty, Nathan; Powers, Kathleen; Crampton, Alexandra L.; Wang, Xiaobin; Friedricks, Natalie; Schilling, Birgit; Brand, Martin D.; O'Connor, Matthew S.

    2016-01-01

    We explore the possibility of re-engineering mitochondrial genes and expressing them from the nucleus as an approach to rescue defects arising from mitochondrial DNA mutations. We have used a patient cybrid cell line with a single point mutation in the overlap region of the ATP8 and ATP6 genes of the human mitochondrial genome. These cells are null for the ATP8 protein, have significantly lowered ATP6 protein levels and no Complex V function. Nuclear expression of only the ATP8 gene with the ATP5G1 mitochondrial targeting sequence appended restored viability on Krebs cycle substrates and ATP synthesis capabilities but, failed to restore ATP hydrolysis and was insensitive to various inhibitors of oxidative phosphorylation. Co-expressing both ATP8 and ATP6 genes under similar conditions resulted in stable protein expression leading to successful integration into Complex V of the oxidative phosphorylation machinery. Tests for ATP hydrolysis / synthesis, oxygen consumption, glycolytic metabolism and viability all indicate a significant functional rescue of the mutant phenotype (including re-assembly of Complex V) following stable co-expression of ATP8 and ATP6. Thus, we report the stable allotopic expression, import and function of two mitochondria encoded genes, ATP8 and ATP6, resulting in simultaneous rescue of the loss of both mitochondrial proteins. PMID:27596602

  4. Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal tubular renin levels in null mutant mice

    PubMed Central

    Prieto, Minolfa C; Das, Subhankar; Somanna, Naveen K; Harrison-Bernard, Lisa M; Navar, L Gabriel; Pandey, Kailash N

    2012-01-01

    Atrial natriuretic peptide (ANP) exerts an inhibitory effect on juxtaglomerular (JG) renin synthesis and release by activating guanylyl cyclase/ natriuretic peptide receptor-A (GC-A/NPRA). Renin has also been localized in connecting tubule cells; however, the effect of ANP/NPRA signaling on tubular renin has not been determined. In the present study, we determined the role of NPRA in regulating both JG and tubular renin using Npr1 (coding for NPRA) gene-disrupted mice, which exhibit a hypertensive phenotype. Renin-positive immunoreactivity in Npr1-/- homozygous null mutant mice was significantly reduced compared with Npr1+/+ wild-type mice (23% vs 69% renin-positive glomeruli). However, after chronic diuretic treatment, Npr1-/- mice showed an increment of JG renin immunoreactivity compared with Npr1+/+ mice (70% vs 81% renin-positive glomeruli). There were no significant differences in the distal tubule renin between Npr1+/+ and Npr1-/- mice. However, after diuretic treatment, Npr1-/- mice showed a significant decrease in renin immunoreactivity in principal cells of cortical collecting ducts (p<0.05). The increased JG renin immunoreactivity after reduction in blood pressure in diuretic-treated Npr1-/- mice, demonstrates an inhibitory action of ANP/NPRA system on JG renin; however, a decreased expression of distal tubular renin suggests a differential effect of ANP/NPRA signaling on JG and distal tubular renin. PMID:23071870

  5. A cyanobacterial light activated adenylyl cyclase partially restores development of a Dictyostelium discoideum, adenylyl cyclase a null mutant.

    PubMed

    Chen, Zhi-Hui; Raffelberg, Sarah; Losi, Aba; Schaap, Pauline; Gärtner, Wolfgang

    2014-12-10

    A light-regulated adenylyl cyclase, mPAC, was previously identified from the cyanobacterium Microcoleus chthonoplastes PCC7420. MPAC consists of a flavin-based blue light-sensing LOV domain and a catalytic domain. In this work, we expressed mPAC in an adenylate cyclase A null mutant (aca-) of the eukaryote Dictyostelium discoideum and tested to what extent light activation of mPAC could restore the cAMP-dependent developmental programme of this organism. Amoebas of Dictyostelium, a well-established model organism, generate and respond to cAMP pulses, which cause them to aggregate and construct fruiting bodies. mPAC was expressed under control of a constitutive actin-15 promoter in D. discoideum and displayed low basal adenylyl cyclase activity in darkness that was about five-fold stimulated by blue light. mPAC expression in aca- cells marginally restored aggregation and fruiting body formation in darkness. However, more and larger fruiting bodies were formed when mPAC expressing cells were incubated in light. Extending former applications of light-regulated AC, these results demonstrate that mPAC can be used to manipulate multicellular development in eukaryotes in a light dependent manner.

  6. Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets

    PubMed Central

    Zhou, Lili; Summa, Keith C.; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.

    2016-01-01

    Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε−/− and CK1εtau/tau mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1εtau/tau mice on a 24 hr LD cycle, a separate set of CK1εtau/tau mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1ε−/− and CK1εtau/tau mutants on a 24 hr LD cycle and CK1εtau/tau mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1εtau/tau mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. PMID:27144030

  7. Characterization of a New Pink-Fruited Tomato Mutant Results in the Identification of a Null Allele of the SlMYB12 Transcription Factor.

    PubMed

    Fernandez-Moreno, Josefina-Patricia; Tzfadia, Oren; Forment, Javier; Presa, Silvia; Rogachev, Ilana; Meir, Sagit; Orzaez, Diego; Aharoni, Aspah; Granell, Antonio

    2016-07-01

    The identification and characterization of new tomato (Solanum lycopersicum) mutants affected in fruit pigmentation and nutritional content can provide valuable insights into the underlying biology, as well as a source of new alleles for breeding programs. To date, all characterized pink-pigmented tomato fruit mutants appear to result from low SlMYB12 transcript levels in the fruit skin. Two new mutant lines displaying a pink fruit phenotype (pf1 and pf2) were characterized in this study. In the pf mutants, SlMYB12 transcripts accumulated to wild-type levels but exhibited the same truncation, which resulted in the absence of the essential MYB activation domain coding region. Allelism and complementation tests revealed that both pf mutants were allelic to the y locus and showed the same recessive null allele in homozygosis: Δy A set of molecular and metabolic effects, reminiscent of those observed in the Arabidopsis (Arabidopsis thaliana) myb11 myb12 myb111 triple mutant, were found in the tomato Δy mutants. To our knowledge, these have not been described previously, and our data support the idea of their being null mutants, in contrast to previously described transcriptional hypomorphic pink fruit lines. We detected a reduction in the expression of several flavonol glycosides and some associated glycosyl transferases. Transcriptome analysis further revealed that the effects of the pf mutations extended beyond the flavonoid pathway into the interface between primary and secondary metabolism. Finally, screening for Myb-binding sites in the candidate gene promoter sequences revealed that 141 of the 152 co-down-regulated genes may be direct targets of SlMYB12 regulation.

  8. A human FSHB transgene encoding the double N-glycosylation mutant (Asn(7Δ) Asn(24Δ)) FSHβ subunit fails to rescue Fshb null mice.

    PubMed

    Wang, Huizhen; Butnev, Vladimir; Bousfield, George R; Kumar, T Rajendra

    2016-05-05

    Follicle-stimulating hormone (FSH) is a gonadotrope-derived heterodimeric glycoprotein. Both the common α- and hormone-specific β subunits contain Asn-linked N-glycan chains. Recently, macroheterogeneous FSH glycoforms consisting of β-subunits that differ in N-glycan number were identified in pituitaries of several species and subsequently the recombinant human FSH glycoforms biochemically characterized. Although chemical modification and in vitro site-directed mutagenesis studies defined the roles of N-glycans on gonadotropin subunits, in vivo functional analyses in a whole-animal setting are lacking. Here, we have generated transgenic mice with gonadotrope-specific expression of either an HFSHB(WT) transgene that encodes human FSHβ WT subunit or an HFSHB(dgc) transgene that encodes a human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, and separately introduced these transgenes onto Fshb null background using a genetic rescue strategy. We demonstrate that the human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, unlike human FSHβ WT subunit, inefficiently combines with the mouse α-subunit in pituitaries of Fshb null mice. FSH dimer containing this mutant FSHβ subunit is inefficiently secreted with very low levels detectable in serum. Fshb null male mice expressing HFSHB(dgc) transgene are fertile and exhibit testis tubule size and sperm number similar to those of Fshb null mice. Fshb null female mice expressing the mutant, but not WT human FSHβ subunit-containing FSH dimer are infertile, demonstrate no evidence of estrus cycles, and many of the FSH-responsive genes remain suppressed in their ovaries. Thus, HFSHB(dgc) unlike HFSHB(WT) transgene does not rescue Fshb null mice. Our genetic approach provides direct in vivo evidence that N-linked glycans on FSHβ subunit are essential for its efficient assembly with the α-subunit to form FSH heterodimer in pituitary. Our studies also reveal that N-glycans on FSHβ subunit are

  9. Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice.

    PubMed

    Bojovic, B; Ho, H-Y; Wu, J; Crowe, D L

    2013-10-24

    To examine the role of telomeric repeat-binding factor 2 (TRF2) in epithelial tumorigenesis, we characterized conditional loss of TRF2 expression in the basal layer of mouse epidermis. These mice exhibit some characteristics of dyskeratosis congenita, a human stem cell depletion syndrome caused by telomere dysfunction. The epidermis in conditional TRF2 null mice exhibited DNA damage response and apoptosis, which correlated with stem cell depletion. The stem cell population in conditional TRF2 null epidermis exhibited shorter telomeres than those in control mice. Squamous cell carcinomas induced in conditional TRF2 null mice developed with increased latency and slower growth due to reduced numbers of proliferating cells as the result of increased apoptosis. TRF2 null epidermal stem cells were found in both primary and metastatic tumors. Despite the low-grade phenotype of the conditional TRF2 null primary tumors, the number of metastatic lesions was similar to control cancers. Basal cells from TRF2 null tumors demonstrated extreme telomere shortening and dramatically increased numbers of telomeric signals by fluorescence in situ hybridization due to increased genomic instability and aneuploidy in these cancers. DNA damage response signals were detected at telomeres in TRF2 null tumor cells from these mice. The increased genomic instability in these tumors correlated with eightfold expansion of the transformed stem cell population compared with that in control cancers. We concluded that genomic instability resulting from loss of TRF2 expression provides biological advantages to the cancer stem cell population.

  10. Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism.

    PubMed

    El-Kordi, Ahmed; Winkler, Daniela; Hammerschmidt, Kurt; Kästner, Anne; Krueger, Dilja; Ronnenberg, Anja; Ritter, Caroline; Jatho, Jasmin; Radyushkin, Konstantin; Bourgeron, Thomas; Fischer, Julia; Brose, Nils; Ehrenreich, Hannelore

    2013-08-15

    Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a 'synapse disorder'. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity.

  11. Coenzyme Q supplementation or over-expression of the yeast Coq8 putative kinase stabilizes multi-subunit Coq polypeptide complexes in yeast coq null mutants*

    PubMed Central

    He, Cuiwen H.; Xie, Letian X.; Allan, Christopher M.; Tran, UyenPhuong C.; Clarke, Catherine F.

    2014-01-01

    Coenzyme Q biosynthesis in yeast requires a multi-subunit Coq polypeptide complex. Deletion of any one of the COQ genes leads to respiratory deficiency and decreased levels of the Coq4, Coq6, Coq7, and Coq9 polypeptides, suggesting that their association in a high molecular mass complex is required for stability. Over-expression of the putative Coq8 kinase in certain coq null mutants restores steady-state levels of the sensitive Coq polypeptides and promotes the synthesis of late-stage Q-intermediates. Here we show that over-expression of Coq8 in yeast coq null mutants profoundly affects the association of several of the Coq polypeptides in high molecular mass complexes, as assayed by separation of digitonin extracts of mitochondria by two-dimensional blue-native/SDS PAGE. The Coq4 polypeptide persists at high molecular mass with over-expression of Coq8 in coq3, coq5, coq6, coq7, coq9, and coq10 mutants, indicating that Coq4 is a central organizer of the Coq complex. Supplementation with exogenous Q6 increased the steady-state levels of Coq4, Coq7, Coq9, and several other mitochondrial polypeptides in select coq null mutants, and also promoted the formation of late-stage Q-intermediates. Q supplementation may stabilize this complex by interacting with one or more of the Coq polypeptides. The stabilizing effects of exogenously added Q6 or over-expression of Coq8 depend on Coq1 and Coq2 production of a polyisoprenyl intermediate. Based on the observed interdependence of the Coq polypeptides, the effect of exogenous Q6, and the requirement for an endogenously produced polyisoprenyl intermediate, we propose a new model for the Q-biosynthetic complex, termed the CoQ-synthome. PMID:24406904

  12. A (p)ppGpp-null mutant of Haemophilus ducreyi is partially attenuated in humans due to multiple conflicting phenotypes.

    PubMed

    Holley, Concerta; Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

    2014-08-01

    (p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species. Haemophilus ducreyi, the causative agent of chancroid, has homologs of both relA and spoT, which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We constructed relA and relA spoT deletion mutants to assess the contribution of (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in trans. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of lspB, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In E. coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi double mutant expressed higher transcript levels of dksA than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.

  13. Analysis of the presence of cell proliferation-related molecules in the Tgf-β3 null mutant mouse palate reveals misexpression of EGF and Msx-1.

    PubMed

    del Río, A; Barrio, M C; Murillo, J; Maldonado, E; López-Gordillo, Y; Martínez-Sanz, E; Martínez, M L; Martínez-Álvarez, C

    2011-01-01

    The Tgf-β(3) null mutant mouse palate presents several cellular anomalies that lead to the appearance of cleft palate. One of them concerns the cell proliferation of both the palatal medial edge epithelium and mesenchyme. In this work, our aim was to determine whether there was any variation in the presence/distribution of several cell proliferation-related molecules that could be responsible for the cell proliferation defects observed in these palates. Our results showed no difference in the presence of EGF-R, PDGF-A, TGF-β(2), Bmp-2, and Bmp-4, and differences were minimal for FGF-10 and Shh. However, the expression of EGF and Msx-1 changed substantially. The shift of the EGF protein expression was the one that most correlated with that of cell proliferation. This molecule is regulated by TGF-β(3), and experiments blocking its activity in culture suggest that EGF misexpression in the Tgf-β(3) null mutant mouse palate plays a role in the cell proliferation defect observed.

  14. Developmental delay in a Streptomyces venezuelae glgE null mutant is associated with the accumulation of α-maltose 1-phosphate.

    PubMed

    Miah, Farzana; Bibb, Maureen J; Barclay, J Elaine; Findlay, Kim C; Bornemann, Stephen

    2016-07-01

    The GlgE pathway is thought to be responsible for the conversion of trehalose into a glycogen-like α-glucan polymer in bacteria. Trehalose is first converted to maltose, which is phosphorylated by maltose kinase Pep2 to give α-maltose 1-phosphate. This is the donor substrate of the maltosyl transferase GlgE that is known to extend α-1,4-linked maltooligosaccharides, which are thought to be branched with α-1,6 linkages. The genome of Streptomyces venezuelae contains all the genes coding for the GlgE pathway enzymes but none of those of related pathways, including glgC and glgA of the glycogen pathway. This provides an opportunity to study the GlgE pathway in isolation. The genes of the GlgE pathway were upregulated at the onset of sporulation, consistent with the known timing of α-glucan deposition. A constructed ΔglgE null mutant strain was viable but showed a delayed developmental phenotype when grown on maltose, giving less cell mass and delayed sporulation. Pre-spore cells and spores of the mutant were frequently double the length of those of the wild-type, implying impaired cross-wall formation, and spores showed reduced tolerance to stress. The mutant accumulated α-maltose 1-phosphate and maltose but no α-glucan. Therefore, the GlgE pathway is necessary and sufficient for polymer biosynthesis. Growth of the ΔglgE mutant on galactose and that of a Δpep2 mutant on maltose were analysed. In both cases, neither accumulation of α-maltose 1-phosphate/α-glucan nor a developmental delay was observed. Thus, high levels of α-maltose 1-phosphate are responsible for the developmental phenotype of the ΔglgE mutant, rather than the lack of α-glucan.

  15. Developmental delay in a Streptomyces venezuelae glgE null mutant is associated with the accumulation of α-maltose 1-phosphate

    PubMed Central

    Miah, Farzana; Bibb, Maureen J.; Barclay, J. Elaine; Findlay, Kim C.

    2016-01-01

    The GlgE pathway is thought to be responsible for the conversion of trehalose into a glycogen-like α-glucan polymer in bacteria. Trehalose is first converted to maltose, which is phosphorylated by maltose kinase Pep2 to give α-maltose 1-phosphate. This is the donor substrate of the maltosyl transferase GlgE that is known to extend α-1,4-linked maltooligosaccharides, which are thought to be branched with α-1,6 linkages. The genome of Streptomyces venezuelae contains all the genes coding for the GlgE pathway enzymes but none of those of related pathways, including glgC and glgA of the glycogen pathway. This provides an opportunity to study the GlgE pathway in isolation. The genes of the GlgE pathway were upregulated at the onset of sporulation, consistent with the known timing of α-glucan deposition. A constructed ΔglgE null mutant strain was viable but showed a delayed developmental phenotype when grown on maltose, giving less cell mass and delayed sporulation. Pre-spore cells and spores of the mutant were frequently double the length of those of the wild-type, implying impaired cross-wall formation, and spores showed reduced tolerance to stress. The mutant accumulated α-maltose 1-phosphate and maltose but no α-glucan. Therefore, the GlgE pathway is necessary and sufficient for polymer biosynthesis. Growth of the ΔglgE mutant on galactose and that of a Δpep2 mutant on maltose were analysed. In both cases, neither accumulation of α-maltose 1-phosphate/α-glucan nor a developmental delay was observed. Thus, high levels of α-maltose 1-phosphate are responsible for the developmental phenotype of the ΔglgE mutant, rather than the lack of α-glucan. PMID:27121970

  16. Gamma Interferon (IFN-γ) Receptor Null-Mutant Mice Are More Susceptible to Herpes Simplex Virus Type 1 Infection than IFN-γ Ligand Null-Mutant Mice

    PubMed Central

    Cantin, Edouard; Tanamachi, Becky; Openshaw, Harry; Mann, Jeff; Clarke, Ken

    1999-01-01

    Mouse strains with null mutations in the gamma interferon gene (Ifng) or the gamma interferon receptor gene (Ifngr) have been engineered. The use of these strains as animal models of viral and bacterial infections has enhanced our understanding of the role of gamma interferon (IFN-γ) in the host immune response. However, direct comparisons between Ifng−/− (GKO) and Ifngr−/− (RGKO) mice have been problematic because previously available strains of these mice have had different genetic backgrounds (i.e., C57BL/6 and BALB/c for GKO mice and 129/Sv//Ev for RGKO mice). To enable direct comparison of herpes simplex virus type 1 (HSV-1) infections in GKO and RGKO mice, we introduced the IFN-γ null mutation into the 129/Sv//Ev background. We report that, after HSV-1 inoculation, mortality was significantly greater in RGKO mice than in GKO mice (38 versus 23%, P = 0.0001). Similarly, the mortality from vaccinia virus challenge was significantly greater in RGKO mice than in GKO mice. With differences in genetic background excluded as a confounding issue, these results are consistent with the existence of an alternative ligand(s) for the IFN-γ receptor that is also capable of mediating protection against viral challenge. PMID:10233988

  17. FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

    PubMed Central

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-01-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (−/−) mice. After a 10 mg/kg methamphetamine injection, FosB(−/−) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(−/−) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(−/−) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(−/−) mice. In addition, methamphetamine-treated FosB(−/−) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood–brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood–brain barrier, and metabolism of serine and glycine, which are important

  18. FosB null mutant mice show enhanced methamphetamine neurotoxicity: potential involvement of FosB in intracellular feedback signaling and astroglial function.

    PubMed

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-02-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (-/-) mice. After a 10 mg/kg methamphetamine injection, FosB(-/-) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(-/-) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(-/-) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(-/-) mice. In addition, methamphetamine-treated FosB(-/-) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood-brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood-brain barrier, and metabolism of serine and glycine, which are important glial modulators of nerve cells.

  19. The physiological roles of membrane ergosterol as revealed by the phenotypes of syr1/erg3 null mutant of Saccharomyces cerevisiae.

    PubMed

    Hemmi, K; Julmanop, C; Hirata, D; Tsuchiya, E; Takemoto, J Y; Miyakawa, T

    1995-03-01

    Ergosterol is a major sterol component of fungal plasma membranes. The effects of disrupting the Saccharomyces cerevisiae SYR1/ERG3 gene, which encodes sterol C-5 desaturase, an enzyme of ergosterol biosynthesis pathway, were markedly different for different S. cerevisiae strains and growth temperatures. The null mutation of SYR1 (delta syr1) in strain RAY-3A had only a slight effect on the growth rate at 28 degrees C. However, at this temperature, the same mutation caused poor growth in strain KA-311A and no growth in strain W303-1A. The delta syr1 disruptant of these strains were able to grow at 37 degrees C, as well as their parental strains. Moreover, the growth of the delta syr1 disruptant of W303-1A and KA-311A strains were severely inhibited at 16 degrees C. These results indicated that ergosterol is essential for growth at low temperatures, and the effects of the gene disruption are variable by the genetic background. The growth defect at low temperatures appeared to be due to the defect of tryptophan uptake in the delta syr1 mutants. The delta syr1 mutants were sensitive to a wide variety of drugs, chemicals, and ions, suggesting that yeast ergosterol is important as permeability barrier against various chemical stresses.

  20. Pathogenic potential of SLC25A15 mutations assessed by transport assays and complementation of Saccharomyces cerevisiae ORT1 null mutant.

    PubMed

    Marobbio, Carlo M T; Punzi, Giuseppe; Pierri, Ciro L; Palmieri, Luigi; Calvello, Rosa; Panaro, Maria A; Palmieri, Ferdinando

    2015-05-01

    HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 gene encoding the mitochondrial ornithine carrier 1, which catalyzes the transport of cytosolic ornithine into the mitochondria in exchange for intramitochondrial citrulline. In this study the functional effects of several SLC25A15 missense mutations p.G27R, p.M37R, p.N74A, p.F188L, p.F188Y, p.S200K, p.R275Q and p.R275K have been tested by transport assays in reconstituted liposomes and complementation of Saccharomyces cerevisiae ORT1 null mutant in arginine-less synthetic complete medium. The HHH syndrome-causing mutations p.G27R, p.M37R, p.F188L and p.R275Q had impaired transport and did not complement ORT1∆ cells (except p.M37R slightly after 5 days in solid medium). The experimentally produced mutations p.N74A, p.S200K and p.R275K exhibited normal or considerable transport activity and complemented ORT1∆ cells after 3 days (p.N74A, p.S200K) or 5 days (p.R275K) incubation. Furthermore, the experimentally produced p.F188Y mutation displayed a substantial transport activity but did not complement the ORT1∆ cells in both liquid and solid media. In view of the disagreement in the results obtained between the two methods, it is recommended that the method of complementing the S. cerevisiae ORT1 knockout strain is used complimentary with the measurement of the catalytic activity, in order to distinguish HHH syndrome-causing mutations from isomorphisms.

  1. Cold-active DnaK of an Antarctic psychrotroph Shewanella sp. Ac10 supporting the growth of dnaK-null mutant of Escherichia coli at cold temperatures.

    PubMed

    Yoshimune, Kazuaki; Galkin, Andrey; Kulakova, Ljudmila; Yoshimura, Tohru; Esaki, Nobuyoshi

    2005-04-01

    Shewanella sp. Ac10 is a psychrotrophic bacterium isolated from the Antarctica that actively grows at such low temperatures as 0 degrees C. Immunoblot analyses showed that a heat-shock protein DnaK is inducibly formed by the bacterium at 24 degrees C, which is much lower than the temperatures causing heat shock in mesophiles such as Escherichia coli. We found that the Shewanella DnaK (SheDnaK) shows much higher ATPase activity at low temperatures than the DnaK of E. coli (EcoDnaK): a characteristic of a cold-active enzyme. The recombinant SheDnaK gene supported neither the growth of a dnaK-null mutant of E. coli at 43 degrees C nor lambda phage propagation at an even lower temperature, 30 degrees C. However, the recombinant SheDnaK gene enabled the E. coli mutant to grow at 15 degrees C. This is the first report of a DnaK supporting the growth of a dnaK-null mutant at low temperatures.

  2. Arabidopsis AtDjA3 Null Mutant Shows Increased Sensitivity to Abscisic Acid, Salt, and Osmotic Stress in Germination and Post-germination Stages

    PubMed Central

    Salas-Muñoz, Silvia; Rodríguez-Hernández, Aída A.; Ortega-Amaro, Maria A.; Salazar-Badillo, Fatima B.; Jiménez-Bremont, Juan F.

    2016-01-01

    DnaJ proteins are essential co-chaperones involved in abiotic and biotic stress responses. Arabidopsis AtDjA3 gene encodes a molecular co-chaperone of 420 amino acids, which belongs to the J-protein family. In this study, we report the functional characterization of the AtDjA3 gene using the Arabidopsis knockout line designated j3 and the 35S::AtDjA3 overexpression lines. Loss of AtDjA3 function was associated with small seed production. In fact, j3 mutant seeds showed a reduction of 24% in seed weight compared to Col-0 seeds. Expression analysis showed that the AtDjA3 gene was modulated in response to NaCl, glucose, and abscisic acid (ABA). The j3 line had increased sensitivity to NaCl and glucose treatments in the germination and cotyledon development in comparison to parental Col-0. Furthermore, the j3 mutant line exhibited higher ABA sensitivity in comparison to parental Col-0 and 35S::AtDjA3 overexpression lines. In addition, we examined the expression of ABI3 gene, which is a central regulator in ABA signaling, in j3 mutant and 35S::AtDjA3 overexpression lines. Under 5 μM ABA treatment at 24 h, j3 mutant seedlings displayed higher ABI3 expression, whereas in 35S::AtDjA3 overexpression lines, ABI3 gene expression was repressed. Taken together, these results demonstrate that the AtDjA3 gene is involved in seed development and abiotic stress tolerance. PMID:26941772

  3. Characterization of Pi-repressible enzymes secreted in culture media by Neurospora crassa wild-type cells and null-type mutants.

    PubMed Central

    Furukawa, K; Hasunuma, K; Shinohara, Y

    1987-01-01

    In wild-type mycelial cultures of Neurospora crassa under Pi-limited conditions, alkaline phosphatase, cyclic phosphodiesterases I, II, III, and IV, 5'-nucleotidase, acid and alkaline nucleases, RNase N1, and a newly detected endonuclease were secreted into the culture media. These enzymes were either not produced or were produced in very reduced levels in mutants nuc-1, -2, -3, -4, -5, -6, and -7 and cpd-4. The proteins were examined by polyacrylamide gel electrophoresis in a manner which allowed the identification of each of them. Images PMID:2820943

  4. Diguanylate cyclase null mutant reveals that C-Di-GMP pathway regulates the motility and adherence of the extremophile bacterium Acidithiobacillus caldus.

    PubMed

    Castro, Matías; Deane, Shelly M; Ruiz, Lina; Rawlings, Douglas E; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process.

  5. Diguanylate Cyclase Null Mutant Reveals That C-Di-GMP Pathway Regulates the Motility and Adherence of the Extremophile Bacterium Acidithiobacillus caldus

    PubMed Central

    Castro, Matías; Deane, Shelly M.; Ruiz, Lina; Rawlings, Douglas E.; Guiliani, Nicolas

    2015-01-01

    An understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. For this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. In many bacteria, the intracellular levels of c-di-GMP molecules regulate the transition from the motile planktonic state to sessile community-based behaviors, such as biofilm development, through different kinds of effectors. Thus, we recently started a study of the c-di-GMP pathway in several biomining bacteria including Acidithiobacillus caldus. C-di-GMP molecules are synthesized by diguanylate cyclases (DGCs) and degraded by phosphodiesterases (PDEs). We previously reported the existence of intermediates involved in c-di-GMP pathway from different Acidithiobacillus species. Here, we report our work related to At. caldus ATCC 51756. We identified several putative-ORFs encoding DGC and PDE and effector proteins. By using total RNA extracted from At. caldus cells and RT-PCR, we demonstrated that these genes are expressed. We also demonstrated the presence of c-di-GMP by mass spectrometry and showed that genes for several of the DGC enzymes were functional by heterologous genetic complementation in Salmonella enterica serovar Typhimurium mutants. Moreover, we developed a DGC defective mutant strain (Δc1319) that strongly indicated that the c-di-GMP pathway regulates the swarming motility and adherence to sulfur surfaces by At. caldus. Together, our results revealed that At. caldus possesses a functional c-di-GMP pathway which could be significant for ores colonization during the bioleaching process. PMID:25689133

  6. Temporal expression of agrB, cidA, and alsS in the early development of Staphylococcus aureus UAMS-1 biofilm formation and the structural role of extracellular DNA and carbohydrates.

    PubMed

    Grande, Rossella; Nistico, Laura; Sambanthamoorthy, Karthik; Longwell, Mark; Iannitelli, Antonio; Cellini, Luigina; Di Stefano, Antonio; Hall Stoodley, Luanne; Stoodley, Paul

    2014-04-01

    Extracellular DNA (eDNA) is an important component of the extracellular polymeric substance matrix and is important in the establishment and persistence of Staphylococcus aureus UAMS-1 biofilms. The aim of the study was to determine the temporal expression of genes involved in early biofilm formation and eDNA production. We used qPCR to investigate expression of agrB, which is associated with secreted virulence factors and biofilm dispersal, cidA, which is associated with biofilm adherence and genomic DNA release, and alsS, which is associated with cell lysis, eDNA release and acid tolerance. The contribution of eDNA to the stability of the biofilm matrix was assessed by digesting with DNase I (Pulmozyme) and quantifying structure by confocal microscopy and comstat image analysis. AgrB expression initially increased at 24 h but then dramatically decreased at 72 h in an inverse relationship to biomass, supporting its role in regulating biofilm dispersal. cidA and alsS expression steadily increased over 72 h, suggesting that eDNA was an important component of early biofilm development. DNase I had no effect on biomass, but did cause the biofilms to become more heterogeneous. Carbohydrates in the matrix appeared to play an important role in structural stability.

  7. Null Killing vectors

    NASA Astrophysics Data System (ADS)

    Lukács, B.; Perjés, Z.; Sebestyén, Á.

    1981-06-01

    Space-times admitting a null Killing vector are studied, using the Newman-Penrose spin coefficient formalism. The properties of the eigenrays (principal null curves of the Killing bivector) are shown to be related to the twist of the null Killing vector. Among the electrovacs, the ones containing a null Maxwell field turn out to belong to the twist-free class. An electrovac solution is obtained for which the null Killing vector is twisting and has geodesic and shear-free eigenrays. This solution is parameterless and appears to be the field of a zero-mass, spinning, and charged source.

  8. Nulling Breadboard for DARWIN

    NASA Astrophysics Data System (ADS)

    Flatscher, Reinhold; Johann, Ulrich; Sodnik, Zoran

    2003-02-01

    This work is funded by ESA under ESTEC/Contract No. 14827/00/NL/CK. Astrium Germany has been awarded this first ESA breadboarding towards nulling interferometry. Interferometric nulling devices are essential ingredients in the TPF and DARWIN missions for suppressing the star light by a factor of 106 over a wide wavelength range in the mid infrared. The current DARWIN baseline concept comprises six telescopes. The coherent combination scheme in the nulling mode operation foresees three nulling assemblies in parallel. The breadboard serves to demonstrate the deep and stable null required for an operational instrument. The demonstrator operates in the near infrared to save costs but its principle is fully applicable to the mid infrared. The nulling device is based on an autobalancing Sagnac core offering just one critical beam combiner. Two different ways of achieving the required π phase shift are implemented: a) arbitrary phase shift by dispersive phase shifter plates b) phase shift of π using periscopes (image flip) The target simulator features two point sources of adjustable radiometry and angular separation, representing a strong star and a weak planet. In addition, the sources can be also used to simulate a double star for demonstrating the basic DARWIN imaging mode. The simulator can be operated in two styles, namely as wavefront dividing star/planet source and, alternatively, as an amplitude dividing source, providing highly symmetric wavefronts to both interferometer arms. Because of its representativity for the DARWIN situation, the latter mode is the preferred simulator for quantitative nulling experiments. The breadboard design has been finalized in January 2002 and verified by detailed simulations. The entire hardware has been manufactured by end of July. Currently, nulling and imaging measurements are in progress to validate the per-formance of the selected approach. The project is part of ESA´s technology preparatory program for DARWIN, paving the

  9. lagC-null and gbf-null cells define key steps in the morphogenesis of Dictyostelium mounds.

    PubMed

    Sukumaran, S; Brown, J M; Firtel, R A; McNally, J G

    1998-08-01

    The transition to multicellularity is a key feature of the Dictyostelium life cycle, and two genes, gbf and lagC, are known to play pivotal roles in regulating this developmental switch. lagC-null and gbf-null cells fail to induce cell-type-specific genes ordinarily expressed during multicellular development. The null mutants also share a similar morphological phenotype: mutant cells repeatedly aggregate to form a loose mound, disperse, and reform a mound, rather than proceeding to form a tip. To characterize defects in morphogenesis in these mutants, we examined cell motion in the mutant mounds. In analogy with the failed transition in gene expression, we found that lagC-null and gbf-null mounds failed to make a morphogenetic transition from random to rotational motion normally observed in the parent strain. One reason for this was the inability of the mutant mounds to establish a single, dominant signaling-wave center. This defect of lagC-null or gbf-null cells could be overcome by the addition of adenosine, which alters cAMP signaling, but then even in the presence of apparently normal signaling waves, cell motility was still aberrant. This motility defect, as well as the signaling-wave defect, could be overcome in lagC-null cells by overexpression of GBF, suggesting that lagC is dispensable if GBF protein levels are high enough. This set of morphogenetic defects that we have observed helps define key steps in mound morphogenesis. These include the establishment of a dominant signaling-wave center and the capacity of cells to move directionally within the cell mass in response to guidance cues.

  10. slender rice, a constitutive gibberellin response mutant, is caused by a null mutation of the SLR1 gene, an ortholog of the height-regulating gene GAI/RGA/RHT/D8.

    PubMed

    Ikeda, A; Ueguchi-Tanaka, M; Sonoda, Y; Kitano, H; Koshioka, M; Futsuhara, Y; Matsuoka, M; Yamaguchi, J

    2001-05-01

    The rice slender mutant (slr1-1) is caused by a single recessive mutation and results in a constitutive gibberellin (GA) response phenotype. The mutant elongates as if saturated with GAs. In this mutant, (1) elongation was unaffected by an inhibitor of GA biosynthesis, (2) GA-inducible alpha-amylase was produced by the aleurone layers without gibberellic acid application, and (3) endogenous GA content was lower than in the wild-type plant. These results indicate that the product of the SLR1 gene is an intermediate of the GA signal transduction pathway. SLR1 maps to OsGAI in rice and has significant homology with height-regulating genes, such as RHT-1Da in wheat, D8 in maize, and GAI and RGA in Arabidopsis. The GAI gene family is likely to encode transcriptional factors belonging to the GRAS gene superfamily. DNA sequence analysis revealed that the slr1-1 mutation is a single basepair deletion of the nuclear localization signal domain, resulting in a frameshift mutation that abolishes protein production. Furthermore, introduction of a 6-kb genomic DNA fragment containing the wild-type SLR1 gene into the slr1-1 mutant restored GA sensitivity to normal. These results indicate that the slr1-1 mutant is caused by a loss-of-function mutation of the SLR1 gene, which is an ortholog of GAI, RGA, RHT, and D8. We also succeeded in producing GA-insensitive dwarf rice by transforming wild-type rice with a modified SLR1 gene construct that has a 17-amino acid deletion affecting the DELLA region. Thus, we demonstrate opposite GA response phenotypes depending on the type of mutations in SLR1.

  11. Under light limiting growth, CpcB lyase null mutants of the Cyanobacterium Synechococcus sp. PCC 7002 are capable of producing pigmented beta phycocyanin but with altered chromophore function.

    PubMed

    Derks, Allen K; Vasiliev, Serguei; Bruce, Doug

    2008-11-11

    Phycobilisomes are the major light-harvesting complexes for cyanobacteria, and phycocyanin is the primary phycobiliprotein of the phycobilisome rod. Phycocyanobilin chromophores are covalently bonded to the phycocyanin beta subunit (CpcB) by specific lyases which have been recently identified in the cyanobacterium Synechococcus sp. PCC 7002. Surprisingly, we found that mutants missing the CpcB lyases were nevertheless capable of producing pigmented phycocyanin when grown under low-light conditions. Absorbance measurements at 10 K revealed the energy states of the beta phycocyanin chromophores to be slightly shifted, and 77 K steady state fluorescence emission spectroscopy showed that excitation energy transfer involving the targeted chromophores was disrupted. This evidence indicates that the position of the phycocyanobilin chromophore within the binding domain of the phycocyanin beta subunit had been modified. We hypothesize that alternate, less specific lyases are able to add chromophores, with varying effectiveness, to the beta binding sites.

  12. Interferometric Remapped Array Nulling

    NASA Astrophysics Data System (ADS)

    Abe, L.; Aristidi, E.; Vakili, F.; Domiciano, A.

    We present an interferometric beam recombination technique which allows achromatic and direct true imaging of targets at very high angular resolution. This technique intrinsically overcomes the main problems of Labeyrie's hypertelescope design, and can be used in a nulling configuration. It is thus particularly well suited for high contrast imaging in the context of exo-planet search and characterization especially for future space-borne arrays. We present the concept on a formal basis, and discuss its instrumental implementation.

  13. Mutator phenotype of MUTYH-null mouse embryonic stem cells.

    PubMed

    Hirano, Seiki; Tominaga, Yohei; Ichinoe, Akimasa; Ushijima, Yasuhiro; Tsuchimoto, Daisuke; Honda-Ohnishi, Yoko; Ohtsubo, Toshio; Sakumi, Kunihiko; Nakabeppu, Yusaku

    2003-10-03

    To evaluate the antimutagenic role of a mammalian mutY homolog, namely the Mutyh gene, which encodes adenine DNA glycosylase excising adenine misincorporated opposite 8-oxoguanine in the template DNA, we generated MUTYH-null mouse embryonic stem (ES) cells. In the MUTYH-null cells carrying no adenine DNA glycosylase activity, the spontaneous mutation rate increased 2-fold in comparison with wild type cells. The expression of wild type mMUTYH or mutant mMUTYH protein with amino acid substitutions at the proliferating cell nuclear antigen binding motif restored the increased spontaneous mutation rates of the MUTYH-null ES cells to the wild type level. The expression of a mutant mMUTYH protein with an amino acid substitution (G365D) that corresponds to a germ-line mutation (G382D) found in patients with multiple colorectal adenomas could not suppress the elevated spontaneous mutation rate of the MUTYH-null ES cells. Although the recombinant mMUTYH(G365D) purified from Escherichia coli cells had a substantial level of adenine DNA glycosylase activity as did wild type MUTYH, no adenine DNA glycosylase activity was detected in the MUTYH-null ES cells expressing the mMUTYH(G365D) mutant protein. The germ-line mutation (G382D) of the human MUTYH gene is therefore likely to be responsible for the occurrence of a mutator phenotype in these patients.

  14. Interferometric Remapped Array Nulling

    NASA Astrophysics Data System (ADS)

    Vakili, F.; Aristidi, E.; Abe, L.; Lopez, B.

    2004-07-01

    This paper describes a method of beam-combination in the so-called hypertelescope imaging technique recently introduced by Labeyrie in optical interferometry. The method we propose is an alternative to the Michelson pupil reconfiguration that suffers from the loss of the classical object-image convolution relation. From elementary theory of Fourier optics we demonstrate that this problem can be solved by reconfiguring images instead of pupils. Imaging is performed in a combined pupil-plane where the point-source intensity distribution (PSID by comparison to the more commonly quoted point-spread function, PSF) tends towards a pseudo Airy disc for a sufficiently large number of telescopes. Our method is applicable to snap-shot imaging of extended sources with a field limited to the Airy pattern of single telescopes operated in a co-phased multi-aperture interferometric array. It thus allows to apply conveniently pupil plane coronagraphy. Our technique called Interferometric Remapped Array Nulling (IRAN) is particularly suitable for high dynamic imaging of extra-solar planetary companions or extra-galactic objects where long baseline interferometry would closely probe the central regions of AGNs for instance. We also discuss the application of IRAN to improve the performances of imaging and/or nulling interferometers like the full-fledged VLTI array or the DARWIN space-borne mission.

  15. Radiant Temperature Nulling Radiometer

    NASA Technical Reports Server (NTRS)

    Ryan, Robert (Inventor)

    2003-01-01

    A self-calibrating nulling radiometer for non-contact temperature measurement of an object, such as a body of water, employs a black body source as a temperature reference, an optomechanical mechanism, e.g., a chopper, to switch back and forth between measuring the temperature of the black body source and that of a test source, and an infrared detection technique. The radiometer functions by measuring radiance of both the test and the reference black body sources; adjusting the temperature of the reference black body so that its radiance is equivalent to the test source; and, measuring the temperature of the reference black body at this point using a precision contact-type temperature sensor, to determine the radiative temperature of the test source. The radiation from both sources is detected by an infrared detector that converts the detected radiation to an electrical signal that is fed with a chopper reference signal to an error signal generator, such as a synchronous detector, that creates a precision rectified signal that is approximately proportional to the difference between the temperature of the reference black body and that of the test infrared source. This error signal is then used in a feedback loop to adjust the reference black body temperature until it equals that of the test source, at which point the error signal is nulled to zero. The chopper mechanism operates at one or more Hertz allowing minimization of l/f noise. It also provides pure chopping between the black body and the test source and allows continuous measurements.

  16. Null testing convex optical surfaces.

    PubMed

    Szulc, A

    1997-09-01

    A new test for convex optical surfaces is presented. It makes use of an auxiliary ellipsoidal mirror that is of approximately the same diameter as the convex mirror tested. The test is a null test of excellent precision. The auxiliary ellipsoid used is also tested in a null fashion, permitting good precision to be obtained.

  17. Gibberellins are involved in effect of near-null magnetic field on Arabidopsis flowering.

    PubMed

    Xu, Chunxiao; Yu, Yang; Zhang, Yuxia; Li, Yue; Wei, Shufeng

    2017-01-01

    We previously found that flowering of Arabidopsis was suppressed by near-null magnetic field, which was related to the modification of cryptochrome. To disclose the physiological mechanism of this effect, we detected gibberellin (GA) levels and expressions of GA biosynthetic and signaling genes in wild type Arabidopsis plants and cryptochrome double mutant, cry1/cry2, grown in near-null magnetic field. We found that levels of GA4 , GA9 , GA34 , and GA51 in wild type plants in near-null magnetic field were significantly decreased compared with local geomagnetic field controls. However, GA levels in cry1/cry2 mutants in near-null magnetic field were similar to controls. Expressions of three GA20-oxidase (GA20ox) genes (GA20ox1, GA20ox2, and GA20ox3) and four GA3-oxidase (GA3ox) genes (GA3ox1, GA3ox2, GA3ox3, and GA3ox4) in wild type plants in near-null magnetic field were significantly reduced compared with controls, while expressions of GA20ox4, GA20ox5, GA2-oxidase (GA2ox) genes, and GA signaling-related genes in wild type plants in near-null magnetic field were not significantly different from controls. In contrast, expressions of all the detected GA biosynthetic and signaling genes in cry1/cry2 mutants were not affected by near-null magnetic field. Moreover, transcriptions of flowering-related genes, LFY and SOC1, in wild type plants were downregulated by near-null magnetic field, while they were not affected by near-null magnetic field in cry1/cry2 mutants. Our results suggest that the effect of near-null magnetic field on Arabidopsis flowering is GA-related, which is caused by cryptochrome-involved suppression of GA biosynthesis. Bioelectromagnetics. 38:1-10, 2017. © 2016 Wiley Periodicals, Inc.

  18. Double targeted gene replacement for creating null mutants.

    PubMed

    Cruz, A; Coburn, C M; Beverley, S M

    1991-08-15

    We have used double gene targeting to create homozygous gene replacements in the protozoan parasite Leishmania major, an asexual diploid. This method uses two independent selectable markers in successive rounds of gene targeting to replace both alleles of an endogenous gene. We developed an improved hygromycin B-resistance cassette encoding hygromycin phosphotransferase (HYG) for use as a selectable marker for Leishmania. HYG-containing vectors functioned equivalently to those containing the neomycin phosphotransferase (NEO) cassette previously used for extrachromosomal transformation or gene targeting. Drug resistances conferred by the NEO and HYG markers were independent, allowing simultaneous selection for both markers. A HYG targeting vector was utilized to replace the single dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene remaining in a line heterozygous for a NEO replacement at the dhfr-ts locus (+/neo), with a targeting efficiency comparable to that seen with wild-type recipients. The resultant dhfr-ts- line (hyg/neo) was auxotrophic for thymidine. The double targeted replacement method will enable functional genetic testing in a variety of asexual diploids, including cultured mammalian cells and fungi such as Candida albicans. Additionally, it may be possible to use Leishmania bearing conditionally auxotrophic gene replacements as safe, improved live vaccines for leishmaniasis.

  19. On the randomness of pulsar nulls

    NASA Astrophysics Data System (ADS)

    Redman, Stephen L.; Rankin, Joanna M.

    2009-05-01

    Pulsar nulling is not always a random process; most pulsars, in fact, null non-randomly. The Wald-Wolfowitz statistical runs test is a simple diagnostic that pulsar astronomers can use to identify pulsars that have non-random nulls. It is not clear at this point how the dichotomy in pulsar nulling randomness is related to the underlying nulling phenomenon, but its nature suggests that there are at least two distinct reasons that pulsars null.

  20. Null lifts and projective dynamics

    SciTech Connect

    Cariglia, Marco

    2015-11-15

    We describe natural Hamiltonian systems using projective geometry. The null lift procedure endows the tangent bundle with a projective structure where the null Hamiltonian is identified with a projective conic and induces a Weyl geometry. Projective transformations generate a set of known and new dualities between Hamiltonian systems, as for example the phenomenon of coupling-constant metamorphosis. We conclude outlining how this construction can be extended to the quantum case for Eisenhart–Duval lifts.

  1. Gravitational action with null boundaries

    NASA Astrophysics Data System (ADS)

    Lehner, Luis; Myers, Robert C.; Poisson, Eric; Sorkin, Rafael D.

    2016-10-01

    We present a complete discussion of the boundary term in the action functional of general relativity when the boundary includes null segments in addition to the more usual timelike and spacelike segments. We confirm that ambiguities appear in the contribution from a null segment, because it depends on an arbitrary choice of parametrization for the generators. We also show that similar ambiguities appear in the contribution from a codimension-two surface at which a null segment is joined to another (spacelike, timelike, or null) segment. The parametrization ambiguity can be tamed by insisting that the null generators be affinely parametrized; this forces each null contribution to the boundary action to vanish, but leaves intact the fredom to rescale the affine parameter by a constant factor on each generator. Once a choice of parametrization is made, the ambiguity in the joint contributions can be eliminated by formulating well-motivated rules that ensure the additivity of the gravitational action. Enforcing these rules, we calculate the time rate of change of the action when it is evaluated for a so-called "Wheeler-DeWitt patch" of a black hole in asymptotically anti de Sitter space. We recover a number of results cited in the literature, obtained with a less complete analysis.

  2. NULL convention floating point multiplier.

    PubMed

    Albert, Anitha Juliette; Ramachandran, Seshasayanan

    2015-01-01

    Floating point multiplication is a critical part in high dynamic range and computational intensive digital signal processing applications which require high precision and low power. This paper presents the design of an IEEE 754 single precision floating point multiplier using asynchronous NULL convention logic paradigm. Rounding has not been implemented to suit high precision applications. The novelty of the research is that it is the first ever NULL convention logic multiplier, designed to perform floating point multiplication. The proposed multiplier offers substantial decrease in power consumption when compared with its synchronous version. Performance attributes of the NULL convention logic floating point multiplier, obtained from Xilinx simulation and Cadence, are compared with its equivalent synchronous implementation.

  3. NULL Convention Floating Point Multiplier

    PubMed Central

    Ramachandran, Seshasayanan

    2015-01-01

    Floating point multiplication is a critical part in high dynamic range and computational intensive digital signal processing applications which require high precision and low power. This paper presents the design of an IEEE 754 single precision floating point multiplier using asynchronous NULL convention logic paradigm. Rounding has not been implemented to suit high precision applications. The novelty of the research is that it is the first ever NULL convention logic multiplier, designed to perform floating point multiplication. The proposed multiplier offers substantial decrease in power consumption when compared with its synchronous version. Performance attributes of the NULL convention logic floating point multiplier, obtained from Xilinx simulation and Cadence, are compared with its equivalent synchronous implementation. PMID:25879069

  4. Achronal averaged null energy condition

    SciTech Connect

    Graham, Noah; Olum, Ken D.

    2007-09-15

    The averaged null energy condition (ANEC) requires that the integral over a complete null geodesic of the stress-energy tensor projected onto the geodesic tangent vector is never negative. This condition is sufficient to prove many important theorems in general relativity, but it is violated by quantum fields in curved spacetime. However there is a weaker condition, which is free of known violations, requiring only that there is no self-consistent spacetime in semiclassical gravity in which ANEC is violated on a complete, achronal null geodesic. We indicate why such a condition might be expected to hold and show that it is sufficient to rule out closed timelike curves and wormholes connecting different asymptotically flat regions.

  5. Suppression of Arabidopsis flowering by near-null magnetic field is affected by light.

    PubMed

    Xu, Chunxiao; Li, Yue; Yu, Yang; Zhang, Yuxia; Wei, Shufeng

    2015-09-01

    We previously reported that a near-null magnetic field suppressed Arabidopsis flowering in white light, which might be related to the function modification of cryptochrome (CRY). To further demonstrate that the effect of near-null magnetic field on Arabidopsis flowering is associated with CRY, Arabidopsis wild type and CRY mutant plants were grown in the near-null magnetic field under blue or red light with different light cycle and photosynthetic photon flux density. We found that Arabidopsis flowering was significantly suppressed by near-null magnetic field in blue light with lower intensity (10 µmol/m(2) /s) and shorter cycle (12 h period: 6 h light/6 h dark). However, flowering time of CRY1/CRY2 mutants did not show any difference between plants grown in near-null magnetic field and in local geomagnetic field under detected light conditions. In red light, no significant difference was shown in Arabidopsis flowering between plants in near-null magnetic field and local geomagnetic field under detected light cycles and intensities. These results suggest that changes of blue light cycle and intensity alter the effect of near-null magnetic field on Arabidopsis flowering, which is mediated by CRY.

  6. Proliferation, differentiation and apoptosis in connexin43-null osteoblasts

    NASA Technical Reports Server (NTRS)

    Furlan, F.; Lecanda, F.; Screen, J.; Civitelli, R.

    2001-01-01

    Osteoblasts are highly coupled by gap junctions formed primarily by connexin43 (Cx43). We have shown that interference with Cx43 expression or function disrupts transcriptional regulation of osteoblast genes, and that deletion of Cx43 in the mouse causes skeletal malformations, delayed mineralization, and osteoblast dysfunction. Here, we studied the mechanisms by which genetic deficiency of Cx43 alters osteoblast development. While cell proliferation rates were similar in osteoblastic cells derived from calvaria of Cx43-null and wild type mice, camptothecin-induced apoptosis was 3-fold higher in mutant compared to wild type osteoblasts. When grown in mineralizing medium, Cx43-null cells were able to produce mineralized matrix but it took one week longer to reach the same mineralization levels as in normal cells. Likewise, expression of alkaline phosphatase activity per cell--a marker of osteoblast differentiation--was maximal only 2 weeks later in Cx43-null relative to wild-type cells. These observations suggest that Cx43 is important for a normal and timely development of the osteoblastic phenotype. Delayed differentiation and increase programmed cell death may explain the skeletal phenotype of Cx43-null mice.

  7. Balloon exoplanet nulling interferometer (BENI)

    NASA Astrophysics Data System (ADS)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Ford, Holland; Petro, Larry; Herman, Jay; Rinehart, Stephen; Carpenter, Kenneth; Marzouk, Joe

    2009-08-01

    We evaluate the feasibility of a balloon-borne nulling interferometer to detect and characterize an exosolar planet and the surrounding debris disk. The existing instrument consists of a three-telescope Fizeau imaging interferometer with thre fast steering mirrors and three delay lines operating at 800 Hz for closed-loop control of wavefront errors and fine pointing. A compact visible nulling interferometer would be coupled to the imaging interferometer and in principle, allows deep starlight suppression. Atmospheric simulations of the environment above 100,000 feet show that balloonborne payloads are a possible path towards the direct detection and characterization of a limited set of exoplanets and debris disks. Furthermore, rapid development of lower cost balloon payloads provide a path towards advancement of NASA technology readiness levels for future space-based exoplanet missions. Discussed are the BENI mission and instrument, the balloon environment and the feasibility of such a balloon-borne mission.

  8. Nulling at the Keck Interferometer

    NASA Technical Reports Server (NTRS)

    Colavita, M. Mark; Serabyn, Gene; Wizinowich, Peter L.; Akeson, Rachel L.

    2006-01-01

    The nulling mode of the Keck Interferometer is being commissioned at the Mauna Kea summit. The nuller combines the two Keck telescope apertures in a split-pupil mode to both cancel the on-axis starlight and to coherently detect the residual signal. The nuller, working at 10 um, is tightly integrated with the other interferometer subsystems including the fringe and angle trackers, the delay lines and laser metrology, and the real-time control system. Since first 10 um light in August 2004, the system integration is proceeding with increasing functionality and performance, leading to demonstration of a 100:1 on-sky null in 2005. That level of performance has now been extended to observations with longer coherent integration times. An overview of the overall system is presented, with emphasis on the observing sequence, phasing system, and differences with respect to the V2 system, along with a presentation of some recent engineering data.

  9. Balloon Exoplanet Nulling Interferometer (BENI)

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Ford, Holland; Petro, Larry; Herman, Jay; Rinehart, Stephen; Carpenter, Kenneth; Marzouk, Joe

    2009-01-01

    We evaluate the feasibility of using a balloon-borne nulling interferometer to detect and characterize exosolar planets and debris disks. The existing instrument consists of a 3-telescope Fizeau imaging interferometer with 3 fast steering mirrors and 3 delay lines operating at 800 Hz for closed-loop control of wavefront errors and fine pointing. A compact visible nulling interferometer is under development which when coupled to the imaging interferometer would in-principle allow deep suppression of starlight. We have conducted atmospheric simulations of the environment above 100,000 feet and believe balloons are a feasible path forward towards detection and characterization of a limited set of exoplanets and their debris disks. Herein we will discuss the BENI instrument, the balloon environment and the feasibility of such as mission.

  10. Broken chiral symmetry on a null plane

    SciTech Connect

    Beane, Silas R.

    2013-10-15

    On a null-plane (light-front), all effects of spontaneous chiral symmetry breaking are contained in the three Hamiltonians (dynamical Poincaré generators), while the vacuum state is a chiral invariant. This property is used to give a general proof of Goldstone’s theorem on a null-plane. Focusing on null-plane QCD with N degenerate flavors of light quarks, the chiral-symmetry breaking Hamiltonians are obtained, and the role of vacuum condensates is clarified. In particular, the null-plane Gell-Mann–Oakes–Renner formula is derived, and a general prescription is given for mapping all chiral-symmetry breaking QCD condensates to chiral-symmetry conserving null-plane QCD condensates. The utility of the null-plane description lies in the operator algebra that mixes the null-plane Hamiltonians and the chiral symmetry charges. It is demonstrated that in a certain non-trivial limit, the null-plane operator algebra reduces to the symmetry group SU(2N) of the constituent quark model. -- Highlights: •A proof (the first) of Goldstone’s theorem on a null-plane is given. •The puzzle of chiral-symmetry breaking condensates on a null-plane is solved. •The emergence of spin-flavor symmetries in null-plane QCD is demonstrated.

  11. Increased Oxidative Stress Impairs Adipose Tissue Function in Sphingomyelin Synthase 1 Null Mice

    PubMed Central

    Nishimura, Naotaka; Gotoh, Tomomi; Watanabe, Ken; Ikeda, Kazutaka; Garan, Yohei; Taguchi, Ryo; Node, Koichi; Okazaki, Toshiro; Oike, Yuichi

    2013-01-01

    Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vitro analysis using cultured cell revealed that SMS1 depletion reduced fatty acid uptake. Proteins extracted from WAT of mutant mice were severely modified by oxidative stress, and up-regulation of mRNAs related to apoptosis, redox adjustment, mitochondrial stress response and mitochondrial biogenesis was observed. ATP content of WAT was reduced in SMS1 null mice. Blue native gel analysis indicated that accumulation of mitochondrial respiratory chain complexes was reduced. These results suggest that WAT of SMS1 null mice is severely damaged by oxidative stress and barely functional. Indeed, mutant mice treated with the anti-oxidant N-acetyl cysteine (NAC) showed partial recovery of lipodystrophic phenotypes together with normalized plasma triglyceride concentrations. Altogether, our data suggest that SMS1 is crucial to control oxidative stress in order to maintain WAT function. PMID:23593476

  12. Visible Nulling Coronagraph Testbed Results

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal; Rizzo, Maxime; Thompson, Patrick

    2009-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept study and a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC would provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 5-year mission lifetime. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables starlight suppression in broadband light from 480-960 nm. To demonstrate the VNC approach and advance it's technology readiness we have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

  13. Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice

    PubMed Central

    Kumar, Ramiya; Mota, Linda C.; Litoff, Elizabeth J.; Rooney, John P.; Boswell, W. Tyler; Courter, Elliott; Henderson, Charles M.; Hernandez, Juan P.; Corton, J. Christopher; Moore, David D.

    2017-01-01

    Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model. Compensatory changes in CYP expression that occur in these models may also occur in polymorphic humans, or may complicate interpretation of ADME studies performed using these models. The loss of CAR causes significant changes in several CYPs probably due to loss of CAR-mediated constitutive regulation of these CYPs. Expression and activity changes include significant repression of Cyp2a and Cyp2b members with corresponding drops in 6α- and 16β-testosterone hydroxylase activity. Further, the ratio of 6α-/15α-hydroxylase activity, a biomarker of sexual dimorphism in the liver, indicates masculinization of female CAR-null mice, suggesting a role for CAR in the regulation of sexually dimorphic liver CYP profiles. The loss of Cyp3a causes fewer changes than CAR. Nevertheless, there are compensatory changes including gender-specific increases in Cyp2a and Cyp2b. Cyp2a and Cyp2b were down-regulated in CAR-null mice, suggesting activation of CAR and potentially PXR following loss of the Cyp3a members. However, the loss of Cyp2b causes few changes in hepatic CYP transcript levels and almost no significant compensatory changes in protein expression or activity with the possible exception of 6α-hydroxylase activity. This lack of a compensatory response in the Cyp2b9/10/13-null mice is probably due to low CYP2B hepatic expression, especially in male mice. Overall, compensatory and

  14. The Importance of Proving the Null

    ERIC Educational Resources Information Center

    Gallistel, C. R.

    2009-01-01

    Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is…

  15. On grating nulls in adaptive arrays

    NASA Astrophysics Data System (ADS)

    Ishide, A.; Compton, R. T., Jr.

    1980-07-01

    The effect of element patterns on grating nulls in adaptive arrays is considered. Two simple array models, a two-element and a three-element array with dipole element patterns, are used to study this question. The element patterns are assumed unequal (i.e., the beam maxima point in different directions). It is shown that element patterns greatly affect the occurrence of grating nulls in the array. Unequal element patterns cause extra grating nulls ('sign reversal grating nulls') to occur, in addition to conventional grating nulls. These sign reversal grating nulls can occur even with element spacing less than a half-wavelength. For a two-element array with dipole element patterns, it turns out that grating nulls cannot be avoided if the spacing is greater than a half-wavelength. However, with more than two elements, the situation is not so bleak. An example is given of a three-element array with dipole patterns and one-wavelength spacing in which all grating nulls are eliminated.

  16. On grating nulls in adaptive arrays

    NASA Astrophysics Data System (ADS)

    Ishide, A.; Compton, R. T., Jr.

    1980-03-01

    This report considers the effect of element patterns on grating nulls in adaptive arrays. Two simple array models, a two-element and a three-element array with dipole element patterns, are used to study this question. The element patterns are assumed unequal (i.e., the beam maxima point in different directions). It is shown that element patterns greatly affect the occurrence of grating nulls in the array. Unequal element patterns cause extra grating nulls (sign reversal grating nulls) to occur, in addition to conventional grating nulls. These sign reversal grating nulls can occur even with element spacing less than a half-wavelength. For a two-element array with dipole element patterns, it turns out that grating nulls cannot be avoided if the spacing is greater than a half wavelength. However, with more than two elements, the situation is not so bleak. An example is given of a three-element array with dipole patterns and one wavelength spacing in which all grating nulls are eliminated.

  17. Automatic null ellipsometry with an interferometer

    SciTech Connect

    Watkins, Lionel R.

    2009-11-10

    A new approach to automatic null ellipsometry is described in which the analyzer of a traditional polarizer compensator sample analyzer (PCSA) null ellipsometer is replaced with a heterodyne Michelson interferometer. One arm of this interferometer is modified such that it produces a fixed, linearly polarized reference beam, irrespective of the input polarization state. This beam is recombined interferometrically with the measurement beam and spatially separated into its p and s polarizations. The relative phase of the resulting temporal fringes is a linear function of the polarizer azimuthal angle P, and thus this component can be driven to its null position without iteration. Once at null, the azimuthal angle of the reflected, linearly polarized light is trivially determined from the relative amplitude of the fringes. Measurements made with this instrument on a native oxide film on a silicon wafer were in excellent agreement with those made with a traditional PCSA null ellipsometer.

  18. IRAN: interferometric remapped array nulling

    NASA Astrophysics Data System (ADS)

    Aristidi, Eric; Vakili, Farrokh; Abe, Lyu; Belu, Adrian; Lopez, Bruno; Lanteri, Henri; Schutz, A.; Menut, Jean-Luc

    2004-10-01

    This paper describes a method of beam-combination in the so-called hypertelescope imaging technique recently introduced by Labeyrie in optical interferometry. The method we propose is an alternative to the Michelson pupil reconfiguration that suffers from the loss of the classical object-image convolution relation. From elementary theory of Fourier optics we demonstrate that this problem can be solved by observing in a combined pupil plane instead of an image plane. The point-source intensity distribution (PSID) of this interferometric "image" tends towards a psuedo Airy disc (similar to that of a giant monolithic telescope) for a sufficiently large number of telescopes. Our method is applicable to snap-shot imaging of extended sources with a field comparable to the Airy pattern of single telescopes operated in a co-phased multi-aperture interferometric array. It thus allows to apply conveniently pupil plane coronagraphy. Our technique called Interferometric Remapped Array Nulling (IRAN) is particularly suitable for high dynamic imaging of extra-solar planetary companions, circumstellar nebulosities or extra-galactic objects where long baseline interferometry would closely probe the central regions of AGNs for instance.

  19. Characterization of the treefrog null allele

    SciTech Connect

    Guttman, S.I. . Dept. of Zoology)

    1990-12-01

    As part of the authors intensive year-long baseline ecological study, they characterized the degree of genetic polymorphism and heterozygosity in selected Feed Materials Production Center (FMPC) populations using electrophoretic techniques. These data are being used as an indicator of stress by comparing populations on and off the FMPC site. The current study was initiated to determine whether this GPI null allele is lethal, when homozygous, in spring peepers. Also, a sampling protocol was implemented to determine whether a linear effect occurs relative to the frequency of the null allele offsite and to determine the origination site of the null allele. 18 refs., 2 figs., 4 tabs.

  20. New null screen design for corneal topography

    NASA Astrophysics Data System (ADS)

    Campos-García, Manuel; Estrada-Molina, Amilcar; Díaz-Uribe, Rufino

    2011-09-01

    In this work we report the design of a null screen for corneal topography. Here we assume that the corneal surface is an ellipsoid with a diameter of 12 mm and a curvature radius of 7.8 mm. To avoid the difficulties in the alignment of the test system due to the face contour (eyebrows, nose, or eyelids), we design a conical null-screen with spots (similar to ellipses) drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact radial array of circular spots if the surface is perfect. Additionally, we performed a numerical simulation introducing Gaussian random errors in the coordinates of the centroids of the spots on the image plane, and in the coordinates of the sources (spots on the null-screen) in order to obtain the conical null-screen that reduces the error in the evaluation of the topography.

  1. On the Penrose inequality along null hypersurfaces

    NASA Astrophysics Data System (ADS)

    Mars, Marc; Soria, Alberto

    2016-06-01

    The null Penrose inequality, i.e. the Penrose inequality in terms of the Bondi energy, is studied by introducing a functional on surfaces and studying its properties along a null hypersurface Ω extending to past null infinity. We prove a general Penrose-type inequality which involves the limit at infinity of the Hawking energy along a specific class of geodesic foliations called Geodesic Asymptotically Bondi (GAB), which are shown to always exist. Whenever this foliation approaches large spheres, this inequality becomes the null Penrose inequality and we recover the results of Ludvigsen-Vickers (1983 J. Phys. A: Math. Gen. 16 3349-53) and Bergqvist (1997 Class. Quantum Grav. 14 2577-83). By exploiting further properties of the functional along general geodesic foliations, we introduce an approach to the null Penrose inequality called the Renormalized Area Method and find a set of two conditions which imply the validity of the null Penrose inequality. One of the conditions involves a limit at infinity and the other a restriction on the spacetime curvature along the flow. We investigate their range of applicability in two particular but interesting cases, namely the shear-free and vacuum case, where the null Penrose inequality is known to hold from the results by Sauter (2008 PhD Thesis Zürich ETH), and the case of null shells propagating in the Minkowski spacetime. Finally, a general inequality bounding the area of the quasi-local black hole in terms of an asymptotic quantity intrinsic of Ω is derived.

  2. Phase-only nulling for transmit antenna

    NASA Astrophysics Data System (ADS)

    Hussain, Moayyed A.; Yu, Kai-Bor

    1999-11-01

    This paper describes a technique for transmit antenna nulling for low-cost large sparse phased array radar system. Radar system described includes an array of elemental antennas, each with a transmit/receive (T/R) module. The T/R modules are operated at or near maximum output to achieve maximum CD-to-RF efficiency. A phase controller controls the phase shift, which are imparted by each module to its signal, to form a mainbeam and its associated sidelobes. A perturbation phase generator adds phase shifts computed, to form wide nulls in the sidelobe structure. The nulls are achieved at very minimal loss of gain, in the order of fraction of a dB. The speed of obtaining these nulls in real time allows a rapid steering of these nulls in a hostile environment. The thinned aperture allow designing a light weigh mobile system. In radar context, these nulls may be placed on a source of ground clutter, a set of jammers or a set of undesirable radio sources.

  3. The alpha glycerophosphate cycle in Drosophila melanogaster V. molecular analysis of alpha glycerophosphate dehydrogenase and alpha glycerophosphate oxidase mutants.

    PubMed

    Carmon, Amber; Chien, Jeff; Sullivan, David; MacIntyre, Ross

    2010-01-01

    Two enzymes, alpha glycerophosphate dehydrogenase (GPDH-1) in the cytoplasm and alpha glycerophosphate oxidase (GPO-1) in the mitochondrion cooperate in Drosophila flight muscles to generate the ATP needed for muscle contraction. Null mutants for either enzyme cannot fly. Here, we characterize 15 ethyl methane sulfonate (EMS)-induced mutants in GPDH-1 at the molecular level and assess their effects on structural and evolutionarily conserved domains of this enzyme. In addition, we molecularly characterize 3 EMS-induced GPO-1 mutants and excisions of a P element insertion in the GPO-1 gene. The latter represent the best candidate for null or amorphic mutants in this gene.

  4. Two roads to the null energy condition

    NASA Astrophysics Data System (ADS)

    Parikh, Maulik

    2015-11-01

    The null energy condition has sweeping consequences in general relativity. I argue here that it has been misunderstood as a property exclusively of matter, when in fact it arises only in a theory of both matter and gravity. I then derive an equivalent geometric formulation of the null energy condition from worldsheet string theory, where it arises beautifully as simple Einstein’s equations in two dimensions. But further, I show that this condition also has a thermodynamic origin, following from a local version of the second law of thermodynamics, applied to gravitational entropy. Thus, far from being an incidental property of matter, the validity of the null energy condition hints at the deep dual origins of gravity.

  5. Adaptive Nulling for Interferometric Detection of Planets

    NASA Technical Reports Server (NTRS)

    Lay, Oliver P.; Peters, Robert D.

    2010-01-01

    An adaptive-nulling method has been proposed to augment the nulling-optical- interferometry method of detection of Earth-like planets around distant stars. The method is intended to reduce the cost of building and aligning the highly precise optical components and assemblies needed for nulling. Typically, at the mid-infrared wavelengths used for detecting planets orbiting distant stars, a star is millions of times brighter than an Earth-sized planet. In order to directly detect the light from the planet, it is necessary to remove most of the light coming from the star. Nulling interferometry is one way to suppress the light from the star without appreciably suppressing the light from the planet. In nulling interferometry in its simplest form, one uses two nominally identical telescopes aimed in the same direction and separated laterally by a suitable distance. The light collected by the two telescopes is processed through optical trains and combined on a detector. The optical trains are designed such that the electric fields produced by an on-axis source (the star) are in anti-phase at the detector while the electric fields from the planet, which is slightly off-axis, combine in phase, so that the contrast ratio between the star and the planet is greatly decreased. If the electric fields from the star are exactly equal in amplitude and opposite in phase, then the star is effectively nulled out. Nulling is effective only if it is complete in the sense that it occurs simultaneously in both polarization states and at all wavelengths of interest. The need to ensure complete nulling translates to extremely tight demands upon the design and fabrication of the complex optical trains: The two telescopes must be highly symmetric, the reflectivities of the many mirrors in the telescopes and other optics must be carefully tailored, the optical coatings must be extremely uniform, sources of contamination must be minimized, optical surfaces must be nearly ideal, and alignments

  6. Characterization of the treefrog null allele, 1991

    SciTech Connect

    Guttman, S.I.

    1992-04-01

    Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

  7. Nulling Measurements with the Keck Interferometer

    SciTech Connect

    Serabyn, Eugene

    2009-08-05

    The Keck Interferometer provides a mid-infrared nulling capability that is designed to detect faint mid-infrared emission from the immediate vicinity of bright stars. The Keck Interferometer Nuller (KIN) has now been used to carry out initial shared-risk science observations, followed by three nulling key-science projects performed in the 2008 observing semesters. This paper describes the novel measurement technique employed by the KIN, and lists some of the initial observations obtained with it. These data sets are now in the process of being analyzed, and results should begin emerging in the near future.

  8. Nulling Measurements with the Keck Interferometer

    NASA Astrophysics Data System (ADS)

    Serabyn, Eugene

    2009-08-01

    The Keck Interferometer provides a mid-infrared nulling capability that is designed to detect faint mid-infrared emission from the immediate vicinity of bright stars. The Keck Interferometer Nuller (KIN) has now been used to carry out initial shared-risk science observations, followed by three nulling key-science projects performed in the 2008 observing semesters. This paper describes the novel measurement technique employed by the KIN, and lists some of the initial observations obtained with it. These data sets are now in the process of being analyzed, and results should begin emerging in the near future.

  9. A vacuum spacetime with closed null geodesics

    SciTech Connect

    Sarma, Debojit Patgiri, Mahadev Ahmed, Faiz Uddin

    2013-02-15

    Here we present a vacuum spacetime with closed null geodesics (CNGs). These CNGs are obtained by analytically solving the geodesic equations. This spacetime is locally isometric to the plane wave spacetime and has very different global properties from metrics of the latter type. - Highlights: Black-Right-Pointing-Pointer Closed null geodesics are found in a vacuum spacetime. Black-Right-Pointing-Pointer These are obtained by analytically solving the geodesic equations. Black-Right-Pointing-Pointer The nature of the spacetime is fully analysed.

  10. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

    PubMed

    Cummings, Erin E; O'Reilly, Linda P; King, Dale E; Silverman, Richard M; Miedel, Mark T; Luke, Cliff J; Perlmutter, David H; Silverman, Gary A; Pak, Stephen C

    2015-01-01

    α1-antitrypsin deficiency (ATD) predisposes patients to both loss-of-function (emphysema) and gain-of-function (liver cirrhosis) phenotypes depending on the type of mutation. Although the Z mutation (ATZ) is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels) or null (<1% normal levels) alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype) induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS), showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of different AT

  11. Polarization nulling interferometry for exoplanet detection.

    PubMed

    Spronck, Julien; Pereira, Silvania F; Braat, Joseph J M

    2006-04-03

    We introduce a new concept of nulling interferometer without any achromatic device, using polarization properties of light. This type of interferometer should enable a high rejection ratio in a theoretically unlimited spectral band. We analyze several consequences of the proposed design, notably, the possibility of fast internal modulation.

  12. A Philosophical Critique of Null Hypothesis Testing.

    ERIC Educational Resources Information Center

    Orey III, Michael A.; And Others

    1989-01-01

    An attempt is made to clarify the philosophical foundations of the debate over research methodology appropriate for psychology in particular and the utility of null hypothesis testing in general. The article also relates the debate to education and suggests that the debate is far from settled. (IAH)

  13. Adaptive Nulling for the Terrestrial Planet Finder Interferometer

    NASA Technical Reports Server (NTRS)

    Peters, Robert D.; Lay, Oliver P.; Jeganathan, Muthu; Hirai, Akiko

    2006-01-01

    A description of adaptive nulling for Terrestrial Planet Finder Interferometer (TPFI) is presented. The topics include: 1) Nulling in TPF-I; 2) Why Do Adaptive Nulling; 3) Parallel High-Order Compensator Design; 4) Phase and Amplitude Control; 5) Development Activates; 6) Requirements; 7) Simplified Experimental Setup; 8) Intensity Correction; and 9) Intensity Dispersion Stability. A short summary is also given on adaptive nulling for the TPFI.

  14. Loss of FAS/FASL signaling does not reduce apoptosis in Sharpin null mice.

    PubMed

    Potter, Christopher S; Silva, Kathleen A; Kennedy, Victoria E; Stearns, Timothy M; HogenEsch, Harm; Sundberg, John P

    2017-01-17

    Mice with mutations in SHANK-associated RH domain interactor (Sharpin) develop a hypereosinophilic auto-inflammatory disease known as chronic proliferative dermatitis. Affected mice have increased apoptosis in the keratinocytes of the skin, esophagus, and forestomach driven by extrinsic TNF receptor mediated apoptotic signaling pathways. FAS receptor signaling is an extrinsic apoptotic signaling mechanism frequently involved in inflammatory skin diseases. Compound mutations in Sharpin and Fas or Fasl were created to determine if these death domain proteins influenced the cutaneous phenotype in Sharpin null mice. Both Sharpin/Fas and Sharpin/Fasl compound mutant mice developed an auto-inflammatory phenotype similar to that seen in Sharpin null mice indicating that initiation of apoptosis by FAS signaling is likely not involved in the pathogenesis of this disease. This article is protected by copyright. All rights reserved.

  15. A mutant of the Arabidopsis thaliana Toc159 gene accumulates reduced levels of linolenic acid and monogalactosyldiacylglycerol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that a null mutant of Arabidopsis that lacks Toc159 receptor is impaired in chloroplast biogenesis and incapable of importing photosynthetic proteins. The mutant is referred to as plastid protein import 2 or ppi2, and has an albino phenotype. In this study, we measured ...

  16. Morphological Uniformity and the Null Subject Parameter in Adult SLA.

    ERIC Educational Resources Information Center

    Davies, William D.

    1996-01-01

    Focuses on the application of the Null Subject Parameter. Data reveals that some second-language learners exhibit knowledge that English is morphologically nonuniform yet still accept English null subject sentences. Findings disprove the Morphological Uniformity Hypothesis, indicating that any reformulation of the Null Subject Parameter must…

  17. Null conformal Killing-Yano tensors and Birkhoff theorem

    NASA Astrophysics Data System (ADS)

    Ferrando, Joan Josep; Sáez, Juan Antonio

    2016-04-01

    We study the space-times admitting a null conformal Killing-Yano tensor whose divergence defines a Killing vector. We analyze the similarities and differences with the recently studied non null case (Ferrando and Sáez in Gen Relativ Gravit 47:1911, 2015). The results by Barnes concerning the Birkhoff theorem for the case of null orbits are analyzed and generalized.

  18. Null Subjects, Filled CPs, and L2 Acquisition.

    ERIC Educational Resources Information Center

    Roebuck, Regina F.; Martinez-Arbelaiz, Maria A.; Perez-Silva, Jorge I.

    1999-01-01

    Investigates the acquisition of a non-null-subject language (English) by speakers of two different null-subject languages (Spanish and Chinese) in light of recent research in theoretical syntax that shows that different syntactic mechanisms are at work in the expression of null subjects in the two languages.(Author/VWL)

  19. Blob dynamics in TORPEX poloidal null configurations

    NASA Astrophysics Data System (ADS)

    Shanahan, B. W.; Dudson, B. D.

    2016-12-01

    3D blob dynamics are simulated in X-point magnetic configurations in the TORPEX device via a non-field-aligned coordinate system, using an isothermal model which evolves density, vorticity, parallel velocity and parallel current density. By modifying the parallel gradient operator to include perpendicular perturbations from poloidal field coils, numerical singularities associated with field aligned coordinates are avoided. A comparison with a previously developed analytical model (Avino 2016 Phys. Rev. Lett. 116 105001) is performed and an agreement is found with minimal modification. Experimental comparison determines that the null region can cause an acceleration of filaments due to increasing connection length, but this acceleration is small relative to other effects, which we quantify. Experimental measurements (Avino 2016 Phys. Rev. Lett. 116 105001) are reproduced, and the dominant acceleration mechanism is identified as that of a developing dipole in a moving background. Contributions from increasing connection length close to the null point are a small correction.

  20. Chromatic assimilation measured by temporal nulling.

    PubMed

    Shevell, Steven K; Cao, Dingcai

    2006-01-01

    Chromatic assimilation is the shift in color appearance toward nearby light. Assimilation was measured using nearby light with time-varying chromaticity. This light induced time-varying assimilation within the test area. Assimilation was quantified by the amplitude of temporally varying test-area light--in counter-phase to the induced assimilation--required to null the assimilation. Unlike previous studies of assimilation, observers here judged only the steadiness of the test area, not its color. The inducing light was varied in luminance, temporal frequency and chromaticity. The measured assimilation could not be explained by only optical factors affecting receptoral quantal absorption. This implies a neural process contributes to assimilation. The nulling measurements showed also that assimilation was not induced independently within the L/M- and S-cone pathways.

  1. Null model analysis of species nestedness patterns.

    PubMed

    Ulrich, Werner; Gotelli, Nicholas J

    2007-07-01

    Nestedness is a common biogeographic pattern in which small communities form proper subsets of large communities. However, the detection of nestedness in binary presence-absence matrices will be affected by both the metric used to quantify nestedness and the reference null distribution. In this study, we assessed the statistical performance of eight nestedness metrics and six null model algorithms. The metrics and algorithms were tested against a benchmark set of 200 random matrices and 200 nested matrices that were created by passive sampling. Many algorithms that have been used in nestedness studies are vulnerable to type I errors (falsely rejecting a true null hypothesis). The best-performing algorithm maintains fixed row and fixed column totals, but it is conservative and may not always detect nestedness when it is present. Among the eight indices, the popular matrix temperature metric did not have good statistical properties. Instead, the Brualdi and Sanderson discrepancy index and Cutler's index of unexpected presences performed best. When used with the fixed-fixed algorithm, these indices provide a conservative test for nestedness. Although previous studies have revealed a high frequency of nestedness, a reanalysis of 288 empirical matrices suggests that the true frequency of nested matrices is between 10% and 40%.

  2. Evidence of altered inhibition in layer V pyramidal neurons from neocortex of Kcna1-null mice.

    PubMed

    van Brederode, J F; Rho, J M; Cerne, R; Tempel, B L; Spain, W J

    2001-01-01

    Mice lacking the potassium channel subunit KCNA1 exhibit a severe epileptic phenotype beginning at an early postnatal age. The precise cellular physiological substrates for these seizures are unclear, as is the site of origin. Since KCNA1 mRNA in normal mice is expressed in the neocortex, we asked whether neurons in the neocortex of three to four week-old Kcna1-null mutants exhibit evidence of hyperexcitability. Layer V pyramidal neurons were directly visualized in brain slices with infrared differential-interference contrast microscopy and evaluated with cellular electrophysiological techniques. There were no significant differences in intrinsic membrane properties and action potential shape between Kcna1-null and wild-type mice, consistent with previous findings in hippocampal slice recordings. However, the frequency of spontaneous post-synaptic currents was significantly higher in Kcna1-null compared to wild-type mice. The frequency of spontaneous inhibitory post-synaptic currents and miniature (action-potential-independent) inhibitory post-synaptic currents was also significantly higher in Kcna1-null compared to wild-type mice. However, the frequency of spontaneous and miniature excitatory post-synaptic currents was not different in these two groups of animals. Comparison of the amplitude and kinetics of miniature inhibitory and excitatory post-synaptic currents revealed differences in amplitude, rise time and half-width between Kcna1-null and wild-type mice. Our data indicate that the inhibitory drive onto layer V pyramidal neurons is increased in Kcna1 knockout mice, either directly through an increased spontaneous release of GABA from presynaptic terminals contacting layer V pyramidal neurons, or an enhanced excitatory synaptic input to inhibitory interneurons.

  3. Magnetic Null Points in Kinetic Simulations of Space Plasmas

    NASA Astrophysics Data System (ADS)

    Olshevsky, Vyacheslav; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni

    2016-03-01

    We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3-9. We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data.

  4. System and Method for Null-Lens Wavefront Sensing

    NASA Technical Reports Server (NTRS)

    Hill, Peter C. (Inventor); Thompson, Patrick L. (Inventor); Aronstein, David L. (Inventor); Bolcar, Matthew R. (Inventor); Smith, Jeffrey S. (Inventor)

    2015-01-01

    A method of measuring aberrations in a null-lens including assembly and alignment aberrations. The null-lens may be used for measuring aberrations in an aspheric optic with the null-lens. Light propagates from the aspheric optic location through the null-lens, while sweeping a detector through the null-lens focal plane. Image data being is collected at locations about said focal plane. Light is simulated propagating to the collection locations for each collected image. Null-lens aberrations may extracted, e.g., applying image-based wavefront-sensing to collected images and simulation results. The null-lens aberrations improve accuracy in measuring aspheric optic aberrations.

  5. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation.

    PubMed

    Buiakova, O I; Xu, J; Lutsenko, S; Zeitlin, S; Das, K; Das, S; Ross, B M; Mekios, C; Scheinberg, I H; Gilliam, T C

    1999-09-01

    The Atp7b protein is a copper-transporting ATPase expressed predominantly in the liver and to a lesser extent in most other tissues. Mutations in the ATP7B gene lead to Wilson disease, a copper toxicity disorder characterized by dramatic build-up of intracellular hepatic copper with subsequent hepatic and neuro-logical abnormalities. Using homologous recombination to disrupt the normal translation of ATP7B, we have generated a strain of mice that are homozygous mutants (null) for the Wilson disease gene. The ATP7B null mice display a gradual accumulation of hepatic copper that increases to a level 60-fold greater than normal by 5 months of age. An increase in copper concentration was also observed in the kidney, brain, placenta and lactating mammary glands of homo-zygous mutants, although milk from the mutant glands was copper deficient. Morphological abnormalities resembling cirrhosis developed in the majority of the livers from homozygous mutants older than 7 months of age. Progeny of the homozygous mutant females demonstrated neurological abnormalities and growth retardation characteristic of copper deficiency. Copper concentration in the livers of the newborn homozygous null mutants was decreased dramatically. In summary, inactivation of the murine ATP7B gene produces a form of cirrhotic liver disease that resembles Wilson disease in humans and the 'toxic milk' phenotype in the mouse.

  6. Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains.

    PubMed

    Martínez-Sanz, Elena; Del Río, Aurora; Barrio, Carmen; Murillo, Jorge; Maldonado, Estela; Garcillán, Beatriz; Amorós, María; Fuerte, Tamara; Fernández, Alvaro; Trinidad, Eva; Rabadán, María Angeles; López, Yamila; Martínez, María Luisa; Martínez-Alvarez, Concepción

    2008-04-01

    Although palatal shelf adhesion is a crucial event during palate development, little work has been carried out to determine which molecules are responsible for this process. Furthermore, whether altered palatal shelf adhesion causes the cleft palate presented by Tgf-beta3 null mutant mice has not yet been clarified. Here, we study the presence/distribution of some extracellular matrix and cell adhesion molecules at the time of the contact of palatal shelves in both wild-type and Tgf-beta3 null mutant palates of two strains of mice (C57/BL/6J (C57), and MF1) that develop cleft palates of different severity. We have performed immunohistochemistry with antibodies against collagens IV and IX, laminin, fibronectin, the alpha5- and beta1-integrins, and ICAM-1; in situ hybridization with a Nectin-1 riboprobe; and palatal shelf cultures treated or untreated with TGF-beta3 or neutralizing antibodies against fibronectin or the alpha5-integrin. Our results show the location of these molecules in the wild-type mouse medial edge epithelium (MEE) of both strains at the time of the contact of palatal shelves; the heavier (C57) and milder (MF1) alteration of their presence in the Tgf-beta3 null mutants; the importance of TGF-beta3 to restore their normal pattern of expression; and the crucial role of fibronectin and the alpha5-integrin in palatal shelf adhesion. We thus provide insight into the molecular bases of this important process and the cleft palate presented by Tgf-beta3 null mutant mice.

  7. Alteration of medial-edge epithelium cell adhesion in two Tgf-β3 null mouse strains

    PubMed Central

    Martínez-Sanz, Elena; Del Río, Aurora; Barrio, Carmen; Murillo, Jorge; Maldonado, Estela; Garcillán, Beatriz; Amorós, María; Fuerte, Tamara; Fernández, Álvaro; Trinidad, Eva; Rabadán, M Ángeles; López, Yamila; Martínez, M Luisa; Martínez-Álvarez, Concepción

    2008-01-01

    Although palatal shelf adhesion is a crucial event during palate development, little work has been carried out to determine which molecules are responsible for this process. Furthermore, whether altered palatal shelf adhesion causes the cleft palate presented by Tgf-β3 null mutant mice has not yet been clarified. Here, we study the presence/distribution of some extracellular matrix and cell adhesion molecules at the time of the contact of palatal shelves in both wild-type and Tgf-β3 null mutant palates of two strains of mice (C57/BL/6J (C57), and MF1) that develop cleft palates of different severity. We have performed immunohistochemistry with antibodies against collagens IV and IX, laminin, fibronectin, the α5- and β1-integrins, and ICAM-1; in situ hybridization with a Nectin-1 riboprobe; and palatal shelf cultures treated or untreated with TGF-β3 or neutralizing antibodies against fibronectin or the α5-integrin. Our results show the location of these molecules in the wild-type mouse medial edge epithelium (MEE) of both strains at the time of the contact of palatal shelves; the heavier (C57) and milder (MF1) alteration of their presence in the Tgf-β3 null mutants; the importance of TGF-β3 to restore their normal pattern of expression; and the crucial role of fibronectin and the α5-integrin in palatal shelf adhesion. We thus provide insight into the molecular bases of this important process and the cleft palate presented by Tgf-β3 null mutant mice. PMID:18431835

  8. Displacing Unpredictable Nulls in Antenna Radiation Patterns

    NASA Technical Reports Server (NTRS)

    Lux, James; Schaefer, Mark

    2005-01-01

    A method of maintaining radio communication despite the emergence of unpredictable fades and nulls in the radiation pattern of an antenna has been proposed. The method was originally intended to be applied in the design and operation of a radio antenna aboard a robotic exploratory vehicle on a remote planet during communication with a spacecraft in orbit around the planet. The method could also be applied in similar terrestrial situations for example, radio communication between two ground vehicles or between a ground vehicle and an aircraft or spacecraft. The method is conceptually simple, is readily adaptable to diverse situations, and can be implemented without adding greatly to the weight, cost, power demand, or complexity of a system to which it may be applied. The unpredictable fades and nulls in an antenna radiation pattern arise because of electromagnetic interactions between the antenna and other objects within the near field of the antenna (basically, objects within a distance of a few wavelengths). These objects can include general vehicle components, masts, robotic arms, other antennas, the ground, and nearby terrain features. Figure 1 presents representative plots of signal strength versus time during a typical pass of a spacecraft or aircraft through the far field of such an antenna, showing typical nulls and fades caused by nearby objects. The traditional approach to ensuring reliability of communication in the presence of deep fades calls for increasing the effective transmitter power and/or reducing the receiver noise figure at the affected ground vehicle, possibly in combination with appropriate redesign of the equipment at the spacecraft or aircraft end of the communication link. These solutions can be expensive and/or risky and, depending on the application, can add significantly to weight, cost, and power demand. The proposed method entails none of these disadvantages.

  9. Sidelobe Sector Nulling with Minimized Phase Perturbations.

    DTIC Science & Technology

    1985-03-01

    Sciences Division FOR THE COMMANDER: ~t~4iq JOHN A. RITZ Acting Chief, Plans Office If your address has changed or if you wish to be removed from the...Perturbations for Arrays of 11, 21, and 41 Elements W~41 z~ 21 7N II -2. 4.0 -J.0 -2.0 -11.6 0.0 1.!0 2.0 3.0 4.0 5.0 LOGI 0 (42141) Figure 3. Look...Trans. Antennas Propag. AP-20:432 -436. 4. Baird , C. A., and Rassweiler, G. G. (1976) Adaptive sidelobe nulling using digitally controlled phase

  10. Null Energy Condition in Dynamic Wormholes

    SciTech Connect

    Hochberg, D.; Visser, M.

    1998-07-01

    We extend previous proofs that violations of the null energy condition are a generic and universal feature of traversable wormholes to completely nonsymmetric time-dependent wormholes. We show that the analysis can be phrased purely in terms of local geometry at and near the wormhole throat, and we do not have to make any technical assumptions about asymptotic flatness or other global properties. A key aspect of the analysis is the demonstration that time-dependent wormholes have {ital two} throats, one for each direction through the wormhole, and that the two throats coalesce only for the case of a static wormhole. {copyright} {ital 1998} {ital The American Physical Society}

  11. Ethanol tolerance and membrane fatty acid adaptation in adh multiple and null mutants of Kluyveromyces lactis.

    PubMed

    Heipieper, H J; Isken, S; Saliola, M

    2000-11-01

    The effects of ethanol and 1-octanol on growth and fatty acid composition of different strains of Kluyveromyces lactis containing a mutation in the four different alcohol dehydrogenase (KlADH) genes were investigated. In the presence of ethanol and 1-octanol K. lactis reduced the fluidity of its lipids by decreasing the unsaturation index (UI) of its membrane fatty acids. In this way, a direct correlation between nonlethal ethanol concentrations and the decrease in the UI could be observed. At concentrations which totally inhibited cell growth no reaction occurred. These adaptive modifications of the fatty acid pattern of K. lactis to ethanol contrasted with those reported for Saccharomyces cerevisiae and Schizosaccharomyces pombe. Whereas these two yeasts increased the fluidity of their membrane lipids in the presence of ethanol, K. lactis reduced the fluidity (UI) of its lipids. Among the different isogenic adh negative strains tested, the strain containing no ADH (adh0) and that containing only KlADH1 were the most alcohol-sensitive. The strain with only KlADH2 showed nearly the same tolerance as reference strain CBS 2359/152 containing all four ADH genes. This suggests that the KlADH2 product could play an important role in the adaptation/detoxification reactions of K. lactis to high ethanol concentrations.

  12. Remodelling of motor nerve terminals in demyelinating axons of periaxin null mutant mice

    PubMed Central

    Court, Felipe A; Brophy, Peter J; Ribchester, Richard R

    2015-01-01

    Myelin formation around axons increases nerve conduction velocity and regulates phenotypic characteristics of the myelinated axon. In the peripheral nervous system, demyelinating forms of hereditary Charcot-Marie-Tooth (CMT) diseases, due to Schwann-cell intrinsic molecular defects, leads to reduced nerve conduction velocity and changes in the axonal phenotype. Several mouse models of CMT diseases have been generated, allowing the study of consequences of demyelination in peripheral nerve fibres. Nevertheless, the effect of demyelination at the level of the neuromuscular synapse has been largely overlooked. Here we show that in the periaxin knock-out mice, a model of CMT condition, neuromuscular junctions develop profound morphological changes in pre-terminal region of motoraxons. These changes include extensive preterminal branches which originate in demyelinated regions of the nerve fibre and axonal swellings associated with residually-myelinated regions of the fibre. Using intracellular recording from muscle fibres we detected asynchronous failure of action potential transmission at high but not low stimulation frequencies, a phenomenon consistent with branch point failure. Taken together, our morphological and electrophysiological findings suggest that preterminal branching due to segmental demyelination near the neuromuscular synapse in periaxin KO mice may underlie phenotypic disabilities present in this mouse model of CMT disease. These results opens a new avenue of research in order to understand the cellular changes responsible for clinical disabilities in demyelinating conditions. PMID:18205176

  13. Recent developments with the visible nulling coronagraph

    NASA Astrophysics Data System (ADS)

    Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter; Helmbrecht, Michael A.; Howard, Joseph M.; Miller, Ian J.

    2016-08-01

    A wide array of general astrophysics studies including detecting and characterizing habitable exoplanets could be enabled by a future large segmented telescope with sensitivity in the UV, optical, and infrared bands. When paired with a starshade or coronagraph, such an observatory could enable direct imaging and detailed spectroscopic observations of nearby Earth-like habitable zone planets. Over the past several years, a laboratory-based Visible Nulling Coronagraph (VNC) has evolved to reach requisite contrasts over a 1 nm bandwidth at narrow source angle separation using a segmented deformable mirror in one arm of a Mach-Zehnder layout. More recent efforts targeted broadband performance following the addition of two sets of half-wave Fresnel rhomb achromatic phase shifters (APS) with the goal of reaching 10-9 contrast, at a separation of 2λ/D, using a 40 nm (6%) bandwidth single mode fiber source. Here we present updates on the VNC broadband nulling effort, including approaches to addressing system contrast limitations.

  14. The impact of the SSIIa null mutations on grain traits and composition in durum wheat

    PubMed Central

    Botticella, Ermelinda; Sestili, Francesco; Ferrazzano, Gianluca; Mantovani, Paola; Cammerata, Alessandro; D’Egidio, Maria Grazia; Lafiandra, Domenico

    2016-01-01

    Starch represents a major nutrient in the human diet providing essentially a source of energy. More recently the modification of its composition has been associated with new functionalities both at the nutritional and technological level. Targeting the major starch biosynthetic enzymes has been shown to be a valuable strategy to manipulate the amylose-amylopectin ratio in reserve starch. In the present work a breeding strategy aiming to produce a set of SSIIa (starch synthases IIa) null durum wheat is described. We have characterized major traits such as seed weight, total starch, amylose, protein and β-glucan content in a set of mutant families derived from the introgression of the SSIIa null trait into Svevo, an elite Italian durum wheat cultivar. A large degree of variability was detected and used to select wheat lines with either improved quality traits or agronomic performances. Semolina of a set of two SSIIa null lines showed new rheological behavior and an increased content of all major dietary fiber components, namely arabinoxylans, β-glucans and resistant starch. Furthermore the investigation of gene expression highlighted important differences in some genes involved in starch and β-glucans biosynthesis. PMID:27795682

  15. On the null origin of the ambitwistor string

    NASA Astrophysics Data System (ADS)

    Casali, Eduardo; Tourkine, Piotr

    2016-11-01

    In this paper we present the null string origin of the ambitwistor string. Classically, the null string is the tensionless limit of string theory, and so too is the ambitwistor string. Both have as constraint algebra the Galilean Conformal Algebra in two dimensions. But something interesting happens in the quantum theory since there is an ambiguity in quantizing the null string. We show that, given a particular choice of quantization scheme and a particular gauge, the null string coincides with the ambitwistor string both classically and quantum mechanically. We also show that the same holds for the spinning versions of the null string and ambitwistor string. With these results we clarify the relationship between the ambitwistor string, the null string, the usual string and the Hohm-Siegel-Zwiebach theory.

  16. Off-Axis Nulling Transfer Function Measurement: A First Assessment

    NASA Technical Reports Server (NTRS)

    Vedova, G. Dalla; Menut, J.-L.; Millour, F.; Petrov, R.; Cassaing, F.; Danchi, W. C.; Jacquinod, S.; Lhome, E.; Lopez, B.; Lozi, J.; Marcotto, A.; Parisot, J.; Reess, J.-M.

    2013-01-01

    We want to study a polychromatic inverse problem method with nulling interferometers to obtain information on the structures of the exozodiacal light. For this reason, during the first semester of 2013, thanks to the support of the consortium PERSEE, we launched a campaign of laboratory measurements with the nulling interferometric test bench PERSEE, operating with 9 spectral channels between J and K bands. Our objective is to characterise the transfer function, i.e. the map of the null as a function of wavelength for an off-axis source, the null being optimised on the central source or on the source photocenter. We were able to reach on-axis null depths better than 10(exp -4). This work is part of a broader project aiming at creating a simulator of a nulling interferometer in which typical noises of a real instrument are introduced. We present here our first results.

  17. Null test of aspheric surfaces in zone-plate interferometer

    NASA Astrophysics Data System (ADS)

    Huang, Junejei; Chang, Chihui

    1992-10-01

    Instead of using lenses or mirrors as a null compensator, the construction of the zone plate interferometer is used to accomplish the null test. By choosing the focal length of the zone plate according to the radius of curvature and conic constant of the test surface, the conventional zone plate interferometer is modified to be a null test of concave conicoids. To test convex conicoids, an imaging lens is added between the zone plate and the test surface. As long as the zone plate is perfectly imaged into the center of the curvature of the test surface, a null test of convex conicoids is the same as that of concave ones.

  18. Adaptive interferometric null testing for unknown freeform optics metrology.

    PubMed

    Huang, Lei; Choi, Heejoo; Zhao, Wenchuan; Graves, Logan R; Kim, Dae Wook

    2016-12-01

    We report an adaptive interferometric null testing method for overcoming the dynamic range limitations of conventional null testing approaches during unknown freeform optics metrology or optics manufacturing processes that require not-yet-completed surface measurements to guide the next fabrication process. In the presented adaptive method, a deformable mirror functions as an adaptable null component for an unknown optical surface. The optimal deformable mirror's shape is determined by the stochastic parallel gradient descent algorithm and controlled by a deflectometry system. An adaptive interferometric null testing setup was constructed, and its metrology data successfully demonstrated superb adaptive capability in measuring an unknown surface.

  19. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice.

    PubMed

    Aaker, Joshua D; Elbaz, Benayahu; Wu, Yuwen; Looney, Timothy J; Zhang, Li; Lahn, Bruce T; Popko, Brian

    2016-10-01

    The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191(null)), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro To determine whether the loss of myelin seen in Zfp191(null) mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient. Interestingly, Mbp(shi) (shiverer) mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies.

  20. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice

    PubMed Central

    Aaker, Joshua D.; Elbaz, Benayahu; Wu, Yuwen; Looney, Timothy J.; Zhang, Li; Lahn, Bruce T.

    2016-01-01

    The transcriptional program that controls oligodendrocyte maturation and central nervous system (CNS) myelination has not been fully characterized. In this study, we use high-throughput RNA sequencing to analyze how the loss of a key transcription factor, zinc finger protein 191 (ZFP191), results in oligodendrocyte development abnormalities and CNS hypomyelination. Using a previously described mutant mouse that is deficient in ZFP191 protein expression (Zfp191null), we demonstrate that key transcripts are reduced in the whole brain as well as within oligodendrocyte lineage cells cultured in vitro. To determine whether the loss of myelin seen in Zfp191null mice contributes indirectly to these perturbations, we also examined the transcriptome of a well-characterized mouse model of hypomyelination, in which the myelin structural protein myelin basic protein (MBP) is deficient. Interestingly, Mbpshi (shiverer) mice had far fewer transcripts perturbed with the loss of myelin alone. This study demonstrates that the loss of ZFP191 disrupts expression of genes involved in oligodendrocyte maturation and myelination, largely independent from the loss of myelin. Nevertheless, hypomyelination in both mouse mutants results in the perturbation of lipid synthesis pathways, suggesting that oligodendrocytes have a feedback system that allows them to regulate myelin lipid synthesis depending on their myelinating state. The data presented are of potential clinical relevance as the human orthologs of the Zfp191 and MBP genes reside on a region of Chromosome 18 that is deleted in childhood leukodystrophies. PMID:27683878

  1. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors

    SciTech Connect

    Brune, W.; Saul, M.; Becker, C.M.

    1996-05-01

    Dominant missense mutations in the human glycine receptor (GlyR) {alpha}1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1{sup null} allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1{sup spd-ot}), the loss of the GlyR {alpha}1 subunit is effectively compensated in man. 38 refs.

  2. Saccharomyces cerevisiae aldolase mutants.

    PubMed Central

    Lobo, Z

    1984-01-01

    Six mutants lacking the glycolytic enzyme fructose 1,6-bisphosphate aldolase have been isolated in the yeast Saccharomyces cerevisiae by inositol starvation. The mutants grown on gluconeogenic substrates, such as glycerol or alcohol, and show growth inhibition by glucose and related sugars. The mutations are recessive, segregate as one gene in crosses, and fall in a single complementation group. All of the mutants synthesize an antigen cross-reacting to the antibody raised against yeast aldolase. The aldolase activity in various mutant alleles measured as fructose 1,6-bisphosphate cleavage is between 1 to 2% and as condensation of triose phosphates to fructose 1,6-bisphosphate is 2 to 5% that of the wild-type. The mutants accumulate fructose 1,6-bisphosphate from glucose during glycolysis and dihydroxyacetone phosphate during gluconeogenesis. This suggests that the aldolase activity is absent in vivo. PMID:6384192

  3. Nulling Infrared Radiometer for Measuring Temperature

    NASA Technical Reports Server (NTRS)

    Ryan, Robert

    2003-01-01

    A nulling, self-calibrating infrared radiometer is being developed for use in noncontact measurement of temperature in any of a variety of industrial and scientific applications. This instrument is expected to be especially well-suited to measurement of ambient or near-ambient temperature and, even more specifically, for measuring the surface temperature of a natural body of water. Although this radiometer would utilize the long-wavelength infrared (LWIR) portion of the spectrum (wavelengths of 8 to 12 m), its basic principle of operation could also be applied to other spectral bands (corresponding to other temperature ranges) in which the atmosphere is transparent and in which design requirements for sensitivity and temperature-measurement accuracy could be satisfied.

  4. Exoplanet detection using a nulling interferometer.

    PubMed

    Cagigal, M; Canales, V

    2001-07-02

    The detection of extra solar planets is a topic of growing interest, which stretches current technology and knowledge to their limits. Indirect measurement confirms the existence of a considerable number. However, direct imaging is the only way to obtain information about the nature of these planets and to detect Earth-like planets, which could support life. The main problem for direct imaging is that planets are associated with a much brighter source of light. Here, we propose the use of the nulling interferometer along with a photon counting technique called Dark Speckle. Using a simple model the behavior of the technique is predicted. The signal-to-noise ratio estimated confirms that it is a promising way to detect faint objects.

  5. Ocular Phenotype of Fbn2-Null Mice

    PubMed Central

    Shi, Yanrong; Tu, Yidong; Mecham, Robert P.; Bassnett, Steven

    2013-01-01

    Purpose. Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during development of the mouse eye. To test its role in morphogenesis, we examined the ocular phenotype of Fbn2−/− mice. Methods. Ocular morphology was assessed by confocal microscopy using antibodies against microfibril components. Results. Fbn2−/− mice had a high incidence of anterior segment dysgenesis. The iris was the most commonly affected tissue. Complete iridal coloboma was present in 37% of eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence of Fbn2 was partially compensated for by increased expression of fibrillin-1, although the resulting PM microfibrils were disorganized, compared with WTs. In colobomatous adult Fbn2−/− eyes, the PM failed to regress normally, especially beneath the notched region of the iris. Segments of the ciliary body were hypoplastic, and zonular fibers, although relatively plentiful, were unevenly distributed around the lens equator. In regions where the zonular fibers were particularly disturbed, the synchronous differentiation of the underlying lens fiber cells was affected. Conclusions. Fbn2 has an indispensable role in ocular morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals implies a previously unsuspected role in optic fissure closure. The observation that fiber cell differentiation was disturbed in Fbn2−/− mice raises the possibility that the attachment of zonular fibers to the lens surface may help specify the equatorial margin of the lens epithelium. PMID:24130178

  6. Technology Advancement of the Visible Nulling Coronagraph

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Thompson, Patrick; Bolcar, Matt; Madison, Timothy; Woodruff, Robert; Noecker, Charley; Kendrick, Steve

    2010-01-01

    The critical high contrast imaging technology for the Extrasolar Planetary Imaging Coronagraph (EPIC) mission concept is the visible nulling coronagraph (VNC). EPIC would be capable of imaging jovian planets, dust/debris disks, and potentially super-Earths and contribute to answering how bright the debris disks are for candidate stars. The contrast requirement for EPIC is 10(exp 9) contrast at 125 milli-arseconds inner working angle. To advance the VNC technology NASA/Goddard Space Flight Center, in collaboration with Lockheed-Martin, previously developed a vacuum VNC testbed, and achieved narrowband and broadband suppression of the core of the Airy disk. Recently our group was awarded a NASA Technology Development for Exoplanet Missions to achieve two milestones: (i) 10(exp 8) contrast in narrowband light, and, (ii) 10(ecp 9) contrast in broader band light; one milestone per year, and both at 2 Lambda/D inner working angle. These will be achieved with our 2nd generation testbed known as the visible nulling testbed (VNT). It contains a MEMS based hex-packed segmented deformable mirror known as the multiple mirror array (MMA) and coherent fiber bundle, i.e. a spatial filter array (SFA). The MMA is in one interferometric arm and works to set the wavefront differences between the arms to zero. Each of the MMA segments is optically mapped to a single mode fiber of the SFA, and the SFA passively cleans the sub-aperture wavefront error leaving only piston, tip and tilt error to be controlled. The piston degree of freedom on each segment is used to correct the wavefront errors, while the tip/tilt is used to simultaneously correct the amplitude errors. Thus the VNT controls both amplitude and wavefront errors with a single MMA in closed-loop in a vacuum tank at approx.20 Hz. Herein we will discuss our ongoing progress with the VNT.

  7. Quasilocal energy exchange and the null cone

    NASA Astrophysics Data System (ADS)

    Uzun, Nezihe

    2016-10-01

    Energy is at best defined quasilocally in general relativity. Quasilocal energy definitions depend on the conditions one imposes on the boundary Hamiltonian, i.e., how a finite region of spacetime is "isolated." Here, we propose a method to define and investigate systems in terms of their matter plus gravitational energy content. We adopt a generic construction, that involves embedding of an arbitrary dimensional world sheet into an arbitrary dimensional spacetime, to a 2 +2 picture. In our case, the closed 2-dimensional spacelike surface S , that is orthogonal to the 2-dimensional timelike world sheet T at every point, encloses the system in question. The integrability conditions of T and S correspond to three null tetrad gauge conditions once we transform our notation to the one of the null cone observables. We interpret the Raychaudhuri equation of T as a work-energy relation for systems that are not in equilibrium with their surroundings. We achieve this by identifying the quasilocal charge densities corresponding to rotational and nonrotational degrees of freedom, in addition to a relative work density associated with tidal fields. We define the corresponding quasilocal charges that appear in our work-energy relation and which can potentially be exchanged with the surroundings. These charges and our tetrad conditions are invariant under type-III Lorentz transformations, i.e., the boosting of the observers in the directions orthogonal to S . We apply our construction to a radiating Vaidya spacetime, a C -metric and the interior of a Lanczos-van Stockum dust metric. The delicate issues related to the axially symmetric stationary spacetimes and possible extensions to the Kerr geometry are also discussed.

  8. MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

    SciTech Connect

    Olshevsky, Vyacheslav; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano

    2016-03-01

    We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3–9. We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data.

  9. Analysis of l-glycerol-3-phosphate dehydrogenase mutants in Drosophila melanogaster: complementation for intracellular degradation of the mutant polypeptide.

    PubMed

    Bewley, G C; DeZurik, J M; Pagelson, G

    1980-01-01

    Null and low activity alleles at the genetic locus coding for L-Glycerol-3-phosphate dehydrogenase (alpha-GPDH, NAD+ oxidoreductase, E.C. 1.1.1.8) in Drosophila melanogaster have been analyzed by a combination of rocket immunoelectrophoresis, interallelic complementation, and two-dimensional gel electrophoresis. In addition to proving information on the molecular weight, charged state, and steady state level of CRM in each of these mutants, it is suggested that each mutation has resulted in a genetic lesion within the structural element, Gpdh+. CRM levels appear to be the result of differential sensitivity to the normal intracellular degradative process and the CRM- mutants represent "hypersensitive" alleles, such that the mutant polypeptide does not accumulate in the intracellular environment.

  10. Null infinity and extremal horizons in AdS-CFT

    NASA Astrophysics Data System (ADS)

    Hickling, Andrew; Lucietti, James; Wiseman, Toby

    2015-02-01

    We consider AdS gravity duals to CFT on background spacetimes with a null infinity. Null infinity on the conformal boundary may extend to an extremal horizon in the bulk. For example it does so for Poincaré-AdS, although does not for planar Schwarzschild-AdS. If null infinity does extend into an extremal horizon in the bulk, we show that the bulk near-horizon geometry is determined by the geometry of the boundary null infinity. Hence the ‘infra-red’ geometry of the bulk is fixed by the large scale behaviour of the CFT spacetime. In addition the boundary stress tensor must have a particular decay at null infinity. As an application, we argue that for CFT on asymptotically flat backgrounds, any static bulk dual containing an extremal horizon extending from the boundary null infinity, must have the near-horizon geometry of Poincaré-AdS. We also discuss a class of boundary null infinity that cannot extend to a bulk extremal horizon, although we give evidence that they can extend to an analogous null surface in the bulk which possesses an associated scale-invariant ‘near-geometry’.

  11. ENERGY DISSIPATION IN MAGNETIC NULL POINTS AT KINETIC SCALES

    SciTech Connect

    Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey; Eriksson, Elin; Markidis, Stefano

    2015-07-10

    We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of “intermittent turbulence” within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging and vanishing, associated with electron streams and small-scale current sheets. The number of spiral nulls in the simulation outweighs the number of radial nulls by a factor of 5–10, in accordance with Cluster observations in the Earth's magnetosheath. Twisted magnetic fields with embedded spiral null points might indicate the regions of major energy dissipation for future space missions such as the Magnetospheric Multiscale Mission.

  12. Exact null controllability of degenerate evolution equations with scalar control

    SciTech Connect

    Fedorov, Vladimir E; Shklyar, Benzion

    2012-12-31

    Necessary and sufficient conditions for the exact null controllability of a degenerate linear evolution equation with scalar control are obtained. These general results are used to examine the exact null controllability of the Dzektser equation in the theory of seepage. Bibliography: 13 titles.

  13. Logarithmic corrections to gravitational entropy and the null energy condition

    NASA Astrophysics Data System (ADS)

    Parikh, Maulik; Svesko, Andrew

    2016-10-01

    Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein-Hawking entropy.

  14. Visual and Plastic Arts in Teaching Literacy: Null Curricula?

    ERIC Educational Resources Information Center

    Wakeland, Robin Gay

    2010-01-01

    Visual and plastic arts in contemporary literacy instruction equal null curricula. Studies show that painting and sculpture facilitate teaching reading and writing (literacy), yet such pedagogy has not been formally adopted into USA curriculum. An example of null curriculum can be found in late 19th - early 20th century education the USA…

  15. The Visible Nulling Coronagraph--Architecture Definition and Technology Development

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Liu, Duncan T.; Schmidtlin, Edouard; Serabyn, Eugene; Mennesson, Bertrand; Green, Joseph J.; Aguayo, Francisco; Fregoso, S. Felipe; Lane, Benjamin F.; Samuele, Rocco; Tuttle, Carl

    2005-01-01

    This paper describes the advantages of visible direct detection and spectroscopy of Earth-like extrasolar planets using a nulling coronagraph instrument behind a moderately sized single aperture space telescope. Our concept synthesizes a nulling interferometer by shearing the telescope pupil, with the resultant producing a deep null. We describe nulling configurations that also include methods to mitigate stellar leakage, such as spatial filtering by a coherent array of single mode fibers, and post-starlight suppression wavefront sensing and control. With diffraction limited telescope optics and similar quality components in the optical train (lambda/20), suppression of the starlight to 1e-10 is readily achievable. We describe key features of the architecture and analysis, present latest results of laboratory measurements demonstrating achievable null depth and component development, and discuss future key technical milestones.

  16. Estimating Relatedness in the Presence of Null Alleles.

    PubMed

    Huang, Kang; Ritland, Kermit; Dunn, Derek W; Qi, Xiaoguang; Guo, Songtao; Li, Baoguo

    2016-01-01

    Studies of genetics and ecology often require estimates of relatedness coefficients based on genetic marker data. However, with the presence of null alleles, an observed genotype can represent one of several possible true genotypes. This results in biased estimates of relatedness. As the numbers of marker loci are often limited, loci with null alleles cannot be abandoned without substantial loss of statistical power. Here, we show how loci with null alleles can be incorporated into six estimators of relatedness (two novel). We evaluate the performance of various estimators before and after correction for null alleles. If the frequency of a null allele is <0.1, some estimators can be used directly without adjustment; if it is >0.5, the potency of estimation is too low and such a locus should be excluded. We make available a software package entitled PolyRelatedness v1.6, which enables researchers to optimize these estimators to best fit a particular data set.

  17. Null Models for Everyone: A Two-Step Approach to Teaching Null Model Analysis of Biological Community Structure

    ERIC Educational Resources Information Center

    McCabe, Declan J.; Knight, Evelyn J.

    2016-01-01

    Since being introduced by Connor and Simberloff in response to Diamond's assembly rules, null model analysis has been a controversial tool in community ecology. Despite being commonly used in the primary literature, null model analysis has not featured prominently in general textbooks. Complexity of approaches along with difficulty in interpreting…

  18. Identification of GRO1 as a critical determinant for mutant p53 gain of function.

    PubMed

    Yan, Wensheng; Chen, Xinbin

    2009-05-01

    Mutant p53 gain of function contributes to cancer progression, increased invasion and metastasis potentials, and resistance to anticancer therapy. The ability of mutant p53 to acquire its gain of function is shown to correlate with increased expression of progrowth genes, such as c-MYC, MDR1, and NF-kappaB2. However, most of the published studies to identify mutant p53 target genes were performed in a cell system that artificially overexpresses mutant p53. Thus, it remains unclear whether such mutant p53 targets can be regulated by endogenous physiological levels of mutant p53. Here, we utilized SW480 and MIA-PaCa-2 cells, in which endogenous mutant p53 can be inducibly knocked down, to identify mutant p53 target genes that potentially mediate mutant p53 gain of function. We found that knockdown of mutant p53 inhibits GRO1 expression, whereas ectopic expression of mutant R175H in p53-null HCT116 cells increases GRO1 expression. In addition, we found that endogenous mutant p53 is capable of binding to and activating the GRO1 promoter. Interestingly, ectopic expression of GRO1 can rescue the proliferative defect in SW480 and MIA-PaCa-2 cells induced by knockdown of mutant p53. Conversely, knockdown of endogenous GRO1 inhibits cell proliferation and thus abrogates mutant p53 gain of function in SW480 cells. Taken together, our findings define a novel mechanism by which mutant p53 acquires its gain of function via transactivating the GRO1 gene in cancer cells. Thus, targeting GRO1 for cancer therapy would be applicable to a large portion of human tumors with mutant p53, but the exploration of GRO1 as a potential target should take the mutation status of p53 into consideration.

  19. Molecular heterogeneity of the Jk(null) phenotype: expression analysis of the Jk(S291P) mutation found in Finns.

    PubMed

    Sidoux-Walter, F; Lucien, N; Nissinen, R; Sistonen, P; Henry, S; Moulds, J; Cartron, J P; Bailly, P

    2000-08-15

    Polymerase chain reaction genotyping of 32 unrelated Jk(null) individuals originating predominantly from Polynesia and Finland indicated that all were homozygous for the JK*B polymorphism and that 17 of 32, including the 14 Polynesians, carried a 3'-acceptor splice site mutation of intron 5 that resulted in the skipping of exon 6 (called mutation Jk delta 6). The remaining 15 Jk(null) donors from Finland were homozygous for a new T871C transition resulting in a S291P amino acid substitution at a consensus N-glycosylation site of the Jk polypeptide. Transcription-translation assays revealed that the Jk(S291P) mutant was translated into a glycosylated component as efficiently as the wild-type Jk polypeptide (wt Jk)] in the presence of microsomes, thus indicating that the S291P mutation has no effect on the N-glycosylation pattern of the Jk protein. Expression studies in Xenopus oocytes revealed that the Jk(S291P) polypeptide functions as a urea transporter, but the transport activity and the membrane expression level of the mutant protein was reduced to a similar extent. A substantial fraction of the mutant protein was retained intracellularly suggesting that the transit to the plasma membrane was reduced, presumably because of the S-->P mutation. After transfection in erythroleukemia K562 cells the wild-type, but not the mutant, protein was efficiently expressed at the cell surface. Because the Jk(S291P) mutant polypeptide was not present in human red cells from Jk(null) individuals, expression data in the erythroid context clearly indicates that the S-->P mutation is the molecular basis of the Finnish Jk(null) phenotype. (Blood. 2000;96:1566-1573)

  20. Wormholes minimally violating the null energy condition

    SciTech Connect

    Bouhmadi-López, Mariam; Lobo, Francisco S N; Martín-Moruno, Prado E-mail: fslobo@fc.ul.pt

    2014-11-01

    We consider novel wormhole solutions supported by a matter content that minimally violates the null energy condition. More specifically, we consider an equation of state in which the sum of the energy density and radial pressure is proportional to a constant with a value smaller than that of the inverse area characterising the system, i.e., the area of the wormhole mouth. This approach is motivated by a recently proposed cosmological event, denoted {sup t}he little sibling of the big rip{sup ,} where the Hubble rate and the scale factor blow up but the cosmic derivative of the Hubble rate does not [1]. By using the cut-and-paste approach, we match interior spherically symmetric wormhole solutions to an exterior Schwarzschild geometry, and analyse the stability of the thin-shell to linearized spherically symmetric perturbations around static solutions, by choosing suitable properties for the exotic material residing on the junction interface radius. Furthermore, we also consider an inhomogeneous generalization of the equation of state considered above and analyse the respective stability regions. In particular, we obtain a specific wormhole solution with an asymptotic behaviour corresponding to a global monopole.

  1. Parallel Reconstruction Using Null Operations (PRUNO)

    PubMed Central

    Zhang, Jian; Liu, Chunlei; Moseley, Michael E.

    2011-01-01

    A novel iterative k-space data-driven technique, namely Parallel Reconstruction Using Null Operations (PRUNO), is presented for parallel imaging reconstruction. In PRUNO, both data calibration and image reconstruction are formulated into linear algebra problems based on a generalized system model. An optimal data calibration strategy is demonstrated by using Singular Value Decomposition (SVD). And an iterative conjugate- gradient approach is proposed to efficiently solve missing k-space samples during reconstruction. With its generalized formulation and precise mathematical model, PRUNO reconstruction yields good accuracy, flexibility, stability. Both computer simulation and in vivo studies have shown that PRUNO produces much better reconstruction quality than autocalibrating partially parallel acquisition (GRAPPA), especially under high accelerating rates. With the aid of PRUO reconstruction, ultra high accelerating parallel imaging can be performed with decent image quality. For example, we have done successful PRUNO reconstruction at a reduction factor of 6 (effective factor of 4.44) with 8 coils and only a few autocalibration signal (ACS) lines. PMID:21604290

  2. A Null Model for Pearson Coexpression Networks

    PubMed Central

    Gobbi, Andrea; Jurman, Giuseppe

    2015-01-01

    Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent simple but effective structures for discovering and interpreting linear gene relationships. In recent years, several approaches have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is most crucial when the number of samples is small, yielding a non-negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The threshold is theoretically derived by means of an analytic approach and, as a deterministic independent null model, it depends only on the dimensions of the starting data matrix, with assumptions on the skewness of the data distribution compatible with the structure of gene expression levels data. We show, on synthetic and array datasets, that the proposed threshold is effective in eliminating all false positive links, with an offsetting cost in terms of false negative detected edges. PMID:26030917

  3. A null model for Pearson coexpression networks.

    PubMed

    Gobbi, Andrea; Jurman, Giuseppe

    2015-01-01

    Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent simple but effective structures for discovering and interpreting linear gene relationships. In recent years, several approaches have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is most crucial when the number of samples is small, yielding a non-negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The threshold is theoretically derived by means of an analytic approach and, as a deterministic independent null model, it depends only on the dimensions of the starting data matrix, with assumptions on the skewness of the data distribution compatible with the structure of gene expression levels data. We show, on synthetic and array datasets, that the proposed threshold is effective in eliminating all false positive links, with an offsetting cost in terms of false negative detected edges.

  4. PDGFRA-mutant syndrome.

    PubMed

    Ricci, Riccardo; Martini, Maurizio; Cenci, Tonia; Carbone, Arnaldo; Lanza, Paola; Biondi, Alberto; Rindi, Guido; Cassano, Alessandra; Larghi, Alberto; Persiani, Roberto; Larocca, Luigi M

    2015-07-01

    Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. 'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to 'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs

  5. Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells

    PubMed Central

    Menendez, Daniel; Lowe, Julie M.; Snipe, Joyce; Resnick, Michael A.

    2016-01-01

    Diversity within the p53 transcriptional network can arise from a matrix of changes that include target response element sequences and p53 expression level variations. We previously found that wild type p53 (WT p53) can regulate expression of most innate immune-related Toll-like-receptor genes (TLRs) in human cells, thereby affecting immune responses. Since many tumor-associated p53 mutants exhibit change-of-spectrum transactivation from various p53 targets, we examined the ability of twenty-five p53 mutants to activate endogenous expression of the TLR gene family in p53 null human cancer cell lines following transfection with p53 mutant expression vectors. While many mutants retained the ability to drive TLR expression at WT levels, others exhibited null, limited, or change-of-spectrum transactivation of TLR genes. Using TLR3 signaling as a model, we show that some cancer-associated p53 mutants amplify cytokine, chemokine and apoptotic responses after stimulation by the cognate ligand poly(I:C). Furthermore, restoration of WT p53 activity for loss-of-function p53 mutants by the p53 reactivating drug RITA restored p53 regulation of TLR3 gene expression and enhanced DNA damage-induced apoptosis via TLR3 signaling. Overall, our findings have many implications for understanding the impact of WT and mutant p53 in immunological responses and cancer therapy. PMID:27533082

  6. Retarded Fields of Null Particles and the Memory Effect

    NASA Astrophysics Data System (ADS)

    Tolish, Alexander; Wald, Robert

    2014-03-01

    We consider the scalar, electromagnetic and linearized gravitational fields produced by a particle moving on a null geodesic. We cut off the null source at a finite time t0 and then consider two limits: (i) the limit as the observation point goes to null infinity at fixed t0, and (ii) the limit t0 --> - ∞ at fixed observation point. Limit (i) gives rise to a velocity kick on distant test particles in the scalar and electromagnetic cases, and a memory effect (permanent change in relative separation of test particles) in the gravitational case, in agreement with past analyses. Limit (ii) does not exist in the scalar case or for the Lorenz gauge potential and metric perturbation in the electromagnetic and gravitational cases. However, we find well defined distributional limits for the electromagnetic field strength and Riemann tensors. In the gravitational case, there is no memory effect associated with this limit. This suggests that the memory effect should not be interpreted as arising simply from the passage of null stress energy to null infinity but rather as arising from a burst of radiation associated with the creation of the null stress-energy (as in case (i)) or, more generally, with radiation present that was not produced by the null stress-energy.

  7. Estimating relatedness and relationships using microsatellite loci with null alleles.

    PubMed

    Wagner, A P; Creel, S; Kalinowski, S T

    2006-11-01

    Relatedness is often estimated from microsatellite genotypes that include null alleles. When null alleles are present, observed genotypes represent one of several possible true genotypes. If null alleles are detected, but analyses do not adjust for their presence (ie, observed genotypes are treated as true genotypes), then estimates of relatedness and relationship can be incorrect. The number of loci available in many wildlife studies is limited, and loci with null alleles are commonly a large proportion of data that cannot be discarded without substantial loss of power. To resolve this problem, we present a new approach for estimating relatedness and relationships from data sets that include null alleles. Once it is recognized that the probability of the observed genotypes is dependent on the probabilities of a limited number of possible true genotypes, the required adjustments are straightforward. The concept can be applied to any existing estimators of relatedness and relationships. We review established maximum likelihood estimators and apply the correction in that setting. In an application of the corrected method to data from striped hyenas, we demonstrate that correcting for the presence of null alleles affect results substantially. Finally, we use simulated data to confirm that this method works better than two common approaches, namely ignoring the presence of null alleles or discarding affected loci.

  8. Laboratory performance of the Keck interferometer nulling beam combiner

    NASA Technical Reports Server (NTRS)

    Mennesson, B.; Crawford, S. L.; Serabyn, E.; Martin, S.; Creech-Eakman, M.; Hardy, G.

    2003-01-01

    Now that regular visibility squared measurements are routinely achieved, mid-infrared nulling is the next observing mode to be implemented on the Keck Interferometer. This mode's main objective is the characterization of exo-zodiacal dust disks around nearby main sequence stars in support of the TPF space mission. Keck Nuller also shares numerious characteristics with an interferometric TPF, and will then serve as a technical precursor for this mission. We report here the results obtained in the laboratory with the KI mid-IR nulling beam combiner, which is based on a dual polarization Modified Mach Zender combiner and dispersion and achromatic nulling through zinc-selenide dielectric plates.

  9. Null fields in the outer Jovian magnetosphere: ULYSSES observations

    NASA Astrophysics Data System (ADS)

    Haynes, P. L.; Balogh, A.; Dougherty, M. K.; Southwood, D. J.; Fazakerley, A.

    1994-03-01

    This paper reports on a magnetic field phenomenon, hereafter referred to as null fields, which were discovered during the inbound pass of the recent flyby of Jupiter by the Ulysses spacecraft. These null fields which were observed in the outer dayside magnetosphere are characterised by brief but sharp decreases of the field magnitude to values less than 1 nT. The nulls are distinguished from the current sheet signatures characteristic of the middle magnetosphere by the fact that the field does not reverse across the event. A field configuration is suggested that accounts for the observed features of the events.

  10. Molecular basis for the CAT-2 null phenotype in maize

    SciTech Connect

    Bethards, L.A.; Scandalios, J.G.

    1988-01-01

    Previous reports have described several maize lines whose developmental patterns of catalase gene expression vary from the typical maize line, W64A. Among these variants are the lines A16 and A338, both found to be null for the CAT-2 protein. Identification of a third CAT-2 null line, designated A340, is described. RNA blots and S1 nuclease protection analysis, using (/sup 32/P)-labeled dCTP, indicate that all three CAT-2 null lines produce a similarly shortened Cat2 transcript. The molecular basis for this aberrant Cat2 transcript is discussed.

  11. Null fields in the outer Jovian magnetosphere: Ulysses observations

    NASA Technical Reports Server (NTRS)

    Haynes, P. L.; Balogh, A.; Dougherty, M. K.; Southwood, D. J.; Fazakerley, A.; Smith, E. J.

    1994-01-01

    This paper reports on a magnetic field phenomenon, hereafter referred to as null fields, which were discovered during the inbound pass of the recent flyby of Jupiter by the Ulysses spacecraft. These null fields which were observed in the outer dayside magnetosphere are characterised by brief but sharp decreases of the field magnitude to values less than 1 nT. The nulls are distinguished from the current sheet signatures characteristic of the middle magnetosphere by the fact that the field does not reverse across the event. A field configuration is suggested that accounts for the observed features of the events.

  12. Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities.

    PubMed

    Kerr, Emma M; Gaude, Edoardo; Turrell, Frances K; Frezza, Christian; Martins, Carla P

    2016-03-03

    The RAS/MAPK (mitogen-activated protein kinase) signalling pathway is frequently deregulated in non-small-cell lung cancer, often through KRAS activating mutations. A single endogenous mutant Kras allele is sufficient to promote lung tumour formation in mice but malignant progression requires additional genetic alterations. We recently showed that advanced lung tumours from Kras(G12D/+);p53-null mice frequently exhibit Kras(G12D) allelic enrichment (Kras(G12D)/Kras(wild-type) > 1) (ref. 7), implying that mutant Kras copy gains are positively selected during progression. Here we show, through a comprehensive analysis of mutant Kras homozygous and heterozygous mouse embryonic fibroblasts and lung cancer cells, that these genotypes are phenotypically distinct. In particular, Kras(G12D/G12D) cells exhibit a glycolytic switch coupled to increased channelling of glucose-derived metabolites into the tricarboxylic acid cycle and glutathione biosynthesis, resulting in enhanced glutathione-mediated detoxification. This metabolic rewiring is recapitulated in mutant KRAS homozygous non-small-cell lung cancer cells and in vivo, in spontaneous advanced murine lung tumours (which display a high frequency of Kras(G12D) copy gain), but not in the corresponding early tumours (Kras(G12D) heterozygous). Finally, we demonstrate that mutant Kras copy gain creates unique metabolic dependences that can be exploited to selectively target these aggressive mutant Kras tumours. Our data demonstrate that mutant Kras lung tumours are not a single disease but rather a heterogeneous group comprising two classes of tumours with distinct metabolic profiles, prognosis and therapeutic susceptibility, which can be discriminated on the basis of their relative mutant allelic content. We also provide the first, to our knowledge, in vivo evidence of metabolic rewiring during lung cancer malignant progression.

  13. The visible nulling coronagraph -- progress towards mission and technology development

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Serabyn, Eugene; Liu, Duncan T.; Lane, Benjamin F.

    2004-01-01

    This paper describes a space mission for visible direct detection and spectroscopy of Earth like extrasolar planets using a nulling coronagraph instrument behind a moderately sized telescope in space.

  14. A new dynamic null model for phylogenetic community structure.

    PubMed

    Pigot, Alex L; Etienne, Rampal S

    2015-02-01

    Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by allopatric speciation, colonisation and local extinction. Incorporating these processes fundamentally alters the structure of communities expected due to chance, with speciation leading to phylogenetic overdispersion compared to a classical statistical null model assuming equal probabilities of community membership. Applying this method to bird and primate communities in South America we show that patterns of phylogenetic overdispersion - often attributed to negative biotic interactions - are instead consistent with a species neutral model of allopatric speciation, colonisation and local extinction. Our findings provide a new null expectation for phylogenetic community patterns and highlight the importance of explicitly accounting for the dynamic history of assembly when testing the mechanisms governing community structure.

  15. Null Controllability for the Dissipative Semilinear Heat Equation

    SciTech Connect

    Sebastian, Anita; Tataru, Daniel

    2002-12-19

    We consider the exact null controllability problem for the semi- linear heat equation with dissipative nonlinearity in a bounded domain of R{sup n} . The main result of the article asserts that if the nonlinearity is even mildly superlinear, then global null controllability in an arbitrarily short time fails; instead we provide sharp estimates for the controllability time in terms of the size of the initial data.

  16. Another Nulling Hall-Effect Current-Measuring Circuit

    NASA Technical Reports Server (NTRS)

    Thibodeau, Phillip E.; Sullender, Craig C.

    1993-01-01

    Lightweight, low-power circuit provides noncontact measurement of alternating or direct current of many ampheres in main conductor. Advantages of circuit over other nulling Hall-effect current-measuring circuits is stability and accuracy increased by putting both analog-to-digital and digital-to-analog converters in nulling feedback loop. Converters and rest of circuit designed for operation at sampling rate of 100 kHz, but rate changed to alter time or frequency response of circuit.

  17. Antimultipath communication by injecting tone into null in signal spectrum

    NASA Technical Reports Server (NTRS)

    Davarian, Faramaz (Inventor)

    1987-01-01

    A transmitter for digital radio communication creates a null by balanced encoding of data modulated on an RF carrier, and inserts a calibration tone within the null. This is accomplished by having the calibration tone coincide in phase and frequency with the transmitted radio frequency output, for coherent demodulation of data at the receiver where the tone calibration signal is extracted and used for multipath fading compensation.

  18. Microsatellite null alleles and estimation of population differentiation.

    PubMed

    Chapuis, Marie-Pierre; Estoup, Arnaud

    2007-03-01

    Microsatellite null alleles are commonly encountered in population genetics studies, yet little is known about their impact on the estimation of population differentiation. Computer simulations based on the coalescent were used to investigate the evolutionary dynamics of null alleles, their impact on F(ST) and genetic distances, and the efficiency of estimators of null allele frequency. Further, we explored how the existing method for correcting genotype data for null alleles performed in estimating F(ST) and genetic distances, and we compared this method with a new method proposed here (for F(ST) only). Null alleles were likely to be encountered in populations with a large effective size, with an unusually high mutation rate in the flanking regions, and that have diverged from the population from which the cloned allele state was drawn and the primers designed. When populations were significantly differentiated, F(ST) and genetic distances were overestimated in the presence of null alleles. Frequency of null alleles was estimated precisely with the algorithm presented in Dempster et al. (1977). The conventional method for correcting genotype data for null alleles did not provide an accurate estimate of F(ST) and genetic distances. However, the use of the genetic distance of Cavalli-Sforza and Edwards (1967) corrected by the conventional method gave better estimates than those obtained without correction. F(ST) estimation from corrected genotype frequencies performed well when restricted to visible allele sizes. Both the proposed method and the traditional correction method have been implemented in a program that is available free of charge at http://www.montpellier.inra.fr/URLB/. We used 2 published microsatellite data sets based on original and redesigned pairs of primers to empirically confirm our simulation results.

  19. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  20. Partial deletion in the JK locus causing a Jk(null) phenotype.

    PubMed

    Lucien, Nicole; Chiaroni, Jacques; Cartron, Jean-Pierre; Bailly, Pascal

    2002-02-01

    A new alteration of the blood group JK*A allele was identified in a Jk(null) patient from Tunisia with an allo-anti-Jk3 in her serum. Southern blot and exon mapping analyses revealed an internal deletion within the Kidd (JK) locus encompassing exons 4 and 5. Sequence analysis of the Jk transcript showed that exons 4 and 5 were missing but were replaced by a 136-base-pair (bp) intron 3 sequence located 315 bp and 179 bp upstream from exon 4. This sequence is flanked by typical donor-acceptor cryptic splice sites used in the mutant but not in the normal JK gene. Because the translation initiation codon is located in exon 4, the Jk protein is not produced.

  1. Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

    PubMed

    Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

    2016-02-01

    This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies.

  2. Divertor conditions near double null in Alcator C-Mod

    NASA Astrophysics Data System (ADS)

    Brunner, Dan; Labombard, Brian; Kuang, Adam; Terry, Jim; Mumgaard, Bob; Wolfe, Steve

    2016-10-01

    Many tokamak reactor designs utilize a double-null equilibrium for the boundary plasma because of the expected benefits of heat flux sharing between the two outer divertor leg as well as the attractiveness of the high-field side scrape-off layer plasma in double-null for RF actuators. However, there has been very little reported on boundary plasma conditions near double null, especially at the divertor plate. And, due to the narrow boundary plasma width, there is concern of the precision to which a double-null equilibrium must be controlled to maintain divertor heat flux sharing. To this end, a series of experiments were performed varying the magnetic balance around double null. The magnetic balance between the two nulls was scanned shot-to-shot in L-, I-, and H-mode plasmas. In addition, current and density scans were performed in L-mode plasmas. Results will be presented for relative balances of divertor particle and energy fluxes to the four divertors (inboard/outboard, upper/lower) as well as the sensitivity of changes in divertor conditions to the magnetic balance. Supported by USDoE Award DE-FC02-99ER54512.

  3. Context-specific protection of TGFα null mice from osteoarthritis

    PubMed Central

    Usmani, Shirine E.; Ulici, Veronica; Pest, Michael A.; Hill, Tracy L.; Welch, Ian D.; Beier, Frank

    2016-01-01

    Transforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα’s potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery, and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear. PMID:27457421

  4. Context-specific protection of TGFα null mice from osteoarthritis.

    PubMed

    Usmani, Shirine E; Ulici, Veronica; Pest, Michael A; Hill, Tracy L; Welch, Ian D; Beier, Frank

    2016-07-26

    Transforming growth factor alpha (TGFα) is a growth factor involved in osteoarthritis (OA). TGFα induces an OA-like phenotype in articular chondrocytes, by inhibiting matrix synthesis and promoting catabolic factor expression. To better understand TGFα's potential as a therapeutic target, we employed two in vivo OA models: (1) post-traumatic and (2) aging related OA. Ten-week old and six-month old male Tgfa null mice and their heterozygous (control) littermates underwent destabilization of the medial meniscus (DMM) surgery. Disease progression was assessed histologically using the Osteoarthritis Research Society International (OARSI) scoring system. As well, spontaneous disease progression was analyzed in eighteen-month-old Tgfa null and heterozygous mice. Ten-week old Tgfa null mice were protected from OA progression at both seven and fourteen weeks post-surgery. No protection was seen however in six-month old null mice after DMM surgery, and no differences were observed between genotypes in the aging model. Thus, young Tgfa null mice are protected from OA progression in the DMM model, while older mice are not. In addition, Tgfa null mice are equally susceptible to spontaneous OA development during aging. Thus, TGFα might be a valuable therapeutic target in some post-traumatic forms of OA, however its role in idiopathic disease is less clear.

  5. Measurement Via Optical Near-Nulling and Subaperture Stitching

    NASA Technical Reports Server (NTRS)

    Forbes, Greg; De Vries, Gary; Murphy, Paul; Brophy, Chris

    2012-01-01

    A subaperture stitching interferometer system provides near-nulling of a subaperture wavefront reflected from an object of interest over a portion of a surface of the object. A variable optical element located in the radiation path adjustably provides near-nulling to facilitate stitching of subaperture interferograms, creating an interferogram representative of the entire surface of interest. This enables testing of aspheric surfaces without null optics customized for each surface prescription. The surface shapes of objects such as lenses and other precision components are often measured with interferometry. However, interferometers have a limited capture range, and thus the test wavefront cannot be too different from the reference or the interference cannot be analyzed. Furthermore, the performance of the interferometer is usually best when the test and reference wavefronts are nearly identical (referred to as a null condition). Thus, it is necessary when performing such measurements to correct for known variations in shape to ensure that unintended variations are within the capture range of the interferometer and accurately measured. This invention is a system for nearnulling within a subaperture stitching interferometer, although in principle, the concept can be employed by wavefront measuring gauges other than interferometers. The system employs a light source for providing coherent radiation of a subaperture extent. An object of interest is placed to modify the radiation (e.g., to reflect or pass the radiation), and a variable optical element is located to interact with, and nearly null, the affected radiation. A detector or imaging device is situated to obtain interference patterns in the modified radiation. Multiple subaperture interferograms are taken and are stitched, or joined, to provide an interferogram representative of the entire surface of the object of interest. The primary aspect of the invention is the use of adjustable corrective optics in the

  6. Behavioral phenotype of maLPA1-null mice: increased anxiety-like behavior and spatial memory deficits

    PubMed Central

    Santin, L.J.; Bilbao, A.; Pedraza, C.; Matas-Rico, E.; López-Barroso, D.; Castilla-Ortega, E.; Sánchez-López, J.; Riquelme, R.; Varela-Nieto, I.; de la Villa, P.; Suardíaz, M.; Chun, J.; De Fonseca, F. Rodriguez; Estivill-Torrús, G.

    2016-01-01

    Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. Here we studied the phenotype of maLPA1–null mice, which bear a targeted deletion at the lpa1 locus, in a battery of tests examining neurologic performance, habituation in exploratory behavior in response to low and mild anxiety environments and spatial memory. MaLPA1-null mutants showed deficits in both olfaction and somesthesis, but not in retinal or auditory functions. Sensorimotor coordination was impaired only in the equilibrium and grasping reflexes. The mice also showed impairments in neuromuscular strength and analgesic response. No additional differences were observed in the rest of the tests used to study sensoriomotor orientation, limb reflexes, and coordinated limb use. At behavioral level, maLPA1-null mice showed an impaired exploration in the open field and increased anxiety-like response when exposed to the elevated plus maze. Furthermore, the mice exhibit impaired spatial memory retention and reduced use of spatial strategies in the Morris water maze. We propose that the LPA1 receptor may play a major role in both spatial memory and response to anxiety-like conditions. PMID:19689455

  7. Estimating Relatedness in the Presence of Null Alleles

    PubMed Central

    Huang, Kang; Ritland, Kermit; Dunn, Derek W.; Qi, Xiaoguang; Guo, Songtao; Li, Baoguo

    2016-01-01

    Studies of genetics and ecology often require estimates of relatedness coefficients based on genetic marker data. However, with the presence of null alleles, an observed genotype can represent one of several possible true genotypes. This results in biased estimates of relatedness. As the numbers of marker loci are often limited, loci with null alleles cannot be abandoned without substantial loss of statistical power. Here, we show how loci with null alleles can be incorporated into six estimators of relatedness (two novel). We evaluate the performance of various estimators before and after correction for null alleles. If the frequency of a null allele is <0.1, some estimators can be used directly without adjustment; if it is >0.5, the potency of estimation is too low and such a locus should be excluded. We make available a software package entitled PolyRelatedness v1.6, which enables researchers to optimize these estimators to best fit a particular data set. PMID:26500259

  8. Evaluation of null-point detection methods on simulation data

    NASA Astrophysics Data System (ADS)

    Olshevsky, Vyacheslav; Fu, Huishan; Vaivads, Andris; Khotyaintsev, Yuri; Lapenta, Giovanni; Markidis, Stefano

    2014-05-01

    We model the measurements of artificial spacecraft that resemble the configuration of CLUSTER propagating in the particle-in-cell simulation of turbulent magnetic reconnection. The simulation domain contains multiple isolated X-type null-points, but the majority are O-type null-points. Simulations show that current pinches surrounded by twisted fields, analogous to laboratory pinches, are formed along the sequences of O-type nulls. In the simulation, the magnetic reconnection is mainly driven by the kinking of the pinches, at spatial scales of several ion inertial lentghs. We compute the locations of magnetic null-points and detect their type. When the satellites are separated by the fractions of ion inertial length, as it is for CLUSTER, they are able to locate both the isolated null-points, and the pinches. We apply the method to the real CLUSTER data and speculate how common are pinches in the magnetosphere, and whether they play a dominant role in the dissipation of magnetic energy.

  9. Forms of null Lagrangians in field theories of continuum mechanics

    NASA Astrophysics Data System (ADS)

    Kovalev, V. A.; Radaev, Yu. N.

    2012-02-01

    The divergence representation of a null Lagrangian that is regular in a star-shaped domain is used to obtain its general expression containing field gradients of order ≤ 1 in the case of spacetime of arbitrary dimension. It is shown that for a static three-component field in the three-dimensional space, a null Lagrangian can contain up to 15 independent elements in total. The general form of a null Lagrangian in the four-dimensional Minkowski spacetime is obtained (the number of physical field variables is assumed arbitrary). A complete theory of the null Lagrangian for the n-dimensional spacetime manifold (including the four-dimensional Minkowski spacetime as a special case) is given. Null Lagrangians are then used as a basis for solving an important variational problem of an integrating factor. This problem involves searching for factors that depend on the spacetime variables, field variables, and their gradients and, for a given system of partial differential equations, ensure the equality between the scalar product of a vector multiplier by the system vector and some divergence expression for arbitrary field variables and, hence, allow one to formulate a divergence conservation law on solutions to the system.

  10. Do Null Subjects (mis-)Trigger Pro-drop Grammars?

    PubMed

    Frazier, Lyn

    2015-12-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [−pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing their grammars to a [−pro] setting. Mack et al. (J Memory Lang 67(1):211-223, 2012) showed that sentences with noise covering the subject are analyzed as having null subjects more often with a first person pronoun and with a present tense--properties correlated with more predictable referents--compared to a third person pronoun and past tense. However, those results might in principle have been due to reporting null subjects for verbs that often occur with null subjects. An experiment is reported here in which comparable results are found for sentences containing nonsense verbs. Participants preferred a null subject more often for first person present tense sentences than for third person past tense sentences. The results are as expected if participants are responding to predictability, the likelihood of reduction, rather than to lexical statistics. The results are argued to be important in removing a class of mis-triggering examples from the language acquisition problem.

  11. Visible Nulling Coronagraphy Testbed Development for Exoplanet Detection

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Chen, Andrew; Petrone, Peter; Booth, Andrew; Madison, Timothy; Bolcar, Matthew; Noecker, M. Charley; Kendrick, Stephen; Melnick, Gary; Tolls, Volker

    2010-01-01

    Three of the recently completed NASA Astrophysics Strategic Mission Concept (ASMC) studies addressed the feasibility of using a Visible Nulling Coronagraph (VNC) as the prime instrument for exoplanet science. The VNC approach is one of the few approaches that works with filled, segmented and sparse or diluted aperture telescope systems and thus spans the space of potential ASMC exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies and has developed an incremental sequence of VNC testbeds to advance the this approach and the technologies associated with it. Herein we report on the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under high bandwidth closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible light nulling milestones of sequentially higher contrasts of 10(exp 8) , 10(exp 9) and 10(exp 10) at an inner working angle of 2*lambda/D and ultimately culminate in spectrally broadband (>20%) high contrast imaging. Each of the milestones, one per year, is traceable to one or more of the ASMC studies. The VNT uses a modified Mach-Zehnder nulling interferometer, modified with a modified "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. Discussed will be the optical configuration laboratory results, critical technologies and the null sensing and control approach.

  12. Angiogenesis in Platelet Endothelial Cell Adhesion Molecule-1-Null Mice

    PubMed Central

    Cao, Gaoyuan; Fehrenbach, Melane L.; Williams, James T.; Finklestein, Jeffrey M.; Zhu, Jing-Xu; DeLisser, Horace M.

    2009-01-01

    Platelet endothelial cell adhesion molecule (PECAM)-1 has been previously implicated in endothelial cell migration; additionally, anti-PECAM-1 antibodies have been shown to inhibit in vivo angiogenesis. Studies were therefore performed with PECAM-1-null mice to further define the involvement of PECAM-1 in blood vessel formation. Vascularization of subcutaneous Matrigel implants as well as tumor angiogenesis were both inhibited in PECAM-1-null mice. Reciprocal bone marrow transplants that involved both wild-type and PECAM-1-deficient mice revealed that the impaired angiogenic response resulted from a loss of endothelial, but not leukocyte, PECAM-1. In vitro wound migration and single-cell motility by PECAM-1-null endothelial cells were also compromised. In addition, filopodia formation, a feature of motile cells, was inhibited in PECAM-1-null endothelial cells as well as in human endothelial cells treated with either anti-PECAM-1 antibody or PECAM-1 siRNA. Furthermore, the expression of PECAM-1 promoted filopodia formation and increased the protein expression levels of Cdc42, a Rho GTPase that is known to promote the formation of filopodia. In the developing retinal vasculature, numerous, long filamentous filopodia, emanating from endothelial cells at the tips of angiogenic sprouts, were observed in wild-type animals, but to a lesser extent in the PECAM-1-null mice. Together, these data further establish the involvement of endothelial PECAM-1 in angiogenesis and suggest that, in vivo, PECAM-1 may stimulate endothelial cell motility by promoting the formation of filopodia. PMID:19574426

  13. Glucose transporter isoform-3-null heterozygous mutation causes sexually dimorphic adiposity with insulin resistance.

    PubMed

    Ganguly, Amit; Devaskar, Sherin U

    2008-06-01

    We examined male and female glucose transporter isoform-3 (GLUT3; placenta)-null heterozygous(+/-) mutation-carrying mice and compared them with age- and sex-matched wild-type(+/+) littermates. No difference in postnatal (1-2 days, 6-7 days, 12-13 days, 20-21 days), postsuckling (1-2 mo), and adult (3-6 mo) growth pattern was seen except for an increase in body weight of 9- to 11-mo-old male but not female GLUT3(+/-) mice. This change in male mutant mice was associated with increased total body fat mass, perirenal and epididymal white adipose tissue weight, and hepatic lipid infiltration. These minimally glucose-intolerant male mutant mice demonstrated no change in caloric intake but a decline in basal metabolic rate and insulin resistance. No perturbation in basal circulating glucose concentrations but an increase in insulin concentrations, triglycerides, and total cholesterol was observed in GLUT3(+/-) male mice. Tissue analysis in males and females demonstrated diminished GLUT3 protein in GLUT3(+/-) brain and skeletal muscle with no change in brain and adipose tissue GLUT1 protein concentrations. Furthermore, the male GLUT3(+/-) mice expressed decreased insulin-responsive GLUT4 in white adipose tissue and skeletal muscle sarcolemma. We conclude that the GLUT3(+/-) male mice develop adult-onset adiposity with insulin resistance.

  14. Null-steering techniques for application to large array antennas

    NASA Astrophysics Data System (ADS)

    Hockham, G. A.; Cho, C.; Parr, J. C.; Wolfson, R. I.

    A multimode waveguide can be employed to design an antenna which produces a beam for each propagating mode. A dual-beam waveguide slot array is particularly attractive. The antenna is compact, highly efficient, and has lower sidelobe-level performance than can be achieved with conventional monopulse techniques. Adaptive phase steering for jammer nulling is considered, taking into account a large phased array using a series feed system. The considered configuration was selected for computer simulation. A description is presented of a multiple beam antenna with independent steerable nulls. The multiple beam low-sidelobe antenna configuration has the ability to provide a radiation pattern with multiple and independently-located nulls, with minimal effect on the sidelobes of the unperturbed pattern.

  15. A linear voltage-tunable distributed null device.

    NASA Technical Reports Server (NTRS)

    Benz, H. F.; Mattauch, R. J.

    1972-01-01

    A linear voltage-tunable null device was predicted, fabricated, and tested. This filter is conceptually a distributed parameter RC representation of the channel of a MOSFET in a network configuration with a second MOSFET that is treated as a variable resistor. Classical transmission-line theory is used to predict a linear tuning curve with applied bias for the device. This concept was used to design a null device having a null that is linearly tunable in the range of 100 kHz. Such devices were fabricated and tested. Typical MOS processing steps were used and the resulting structures are compatible with the planar technology. The compatibility leads towards extension of this work to different frequency ranges for other specific applications.

  16. sirt1-null mice develop an autoimmune-like condition

    SciTech Connect

    Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

    2008-10-01

    The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.

  17. Strehl ratio: a tool for optimizing optical nulls and singularities.

    PubMed

    Hénault, François

    2015-07-01

    In this paper a set of radial and azimuthal phase functions are reviewed that have a null Strehl ratio, which is equivalent to generating a central extinction in the image plane of an optical system. The study is conducted in the framework of Fraunhofer scalar diffraction, and is oriented toward practical cases where optical nulls or singularities are produced by deformable mirrors or phase plates. The identified solutions reveal unexpected links with the zeros of type-J Bessel functions of integer order. They include linear azimuthal phase ramps giving birth to an optical vortex, azimuthally modulated phase functions, and circular phase gratings (CPGs). It is found in particular that the CPG radiometric efficiency could be significantly improved by the null Strehl ratio condition. Simple design rules for rescaling and combining the different phase functions are also defined. Finally, the described analytical solutions could also serve as starting points for an automated searching software tool.

  18. Statefinder hierarchy: An extended null diagnostic for concordance cosmology

    NASA Astrophysics Data System (ADS)

    Arabsalmani, Maryam; Sahni, Varun

    2011-02-01

    We show how higher derivatives of the expansion factor can be developed into a null diagnostic for concordance cosmology (ΛCDM). It is well known that the Statefinder—the third derivative of the expansion factor written in dimensionless form, a(3)/aH3, equals unity for ΛCDM. We generalize this result and demonstrate that the hierarchy, a(n)/aHn, can be converted to a form that stays pegged at unity in concordance cosmology. This remarkable property of the Statefinder hierarchy enables it to be used as an extended null diagnostic for the cosmological constant. The Statefinder hierarchy combined with the growth rate of matter perturbations defines a composite null diagnostic which can distinguish evolving dark energy from ΛCDM.

  19. Characterizing the Properties of Coronal Magnetic Null Points

    NASA Astrophysics Data System (ADS)

    Barnes, Graham; DeRosa, Marc; Wagner, Eric

    2015-08-01

    The topology of the coronal magnetic field plays a role in a wide range of phenomena, from Coronal Mass Ejections (CMEs) through heating of the corona. One fundamental topological feature is the null point, where the magnetic field vanishes. These points are natural sites of magnetic reconnection, and hence the release of energy stored in the magnetic field. We present preliminary results of a study using data from the Helioseismic and Magnetic Imager aboard NASA's Solar Dynamics Observatory to characterize the properties and evolution of null points in a Potential Field Source Surface model of the coronal field. The main properties considered are the lifetime of the null points, their distribution with height, and how they form and subsequently vanish.This work is supported by NASA/LWS Grant NNX14AD45G, and by NSF/SHINE grant 1357018.

  20. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

    PubMed Central

    Edelman, Theresa L. B.; McCulloch, Katherine A.; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M.; Rougvie, Ann E.

    2016-01-01

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing. PMID:27729432

  1. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing.

    PubMed

    Edelman, Theresa L B; McCulloch, Katherine A; Barr, Angela; Frøkjær-Jensen, Christian; Jorgensen, Erik M; Rougvie, Ann E

    2016-12-07

    The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

  2. Interpreting null findings from trials of alcohol brief interventions.

    PubMed

    Heather, Nick

    2014-01-01

    The effectiveness of alcohol brief intervention (ABI) has been established by a succession of meta-analyses but, because the effects of ABI are small, null findings from randomized controlled trials are often reported and can sometimes lead to skepticism regarding the benefits of ABI in routine practice. This article first explains why null findings are likely to occur under null hypothesis significance testing (NHST) due to the phenomenon known as "the dance of the p-values." A number of misconceptions about null findings are then described, using as an example the way in which the results of the primary care arm of a recent cluster-randomized trial of ABI in England (the SIPS project) have been misunderstood. These misinterpretations include the fallacy of "proving the null hypothesis" that lack of a significant difference between the means of sample groups can be taken as evidence of no difference between their population means, and the possible effects of this and related misunderstandings of the SIPS findings are examined. The mistaken inference that reductions in alcohol consumption seen in control groups from baseline to follow-up are evidence of real effects of control group procedures is then discussed and other possible reasons for such reductions, including regression to the mean, research participation effects, historical trends, and assessment reactivity, are described. From the standpoint of scientific progress, the chief problem about null findings under the conventional NHST approach is that it is not possible to distinguish "evidence of absence" from "absence of evidence." By contrast, under a Bayesian approach, such a distinction is possible and it is explained how this approach could classify ABIs in particular settings or among particular populations as either truly ineffective or as of unknown effectiveness, thus accelerating progress in the field of ABI research.

  3. Magnetoacoustic Waves in Stratified Atmospheres with a Magnetic Null Point

    NASA Astrophysics Data System (ADS)

    Tarr, Lucas A.; Linton, Mark; Leake, James E.

    2016-05-01

    Magnetic fields strongly modify the propagation of MHD waves from the photosphere to the low corona, as can be shown exactly for the most simple case of a uniform magnetic field and isothermally stratrified atmosphere. For slightly more realistic scenarios, where both the atmospheric parameters and the magnetic field vary spatially, the linear MHD equations typically cannot be solved analytically. We use the Lagrangian Remap code--a nonlinear, shock-capturing MHD code--to study the propagation of initially acoustic wavepackets through a model 2D atmosphere that includes a gravitationally stratified chromosphere, transition region, and low corona. The magnetic field is formed by three photospheric concentrations and includes a single magnetic null point, resulting in an inhomogeneous system with a magnetic dome topology. A portion of an introduced wavepacket will refract toward the null due to the varying Alfven speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfven speeds coincide, partially transmit, reflect, and mode convert between branches of the local dispersion relation. Outward propagating slow modes generated during conversion become strongly concentrated along the set of field lines passing near the null. Acoustic energy is beamed back downwards towards each photospheric foot point, and upwards along one separatrix that exits the top of the numerical domain. Changes in the dominant restoring force for the wavepacket, between the Lorentz and pressure gradient forces, lead to a buildup of current density along topologically important features of the system (the null point and its four separatrices) and can drive reconnection at the null point itself. Ohmic dissipation of the currents locally heats the plasma. We find that the amount of current accumulation depends on where the centroid of a wavepacket initial crosses the photosphere, but does not simply coincide with regions of open versus closed magnetic field or

  4. Retention of crab larvae in a coastal null zone

    NASA Astrophysics Data System (ADS)

    Tilburg, Charles E.; Dittel, Ana I.; Epifanio, Charles E.

    2007-05-01

    Alongshelf transport in the southern Middle Atlantic Bight is forced by buoyancy-driven currents originating in three large estuaries along the bight. These currents are strongest in the coastal ocean near the southern terminus of each estuary, while the analogous region on the northern side is characterized by weak subtidal flow. We used a combination of field observations and numerical modeling to test the hypothesis that these regions of weak subtidal flow are coastal null zones that serve as retention areas for larvae. The field study consisted of a four-day, shipboard investigation of the distribution of blue crab larvae ( Callinectes sapidus) near the mouth of Delaware Bay (˜39°N, 75°W) in late summer, 2004. Hydrographic surveys of the study site were conducted with a hull-mounted, surface-measuring system. Results showed a sharp boundary between the null zone and the buoyancy-driven current to the south. Blue crab larvae were collected in surface plankton tows along a 30-km transect that encompassed these two areas. Stations with higher densities of larvae were clustered in the null zone during both ebb and flood tides. A numerical model was used to examine the physical mechanisms responsible for the observed distribution. Model results agreed with the field survey and showed that simulated larvae are aggregated in the null zone. The simulations also demonstrated that larvae spawned within the null zone have a much greater probability of settling in juvenile nursery habitat within the bay. The close agreement between field and model results provides consistent support for the hypothesis that coastal null zones associated with the buoyancy-driven circulation of large estuaries may allow retention of larvae in the vicinity of the natal spawning population.

  5. A Novel Positive Selection for Identifying Cold-Sensitive Myosin II Mutants in Dictyostelium

    PubMed Central

    Patterson, B.; Spudich, J. A.

    1995-01-01

    We developed a positive selection for myosin heavy chain mutants in Dictyostelium. This selection is based on the fact that brief exposure to azide causes wild-type cells to release from the substrate, whereas myosin null cells remain adherent. This procedure assays myosin function on a time scale of minutes and has therefore allowed us to select rapid-onset cold-sensitive mutants after random chemical mutagenesis of Dictyostelium cells. We developed a rapid technique for determining which mutations lie in sequences of the myosin gene that encode the head (motor) domain and localized 27 of 34 mutants to this domain. We recovered the appropriate sequences from five of the mutants and demonstrated that they retain their cold-sensitive properties when expressed from extrachromosomal plasmids. PMID:7498732

  6. The zebrafish early arrest mutants.

    PubMed

    Kane, D A; Maischein, H M; Brand, M; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Heisenberg, C P; Jiang, Y J; Kelsh, R N; Mullins, M C; Odenthal, J; Warga, R M; Nüsslein-Volhard, C

    1996-12-01

    This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes.

  7. Rapamycin requires AMPK activity and p27 expression for promoting autophagy-dependent Tsc2-null cell survival.

    PubMed

    Campos, Tania; Ziehe, Javiera; Fuentes-Villalobos, Francisco; Riquelme, Orlando; Peña, Daniela; Troncoso, Rodrigo; Lavandero, Sergio; Morin, Violeta; Pincheira, Roxana; Castro, Ariel F

    2016-06-01

    Tuberous sclerosis complex (TSC) disease results from inactivation of the TSC1 or TSC2 gene, and is characterized by benign tumors in several organs. Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Rapamycin-induced tumor shrinkage has been reported, but tumor recurrence occurs on withdrawal from rapamycin. Autophagy has been associated with development of TSC tumors and with tumor cell survival during rapamycin treatment. mTORC1 and AMPK directly inhibit and activate autophagy, respectively. AMPK is hyperactivated in TSC cells and tumors, and drives cytoplasmic sequestration of the cell-cycle inhibitor p27KIP (p27). Whether AMPK and p27 are involved in rapamycin-induced autophagy and survival of TSC cells remain unexplored. Here, we show that inhibition of AMPK by compound C or by shRNA-mediated depletion of LKB1 reduces activation of autophagy by rapamycin in Tsc2-null cells. Similarly, shRNA-mediated depletion of p27 inhibited rapamycin-induced autophagy. In support of p27 lying downstream of AMPK on the activation of autophagy in Tsc2-null cells, a p27 mutant that preferentially localizes in the cytosol recovered the effect of rapamycin on autophagy in both p27- and LKB1-depleted cells, but a nuclear p27 mutant was inactive. Finally, we show that p27-dependent activation of autophagy is involved in Tsc2-null cell survival under rapamycin treatment. These results indicate that an AMPK/p27 axis is promoting a survival mechanism that could explain in part the relapse of TSC tumors treated with rapamycin, exposing new avenues for designing more efficient treatments for TSC patients.

  8. Adaptive Nulling for the Terrestrial Planet Finder Interferometer

    NASA Technical Reports Server (NTRS)

    Jeganathan, Muthu; Hirai, Akiko; Lay, Oliver P.; Peters, Robert D.

    2006-01-01

    Deep, stable starlight nulls are needed for the direct detection of Earth-like planets and require careful control of the intensity and phases of the beams that are being combined. We are testing a novel compensator based on a deformable mirror to correct the intensity and phase at each wavelength and polarization across the nulling bandwidth. We have successfully demonstrated intensity and phase control using a deformable mirror across a 100nm wide band in the near-IR, and are in the process of conducting experiments in the mid-IR wavelengths. This paper covers the current results and in the mid-IR.

  9. Effect of residual phase gradients in optical null interference.

    PubMed

    Naik, Dinesh N; Pradeep Chakravarthy, T; Viswanathan, Nirmal K

    2016-01-01

    A scheme to study the effect of residual phase gradients in an optical interference between two out-of-phase Gaussian beams is proposed. In a Sagnac interferometer configured to provide a null output, a variable linear phase swept across the null point unfolds an optical field rotation due to an apparently negligible residual phase gradient present orthogonal to the linear phase sweep. As the optical beam that rotates around its propagation axis carries orbital angular momentum, the experimental results presented in this Letter could provide an insight into the momentum change associated with the energy redistribution in the fundamental phenomenon of optical interference.

  10. Suppression of inhibitor of differentiation 2, a target of mutant p53, is required for gain-of-function mutations.

    PubMed

    Yan, Wensheng; Liu, Gang; Scoumanne, Ariane; Chen, Xinbin

    2008-08-15

    Overexpression of mutant p53 is a common theme in human tumors, suggesting a tumor-promoting gain-of-function for mutant p53. To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p53 is inducibly knocked down in the SW480 colon cancer cell line, which contains mutant p53(R273H/P309S), and the MIA PaCa-2 pancreatic cancer cell line, which contains mutant p53(R248W). We found that knockdown of mutant p53 markedly inhibits cell proliferation. In addition, knockdown of mutant p53 sensitizes tumor cells to growth suppression by various chemotherapeutic drugs. To determine whether a gene involved in cell growth and survival is regulated by mutant p53, gene expression profiling analysis was performed and showed that the expression level of Id2, a member of the inhibitor of differentiation (Id) family, was markedly increased upon knockdown of mutant p53. To confirm this, Northern blot analysis was performed and showed that the expression level of Id2 was regulated by various mutant p53s in multiple cell lines. In addition, we found that the Id2 promoter is responsive to mutant but not wild-type p53, and mutant p53 binds to the Id2 promoter. Consistent with these observations, expression of endogenous Id2 was found to be inhibited by exogenous mutant p53 in p53-null HCT116 cells. Finally, we showed that knockdown of Id2 can restore the proliferative potential of tumor cells inhibited by withdrawal of mutant p53. Together, these findings suggest that one mechanism by which mutant p53 acquires its gain-of-function is through the inhibition of Id2 expression.

  11. Fast and Efficient Screening for Wheat Loss-of-Gene Mutants Using Multiplexed Melt Curve Analyses.

    PubMed

    Mieog, Jos C; Ral, Jean-Philippe F

    2016-01-01

    This study describes a new approach in the screening for loss-of-gene mutants in Heavy Ion Bombardment (HIB) mutant populations of genetically complex organisms such as hexaploid bread wheat using multiplexed single-color (SYBR Green) melt curve analyses. The assay was set up for three target genes to test its validity and applicability. For each gene, three genome-specific primer pairs (one for each genome) with distinct melt curves were developed and multiplexed. This allowed screening for "single null mutants" (plants with the target gene deleted in one of the three genomes) for all three genomes in a single reaction. The first two genes (α-Amylase 3 and Epsilon Cyclase) were used to test the approach as HIB null lines for all three genomes were already available for these. The third assay was successfully applied to identify new single null lines of the target gene α-Amylase 2 in an in-house HIB wheat collection. The use of SYBR Green greatly reduced the time and/or cost investment compared to other techniques and the approach proved highly suitable for high-throughput applications.

  12. Redox crisis underlies conditional light-dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA.

    PubMed

    Diamond, Spencer; Rubin, Benjamin E; Shultzaberger, Ryan K; Chen, You; Barber, Chase D; Golden, Susan S

    2017-01-24

    Cyanobacteria evolved a robust circadian clock, which has a profound influence on fitness and metabolism under daily light-dark (LD) cycles. In the model cyanobacterium Synechococcus elongatus PCC 7942, a functional clock is not required for diurnal growth, but mutants defective for the response regulator that mediates transcriptional rhythms in the wild-type, regulator of phycobilisome association A (RpaA), cannot be cultured under LD conditions. We found that rpaA-null mutants are inviable after several hours in the dark and compared the metabolomes of wild-type and rpaA-null strains to identify the source of lethality. Here, we show that the wild-type metabolome is very stable throughout the night, and this stability is lost in the absence of RpaA. Additionally, an rpaA mutant accumulates excessive reactive oxygen species (ROS) during the day and is unable to clear it during the night. The rpaA-null metabolome indicates that these cells are reductant-starved in the dark, likely because enzymes of the primary nighttime NADPH-producing pathway are direct targets of RpaA. Because NADPH is required for processes that detoxify ROS, conditional LD lethality likely results from inability of the mutant to activate reductant-requiring pathways that detoxify ROS when photosynthesis is not active. We identified second-site mutations and growth conditions that suppress LD lethality in the mutant background that support these conclusions. These results provide a mechanistic explanation as to why rpaA-null mutants die in the dark, further connect the clock to metabolism under diurnal growth, and indicate that RpaA likely has important unidentified functions during the day.

  13. The appearance, motion, and disappearance of three-dimensional magnetic null points

    SciTech Connect

    Murphy, Nicholas A.; Parnell, Clare E.; Haynes, Andrew L.

    2015-10-15

    While theoretical models and simulations of magnetic reconnection often assume symmetry such that the magnetic null point when present is co-located with a flow stagnation point, the introduction of asymmetry typically leads to non-ideal flows across the null point. To understand this behavior, we present exact expressions for the motion of three-dimensional linear null points. The most general expression shows that linear null points move in the direction along which the magnetic field and its time derivative are antiparallel. Null point motion in resistive magnetohydrodynamics results from advection by the bulk plasma flow and resistive diffusion of the magnetic field, which allows non-ideal flows across topological boundaries. Null point motion is described intrinsically by parameters evaluated locally; however, global dynamics help set the local conditions at the null point. During a bifurcation of a degenerate null point into a null-null pair or the reverse, the instantaneous velocity of separation or convergence of the null-null pair will typically be infinite along the null space of the Jacobian matrix of the magnetic field, but with finite components in the directions orthogonal to the null space. Not all bifurcating null-null pairs are connected by a separator. Furthermore, except under special circumstances, there will not exist a straight line separator connecting a bifurcating null-null pair. The motion of separators cannot be described using solely local parameters because the identification of a particular field line as a separator may change as a result of non-ideal behavior elsewhere along the field line.

  14. Red hair is the null phenotype of MC1R.

    PubMed

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  15. Self-Nulling Beam Combiner Using No External Phase Inverter

    NASA Technical Reports Server (NTRS)

    Bloemhof, Eric E.

    2010-01-01

    A self-nulling beam combiner is proposed that completely eliminates the phase inversion subsystem from the nulling interferometer, and instead uses the intrinsic phase shifts in the beam splitters. Simplifying the flight instrument in this way will be a valuable enhancement of mission reliability. The tighter tolerances on R = T (R being reflection and T being transmission coefficients) required by the self-nulling configuration actually impose no new constraints on the architecture, as two adaptive nullers must be situated between beam splitters to correct small errors in the coatings. The new feature is exploiting the natural phase shifts in beam combiners to achieve the 180 phase inversion necessary for nulling. The advantage over prior art is that an entire subsystem, the field-flipping optics, can be eliminated. For ultimate simplicity in the flight instrument, one might fabricate coatings to very high tolerances and dispense with the adaptive nullers altogether, with all their moving parts, along with the field flipper subsystem. A single adaptive nuller upstream of the beam combiner may be required to correct beam train errors (systematic noise), but in some circumstances phase chopping reduces these errors substantially, and there may be ways to further reduce the chop residuals. Though such coatings are beyond the current state of the art, the mechanical simplicity and robustness of a flight system without field flipper or adaptive nullers would perhaps justify considerable effort on coating fabrication.

  16. DARWIN nulling interferometer breadboard I: System engineering and measurements

    NASA Astrophysics Data System (ADS)

    Flatscher, Reinhold; Sodnik, Zoran; Ergenzinger, Klaus; Johann, Ulrich; Vink, Rob

    2003-10-01

    The presented work has been funded by ESA under ESTEC/Contract No. 14827/00/NL/CK and Astrium Germany has been awarded with this first ESA breadboarding towards nulling interferometry. Astrium designed and manufactured a nulling breadboard operating in the near infrared. The selected concept is fully transferable to the mid infrared. The interferometer is based on a highly symmetric Sagnac core. A dispersive phase shifter or a periscope system maintains the required phase shift of π. Two different source simulators have been built to test the interferometer's performance. They provide two point sources simulating a typical star and a planet signal. Angular separation of the point sources and intensity can be adapted to both operation modes, nulling and imaging. The OPD is actively stabilized to a gray fringe at a shorter wavelength without wobbling the system's OPD. The best results obtained with a diode laser source were a star suppression of 408,000 and a suppression of 32,000 using a broad-band ASE source. A stable deep null with a star suppression of 50,000 to 70,000 could be achieved over half an hour.

  17. Null matrices and the analysis of species co-occurrences.

    PubMed

    Sanderson, James G; Moulton, Michael P; Selfridge, Ralph G

    1998-08-01

    Patterns in species occurrences on islands have been analyzed by several authors. At issue is the number of non-occurring pairs of species (also known as checkerboards). Previous authors have suggested that if the number of checkerboards differs from what is expected by chance, then island communities might have been structured by competition. Investigators have pursued this problem by first generating random (or null) matrices and then testing a metric derived from the collection of null matrices against the metric calculated from the actual species co-occurrence matrix. The random matrices were constrained by requiring the number of species on each island, and the number of islands on which each species occurred to be equal to their observed values. We show that results from previous studies are generally flawed. We present a fast, efficient algorithm to generate null matrices for any set of fixed row and column sums, and propose a modification of a previously proposed metric as a test statistic. We evaluated the efficacy of our construction method for null creation and our metric using incidence matrices from the avifauna of Vanuatu (formerly New Hebrides).

  18. Traversable wormholes: Minimum violation of the null energy condition revisited

    SciTech Connect

    Zaslavskii, O. B.

    2007-08-15

    It was argued in literature that traversable wormholes can exist with an arbitrarily small violation of null energy conditions. I show that if the amount of exotic material near the wormhole throat tends to zero, either this leads to a horn instead of a wormhole or the throat approaches the horizon in such a way that infinitely large stresses develop on the throat.

  19. Null Lens Assembly for X-Ray Mirror Segments

    NASA Technical Reports Server (NTRS)

    Robinson, David W.

    2011-01-01

    A document discusses a null lens assembly that allows laser interferometry of 60 deg. slumped glass mirror segments used in x-ray mirrors. The assembly consists of four lenses in precise alignment to each other, with incorporated piezoelectric nanometer stepping actuators to position the lenses in six degrees of freedom for positioning relative to each other.

  20. Null Objects in Second Language Acquisition: Grammatical vs. Performance Models

    ERIC Educational Resources Information Center

    Zyzik, Eve C.

    2008-01-01

    Null direct objects provide a favourable testing ground for grammatical and performance models of argument omission. This article examines both types of models in order to determine which gives a more plausible account of the second language data. The data were collected from second language (L2) learners of Spanish by means of four oral…

  1. Effectiveness of Null Signal Sky Localization in Pulsar Timing Arrays

    NASA Astrophysics Data System (ADS)

    Shafiq Hazboun, Jeffrey

    2017-01-01

    A null stream is constructed from the timing residuals of three pulsars by noting that the same source polarization amplitudes appear in the data stream from each pulsar. Linear combinations of a set of individual pulsar data streams can be shown to be a two-parameter family (the two sky position angles of the source) that can be minimized to determine the location of the source on the sky. Taking the product of a number of null streams allows for an even stronger localization of the gravitational wave's source; a large advantage in a PTA where there are more independent signals than other gravitational wave detectors. While a null stream contains the same information as any other data stream with the same number of pulsars, the statistics of a product of noisy signals is inherently different than for a sum of those same signals.A comparison of how null signal searches compare to other techniques for sky localization of PTA sources will be discussed, as well as an assessment of the types of searches for which the method may be useful.

  2. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars?

    ERIC Educational Resources Information Center

    Frazier, Lyn

    2015-01-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing…

  3. Null point of discrimination in crustacean polarisation vision.

    PubMed

    How, Martin J; Christy, John; Roberts, Nicholas W; Marshall, N Justin

    2014-07-15

    The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90 and 135 deg relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45 deg than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not.

  4. Testing the null hypothesis: the forgotten legacy of Karl Popper?

    PubMed

    Wilkinson, Mick

    2013-01-01

    Testing of the null hypothesis is a fundamental aspect of the scientific method and has its basis in the falsification theory of Karl Popper. Null hypothesis testing makes use of deductive reasoning to ensure that the truth of conclusions is irrefutable. In contrast, attempting to demonstrate the new facts on the basis of testing the experimental or research hypothesis makes use of inductive reasoning and is prone to the problem of the Uniformity of Nature assumption described by David Hume in the eighteenth century. Despite this issue and the well documented solution provided by Popper's falsification theory, the majority of publications are still written such that they suggest the research hypothesis is being tested. This is contrary to accepted scientific convention and possibly highlights a poor understanding of the application of conventional significance-based data analysis approaches. Our work should remain driven by conjecture and attempted falsification such that it is always the null hypothesis that is tested. The write up of our studies should make it clear that we are indeed testing the null hypothesis and conforming to the established and accepted philosophical conventions of the scientific method.

  5. Overt and Null Subject Pronouns in Jordanian Arabic

    ERIC Educational Resources Information Center

    Al-Momani, Islam M.

    2015-01-01

    The paper aims at examining the role that morphology plays in allowing and/or motivating sentences in Jordanian Arabic (hereafter JA) to be formed with or without subject pronouns. It also aims at giving a comprehensive and descriptive presentation of the distribution of overt and null subject pronouns in JA, and tries to determine to what extent…

  6. Retarded fields of null particles and the memory effect

    NASA Astrophysics Data System (ADS)

    Tolish, Alexander; Wald, Robert M.

    2014-03-01

    We consider the retarded solution to the scalar, electromagnetic, and linearized gravitational field equations in Minkowski spacetime, with source given by a particle moving on a null geodesic. In the scalar case and in the Lorenz gauge in the electromagnetic and gravitational cases, the retarded integral over the infinite past of the source does not converge as a distribution, so we cut off the null source suitably at a finite time t0 and then consider two different limits: (i) the limit as the observation point goes to null infinity at fixed t0, from which the "1/r" part of the fields can be extracted and (ii) the limit t0→-∞ at fixed "observation point." The limit (i) gives rise to a "velocity kick" on distant test particles in the scalar and electromagnetic cases, and it gives rise to a "memory effect" (i.e., a permanent change in relative separation of two test particles) in the linearized gravitational case, in agreement with previous analyses. As already noted, the second limit does not exist in the scalar case or for the Lorenz gauge vector potential and Lorenz gauge metric perturbation in the electromagnetic and linearized gravitational cases. However, in the electromagnetic case, we obtain a well-defined distributional limit for the electromagnetic field strength, and in the linearized gravitational case, we obtain a well-defined distributional limit for the linearized Riemann tensor. In the gravitational case, this limit agrees with the Aichelberg-Sexl solution. There is no memory effect associated with this limiting solution. This strongly suggests that the memory effect—including nonlinear memory effect of Christodoulou—should not be interpreted as arising simply from the passage of (effective) null stress energy to null infinity but rather as arising from a "burst of radiation" associated with the creation of the null stress energy [as in case (i) above] or, more generally, with radiation present in the spacetime that was not "produced" by the

  7. ECB deacylase mutants

    DOEpatents

    Arnold, Frances H.; Shao, Zhixin; Zhao, Huimin; Giver, Lorraine J.

    2002-01-01

    A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

  8. Thermodynamical interpretation of the geometrical variables associated with null surfaces

    NASA Astrophysics Data System (ADS)

    Chakraborty, Sumanta; Padmanabhan, T.

    2015-11-01

    The emergent gravity paradigm interprets gravitational field equations as describing the thermodynamic limit of the underlying statistical mechanics of microscopic degrees of freedom of the spacetime. The connection is established by attributing a heat density T s to the null surfaces where T is the appropriate Davies-Unruh temperature and s is the entropy density. The field equations can be obtained from a thermodynamic variational principle which extremizes the total heat density of all null surfaces. The explicit form of s determines the nature of the theory. We explore the consequences of this paradigm for an arbitrary null surface and highlight the thermodynamic significance of various geometrical quantities. In particular, we show that (a) a conserved current, associated with the time development vector in a natural fashion, has direct thermodynamic interpretation in all Lanczos-Lovelock models of gravity; (b) one can generalize the notion of gravitational momentum, introduced in T. Padmanabhan, [arXiv:1506.03814] to all Lanczos-Lovelock models of gravity such that the conservation of the total momentum leads to the relevant field equations; (c) the thermodynamic variational principle which leads to the field equations of gravity can also be expressed in terms of the gravitational momentum in all Lanczos-Lovelock models; and (d) three different projections of gravitational momentum related to an arbitrary null surface in the spacetime lead to three different equations, all of which have thermodynamic interpretation. The first one reduces to a Navier-Stokes equation for the transverse drift velocity. The second can be written as a thermodynamic identity T d S =d E +P d V . The third describes the time evolution of the null surface in terms of suitably defined surface and bulk degrees of freedom. The implications are discussed.

  9. Identification of several gy4 nulls from the USDA soybean germplasm collection provides new genetic resources for the development of high-quality tofu cultivars.

    PubMed

    Kim, Won-Seok; Ho, Heo Jae; Nelson, Randall L; Krishnan, Hari B

    2008-12-10

    Tofu, a cheese-like food made by curdling soy milk, is a major dietary staple of Asian countries. Consumption of tofu and other soy products is steadily increasing in North America due to its well-known health benefits. Soybean A(5), A(4), and B(3) peptide null lines 'Enrei' and 'Raiden' are commonly utilized in breeding programs to develop high-quality tofu cultivars. To expand the genetic diversity it is desirable to identify and utilize other A(5), A(4), and B(3) null genotypes in the development of improved tofu cultivars that are adapted to North American conditions. In this study were screened diverse soybean accessions from the USDA Soybean Germplasm Collection to identify Gy4 mutants, the locus that controls A(5), A(4), and B(3) peptide production. Analysis of total seed proteins from 485 soybean lines by SDS-PAGE enabled the identification of 38 accessions that lacked the A(5), A(4), and B(3) peptides. These accessions showed marked differences in seed size and seed coat color and represented different maturity groups ranging from 0 to IX. To ascertain the molecular basis for the lack of A(5), A(4), and B(3) peptides in the newly identified Gy4 mutants, the nucleotide sequence of a portion of the Gy4 gene was determined from eight soybean accessions representing different maturity groups. These eight Gy4 mutants revealed a single point mutation that changed the translation initiation codon ATG to ATA, resulting in the A(5), A(4), and B(3) null phenotype. The newly identified Gy4 mutants from this study will enable plant breeders to expand the genetic diversity of North American food-quality soybeans and also aid in the development of hypoallergenic soybeans.

  10. Reduced wheel running and blunted effects of voluntary exercise in LPA1-null mice: The importance of assessing the amount of running in transgenic mice studies

    PubMed Central

    Castilla-Ortega, Estela; Rosell-Valle, Cristina; Blanco, Eduardo; Pedraza, Carmen; Chun, Jerold; de Fonseca, Fernando Rodríguez; Estivill-Torrús, Guillermo; Santín, Luis J.

    2014-01-01

    This work was aimed to assess whether voluntary exercise rescued behavioral and hippocampal alterations in mice lacking the lysophosphatidic acid LPA1 receptor (LPA1-null mice), studying the potential relationship between the amount of exercise performed and its effects. Normal and LPA1-null mice underwent 23 days of free wheel running and were tested for open-field behavior and adult hippocampal neurogenesis (cell proliferation, immature neurons, cell survival). Running decreased anxiety-like behavior in both genotypes but increased exploration only in the normal mice. While running affected all neurogenesis-related measures in normal mice (especially in the suprapyramidal blade of the dentate gyrus), only a moderate increase in cell survival was found in the mutants. Importantly, the LPA1-nulls showed notably reduced running. Analysis suggested that defective running in the LPA1-null mice could contribute to explain the scarce benefit of the voluntary exercise treatment. On the other hand, a literature review revealed that voluntary exercise is frequently used to modulate behavior and the hippocampus in transgenic mice, but half of the studies did not assess the quantity of running, overlooking any potential running impairments. This study adds evidence to the relevance of the quantity of exercise performed, emphasizing the importance of its assessment in transgenic mice research. PMID:24055600

  11. Suppression of gain-of-function mutant p53 with metabolic inhibitors reduces tumor growth in vivo

    PubMed Central

    Jung, Chae Lim; Mun, Hyemin; Jo, Se-Young; Oh, Ju-Hee; Lee, ChuHee; Choi, Eun-Kyung; Jang, Se Jin; Suh, Young-Ah

    2016-01-01

    Mutation of p53 occasionally results in a gain of function, which promotes tumor growth. We asked whether destabilizing the gain-of-function protein would kill tumor cells. Downregulation of the gene reduced cell proliferation in p53-mutant cells, but not in p53-null cells, indicating that the former depended on the mutant protein for survival. Moreover, phenformin and 2-deoxyglucose suppressed cell growth and simultaneously destabilized mutant p53. The AMPK pathway, MAPK pathway, chaperone proteins and ubiquitination all contributed to this process. Interestingly, phenformin and 2-deoxyglucose also reduced tumor growth in syngeneic mice harboring the p53 mutation. Thus, destabilizing mutant p53 protein in order to kill cells exhibiting “oncogene addiction” could be a promising strategy for combatting p53 mutant tumors. PMID:27765910

  12. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure.

    PubMed

    Harris, Muriel J; Juriloff, Diana M

    2010-08-01

    The number of mouse mutants and strains with neural tube defects (NTDs) now exceeds 240, including 205 representing specific genes, 30 for unidentified genes, and 9 multifactorial strains. These mutants identify genes needed for embryonic neural tube closure. Reports of 50 new NTD mutants since our 2007 review (Harris and Juriloff, 2007) were considered in relation to the previously reviewed mutants to obtain new insights into mechanisms of NTD etiology. In addition to null mutations, some are hypomorphs or conditional mutants. Some mutations do not cause NTDs on their own, but do so in digenic, trigenic, and oligogenic combinations, an etiology that likely parallels the nature of genetic etiology of human NTDs. Mutants that have only exencephaly are fourfold more frequent than those that have spina bifida aperta with or without exencephaly. Many diverse cellular functions and biochemical pathways are involved; the NTD mutants draw new attention to chromatin modification (epigenetics), the protease-activated receptor cascade, and the ciliopathies. Few mutants directly involve folate metabolism. Prevention of NTDs by maternal folate supplementation has been tested in 13 mutants and reduces NTD frequency in six diverse mutants. Inositol reduces spina bifida aperta frequency in the curly tail mutant, and three new mutants involve inositol metabolism. The many NTD mutants are the foundation for a future complete genetic understanding of the processes of neural fold elevation and fusion along mechanistically distinct cranial-caudal segments of the neural tube, and they point to several candidate processes for study in human NTD etiology.

  13. Defective intestinal amino acid absorption in Ace2 null mice.

    PubMed

    Singer, Dustin; Camargo, Simone M R; Ramadan, Tamara; Schäfer, Matthias; Mariotta, Luca; Herzog, Brigitte; Huggel, Katja; Wolfer, David; Werner, Sabine; Penninger, Josef M; Verrey, François

    2012-09-15

    Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations.

  14. Genes and Alcohol Consumption: Studies with Mutant Mice

    PubMed Central

    Mayfield, Jody; Arends, Michael A.; Harris, R. Adron; Blednov, Yuri A.

    2017-01-01

    In this chapter, we review the effects of global null mutant and overexpressing transgenic mouse lines on voluntary self-administration of alcohol. We examine approximately 200 publications pertaining to the effects of 155 mouse genes on alcohol consumption in different drinking models. The targeted genes vary in function and include neurotransmitter, ion channel, neuroimmune, and neuropeptide signaling systems. The alcohol self-administration models include operant conditioning, two- and four-bottle choice continuous and intermittent access, drinking in the dark limited access, chronic intermittent ethanol, and scheduled high alcohol consumption tests. Comparisons of different drinking models using the same mutant mice are potentially the most informative, and we will highlight those examples. More mutants have been tested for continuous two-bottle choice consumption than any other test; of the 137 mouse genes examined using this model, 97 (72%) altered drinking in at least one sex. Overall, the effects of genetic manipulations on alcohol drinking often depend on the sex of the mice, alcohol concentration and time of access, genetic background, as well as the drinking test. PMID:27055617

  15. Chromatism compensation in wide-band nulling interferometry for exoplanet detection.

    PubMed

    Spronck, Julien; Pereira, Silvania F; Braat, Joseph J M

    2006-02-01

    We introduce the concept of chromatism compensation in nulling interferometry that enables a high rejection ratio in a wide spectral band. Therefore the achromaticity condition considered in most nulling interferometers can be relaxed. We show that this chromatism compensation cannot be applied to a two-beam nulling interferometer, and we make an analysis of the particular case of a three-telescope configuration.

  16. Somatic-cell mutation induced by short exposures to cigarette smoke in urate-null, oxidative stress-sensitive Drosophila.

    PubMed

    Uchiyama, Tomoyo; Koike, Ryota; Yuma, Yoko; Okamoto, Keinosuke; Arimoto-Kobayashi, Sakae; Suzuki, Toshinori; Negishi, Tomoe

    2016-01-01

    We previously reported that a urate-null strain of Drosophila is hypersensitive to cigarette smoke (CS), and we suggested that CS induces oxidative stress in Drosophila because uric acid is a potent antioxidant. Although the carcinogenic risk of CS exposure is widely recognized; documentation of in vivo genotoxic activity of environmental CS, especially gaseous-phase CS, remains inconclusive. To date, somatic-cell mutations in Drosophila resulting from exposure to CS have not been detected via the somatic mutation and recombination test (wing spot test) with wild-type flies, a widely used Drosophila assay for the detection of somatic-cell mutation; moreover, genotoxicity has not been documented via a DNA repair test that involves DNA repair-deficient Drosophila. In this study, we used a new Drosophila strain (y v ma-l; mwh) to examine the mutagenicity induced by gaseous-phase CS; these flies are urate-null due to a mutation in ma-l, and they are heterozygous for multiple wing hair (mwh), a mutation that functions as a marker for somatic-cell mutation. In an assay with this newly developed strain, a superoxide anion-producing weed-killer, paraquat, exhibited significant mutagenicity; in contrast, paraquat was hardly mutagenic with a wild-type strain. Drosophila larvae were exposed to CS for 2, 4 or 6h, and then kept at 25°C on instant medium until adulthood. After eclosion, mutant spots, which consisted of mutant hairs on wings, were scored. The number of mutant spots increased significantly in an exposure time-dependent manner in the urate-null females (ma-l (-/-)), but not in the urate-positive females (ma-l (+/-)). In this study, we showed that short-term exposure to CS was mutagenic in this in vivo system. In addition, we obtained suggestive data regarding reactive oxygen species production in larva after CS exposure using the fluorescence probe H2DCFDA. These results suggest that oxidative damage, which might be countered by uric acid, was partly responsible

  17. Repeated Names, Overt Pronouns, and Null Pronouns in Spanish

    PubMed Central

    Lezama, Carlos Gelormini; Almor, Amit

    2010-01-01

    In two self-paced, sentence-by-sentence reading experiments we examined the difference in the processing of Spanish discourses with repeated names, overt pronouns, and null pronouns in emphatic and non-emphatic contexts. In Experiment 1, repeated names and overt pronouns caused a processing delay when they referred to salient antecedents in non-emphatic contexts. In Experiment 2, both processing delays were eliminated when an emphatic cleft-structure was used. The processing delay caused by overt pronouns referring to salient antecedents in non-emphatic contexts in Spanish contrasts with previous findings in Chinese, where null and overt pronouns elicited similar reading times. We explain both our Spanish findings and the Chinese findings in a unified framework based on the notion of balance between processing cost and discourse function in line with the Informational Load Hypothesis. PMID:21552376

  18. Exact Null Controllability of a Nonlinear Thermoelastic Contact Problem

    SciTech Connect

    Sivergina, Irina F. Polis, Michael P.

    2005-01-15

    We study the controllability properties of a nonlinear parabolic system that models the temperature evolution of a one-dimensional thermoelastic rod that may come into contact with a rigid obstacle. Basically the system dynamics is described by a one-dimensional nonlocal heat equation with a nonlinear and nonlocal boundary condition of Newmann type.We focus on the control problem and treat the case when the control is distributed over the whole space domain. In this case the system is proved to be exactly null controllable provided the parameters of the system are smooth.The proof is based on changing the control variable and using Aubin's Compactness Lemma to obtain an invariant set for the linearized controllability map. Then, by proving that the found solution is sufficiently smooth, we get the null controllability for the original system.

  19. Three-dimensional kinematic reconnection of plasmoids with nulls

    NASA Technical Reports Server (NTRS)

    Lau, Yun-Tung; Finn, John M.

    1992-01-01

    The global nonlinear dynamics of magnetic field lines in plasmoids with a pair of nulls, where B = 0, is studied. The aim of this analysis is to describe the separatrix surfaces on which singularities can occur in ideal magnetohydrodynamics because of topological changes in the field. These separatrix surfaces should locate the boundary layers associated with 3D reconnection in the presence of resistivity or inertia. It is found that the field lines exhibit chaotic scattering with several properties in common with plasmoid models without nulls (in which one component of the magnetic field never changes sign). In particular, the singular surfaces can be fractal, implying complex current density structures down to the dissipation scale. These generic features are expected to exist in typical coronal magnetic geometries exhibiting three-dimensional reconnection and the formation of current sheets.

  20. Advances in corneal topography measurements with conical null-screens

    NASA Astrophysics Data System (ADS)

    Campos-García, Manuel; Cossio-Guerrero, Cesar; Huerta-Carranza, Oliver; Moreno-Oliva, Víctor I.

    2015-09-01

    In this work we report the design of a null-screen for corneal topography. To avoid the difficulties in the alignment of the test system due to the face contour (eyebrows, nose, or eyelids), we design a conical null-screen with a novel radial points distribution drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact array of circular spots if the surface is perfect. Additionally, an algorithm to compute the sagittal and meridional radii of curvature for the corneal surface is presented. The sagittal radius is obtained from the surface normal, and the meridional radius is calculated from a function fitted to the derivative of the sagittal curvature by using the surfacenormals raw data. Experimental results for the testing a calibration spherical surface are shown. Also, we perform some corneal topography measurements.

  1. Axon and muscle spindle hyperplasia in the myostatin null mouse.

    PubMed

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan

    2011-02-01

    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres.

  2. Avoid a Void: The Eradication of Null Dereferencing

    NASA Astrophysics Data System (ADS)

    Meyer, Bertrand; Kogtenkov, Alexander; Stapf, Emmanuel

    All object-oriented programs, but also those in C or Pascal as soon as they use pointers, are subject to the risk of run-time crash due to "null pointer dereferencing". Until recently this was the case even in statically typed languages. Tony Hoare has called this problem his "billion-dollar mistake". In the type system of ISO-standard Eiffel, the risk no longer exists: void safety (the absence of null pointer dereferencing) has become a property guaranteed by the type system and enforced by the compiler. The mechanism is fully implemented and major libraries and applications have been made void-safe. This presentation describes the principles of Eiffel's void safety, their implementation and the lessons gained.

  3. Defocusing of null rays in infinite derivative gravity

    NASA Astrophysics Data System (ADS)

    Conroy, Aindriú; Koshelev, Alexey S.; Mazumdar, Anupam

    2017-01-01

    Einstein's General theory of relativity permits spacetime singularities, where null geodesic congruences focus in the presence of matter, which satisfies an appropriate energy condition. In this paper, we provide a minimal defocusing condition for null congruences without assuming any ansatz-dependent background solution. The two important criteria are: (1) an additional scalar degree of freedom, besides the massless graviton must be introduced into the spacetime; and (2) an infinite derivative theory of gravity is required in order to avoid tachyons or ghosts in the graviton propagator. In this regard, our analysis strengthens earlier arguments for constructing non-singular bouncing cosmologies within an infinite derivative theory of gravity, without assuming any ansatz to solve the full equations of motion.

  4. A phenotypic null hypothesis for the genetics of personality.

    PubMed

    Turkheimer, Eric; Pettersson, Erik; Horn, Erin E

    2014-01-01

    We review the genetically informed literature on the genetics of personality. Over the past century, quantitative genetic studies, using identical and fraternal twins, have demonstrated that differences in human personality are substantially heritable. We focus on more contemporary questions to which that basic observation has led. We examine whether differences in the heritability of personality are replicable across different traits, samples, and studies; how the heritability of personality relates to its reliability; and how behavior genetics can be employed in studies of validity, and we discuss the stability of personality in genetic and environmental variance. The appropriate null hypothesis in behavior genetics is not that genetic or environmental influence on personality is zero. Instead, we offer a phenotypic null hypothesis, which states that genetic variance is not an independent mechanism of individual differences in personality but rather a reflection of processes that are best conceptualized at the phenotypic level.

  5. Null result for the weight change of a spinning gyroscope

    SciTech Connect

    Nitschke, J.M.; Wilmarth, P.A. )

    1990-04-30

    A null result was obtained for the weight change of a right-spinning gyroscope, contradicting the results recently reported by Hayasaka and Takeuchi. No weight change could be observed under a variety of spin directions for rotational frequencies between 0 and 2.2{times}10{sup 4} rpm. Our limit of {minus}0.025{plus minus}0.07 mg is more than 2 orders of magnitude smaller than the effect reported by Hayasaka and Takeuchi.

  6. (abstract) Ulysses Observations of Magnetic Nulls in the Solar Wind

    NASA Technical Reports Server (NTRS)

    Winterhalter, D.; Murphy, N.; Tsurutani, B. T.; Smith, E. J.; Balogh, A.; Erdos, G.

    1993-01-01

    High time resolution magnetic field measurements (1 vector/s) at radial distances out to 5.3 AU and heliographic latitudes from 0(deg) to > 35(deg) S reveal the presence of solitary pulses lasting tens of seconds in which the field magnitude approaches or reaches zero. The properties of these nulls, their spatial distribution and relation to solar wind structures and to similar-apppearing interplanetary and magnetospheric impulses will be discussed.

  7. 4-dimensional spacetimes from 2-dimensional conformal null data

    NASA Astrophysics Data System (ADS)

    Goswami, Rituparno; Ellis, George F. R.

    2017-03-01

    In this paper we investigate whether the holographic principle proposed in string theory has a classical counterpart in general relativity theory. We show that there is a partial correspondence: at least in the case of vacuum Petrov type D spacetimes that admit a non-trivial Killing tensor, which encompass all the astrophysical black hole spacetimes, there exists a one-to-one correspondence between gravity in bulk and a 2-dimensional classical conformal scalar field on a null boundary.

  8. Uniqueness of Kerr space-time near null infinity

    SciTech Connect

    Wu Xiaoning; Bai Shan

    2008-12-15

    We reexpress the Kerr metric in standard Bondi-Sachs coordinates near null infinity I{sup +}. Using the uniqueness result of the characteristic initial value problem, we prove the Kerr metric is the only asymptotically flat, stationary, axially symmetric, type-D solution of the vacuum Einstein equation. The Taylor series of Kerr space-time is expressed in terms of Bondi-Sachs coordinates, and the Newman-Penrose constants have been calculated.

  9. Nulling Hall-Effect Current-Measuring Circuit

    NASA Technical Reports Server (NTRS)

    Sullender, Craig C.; Vazquez, Juan M.; Berru, Robert I.

    1993-01-01

    Circuit measures electrical current via combination of Hall-effect-sensing and magnetic-field-nulling techniques. Known current generated by feedback circuit adjusted until it causes cancellation or near cancellation of magnetic field produced in toroidal ferrite core by current measured. Remaining magnetic field measured by Hall-effect sensor. Circuit puts out analog signal and digital signal proportional to current measured. Accuracy of measurement does not depend on linearity of sensing components.

  10. Molecular basis for the catalytic inactivity of a naturally occurring near-null variant of human ALOX15.

    PubMed

    Horn, Thomas; Ivanov, Igor; Di Venere, Almerinda; Kakularam, Kumar Reddy; Reddanna, Pallu; Conrad, Melanie L; Richter, Constanze; Scheerer, Patrick; Kuhn, Hartmut

    2013-12-01

    Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which have been implicated in cardiovascular, hyperproliferative and neurodegenerative diseases. Here we report that a naturally occurring mutation in the hALOX15 gene leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The inactivity may be related to severe misfolding of the enzyme protein, which was concluded from CD-spectra as well as from thermal and chemical stability assays. In silico mutagenesis experiments suggest that most mutations at hGly422 have the potential to induce sterical clash, which might be considered a reason for protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE formation. Taken together, our data indicate that the conserved glycine is of functional importance for these enzyme variants and most mutants at this position lose catalytic activity.

  11. Metabolite profiling of Phycomyces blakesleeanus carotene mutants reveals global changes across intermediary metabolism.

    PubMed

    Alcalde, Eugenio; Fraser, Paul David

    2016-11-01

    The filamentous fungus Phycomyces blakesleeanus provides a renewable biosource of industrial high-value compounds such as carotenes, other isoprenoids (ubiquinone and sterols), organic acids and fatty acids. Several Phycomyces mutants involved in the formation of β-carotene are available. For example, the carA mutants have a leaky mutation in the phytoene synthase and produce significantly lower amounts of carotenes, while the carB and carR mutants produce phytoene and lycopene, respectively, due to a null mutation in the genes encoding the phytoene dehydrogenase and lycopene cyclase, respectively. The carS mutants are mutated in the gene encoding the oxygenase responsible for the conversion of β-carotene into apocarotenoids and, as a result, β-carotene accumulates. In order to ascertain further the biochemical changes arising in these potential industrial strains, a metabolite profiling workflow was implemented for Phycomyces. GC-MS and ultra-performance liquid chromatography-photodiode array platforms enabled the identification of over 100 metabolites in 11 carA, carB, carR and carS mutant strains and their wild-type comparator. All mutant strains possessed decreased TCA cycle intermediates, galactose, alanine and ribitol, while dodecanol and valine showed a general increase. As predicted, other terpenoid levels were affected in the carB, carR and carS mutants but not in the carA mutants. The global changes across intermediary metabolism of the mutants suggest that complex metabolic networks exist between intermediary and secondary metabolism or that other mutations beyond the carotene pathway may exist in these mutants. These data show the utility of the methodology in metabolically phenotyping Phycomyces strains with potential industrial exploitation.

  12. Non-null annular subaperture stitching interferometry for aspheric test

    NASA Astrophysics Data System (ADS)

    Zhang, Lei; Liu, Dong; Shi, Tu; Yang, Yongying; Chong, Shiyao; Miao, Liang; Huang, Wei; Shen, Yibing; Bai, Jian

    2015-10-01

    A non-null annular subaperture stitching interferometry (NASSI), combining the subaperture stitching idea and non-null test method, is proposed for steep aspheric testing. Compared with standard annular subaperture stitching interferometry (ASSI), a partial null lens (PNL) is employed as an alternative to the transmission sphere, to generate different aspherical wavefronts as the references. The coverage subaperture number would thus be reduced greatly for the better performance of aspherical wavefronts in matching the local slope of aspheric surfaces. Instead of various mathematical stitching algorithms, a simultaneous reverse optimizing reconstruction (SROR) method based on system modeling and ray tracing is proposed for full aperture figure error reconstruction. All the subaperture measurements are simulated simultaneously with a multi-configuration model in a ray-tracing program, including the interferometric system modeling and subaperture misalignments modeling. With the multi-configuration model, full aperture figure error would be extracted in form of Zernike polynomials from subapertures wavefront data by the SROR method. This method concurrently accomplishes subaperture retrace error and misalignment correction, requiring neither complex mathematical algorithms nor subaperture overlaps. A numerical simulation exhibits the comparison of the performance of the NASSI and standard ASSI, which demonstrates the high accuracy of the NASSI in testing steep aspheric. Experimental results of NASSI are shown to be in good agreement with that of Zygo® VerifireTM Asphere interferometer.

  13. Hoxa10 null animals exhibit reduced platelet biogenesis

    PubMed Central

    Konieczna, Iwona M.; DeLuca, Teresa A.; Eklund, Elizabeth A.; Miller, William M.

    2016-01-01

    Summary The transcription factor HOXA10 is an important regulator of myelopoiesis. Engineered over-expression of Hoxa10 in mice results in a myeloproliferative disorder that progresses to acute myeloid leukaemia (AML) over time, and in humans over-expression is associated with poor outcomes in AML. Here, we report that loss of Hoxa10 expression in mice results in reduced platelet count and platelet production, but does not affect clotting efficiency. About 40% fewer platelets were found in Hoxa10 null animals in comparison to wild type littermates. We found a nearly 50% reduction in the percentage of reticulated platelets in Hoxa10 null mice, suggesting deficient platelet production. Furthermore, Hoxa10 null animals recovered less efficiently from induced thrombocytopenia, supporting our hypothesis of defective platelet production. This also correlated with reduced colony formation potential of stem and progenitor cells seeded in megakaryocyte-enhancing conditions in vitro. Together, our results indicate that HOXA10 is important for megakaryopoiesis and platelet biogenesis. PMID:26847476

  14. Generation of a Conditional Null Allele of Jumonji

    PubMed Central

    Mysliwiec, Matthew R.; Chen, Junqin; Powers, Patricia A.; Bartley, Christopher R.; Schneider, Michael D.; Lee, Youngsook

    2007-01-01

    Summary: The jumonji (jmj) gene plays important roles in multiple organ development in mouse, including cardiovascular development. Since JMJ is expressed widely during mouse development, it is essential that conditional knockout approaches be employed to ablate JMJ in a tissue-specific manner to identify the cell lineage specific roles of JMJ. In this report, we describe the establishment of a jmj conditional null allele in mice by generating a loxP-flanked (floxed) jmj allele, which allows the in vivo ablation of jmj via Cre recombinase-mediated deletion. Gene targeting was used to introduce loxP sites flanking exon 3 of the jmj allele to mouse embryonic stem cells. Our results indicate that the jmj floxed allele converts to a null allele in a heart-specific manner when embryos homozygous for the floxed jmj allele and carrying the α-myosin heavy chain promoter-Cre transgene were analyzed by Southern and Northern blot analyses. Therefore, this mouse line harboring the conditional jmj null allele will provide a valuable tool for deciphering the tissue and cell lineage specific roles of JMJ. PMID:16900512

  15. Neuropathy in Human and Mice with PMP22 null

    PubMed Central

    Saporta, Mario Andre; Katona, Istvan; Zhang, Xuebao; Roper, Helen P.; Carr, Louise; Macdonald, Fiona; Brueton, Louise; Blake, Julian; Suter, Ueli; Reilly, Mary M.; Shy, Michael E.; Li, Jun

    2013-01-01

    Background/Objective Haploinsufficiency of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP). However, the biological functions of PMP22 in humans are largely unexplored due to the absence of patients with PMP22 null mutations. Design, Setting and Participants We have evaluated a 7-year-old boy with PMP22 null. Findings were compared with those from nerves of Pmp22 null mice. Results Motor and sensory deficits in the proband were non-length dependent. Weakness was found in cranial muscles, but not in the limbs. Large fiber sensory modalities were profoundly abnormal, which started prior to the maturation of myelin. This is in line with the temporal pattern of PMP22 expression predominantly in cranial motor neurons and DRG during embryonic development, becoming undetectable in adulthood. Moreover, there were conspicuous maturation defects of myelinating Schwann cells that were more significant in motor nerve fibers than in sensory nerve fibers. Conclusions Taken together, these data suggest that PMP22 is important for the normal function of neurons that express PMP22 during early development, such as cranial motor neurons and spinal sensory neurons. Moreover, PMP22 deficiency differentially affects myelination between motor and sensory nerves, which may have contributed to the unique clinical phenotype in the patient with absence of PMP22. PMID:21670407

  16. Averaged null energy condition in loop quantum cosmology

    SciTech Connect

    Li Lifang; Zhu Jianyang

    2009-02-15

    Wormholes and time machines are objects of great interest in general relativity. However, to support them it needs exotic matters which are impossible at the classical level. Semiclassical gravity introduces the quantum effects into the stress-energy tensor and constructs many self-consistent wormholes. But they are not traversable due to the averaged null energy condition. Loop quantum gravity (LQG) significantly modifies the Einstein equation in the deep quantum region. If we write the modified Einstein equation in the form of the standard one but with an effective stress-energy tensor, it is convenient to analyze the geometry in LQG through the energy condition. Loop quantum cosmology (LQC), an application of LQG, has an effective stress-energy tensor which violates some kinds of local energy conditions. So it is natural that the inflation emerges in LQC. In this paper, we investigate the averaged null energy condition in LQC in the framework of the effective Hamiltonian, and we find that the effective stress-energy tensor in LQC violates the averaged null energy condition in the massless scalar field coupled model.

  17. Null-space function estimation for the interior problem

    NASA Astrophysics Data System (ADS)

    Zeng, Gengsheng L.; Gullberg, Grant T.

    2012-04-01

    In single-photon emission computed tomography (SPECT), projection data can be truncated when the camera's field of view is smaller than the object to be imaged. Using truncated projections to reconstruct a region of interest (ROI) is a reality we must face if small detectors are used. The truncated data result in an underdetermined system of imaging equations, which may lead to non-unique solutions. Data sampling and photon attenuation may also affect the solution uniqueness and stability. The uniqueness of the solutions in the ROI can be investigated by studying the null-space functions in the ROI. This paper uses an iterative algorithm to estimate the null-space image, to determine the sampling conditions under which a stable ROI reconstruction is possible with truncated data and to investigate whether attenuation can influence the ROI reconstruction bias. This iterative algorithm is validated by the singular value decomposition method. We show that if the ROI is sufficiently sampled, the null-space image is close to zero inside the ROI, and any almost-zero offset is insignificant in SPECT, because the noise is a much more dominating degradation factor.

  18. Null model analysis of species associations using abundance data.

    PubMed

    Ulrich, Werner; Gotelli, Nicholas J

    2010-11-01

    The influence of negative species interactions has dominated much of the literature on community assembly rules. Patterns of negative covariation among species are typically documented through null model analyses of binary presence/absence matrices in which rows designate species, columns designate sites, and the matrix entries indicate the presence (1) or absence (0) of a particular species in a particular site. However, the outcome of species interactions ultimately depends on population-level processes. Therefore, patterns of species segregation and aggregation might be more clearly expressed in abundance matrices, in which the matrix entries indicate the abundance or density of a species in a particular site. We conducted a series of benchmark tests to evaluate the performance of 14 candidate null model algorithms and six covariation metrics that can be used with abundance matrices. We first created a series of random test matrices by sampling a metacommunity from a lognormal species abundance distribution. We also created a series of structured matrices by altering the random matrices to incorporate patterns of pairwise species segregation and aggregation. We next screened each algorithm-index combination with the random and structured matrices to determine which tests had low Type I error rates and good power for detecting segregated and aggregated species distributions. In our benchmark tests, the best-performing null model does not constrain species richness, but assigns individuals to matrix cells proportional to the observed row and column marginal distributions until, for each row and column, total abundances are reached. Using this null model algorithm with a set of four covariance metrics, we tested for patterns of species segregation and aggregation in a collection of 149 empirical abundance matrices and 36 interaction matrices collated from published papers and posted data sets. More than 80% of the matrices were significantly segregated, which

  19. Null Mutants of Individual RABA Genes Impact the Proportion of Different Cell Wall Components in Stem Tissue of Arabidopsis thaliana

    PubMed Central

    Lunn, Daniel; Gaddipati, Sanyasi R.; Tucker, Gregory A.; Lycett, Grantley W.

    2013-01-01

    In Arabidopsis, and other plants, the RABA GTPases (orthologous to the Rab11a of mammals) have expanded in number and diversity and have been shown to belong to eight sub clades, some of which have been implicated in controlling vesicles that traffic cell wall polymers and enzymes that synthesise or modify them to the cell wall. In order to investigate this, we have investigated whether T-DNA insertion knockouts of individual RABA genes belonging to different sub clades, impact on the composition of the plant cell wall. Single gene knockouts of the RABA1, RABA2 and RABA4 sub clades primarily affected the percentage composition of pectin, cellulose and hemicellulose within the cell wall, respectively, despite having no obvious phenotype in the whole plant. We hypothesise that vesicles carrying specific types of cargoes from the Golgi to the cell surface may be regulated by particular sub types of RABA proteins, a finding that could have wider implications for how trafficking systems work and could be a useful tool in cell wall research and other fields of plant biology. PMID:24124508

  20. Increased lipolysis and altered lipid homeostasis protect y-synuclein null mutant mice from diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. In neurons a-synuclein promotes assembly of SNARE complexes required for fusion of synaptic vesicles with the plasma membrane during neurotransmitter release. Y-synuclein is highly expressed ...

  1. Proteomic analysis of the Rett syndrome experimental model mecp2(Q63X) mutant zebrafish.

    PubMed

    Cortelazzo, Alessio; Pietri, Thomas; De Felice, Claudio; Leoncini, Silvia; Guerranti, Roberto; Signorini, Cinzia; Timperio, Anna Maria; Zolla, Lello; Ciccoli, Lucia; Hayek, Joussef

    2017-02-10

    Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs. wild-type larvae and adult zebrafish. We found a total of 20 proteins differentially expressed between wild-type and mutant zebrafish, suggesting skeletal and cardiac muscle functional defects, a stunted glycolysis and depleted energy availability. This molecular evidence is directly linked to the mecp2-null zebrafish observed phenotype. In addition, we identified changes in expression of proteins critical for a proper redox balance, suggesting an enhanced oxidative stress, a phenomenon also documented in human patients and RTT murine models. The molecular alterations observed in the mecp2-null zebrafish expand our knowledge on the molecular cascade of events that lead to the RTT phenotype.

  2. Three-dimensional kinematic reconnection in the presence of field nulls and closed field lines

    NASA Technical Reports Server (NTRS)

    Lau, Yun-Tung; Finn, John M.

    1990-01-01

    The present investigation of three-dimensional reconnection of magnetic fields with nulls and of fields with closed lines gives attention to the geometry of the former, with a view to their gamma-line and Sigma-surface structures. The geometric structures of configurations with a pair of type A and B nulls permit reconnection across the null-null lines; these are the field lines which join the two nulls. Also noted is the case of magnetostatic reconnection, in which the magnetic field is time-independent and the electrostatic potential is constant along field lines.

  3. Modeling the Cell Muscle Membrane from Normal and Desmin- or Dystrophin-null Mice as an Elastic System

    NASA Astrophysics Data System (ADS)

    García-Pelagio, Karla P.; Santamaría-Holek, Ivan; Bloch, Robert J.; Ortega, Alicia; González-Serratos, Hugo

    2010-12-01

    Two of the most important proteins linking the contractile apparatus and costameres at the sarcolemma of skeletal muscle fibers are dystrophin and desmin. We have developed an elastic model of the proteins that link the sarcolemma to the myofibrils. This is a distributed model, with an elastic constant, k, that includes the main protein components of the costameres. The distributed spring model is composed of parallel units attached in series. To test the model, we performed experiments in which we applied negative pressure, generated by an elastimeter, to a small area of the sarcolemma from single myofiber. The negative pressure formed a bleb of variable height, dependent on the pressure applied. We normalized our measurements of k in dystrophin-null (mdx) and desmin-null (des-/-) mice to the value we obtained for wild type (WT) mice, which was set at 1.0. The relative experimental value for the stiffness of myofibers from mice lacking dystrophin or desmin was 0.5 and 0.7, respectively. The theoretical k values of the individual elements were obtained using neural networks (NN), in which the input was the k value for each parallel spring component and the output was the solution of each resulting parallel system. We compare the experimental values of k in control and mutant muscles to the theoretical values obtained by NN for each protein. Computed theoretical values were 0.4 and 0.8 for dystrophin- and desmin-null muscles, respectively, and 0.9 for WT, in reasonable agreement with our experimental results. This suggests that, although it is a simplified spring model solved by NN, it provides a good approximation of the distribution of spring elements and the elastic constants of the proteins that form the costameres. Our results show that dystrophin is the protein that contributes more than any other to the strength of the connections between the sarcolemma and the contractile apparatus, the costameres.

  4. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    PubMed Central

    Picard, Brigitte; Kammoun, Malek; Gagaoua, Mohammed; Barboiron, Christiane; Meunier, Bruno; Chambon, Christophe; Cassar-Malek, Isabelle

    2016-01-01

    Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1), contraction (TnnT3), energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1) and the Hsp proteins family (HspA9). These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps. PMID:28248227

  5. Lack of major genome instability in tumors of p53 null rats.

    PubMed

    Hermsen, Roel; Toonen, Pim; Kuijk, Ewart; Youssef, Sameh A; Kuiper, Raoul; van Heesch, Sebastiaan; de Bruin, Alain; Cuppen, Edwin; Simonis, Marieke

    2015-01-01

    Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions.

  6. Lack of Major Genome Instability in Tumors of p53 Null Rats

    PubMed Central

    Hermsen, Roel; Toonen, Pim; Kuijk, Ewart; Youssef, Sameh A.; Kuiper, Raoul; van Heesch, Sebastiaan; de Bruin, Alain; Cuppen, Edwin; Simonis, Marieke

    2015-01-01

    Tumorigenesis is often associated with loss of tumor suppressor genes (such as TP53), genomic instability and telomere lengthening. Previously, we generated and characterized a rat p53 knockout model in which the homozygous rats predominantly develop hemangiosarcomas whereas the heterozygous rats mainly develop osteosarcomas. Using genome-wide analyses, we find that the tumors that arise in the heterozygous and homozygous Tp53C273X mutant animals are also different in their genomic instability profiles. While p53 was fully inactivated in both heterozygous and homozygous knockout rats, tumors from homozygous animals show very limited aneuploidy and low degrees of somatic copy number variation as compared to the tumors from heterozygous animals. In addition, complex structural rearrangements such as chromothripsis and breakage-fusion-bridge cycles were never found in tumors from homozygous animals, while these were readily detectable in tumors from heterozygous animals. Finally, we measured telomere length and telomere lengthening pathway activity and found that tumors of homozygous animals have longer telomeres but do not show clear telomerase or alternative lengthening of telomeres (ALT) activity differences as compared to the tumors from heterozygous animals. Taken together, our results demonstrate that host p53 status in this rat p53 knockout model has a large effect on both tumor type and genomic instability characteristics, where full loss of functional p53 is not the main driver of large-scale structural variations. Our results also suggest that chromothripsis primarily occurs under p53 heterozygous rather than p53 null conditions. PMID:25811670

  7. Null alleles of the aldolase B gene in patients with hereditary fructose intolerance.

    PubMed

    Ali, M; Tunçman, G; Cross, N C; Vidailhet, M; Bökesoy, I; Gitzelmann, R; Cox, T M

    1994-06-01

    We report three new mutations in the gene for aldolase B that are associated with hereditary fructose intolerance (HFI). Two nonsense mutations create opal termination codons: R3op (C-->T, Arg3-->ter, exon 2) was found in homozygous form in four affected members of a large consanguineous Turkish pedigree and R59op (C-->T, Arg59-->ter, exon 3) was found on one allele in a woman of Austrian origin known to harbour one copy of the east European mutation, N334K (Asn334-->Lys). The third mutation occurred in a French HFI patient known to be heterozygous for the widespread mutation, A174D (Ala174-->Asp): a single mutation, G-->A, in the consensus acceptor site 3' of intron 6 was found on the remaining allele. These mutations are predicted to abrogate synthesis of functional protein and thus represent null alleles of aldolase B. The mutant alleles can be readily detected in the amplification refractory mutation system (ARMS) or (for R59op and 3' intron 6) by digestion of amplified genomic fragments with DdeI or A1wNI, respectively, to facilitate direct diagnosis of HFI by molecular analysis of aldolase B genes.

  8. Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice

    PubMed Central

    Villani, Claudia; Sacchetti, Giuseppina; Bagnati, Renzo; Passoni, Alice; Fusco, Federica; Carli, Mirjana; Invernizzi, Roberto William

    2016-01-01

    Previous studies provided evidence for the alteration of brain cholesterol homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The efficacy of statins in improving motor symptoms and prolonging survival of mutant mice suggested a potential role of statins in the therapy of Rett syndrome. In the present study, we show that Mecp2 deletion had no effect on brain and reduced serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the previous study) had no effects on motor deficits and survival when Mecp2 deletion was expressed on a background strain (C57BL/6J; B6) differing from that used in the earlier study. These findings indicate that the effects of statins may be background specific and raise important issues to consider when contemplating clinical trials. The reduction of the brain cholesterol metabolite 24S-hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence of changes in brain cholesterol metabolism and the potential utility of using plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT. DOI: http://dx.doi.org/10.7554/eLife.22409.001 PMID:27892851

  9. Transforming growth factor-beta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction.

    PubMed

    Ingman, Wendy V; Robertson, Sarah A

    2007-08-01

    TGFbeta1 is a multifunctional cytokine implicated in gonad and secondary sex organ development, steroidogenesis, and spermatogenesis. To determine the physiological requirement for TGFbeta1 in male reproduction, Tgfb1 null mutant mice on a Prkdc(scid) immunodeficient background were studied. TGFbeta1-deficient males did not deposit sperm or induce pseudopregnancy in females, despite an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes. Serum and intratesticular testosterone and serum androstenedione were severely diminished in TGFbeta1-deficient males. Testosterone deficiency was secondary to disrupted pituitary gonadotropin secretion because serum LH and to a lesser extent serum FSH were reduced, and exogenous LH replacement with human chorionic gonadotropin (hCG) induced serum testosterone to control levels. In the majority of TGFbeta1-deficient males, spermatogenesis was normal and sperm were developmentally competent as assessed by in vitro fertilization. Analysis of sexual behavior revealed that although TGFbeta1 null males showed avid interest in females and engaged in mounting activity, intromission was infrequent and brief, and ejaculation was not attained. Administration of testosterone to adult males, even after neonatal androgenization, was ineffective in restoring sexual function; however, erectile reflexes and ejaculation could be induced by electrical stimulation. These studies demonstrate the profound effect of genetic deficiency in TGFbeta1 on male fertility, implicating this cytokine in essential roles in the hypothalamic-pituitary-gonadal axis and in testosterone-independent regulation of mating competence.

  10. TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts

    PubMed Central

    Kucab, Jill E.; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H.; White, Paul A.; Phillips, David H.; Arlt, Volker M.

    2015-01-01

    Somatic mutations in the tumour suppressor gene TP53 occur in more than 50% of human tumours; in some instances exposure to environmental carcinogens can be linked to characteristic mutational signatures. The Hupki (human TP53 knock-in) mouse embryo fibroblast (HUF) immortalization assay (HIMA) is a useful model for studying the impact of environmental carcinogens on TP53 mutagenesis. In an effort to increase the frequency of TP53-mutated clones achievable in the HIMA, we generated nucleotide excision repair (NER)-deficient HUFs by crossing the Hupki mouse with an Xpa-knockout (Xpa-Null) mouse. We hypothesized that carcinogen-induced DNA adducts would persist in the TP53 sequence of Xpa-Null HUFs leading to an increased propensity for mismatched base pairing and mutation during replication of adducted DNA. We found that Xpa-Null Hupki mice, and HUFs derived from them, were more sensitive to the environmental carcinogen benzo[a]pyrene (BaP) than their wild-type (Xpa-WT) counterparts. Following treatment with the reactive metabolite of BaP, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), Xpa-WT and Xpa-Null HUF cultures were subjected to the HIMA. A significant increase in TP53 mutations on the transcribed strand was detected in Xpa-Null HUFs compared to Xpa-WT HUFs, but the TP53-mutant frequency overall was not significantly different between the two genotypes. BPDE induced mutations primarily at G:C base pairs, with approximately half occurring at CpG sites, and the predominant mutation type was G:C > T:A in both Xpa-WT and Xpa-Null cells. Further, several of the TP53 mutation hotspots identified in smokers’ lung cancer were mutated by BPDE in HUFs (codons 157, 158, 245, 248, 249, 273). Therefore, the pattern and spectrum of BPDE-induced TP53 mutations in the HIMA are consistent with TP53 mutations detected in lung tumours of smokers. While Xpa-Null HUFs exhibited increased sensitivity to BPDE-induced damage on the transcribed strand, NER-deficiency did not

  11. TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts.

    PubMed

    Kucab, Jill E; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H; White, Paul A; Phillips, David H; Arlt, Volker M

    2015-03-01

    Somatic mutations in the tumour suppressor gene TP53 occur in more than 50% of human tumours; in some instances exposure to environmental carcinogens can be linked to characteristic mutational signatures. The Hupki (human TP53 knock-in) mouse embryo fibroblast (HUF) immortalization assay (HIMA) is a useful model for studying the impact of environmental carcinogens on TP53 mutagenesis. In an effort to increase the frequency of TP53-mutated clones achievable in the HIMA, we generated nucleotide excision repair (NER)-deficient HUFs by crossing the Hupki mouse with an Xpa-knockout (Xpa-Null) mouse. We hypothesized that carcinogen-induced DNA adducts would persist in the TP53 sequence of Xpa-Null HUFs leading to an increased propensity for mismatched base pairing and mutation during replication of adducted DNA. We found that Xpa-Null Hupki mice, and HUFs derived from them, were more sensitive to the environmental carcinogen benzo[a]pyrene (BaP) than their wild-type (Xpa-WT) counterparts. Following treatment with the reactive metabolite of BaP, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), Xpa-WT and Xpa-Null HUF cultures were subjected to the HIMA. A significant increase in TP53 mutations on the transcribed strand was detected in Xpa-Null HUFs compared to Xpa-WT HUFs, but the TP53-mutant frequency overall was not significantly different between the two genotypes. BPDE induced mutations primarily at G:C base pairs, with approximately half occurring at CpG sites, and the predominant mutation type was G:C>T:A in both Xpa-WT and Xpa-Null cells. Further, several of the TP53 mutation hotspots identified in smokers' lung cancer were mutated by BPDE in HUFs (codons 157, 158, 245, 248, 249, 273). Therefore, the pattern and spectrum of BPDE-induced TP53 mutations in the HIMA are consistent with TP53 mutations detected in lung tumours of smokers. While Xpa-Null HUFs exhibited increased sensitivity to BPDE-induced damage on the transcribed strand, NER-deficiency did not enhance TP53

  12. ID4 regulates transcriptional activity of wild type and mutant p53 via K373 acetylation.

    PubMed

    Morton, Derrick J; Patel, Divya; Joshi, Jugal; Hunt, Aisha; Knowell, Ashley E; Chaudhary, Jaideep

    2017-01-10

    Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis. Specifically, by using wild type, mutant (P223L, V274F, R175H, R273H), acetylation mimics (K320Q and K373Q) and non-acetylation mimics (K320R and K373R) of p53, we identify that ID4 promotes acetylation of K373 and to a lesser extent K320, in turn restoring p53-dependent biological activities. Together, our data provides a molecular understanding of ID4 dependent acetylation that suggests a strategy of enhancing p53 acetylation at sites K373 and K320 that may serve as a viable mechanism of physiological restoration of mutant p53 to its wild type biological function.

  13. Similar L-dopa-stimulated motor activity in mice with adult-onset 6-hydroxydopamine-induced symmetric dopamine denervation and in transcription factor Pitx3 null mice with perinatal-onset symmetric dopamine denervation.

    PubMed

    Li, Li; Sagot, Ben; Zhou, Fu-Ming

    2015-07-30

    The transcription factor Pitx3 null mutant (Pitx3Null) mice have a constitutive perinatal-onset and symmetric bilateral dopamine (DA) loss in the striatum. In these mice l-3,4-dihydroxyphenylalanine (l-dopa) induces apparently normal horizontal movements (walking) but also upward movements consisting of the vertical body trunk and waving paws that are absent in normal animals and in animals with the classic unilateral 6-hydroxydopamine (6-OHDA) lesion-induced DA denervation. Thus, a concern is that the perinatal timing of the DA loss and potential developmental abnormalities in Pitx3Null mice may underlie these upward movements, thus reducing the usefulness as a DA denervation model. Here we show that in normal wild-type (Pitx3WT) mice with adult-onset symmetric, bilateral 6-OHDA-induced DA lesion in the dorsal striatum, l-dopa induces normal horizontal movements and upward movements that are qualitatively identical to those in Pitx3Null mice. Furthermore, after unilateral 6-OHDA lesion of the residual DA innervation in the striatum in Pitx3Null mice, l-dopa induces contraversive rotation that is similar to that in Pitx3WT mice with the classic unilateral 6-OHDA lesion. These results indicate that in Pitx3Null mice, the bilateral symmetric DA denervation in the dorsal striatum is sufficient for expressing the l-dopa-induced motor phenotype and the perinatal timing of their DA loss is not a determining factor, providing further evidence that Pitx3Null mice are a convenient and suitable mouse model to study the consequences of DA loss and dopaminergic replacement therapy in Parkinson's disease.

  14. Functional complementation of Leishmania (Leishmania) amazonensis AP endonuclease gene (lamap) in Escherichia coli mutant strains challenged with DNA damage agents

    PubMed Central

    Verissimo-Villela, Erika; Kitahara-Oliveira, Milene Yoko; dos Reis, Ana Beatriz de Bragança; Albano, Rodolpho Mattos; Da-Cruz, Alda Maria; Bello, Alexandre Ribeiro

    2016-01-01

    During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins. PMID:27223868

  15. Broadband Achromatic Phase Shifter for a Nulling Interferometer

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew R.; Lyon, Richard G.

    2011-01-01

    Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with

  16. Polytropic spheres containing regions of trapped null geodesics

    NASA Astrophysics Data System (ADS)

    Novotný, Jan; Hladík, Jan; Stuchlík, Zdeněk

    2017-02-01

    We demonstrate that in the framework of standard general relativity, polytropic spheres with properly fixed polytropic index n and relativistic parameter σ , giving a ratio of the central pressure pc to the central energy density ρc , can contain a region of trapped null geodesics. Such trapping polytropes can exist for n >2.138 , and they are generally much more extended and massive than the observed neutron stars. We show that in the n - σ parameter space, the region of allowed trapping increases with the polytropic index for intervals of physical interest, 2.138 null geodesics increases with both increasing n and σ >0.677 from the allowed region. In order to relate the trapping phenomenon to astrophysically relevant situations, we restrict the validity of the polytropic configurations to their extension rextr corresponding to the gravitational mass M ˜2 M⊙ of the most massive observed neutron stars. Then, for the central density ρc˜1 015 g cm-3 , the trapped regions are outside rextr for all values of 2.138 null geodesics is located close to the polytrope center and could have a relevant influence on the cooling of such polytropes or binding of gravitational waves in their interior.

  17. Vacuum Nuller Testbed Performance, Characterization and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, R. G.; Clampin, M.; Petrone, P.; Mallik, U.; Madison, T.; Bolcar, M.; Noecker, C.; Kendrick, S.; Helmbrecht, M. A.

    2011-01-01

    The Visible Nulling Coronagraph (VNC) can detect and characterize exoplanets with filled, segmented and sparse aperture telescopes, thereby spanning the choice of future internal coronagraph exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has developed a Vacuum Nuller Testbed (VNT) to advance this approach, and assess and advance technologies needed to realize a VNC as a flight instrument. The VNT is an ultra-stable testbed operating at 15 Hz in vacuum. It consists of a MachZehnder nulling interferometer; modified with a "W" configuration to accommodate a hexpacked MEMS based deformable mirror (DM), coherent fiber bundle and achromatic phase shifters. The 2-output channels are imaged with a vacuum photon counting camera and conventional camera. Error-sensing and feedback to DM and delay line with control algorithms are implemented in a real-time architecture. The inherent advantage of the VNC is that it is its own interferometer and directly controls its errors by exploiting images from bright and dark channels simultaneously. Conservation of energy requires the sum total of the photon counts be conserved independent of the VNC state. Thus sensing and control bandwidth is limited by the target stars throughput, with the net effect that the higher bandwidth offloads stressing stability tolerances within the telescope. We report our recent progress with the VNT towards achieving an incremental sequence of contrast milestones of 10(exp 8) , 10(exp 9) and 10(exp 10) respectively at inner working angles approaching 2A/D. Discussed will be the optics, lab results, technologies, and null control. Shown will be evidence that the milestones have been achieved.

  18. EADS Astrium Nulling Interferometer Breadboard for DARWIN and GENIE

    NASA Astrophysics Data System (ADS)

    Ergenzinger, Klaus; Flatscher, Reinhold; Johann, Ulrich; Vink, Rob; Sodnik, Zoran

    2004-06-01

    Within the context of the ESA TRP programme for DARWIN, a Nulling Interferometer Breadboard for the Near-Infrared was developed and tested. Its basic principle is recombining two light beams relying on a highly symmetric optical design (autobalanced Sagnac Core). Two different star simulators have been implemented, based on a) amplitude division and b) on wavefront division. The required achromatic Pi phase shift was implemented using a) dispersive phase shifter, and b) periscopes (geometrical pupil and field rotation). Due to the extremely symmetric optical design, very good star suppression up to 400000 has been achieved. OPD control better than 1 nm RMS has been demonstrated over hours.

  19. Speckle nulling wavefront control for Palomar and Keck

    NASA Astrophysics Data System (ADS)

    Bottom, Michael; Femenia, Bruno; Huby, Elsa; Mawet, Dimitri; Dekany, Richard; Milburn, Jennifer; Serabyn, Eugene

    2016-07-01

    We present a speckle nulling code currently being used for high contrast imaging at the Palomar and Keck telescopes. The code can operate in open and closed loop and is self-calibrating, requiring no system model and minimal hand-coded parameters. Written in a modular fashion, it is straightforward to port to different instruments. It has been used with systems operating in the optical through thermal infrared, and can deliver nearly an order of magnitude improvement in raw contrast. We will be releasing this code to the public in the near future.

  20. Null Values and Quantum State Discrìmination

    NASA Astrophysics Data System (ADS)

    Zilberberg, Oded; Romito, Alessandro; Starling, David J.; Howland, Gregory A.; Broadbent, Curtis J.; Howell, John C.; Gefen, Yuval

    2013-04-01

    We present a measurement protocol for discriminating between two different quantum states of a qubit with high fidelity. The protocol, called null value, is comprised of a projective measurement performed on the system with a small probability (also known as partial collapse), followed by a tuned postselection. We report on an optical experimental implementation of the scheme. We show that our protocol leads to an amplified signal-to-noise ratio (as compared with a straightforward strong measurement) when discerning between the two quantum states.

  1. Structural Determinants of the Gain-of-Function Phenotype of Human Leukemia-associated Mutant CBL Oncogene.

    PubMed

    Nadeau, Scott A; An, Wei; Mohapatra, Bhopal C; Mushtaq, Insha; Bielecki, Timothy A; Luan, Haitao; Zutshi, Neha; Ahmad, Gulzar; Storck, Matthew D; Sanada, Masashi; Ogawa, Seishi; Band, Vimla; Band, Hamid

    2017-03-03

    Mutations of the tyrosine kinase-directed ubiquitin ligase CBL cause myeloid leukemias, but the molecular determinants of the dominant leukemogenic activity of mutant CBL oncogenes are unclear. Here, we first define a gain-of-function attribute of the most common leukemia-associated CBL mutant, Y371H, by demonstrating its ability to increase proliferation of hematopoietic stem/progenitor cells (HSPCs) derived from CBL-null and CBL/CBL-B-null mice. Next, we express second-site point/deletion mutants of CBL-Y371H in CBL/CBL-B-null HSPCs or the cytokine-dependent human leukemic cell line TF-1 to show that individual or combined Tyr → Phe mutations of established phosphotyrosine residues (Tyr-700, Tyr-731, and Tyr-774) had little impact on the activity of the CBL-Y371H mutant in HSPCs, and the triple Tyr → Phe mutant was only modestly impaired in TF-1 cells. In contrast, intact tyrosine kinase-binding (TKB) domain and proline-rich region (PRR) were critical in both cell models. PRR deletion reduced the stem cell factor (SCF)-induced hyper-phosphorylation of the CBL-Y371H mutant and the c-KIT receptor and eliminated the sustained p-ERK1/2 and p-AKT induction by SCF. GST fusion protein pulldowns followed by phospho-specific antibody array analysis identified distinct CBL TKB domains or PRR-binding proteins that are phosphorylated in CBL-Y371H-expressing TF-1 cells. Our results support a model of mutant CBL gain-of-function in which mutant CBL proteins effectively compete with the remaining wild type CBL-B and juxtapose TKB domain-associated PTKs with PRR-associated signaling proteins to hyper-activate signaling downstream of hematopoietic growth factor receptors. Elucidation of mutant CBL domains required for leukemogenesis should facilitate targeted therapy approaches for patients with mutant CBL-driven leukemias.

  2. Novel CDC34 (UBC3) ubiquitin-conjugating enzyme mutants obtained by charge-to-alanine scanning mutagenesis.

    PubMed

    Pitluk, Z W; McDonough, M; Sangan, P; Gonda, D K

    1995-03-01

    CDC34 (UBC3) encodes a ubiquitin-conjugating (E2) enzyme required for transition from the G1 phase to the S phase of the budding yeast cell cycle. CDC34 consists of a 170-residue catalytic N-terminal domain onto which is appended an acidic C-terminal domain. A portable determinant of cell cycle function resides in the C-terminal domain, but determinants for specific function must reside in the N-terminal domain as well. We have explored the utility of "charge-to-alanine" scanning mutagenesis to identify novel N-terminal domain mutants of CDC34 that are enzymatically competent with respect to unfacilitated (E3-independent) ubiquitination but that nevertheless are defective with respect to its cell cycle function. Such mutants may reveal determinants of specific in vivo function, such as those required for interaction with substrates or trans-acting regulators of activity and substrate selectivity. Three of 18 "single-scan" mutants (in which small clusters of charged residues were mutated to alanine) were compromised with respect to in vivo function. One mutant (cdc34-109, 111, 113A) targeted a 12-residue segment of the Cdc34 protein not found in most other E2s and was unable to complement a cdc34 null mutant at low copy numbers but could complement a null mutant when overexpressed from an induced GAL1 promoter. Combining adjacent pairs of single-scan mutants to produce "double-scan" mutants yielded four additional mutants, two of which showed heat and cold sensitivity conditional defects. Most of the mutant proteins expressed in Escheria coli displayed unfacilitated (E3-independent) ubiquitin-conjugating activity, but two mutants differed from wild-type and other mutant Cdc34 proteins in the extent of multiubiquitination they catalyzed during an autoubiquitination reation-conjugating enzyme function and have identified additional mutant alleles of CDC34 that will be valuable in further genetic and biochemical studies of Cdc34-dependent ubiquitination.

  3. Adaptive Nulling: A New Enabling Technology for Interferometric Exoplanet

    NASA Technical Reports Server (NTRS)

    Lay, Oliver P.; Jeganathan, Muthu; Peters, Robert

    2003-01-01

    Deep, stable nulling of starlight requires careful control of the amplitudes and phases of the beams that are being combined. The detection of earth-like planets using the interferometer architectures currently being considered for the Terrestrial Planet Finder mission require that the E-field amplitudes are balanced at the level of approx. 0.1%, and the phases are controlled at the level of 1 mrad (corresponding to approx.1.5 nm for a wavelength of 10 microns). These conditions must be met simultaneously at all wavelengths across the science band, and for both polarization states, imposing unrealistic tolerances on the symmetry between the optical beamtrains. We introduce the concept of a compensator that is inserted into the beamtrain, which can adaptively correct for the mismatches across the spectrum, enabling deep nulls with realistic, imperfect optics. The design presented uses a deformable mirror to adjust the amplitude and phase of each beam as an arbitrary function of wavelength and polarization. A proof-of-concept experiment will be conducted at visible/near-IR wavelengths, followed by a system operating in the Mid-IR band.

  4. Partial rescue of the amelogenin null dental enamel phenotype.

    PubMed

    Li, Yong; Suggs, Cynthia; Wright, J Timothy; Yuan, Zhi-an; Aragon, Melissa; Fong, Hanson; Simmons, Darrin; Daly, Bill; Golub, Ellis E; Harrison, Gerald; Kulkarni, Ashok B; Gibson, Carolyn W

    2008-05-30

    The amelogenins are the most abundant secreted proteins in developing dental enamel. Enamel from amelogenin (Amelx) null mice is hypoplastic and disorganized, similar to that observed in X-linked forms of the human enamel defect amelogenesis imperfecta resulting from amelogenin gene mutations. Both transgenic strains that express the most abundant amelogenin (TgM180) have relatively normal enamel, but strains of mice that express a mutated amelogenin (TgP70T), which leads to amelogenesis imperfecta in humans, have heterogeneous enamel structures. When Amelx null (KO) mice were mated with transgenic mice that produce M180 (TgM180), the resultant TgM180KO offspring showed evidence of rescue in enamel thickness, mineral density, and volume in molar teeth. Rescue was not observed in the molars from the TgP70TKO mice. It was concluded that a single amelogenin protein was able to significantly rescue the KO phenotype and that one amino acid change abrogated this function during development.

  5. Analysis of nulling phase functions suitable to image plane coronagraphy

    NASA Astrophysics Data System (ADS)

    Hénault, François; Carlotti, Alexis; Vérinaud, Christophe

    2016-07-01

    Coronagraphy is a very efficient technique for identifying and characterizing extra-solar planets orbiting in the habitable zone of their parent star, especially in a space environment. An important family of coronagraphs is actually based on phase plates located at an intermediate image plane of the optical system, and spreading the starlight outside the "Lyot" exit pupil plane of the instrument. In this commutation we present a set of candidate phase functions generating a central null at the Lyot plane, and study how it propagates to the image plane of the coronagraph. These functions include linear azimuthal phase ramps (the well-known optical vortex), azimuthally cosine-modulated phase profiles, and circular phase gratings. Nnumerical simulations of the expected null depth, inner working angle, sensitivity to pointing errors, effect of central obscuration located at the pupil or image planes, and effective throughput including image mask and Lyot stop transmissions are presented and discussed. The preliminary conclusion is that azimuthal cosine functions appear as an interesting alternative to the classical optical vortex of integer topological charge.

  6. Exoplanet detection and characterization via parallel broadband nulling coronagraphy

    NASA Astrophysics Data System (ADS)

    Hicks, Brian A.

    2016-01-01

    The contrast and angular resolution required to directly image and characterize mature exoplanetary systems place stringent requirements on the space-based telescopes and starlight suppression systems needed to study spatial distributions of debris disks, exozodiacal dust, and individual planets at multiple epochs in their orbits. A nulling interferometer (nuller) is a coronagraphic suppression system that can be used with all telescope types, including those with obscured and segmented apertures envisioned for upcoming and future observatories. One of the challenges for detection and characterization of exoplanetary signals is achieving high contrast with broad spectral coverage. This work presents design concepts for broadband nulling over four parallel ˜20% bandpasses spanning the visible spectrum. Contrast-limiting effects of stellar angular extent, residual chromaticity of broadband phase shifters, and aperture diffraction are considered to reach simultaneous ≲2×10-8 contrast over separations spanning 0.2 to 0.9 arc sec for a 2.4-m telescope observing a Sun-like star at 10 pc. With added dark hole wavefront control and postprocessing point spread function subtraction techniques to further reduce scattered starlight, such a system could be capable of detecting the very the nearest Earth-like exoplanets and spectral characterization of several nearby extrasolar gas giants.

  7. A search for optical beacons: implications of null results.

    PubMed

    Blair, David G; Zadnik, Marjan G

    2002-01-01

    Over the past few years a series of searches for interstellar radio beacons have taken place using the Parkes radio telescope. Here we report hitherto unpublished results from a search for optical beacons from 60 solar-type stars using the Perth-Lowell telescope. We discuss the significance of the null results from these searches, all of which were based on the interstellar contact channel hypothesis. While the null results of all searches to date can be explained simply by the nonexistence of electromagnetically communicating life elsewhere in the Milky Way, four other possible explanations that do not preclude its existence are proposed: (1) Extraterrestrial civilizations desiring to make contact through the use of electromagnetic beacons have a very low density in the Milky Way. (2) The interstellar contact channel hypothesis is incorrect, and beacons exist at frequencies that have not yet been searched. (3) The search has been incomplete in terms of sensitivity and/or target directions: Beacons exist, but more sensitive equipment and/or more searching is needed to achieve success. (4) The search has occurred before beacon signals can be expected to have arrived at the Earth, and beacon signals may be expected in the future. Based on consideration of the technology required for extraterrestrial civilizations to identify target planets, we argue that the fourth possibility is likely to be valid and that powerful, easily detectable beacons could be received in coming centuries.

  8. A Search for Optical Beacons: Implications of Null Results

    NASA Astrophysics Data System (ADS)

    Blair, David G.; Zadnik, Marjan G.

    2002-08-01

    Over the past few years a series of searches for interstellar radio beacons have taken place using the Parkes radio telescope. Here we report hitherto unpublished results from a search for optical beacons from 60 solar-type stars using the Perth-Lowell telescope. We discuss the significance of the null results from these searches, all of which were based on the interstellar contact channel hypothesis. While the null results of all searches to date can be explained simply by the nonexistence of electromagnetically communicating life elsewhere in the Milky Way, four other possible explanations that do not preclude its existence are proposed: (1) Extraterrestrial civilizations desiring to make contact through the use of electromagnetic beacons have a very low density in the Milky Way. (2) The interstellar contact channel hypothesis is incorrect, and beacons exist at frequencies that have not yet been searched. (3) The search has been incomplete in terms of sensitivity and/or target directions: Beacons exist, but more sensitive equipment and/or more searching is needed to achieve success. (4) The search has occurred before beacon signals can be expected to have arrived at the Earth, and beacon signals may be expected in the future. Based on consideration of the technology required for extraterrestrial civilizations to identify target planets, we argue that the fourth possibility is likely to be valid and that powerful, easily detectable beacons could be received in coming centuries.

  9. A new interferometer architecture combining nulling with phase closure measurements

    NASA Astrophysics Data System (ADS)

    Lacour, S.; Tuthill, P.; Monnier, J. D.; Kotani, T.; Gauchet, L.; Labeye, P.

    2014-04-01

    Imaging the direct light signal from a faint exoplanet against the overwhelming glare of its host star presents one of the fundamental challenges to modern astronomical instrumentation. Achieving sufficient signal-to-noise ratio for detection by direct imaging is limited by three basic physical processes: aberration of the wavefronts (both instrumental and atmospheric), photon noise and detector noise. In this paper, we advance a novel optical setup which synthesizes the advantages of two different techniques: nulling interferometry to mitigate photon noise, and closure phase to combat optical aberrations. Our design, which employs technology from integrated optics and photonics, is intended to combine the advantageous aspects of both a coronagraph and a non-redundant interferometer inside a single optical device. We show that such an instrument would have a dynamic range limited by either (i) the readout noise (if perfect co-phasing), or (ii) the photon noise due to stellar flux leakage (in the case of imperfect nulling). This concept is optimal when the readout noise is not the main limitation, i.e. for space interferometry or for ground-based observations of bright stellar hosts (apparent magnitude brighter than 10).

  10. Non-dissipative electromagnetic media with two Lorentz null cones

    SciTech Connect

    Dahl, Matias F.

    2013-03-15

    We study Maxwell's equations on a 4-manifold where the electromagnetic medium is modeled by an antisymmetric (2/2 )-tensor with 21 real coefficients. In this setting the Fresnel surface is a fourth-order polynomial surface that describes the dynamical response of the medium in the geometric optics limit. For example, in an isotropic medium the Fresnel surface is a Lorentz null cone. The contribution of this paper is the pointwise description of all electromagnetic medium tensors {kappa} with real coefficients that satisfy the following three conditions: (i)medium {kappa} is invertible, (ii)medium {kappa} is skewon-free, or non-dissipative, (iii)the Fresnel surface of {kappa} is the union of two distinct Lorentz null cones. We show that there are only three classes of media with these properties and give explicit expressions in local coordinates for each class. - Highlights: Black-Right-Pointing-Pointer We find two new electromagnetic media classes for which the Fresnel surface decomposes into two light cones. Black-Right-Pointing-Pointer In a suitable setting we classify all electromagnetic media where this is the case. Black-Right-Pointing-Pointer We find an electromagnetic medium tensor with three different signal speeds in one direction. Black-Right-Pointing-Pointer The work is related to [5], which classifies all media with one light cone (in a suitable setting).

  11. Extrasolar Planetary Imaging Coronagraph: Visible Nulling Coronagraph Testbed Results

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.

    2008-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime ( 5 year goal) and will revisit planets at least three times at intervals of 9 months. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed,

  12. Pituitary null cell adenoma in a domestic llama (Lama glama).

    PubMed

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama.

  13. Geometry of extended null supersymmetry in M theory

    SciTech Connect

    Conamhna, Oisin A.P. Mac

    2006-02-15

    For supersymmetric spacetimes in 11 dimensions admitting a null Killing spinor, a set of explicit necessary and sufficient conditions for the existence of any number of arbitrary additional Killing spinors is derived. The necessary and sufficient conditions are comprised of algebraic relationships, linear in the spinorial components, between the spinorial components and their first derivatives, and the components of the spin connection and four-form. The integrability conditions for the Killing spinor equation are also analyzed in detail, to determine which components of the field equations are implied by arbitrary additional supersymmetries and the four-form Bianchi identity. This provides a complete formalism for the systematic and exhaustive investigation of all spacetimes with extended null supersymmetry in 11 dimensions. The formalism is employed to show that the general bosonic solution of 11 dimensional supergravity admitting a G{sub 2} structure defined by four Killing spinors is either locally the direct product of R{sup 1,3} with a seven-manifold of G{sub 2} holonomy, or locally the Freund-Rubin direct product of AdS{sub 4} with a seven-manifold of weak G{sub 2} holonomy. In addition, all supersymmetric spacetimes admitting a (G{sub 2}xR{sup 7})xR{sup 2} structure are classified.

  14. Error analysis and system optimization of non-null aspheric testing system

    NASA Astrophysics Data System (ADS)

    Luo, Yongjie; Yang, Yongying; Liu, Dong; Tian, Chao; Zhuo, Yongmo

    2010-10-01

    A non-null aspheric testing system, which employs partial null lens (PNL for short) and reverse iterative optimization reconstruction (ROR for short) technique, is proposed in this paper. Based on system modeling in ray tracing software, the parameter of each optical element is optimized and this makes system modeling more precise. Systematic error of non-null aspheric testing system is analyzed and can be categorized into two types, the error due to surface parameters of PNL in the system modeling and the rest from non-null interferometer by the approach of error storage subtraction. Experimental results show that, after systematic error is removed from testing result of non-null aspheric testing system, the aspheric surface is precisely reconstructed by ROR technique and the consideration of systematic error greatly increase the test accuracy of non-null aspheric testing system.

  15. The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid.

    PubMed

    Afitlhile, Meshack; Duffield-Duncan, Kayla; Fry, Morgan; Workman, Samantha; Hum-Musser, Sue; Hildebrand, David

    2015-11-01

    A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER-localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7-fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts.

  16. Survival of glucose phosphate isomerase null somatic cells and germ cells in adult mouse chimaeras.

    PubMed

    Keighren, Margaret A; Flockhart, Jean H; West, John D

    2016-05-15

    The mouse Gpi1 gene encodes the glycolytic enzyme glucose phosphate isomerase. Homozygous Gpi1(-/-) null mouse embryos die but a previous study showed that some homozygous Gpi1(-/-) null cells survived when combined with wild-type cells in fetal chimaeras. One adult female Gpi1(-/-)↔Gpi1(c/c) chimaera with functional Gpi1(-/-) null oocytes was also identified in a preliminary study. The aims were to characterise the survival of Gpi1(-/-) null cells in adult Gpi1(-/-)↔Gpi1(c/c) chimaeras and determine if Gpi1(-/-) null germ cells are functional. Analysis of adult Gpi1(-/-)↔Gpi1(c/c) chimaeras with pigment and a reiterated transgenic lineage marker showed that low numbers of homozygous Gpi1(-/-) null cells could survive in many tissues of adult chimaeras, including oocytes. Breeding experiments confirmed that Gpi1(-/-) null oocytes in one female Gpi1(-/-)↔Gpi1(c/c) chimaera were functional and provided preliminary evidence that one male putative Gpi1(-/-)↔Gpi1(c/c) chimaera produced functional spermatozoa from homozygous Gpi1(-/-) null germ cells. Although the male chimaera was almost certainly Gpi1(-/-)↔Gpi1(c/c), this part of the study is considered preliminary because only blood was typed for GPI. Gpi1(-/-) null germ cells should survive in a chimaeric testis if they are supported by wild-type Sertoli cells. It is also feasible that spermatozoa could bypass a block at GPI, but not blocks at some later steps in glycolysis, by using fructose, rather than glucose, as the substrate for glycolysis. Although chimaera analysis proved inefficient for studying the fate of Gpi1(-/-) null germ cells, it successfully identified functional Gpi1(-/-) null oocytes and revealed that some Gpi1(-/-) null cells could survive in many adult tissues.

  17. Impact of Serotonin 2C Receptor Null Mutation on Physiology and Behavior Associated with Nigrostriatal Dopamine Pathway Function

    PubMed Central

    Abdallah, Luna; Bonasera, Stephen J.; Hopf, F. Woodward; O’Dell, Laura; Giorgetti, Marco; Jongsma, Minke; Carra, Scott; Pierucci, Massimo; Di Giovanni, Giuseppe; Esposito, Ennio; Parsons, Loren H.; Bonci, Antonello; Tecott, Laurence H.

    2011-01-01

    The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the nucleus accumbens. The influence of this receptor subtype on functions mediated by the nigrostriatal dopaminergic pathway is less clear. Here we report that a null mutation eliminating expression of 5-HT2CRs produces marked alterations in the activity and functional output of this pathway. 5-HT2CR mutant mice displayed increased activity of substantia nigra pars compacta (SNc) dopaminergic neurons, elevated baseline extracellular dopamine concentrations in the dorsal striatum (DSt), alterations in grooming behavior, and enhanced sensitivity to the stereotypic behavioral effects of D-amphetamine and GBR 12909. These psychostimulant responses occurred in the absence of phenotypic differences in drug-induced extracellular dopamine concentration, suggesting a phenotypic alteration in behavioral responses to released dopamine. This was further suggested by enhanced behavioral responses of mutant mice to the D1 receptor agonist SKF 81297. Differences in DSt D1 or D2 receptor expression were not found, nor were differences in medium spiny neuron firing patterns or intrinsic membrane properties following dopamine stimulation. We conclude that 5-HT2CRs regulate nigrostriatal dopaminergic activity and function both at SNc dopaminergic neurons and at a locus downstream of the DSt. PMID:19553455

  18. Alignment of optical system components using an ADM beam through a null assembly

    NASA Technical Reports Server (NTRS)

    Hayden, Joseph E. (Inventor); Olczak, Eugene G. (Inventor)

    2010-01-01

    A system for testing an optical surface includes a rangefinder configured to emit a light beam and a null assembly located between the rangefinder and the optical surface. The null assembly is configured to receive and to reflect the emitted light beam toward the optical surface. The light beam reflected from the null assembly is further reflected back from the optical surface toward the null assembly as a return light beam. The rangefinder is configured to measure a distance to the optical surface using the return light beam.

  19. How to Find Magnetic Nulls and Reconstruct Field Topology with MMS Data?

    NASA Astrophysics Data System (ADS)

    Fu, H.; Vaivads, A.; Khotyaintsev, Y. V.; Olshevsky, V.; Andre, M.; Cao, J.; Huang, S.; Retino, A.; Lapenta, G.

    2015-12-01

    In this study, we apply a new method—the first-order Taylor expansion (FOTE)—to find magnetic nulls and reconstruct magnetic field topology, in order to use it with the data from the forth-coming MMS mission. We compare this method with the previously used Poincare index (PI), and find that they are generally consistent, except that the PI method can only find a null inside the spacecraft (SC) tetrahedron, while the FOTE method can find a null both inside and outside the tetrahedron and also deduce its drift velocity. In addition, the FOTE method can (1) avoid limitations of the PI method such as data resolution, instrument uncertainty (Bz offset), and SC separation; (2) identify 3D null types (A, B, As, and Bs) and determine whether these types can degenerate into 2D (X and O); (3) reconstruct the magnetic field topology. We quantitively test the accuracy of FOTE in positioning magnetic nulls and reconstructing field topology, by using the data from 3D kinetic simulations. The influences of SC separation (0.05~1 di) and null-SC distance (0~1 di) on the accuracy are both considered. We find that: (1) for an isolated null, the method is accurate when the SC separation is smaller than 1 di, and the null-SC distance is smaller than 0.25~0.5 di; (2) for a null pair, the accuracy is same as in the isolated-null situation, except at the separator line, where the field is nonlinear. We define a parameter in terms of the eigenvalues of the null to quantify the quality of our method—the smaller this parameter the better the results. Comparing to the previously used one, this parameter is more relevant for null identification. Using the new method, we reconstruct the magnetic field topology around a radial-type null and a spiral-type null, and find that the topologies are well consistent with those predicted in theory. We therefore suggest using this method to find magnetic nulls and reconstruct field topology with four-point measurements, particularly from Cluster and

  20. Hubble Space Telescope primary-mirror characterization by measurement of the reflective null corrector.

    PubMed

    Furey, L; Dubos, T; Hansen, D; Samuels-Schwartz, J

    1993-04-01

    The reflective null corrector used to manufacture of the Hubble Space Telescope contains valuable information about the prescription of the primary mirror since an excellent null was achieved between the null-corrector wave front and the primary-mirror wave front. During the Phase I measurements, the leading cause of the spherical aberration, the field lens position error, was discovered and remeasured to an accuracy of +/-0.005 mm. To derive the conic constant of the primary mirror to an accuracy of +/-0.0003, we remeasured the parameters of the reflective null corrector that could contribute to the spherical aberration of the primary mirror.

  1. Lung mechanics in the TIMP3 null mouse and its response to mechanical ventilation.

    PubMed

    Martin, Erica L; Truscott, Emily A; Bailey, Timothy C; Leco, Kevin J; McCaig, Lynda A; Lewis, James F; Veldhuizen, Ruud A W

    2007-03-01

    Tissue inhibitor of metalloproteinase-3 (TIMP3) null mice develop emphysema-like airspace enlargement due to an enzymatic imbalance. This study investigates how these abnormalities alter lung mechanics and the response to 2 different mechanical ventilation strategies. Phenotypically, TIMP3 null mice had increased compliance, and decreased resistance, tissue damping, and tissue elastance over wild-type controls. Decreased compliance and increased resistance were observed following the injurious ventilation strategy; however, the TIMP3 null response to both ventilation strategies was similar to wild-type mice. In conclusion, TIMP3 null mice have significant alterations in lung mechanics; however, this does not affect their response to ventilation.

  2. Talin-Null Cells of Dictyostelium Are Strongly Defective in Adhesion to Particle and Substrate Surfaces and Slightly Impaired in Cytokinesis

    PubMed Central

    Niewöhner, Jens; Weber, Igor; Maniak, Markus; Müller-Taubenberger, Annette; Gerisch, Günther

    1997-01-01

    Dictyostelium discoideum contains a full-length homologue of talin, a protein implicated in linkage of the actin system to sites of cell-to-substrate adhesion in fibroblasts and neuronal growth cones. Gene replacement eliminated the talin homologue in Dictyostelium and led to defects in phagocytosis and cell-to-substrate interaction of moving cells, two processes dependent on a continuous cross talk between the cell surface and underlying cytoskeleton. The uptake rate of yeast particles was reduced, and only bacteria devoid of the carbohydrate moiety of cell surface lipopolysaccharides were adhesive enough to be recruited by talin-null cells in suspension and phagocytosed. Cell-to-cell adhesion of undeveloped cells was strongly impaired in the absence of talin, in contrast with the cohesion of aggregating cells mediated by the phospholipid-anchored contact site A glycoprotein, which proved to be less talin dependent. The mutant cells were still capable of moving and responding to a chemoattractant, although they attached only loosely to a substrate via small areas of their surface. With their high proportion of binucleated cells, the talin-null mutants revealed interactions of the mitotic apparatus with the cell cortex that were not obvious in mononucleated cells. PMID:9230077

  3. Characterization of an Arabidopsis thaliana mutant lacking a cytosolic non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase.

    PubMed

    Rius, Sebastián P; Casati, Paula; Iglesias, Alberto A; Gomez-Casati, Diego F

    2006-08-01

    Non-phosphorylating glyceraldehyde- 3-phosphate dehydrogenase (NP-GAPDH) is a conserved cytosolic protein found in higher plants. In photosynthetic cells, the enzyme is involved in a shuttle transfer mechanism to export NADPH from the chloroplast to the cytosol. To investigate the role of this enzyme in plant tissues, we characterized a mutant from Arabidopsis thaliana having an insertion at the NP-GAPDH gene locus. The homozygous mutant was determined to be null respect to NP-GAPDH, as it exhibited undetectable levels of both transcription of NP-GAPDH mRNA, protein expression and enzyme activity. Transcriptome analysis demonstrated that the insertion mutant plant shows altered expression of several enzymes involved in carbohydrate metabolism. Significantly, cytosolic phosphorylating (NAD-dependent) glyceraldehyde-3-phosphate dehydrogenase mRNA levels are induced in the mutant, which correlates with an increase in enzyme activity. mRNA levels and enzymatic activity of glucose-6-phosphate dehydrogenase were also elevated, correlating with an increase in NADPH concentration. Moreover, increased ROS levels were measured in the mutant plants. Down-regulation of several glycolytic and photosynthetic genes suggests that NP-GAPDH is important for the efficiency of both metabolic processes. The results presented demonstrate that NP-GAPDH has a relevant role in plant growth and development.

  4. A symbiotic mutant of Sinorhizobium meliloti reveals a novel genetic pathway involving succinoglycan biosynthetic functions.

    PubMed

    Griffitts, Joel S; Long, Sharon R

    2008-03-01

    A large-scale screen for symbiotic mutants was carried out using the model root nodulating bacterium Sinorhizobium meliloti. Several mutations in the previously uncharacterized gene msbA2 were isolated. msbA2 encodes a member of the ATP-binding cassette exporter family. This protein family is known to export a wide variety of compounds from bacterial cells. S. meliloti MsbA2 is required for the invasion of nodule tissue, with msbA2 mutant cells stimulating nodule primordium morphogenesis, but failing to invade plant tissue beyond the epidermal cell layer. msbA2 mutants do not exhibit any of the free-living traits often found to correlate with symbiotic defects, suggesting that MsbA2 may take part in a specifically symbiotic function. In strains that overproduce the symbiotic signalling polysaccharide succinoglycan, loss of MsbA2 function is extremely deleterious. This synthetic lethal phenotype can be suppressed by disrupting the succinoglycan biosynthetic genes exoY or exoA. It can also be suppressed by disrupting putative glycosyltransferase-encoding genes found upstream of msbA2. Finally, the symbiotic phenotype of a msbA2 null mutant is suppressed by secondary mutations in these upstream transferase genes, indicating that the msbA2 mutant phenotype may be caused by an inhibitory accumulation of a novel polysaccharide that is synthesized from succinoglycan precursors.

  5. The Yeast V159N Actin Mutant Reveals Roles for Actin Dynamics In Vivo

    PubMed Central

    Belmont, Lisa D.; Drubin, David G.

    1998-01-01

    Actin with a Val 159 to Asn mutation (V159N) forms actin filaments that depolymerize slowly because of a failure to undergo a conformational change after inorganic phosphate release. Here we demonstrate that expression of this actin results in reduced actin dynamics in vivo, and we make use of this property to study the roles of rapid actin filament turnover. Yeast strains expressing the V159N mutant (act1-159) as their only source of actin have larger cortical actin patches and more actin cables than wild-type yeast. Rapid actin dynamics are not essential for cortical actin patch motility or establishment of cell polarity. However, fluid phase endocytosis is defective in act1-159 strains. act1-159 is synthetically lethal with cofilin and profilin mutants, supporting the conclusion that mutations in all of these genes impair the polymerization/ depolymerization cycle. In contrast, act1-159 partially suppresses the temperature sensitivity of a tropomyosin mutant, and the loss of cytoplasmic cables seen in fimbrin, Mdm20p, and tropomyosin null mutants, suggesting filament stabilizing functions for these actin-binding proteins. Analysis of the cables in these double-mutant cells supports a role for fimbrin in organizing cytoplasmic cables and for Mdm20p and tropomyosin in excluding cofilin from the cables. PMID:9732289

  6. Temperature sensitivity of human wild-type and mutant p53 proteins expressed in vivo.

    PubMed Central

    Ponchel, F.; Milner, J.

    1998-01-01

    p53 is activated in response to DNA damage and functions in the maintenance of genetic integrity. Loss of p53 function because of mutation of the p53 gene is associated with over half all human cancers. Certain human p53 mutants are conformationally flexible in vitro and are temperature sensitive, with partial or complete recovery of wild-type (wt) properties at 32 degrees C. We have now tested the functional capacities of selected p53 mutants in vivo, by transfection into established human cell lines. Unexpectedly, we found that wt p53 can be temperature sensitive for transactivation of a co-transfected target gene in vivo. Flexible mutants retained varying degrees of functional capacity in transfected cells, and the recipient cell line appeared to be a significant determinant of both wt and mutant p53 function; importantly, two p53 null cell lines commonly used to study p53 function (Saos-2 and Hep3B) differed markedly in this latter respect. We also show that the p53 mutant V272M, which exhibits sequence-specific DNA binding in vitro, is nonetheless defective for transactivation and is unable to induce apoptosis in vivo. The valine 272 residue may thus be crucial for properties (other than sequence-specific DNA binding) that are important for p53 function(s) in vivo. Images Figure 4 PMID:9635828

  7. Infinitesimal deformations of null-filiform Leibniz superalgebras

    NASA Astrophysics Data System (ADS)

    Khudoyberdiyev, A. Kh.; Omirov, B. A.

    2013-12-01

    In this paper we describe the infinitesimal deformations of null-filiform Leibniz superalgebras over a field of zero characteristic. It is known that up to isomorphism in each dimension there exist two such superalgebras NF. One of them is a Leibniz algebra (that is m=0) and the second one is a pure Leibniz superalgebra (that is m≠0) of maximum nilindex. We show that the closure of the union of orbits of single-generated Leibniz algebras forms an irreducible component of the variety of Leibniz algebras. We prove that any single-generated Leibniz algebra is a linear integrable deformation of the algebra NFn. Similar results for the case of Leibniz superalgebras are obtained.

  8. Twistor Geometry of Null Foliations in Complex Euclidean Space

    NASA Astrophysics Data System (ADS)

    Taghavi-Chabert, Arman

    2017-01-01

    We give a detailed account of the geometric correspondence between a smooth complex projective quadric hypersurface Q^n of dimension n ≥ 3, and its twistor space PT, defined to be the space of all linear subspaces of maximal dimension of Q^n. Viewing complex Euclidean space CE^n as a dense open subset of Q^n, we show how local foliations tangent to certain integrable holomorphic totally null distributions of maximal rank on CE^n can be constructed in terms of complex submanifolds of PT. The construction is illustrated by means of two examples, one involving conformal Killing spinors, the other, conformal Killing-Yano 2-forms. We focus on the odd-dimensional case, and we treat the even-dimensional case only tangentially for comparison.

  9. On the null trajectories in conformal Weyl gravity

    NASA Astrophysics Data System (ADS)

    Villanueva, J. R.; Olivares, Marco

    2013-06-01

    In this work we find analytical solutions to the null geodesics around a black hole in the conformal Weyl gravity. Exact expressions for the horizons are found, and they depend on the cosmological constant and the coupling constants of the conformal Weyl gravity. Then, we study the radial motion from the point of view of the proper and coordinate frames, and compare it with that found in spacetimes of general relativity. The angular motion is also examined qualitatively by means of an effective potential; quantitatively, the equation of motion is solved in terms of wp-Weierstrass elliptic function. Thus, we find the deflection angle for photons without using any approximation, which is a novel result for this kind of gravity.

  10. Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells.

    PubMed

    Bang, You-Lim; Nguyen, Trang T T; Trinh, Tram T B; Kim, Yun J; Song, Junghan; Song, Young-Han

    2009-04-01

    Galactosemia is caused by defects in the galactose metabolic pathway, which consists of three enzymes, including UDP-galactose-4-epimerase (GALE). We previously reported nine mutations in Korean patients with epimerase-deficiency galactosemia. In order to determine the functional consequences of these mutations, we expressed wild-type and mutant GALE proteins in 293T cells. GALE(E165K) and GALE(W336X) proteins were unstable, had reduced half-life, formed aggregates and were partly degraded by the proteasome complex. When expressed in GALE-null ldlD cells GALE(E165K), GALE(R239W), GALE(G302D) and GALE(W336X) had no detectable enzyme activity, although substantial amounts of protein were detected in western blots. The relative activities of other mutants were lower than that of wild-type. In addition, unlike wild-type, GALE(R239W) and GALE(G302D) were not able to rescue galactose-sensitive cell proliferation when stably expressed in ldlD cells. The four inactive mutant proteins did not show defects in dimerization or affect the activity of other mutant alleles identified in patients. Our observations show that altered protein stability is due to misfolding and that loss or reduction of enzyme activity is responsible for the molecular defects underlying GALE-deficiency galactosemia.

  11. Development of pheochromocytoma in ceramide synthase 2 null mice.

    PubMed

    Park, Woo-Jae; Brenner, Ori; Kogot-Levin, Aviram; Saada, Ann; Merrill, Alfred H; Pewzner-Jung, Yael; Futerman, Anthony H

    2015-08-01

    Pheochromocytoma (PCC) and paraganglioma are rare neuroendocrine tumors of the adrenal medulla and sympathetic and parasympathetic paraganglia, for which mutations in ∼15 disease-associated genes have been identified. We now document the role of an additional gene in mice, the ceramide synthase 2 (CerS2) gene. CerS2, one of six mammalian CerS, synthesizes ceramides with very-long (C22-C24) chains. The CerS2 null mouse has been well characterized and displays lesions in several organs including the liver, lung and the brain. We now demonstrate that changes in the sphingolipid acyl chain profile of the adrenal gland lead to the generation of adrenal medullary tumors. Histological analyses revealed that about half of the CerS2 null mice developed PCC by ∼13 months, and the rest showed signs of medullary hyperplasia. Norepinephrine and normetanephrine levels in the urine were elevated at 7 months of age consistent with the morphological abnormalities found at later ages. Accumulation of ceroid in the X-zone was observed as early as 2 months of age and as a consequence, older mice displayed elevated levels of lysosomal cathepsins, reduced proteasome activity and reduced activity of mitochondrial complex IV by 6 months of age. Together, these findings implicate an additional pathway that can lead to PCC formation, which involves alterations in the sphingolipid acyl chain length. Analysis of the role of sphingolipids in PCC may lead to further understanding of the mechanism by which PCC develops, and might implicate the sphingolipid pathway as a possible novel therapeutic target for this rare tumor.

  12. Cadmium modulates adipocyte functions in metallothionein-null mice

    SciTech Connect

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  13. Does horizon entropy satisfy a quantum null energy conjecture?

    NASA Astrophysics Data System (ADS)

    Fu, Zicao; Marolf, Donald

    2016-12-01

    A modern version of the idea that the area of event horizons gives 4G times an entropy is the Hubeny-Rangamani causal holographic information (CHI) proposal for holographic field theories. Given a region R of a holographic QFTs, CHI computes A/4G on a certain cut of an event horizon in the gravitational dual. The result is naturally interpreted as a coarse-grained entropy for the QFT. CHI is known to be finitely greater than the fine-grained Hubeny-Rangamani-Takayanagi (HRT) entropy when \\partial R lies on a Killing horizon of the QFT spacetime, and in this context satisfies other non-trivial properties expected of an entropy. Here we present evidence that it also satisfies the quantum null energy condition (QNEC), which bounds the second derivative of the entropy of a quantum field theory on one side of a non-expanding null surface by the flux of stress-energy across the surface. In particular, we show CHI to satisfy the QNEC in 1  +  1 holographic CFTs when evaluated in states dual to conical defects in AdS3. This surprising result further supports the idea that CHI defines a useful notion of coarse-grained holographic entropy, and suggests unprecedented bounds on the rate at which bulk horizon generators emerge from a caustic. To supplement our motivation, we include an appendix deriving a corresponding coarse-grained generalized second law for 1  +  1 holographic CFTs perturbatively coupled to dilaton gravity.

  14. Observation of a 3D Magnetic Null Point

    NASA Astrophysics Data System (ADS)

    Romano, P.; Falco, M.; Guglielmino, S. L.; Murabito, M.

    2017-03-01

    We describe high-resolution observations of a GOES B-class flare characterized by a circular ribbon at the chromospheric level, corresponding to the network at the photospheric level. We interpret the flare as a consequence of a magnetic reconnection event that occurred at a three-dimensional (3D) coronal null point located above the supergranular cell. The potential field extrapolation of the photospheric magnetic field indicates that the circular chromospheric ribbon is cospatial with the fan footpoints, while the ribbons of the inner and outer spines look like compact kernels. We found new interesting observational aspects that need to be explained by models: (1) a loop corresponding to the outer spine became brighter a few minutes before the onset of the flare; (2) the circular ribbon was formed by several adjacent compact kernels characterized by a size of 1″–2″ (3) the kernels with a stronger intensity emission were located at the outer footpoint of the darker filaments, departing radially from the center of the supergranular cell; (4) these kernels started to brighten sequentially in clockwise direction; and (5) the site of the 3D null point and the shape of the outer spine were detected by RHESSI in the low-energy channel between 6.0 and 12.0 keV. Taking into account all these features and the length scales of the magnetic systems involved in the event, we argue that the low intensity of the flare may be ascribed to the low amount of magnetic flux and to its symmetric configuration.

  15. Over-fitting Time Series Models of Air Pollution Health Effects: Smoothing Tends to Bias Non-Null Associations Towards the Null.

    EPA Science Inventory

    Background: Simulation studies have previously demonstrated that time-series analyses using smoothing splines correctly model null health-air pollution associations. Methods: We repeatedly simulated season, meteorology and air quality for the metropolitan area of Atlanta from cyc...

  16. Renal NHE expression and activity in neonatal NHE3- and NHE8-null mice.

    PubMed

    Pirojsakul, Kwanchai; Gattineni, Jyothsna; Dwarakanath, Vangipuram; Baum, Michel

    2015-01-01

    Na(+)/H(+) exchanger (NHE)3 is the predominant NHE on the brush-border membrane of the proximal tubule in adult animals. NHE8 has been localized to the brush-border membrane of proximal tubules and is more highly expressed in neonates than in adult animals. However, the relative role of NHE8 in neonatal renal acidification is unclear. The present study examined if there was a compensatory increase in NHE3 in NHE8-null neonatal mice and whether there was a compensatory increase in NHE8 in NHE3-null neonatal mice. In addition, we examined whether wild-type, NHE3-null, and NHE8-null mice had an increase in NHE activity in response to metabolic acidosis. We found that at baseline, there was comparable renal NHE3 mRNA, total protein, and brush-border membrane protein abundance as in neonatal control and NHE8-null mice. There was comparable renal NHE8 mRNA, total protein, and brush-border membrane protein abundance in NHE3-null neonatal and control mice. Both NHE3- and NHE8-null mice had a comparable but lower rate of NHE activity than control mice. We next imposed metabolic acidosis in wild-type, NHE3-null, and NHE8-null mice. Acidemic NHE8-null mice had an increase in brush-border membrane vesicle NHE3 protein abundance and NHE activity compared with vehicle-treated mice. Likewise, NHE3-null mice had an increase in NHE8 brush-border membrane protein abundance and NHE activity in response to metabolic acidosis. In conclusion, both NHE3 and NHE8 likely play a role in neonatal acidification.

  17. Mutant power: using mutant allele collections for yeast functional genomics.

    PubMed

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology.

  18. Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine.

    PubMed

    Fiorini, Claudia; Cordani, Marco; Padroni, Chiara; Blandino, Giovanni; Di Agostino, Silvia; Donadelli, Massimo

    2015-01-01

    Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide; PDAC is characterized by poor prognosis, resistance to conventional chemotherapy and high mortality rate. TP53 tumor suppressor gene is frequently mutated in PDAC, resulting in the accumulation of mutated protein with potential gain-of-function (GOF) activities, such as genomic instability, hyperproliferation and chemoresistance. The purpose of this study was to assess the relevance of the p53 status on the PDAC cells response to the standard drug gemcitabine. We also examined the potential therapeutic effect of p53-reactivating molecules to restore the mutant p53 function in GEM treated PDAC cells. We showed that gemcitabine stabilized mutant p53 protein in the nuclei and induced chemoresistance, concurrent with the mutant p53-dependent expression of Cdk1 and CCNB1 genes, resulting in a hyperproliferation effect. Despite the adverse activation of mutant p53 by gemcitabine, simultaneous treatment of PDAC cells with gemcitabine and p53-reactivating molecules (CP-31398 and RITA) reduced growth rate and induced apoptosis. This synergistic effect was observed in both wild-type and mutant p53 cell lines and was absent in p53-null cells. The combination drug treatment induced p53 phosphorylation on Ser15, apoptosis and autophagosome formation. Furthermore, pharmacological inhibition of autophagy further increased apoptosis stimulated by gemcitabine/CP-31398 treatment. Together, our results show that gemcitabine aberrantly stimulates mutant p53 activity in PDAC cells identifying key processes with potential for therapeutic targeting. Our data also support an anti-tumoral strategy based on inhibition of autophagy combined with p53 activation and standard chemotherapy for both wild-type and mutant p53 expressing PDACs.

  19. Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones.

    PubMed

    Gordo-Gilart, Raquel; Andueza, Sara; Hierro, Loreto; Jara, Paloma; Alvarez, Luis

    2016-01-01

    Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability. Incubation of transfected cells at a reduced temperature (30°C) or exposure to pharmacological doses of either 4-PBA or curcumin restored cell surface expression of mutants G228R and A934T. The delivery of these mutants to the plasma membrane was accompanied by a switch in the ratio of mature to inmature protein forms, leading to a predominant expression of the mature protein. This effect was due to an improvement in the maturation rate and not to the stabilization of the mature forms. Both mutants were also functionally rescued, displaying bile salt-dependent phospholipid efflux activity after addition of 4-PBA or curcumin. Drug-induced rescue was mutant specific, given neither 4-PBA nor curcumin had an effect on the ABCB4 mutants G68R and A934T. Collectively, these data indicate that the functionality of selected trafficking-defective ABCB4 mutants can be recovered by chemical chaperones through restoration of membrane localization, suggesting a potential treatment for patients carrying such mutations.

  20. Learning How to License Null Noun-Class Prefixes in Sesotho

    ERIC Educational Resources Information Center

    Demuth, Katherine; Machobane, Malillo; Moloi, Francina

    2009-01-01

    Noun-class prefixes are obligatory in most Bantu languages. However, the Sotho languages (Sesotho, Setswana, Sepedi) permit a subset of prefixes to be realized as null at the intersection of "unmarked" phonological, syntactic, and discourse conditions. This raises the question of how and when the licensing of null prefixes is learned. Using…

  1. Qualification of a Null Lens Using Image-Based Phase Retrieval

    NASA Technical Reports Server (NTRS)

    Bolcar, Matthew R.; Aronstein, David L.; Hill, Peter C.; Smith, J. Scott; Zielinski, Thomas P.

    2012-01-01

    In measuring the figure error of an aspheric optic using a null lens, the wavefront contribution from the null lens must be independently and accurately characterized in order to isolate the optical performance of the aspheric optic alone. Various techniques can be used to characterize such a null lens, including interferometry, profilometry and image-based methods. Only image-based methods, such as phase retrieval, can measure the null-lens wavefront in situ - in single-pass, and at the same conjugates and in the same alignment state in which the null lens will ultimately be used - with no additional optical components. Due to the intended purpose of a Dull lens (e.g., to null a large aspheric wavefront with a near-equal-but-opposite spherical wavefront), characterizing a null-lens wavefront presents several challenges to image-based phase retrieval: Large wavefront slopes and high-dynamic-range data decrease the capture range of phase-retrieval algorithms, increase the requirements on the fidelity of the forward model of the optical system, and make it difficult to extract diagnostic information (e.g., the system F/#) from the image data. In this paper, we present a study of these effects on phase-retrieval algorithms in the context of a null lens used in component development for the Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission. Approaches for mitigation are also discussed.

  2. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    PubMed

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities.

  3. A Minimalist Approach to Null Subjects and Objects in Second Language Acquisition

    ERIC Educational Resources Information Center

    Park, H.

    2004-01-01

    Studies of the second language acquisition of pronominal arguments have observed that: (1) L1 speakers of null subject languages of the Spanish type drop more subjects in their second language (L2) English than first language (L1) speakers of null subject languages of the Korean type and (2) speakers of Korean-type languages drop more objects than…

  4. Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse.

    PubMed

    Gibertini, Sara; Zanotti, Simona; Savadori, Paolo; Curcio, Maurizio; Saredi, Simona; Salerno, Franco; Andreetta, Francesca; Bernasconi, Pia; Mantegazza, Renato; Mora, Marina

    2014-05-01

    The Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis

  5. Optical testing of a parabolic trough solar collector by a null screen with stitching

    NASA Astrophysics Data System (ADS)

    Moreno-Oliva, V., I.; Campos-Garcia, M.; Granados-Agustin, F.; Arjona-Pérez, M. J.; Díaz-Uribe, R.; Avendaño-Alejo, M.

    2009-06-01

    In this work we report a method for testing a parabolic trough solar collector (PTSC) based on the null screen principles. For surfaces with symmetry of revolution a cylindrical null screen is used, now, for testing the PTSC we use a flat null screen. The design of the null screen with ellipsoidal spots is described; its image, which is formed by reflection on the test surface, becomes an exact square array of circular spots if the surface is perfect. Any departure from this geometry is indicative of defects on the surface. The flat null screen design and the surface evaluation algorithm are presented. Here the surface is tested in sections and the evaluation of the shape of the surface is performed with stitching method. Results of the evaluation for a square PTSC with 1000 mm by side (F/0.49) are shown.

  6. PSF and field of view characteristics of imaging and nulling interferometers

    NASA Astrophysics Data System (ADS)

    Hénault, François

    2010-07-01

    In this communication are presented some complements to a recent paper entitled "Simple Fourier optics formalism for high angular resolution systems and nulling interferometry" [1], dealing with imaging and nulling capacities of a few types of multi-aperture optical systems. Herein the characteristics of such systems in terms of Point Spread Function (PSF) and Field of View (FoV) are derived from simple analytical expressions that are further evaluated numerically for various configurations. We consider successively the general cases of Fizeau and Michelson interferometers, and those of a monolithic pupil, nulling telescope, of a nulling, Sheared-Pupil Telescope (SPT), and of a sparse aperture, Axially Combined Interferometer (ACI). The analytical formalism also allows establishing the exact Object-Image relationships applicable to nulling PSTs or ACIs that are planned for future space missions searching for habitable extra-solar planets.

  7. Computer generated hologram null test of a freeform optical surface with rectangular aperture

    NASA Astrophysics Data System (ADS)

    Su, Ping; Ma, Jianshe; Tan, Qiaofeng; Kang, Guoguo; Liu, Yi; Jin, Guofan

    2012-02-01

    In null computed generated hologram (CGH) test of optical elements, fitting method is needed in null CGH design to generate continuous phase function from the ray-traced discrete phase data. The null CGH for freeform testing usually has a deformed aperture and a high order phase function, because of the aberrations introduced by freeform wavefront propagation. With traditional Zernike polynomial fitting method, selection of an orthogonal basis set and choosing number of terms are needed before fitting. Zernike polynomial fitting method is not suitable in null CGH design for freeform testing; a novel CGH design method with cubic B-spline interpolation is developed. For a freeform surface with 18×18 mm2 rectangular aperture and 630 μm peak-to-valley undulation, the null CGH with a curved rectangular aperture is designed by using the method proposed. Simulation and experimental results proved the feasibility of the novel CGH design method.

  8. Null results in TMS: from absence of evidence to evidence of absence.

    PubMed

    de Graaf, T A; Sack, A T

    2011-01-01

    It is always difficult to interpret null results. But as a research method, transcranial magnetic stimulation (TMS) has so many degrees of freedom that null results are often dismissed as meaningless. We feel that this may be unnecessary, if not counterproductive. Null results seem to inherently fulfill an important role in brain mapping. In fact, without null results, neuroimaging as an enterprise would not make sense. We argue that null results are similarly important in TMS research. By itself, neuroimaging research leaves room for doubt concerning whether or not an activated region is actually necessary for intact task performance. Interference methods such as TMS can therefore complement brain research by testing the functional relevance of that region. However, if then only positive TMS results are taken seriously, the brain interference paradigm seems less informative than promised. But how can null results inform us if they only constitute absence of evidence? We suggest that three main arguments contravene interpretation of null results in TMS. These we call the localization argument, the neural efficacy argument, and the power argument. We proceed to discuss in turn how, and under which conditions, each of these arguments may be nuanced. These considerations lead us to value null results along a gradient of meaningfulness, rather than a dichotomy. This perspective may open up a new range of TMS applications, where research questions about the lack of functional relevance of a particular brain region become valid. In this context we make specific recommendations on experimentation and interpretation. We propose that it is often not only meaningful to interpret null results, but also useful to make such findings available to the community, especially now that improved methods and an expanded knowledge base make null results more interpretable than they have been in the past.

  9. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.

    PubMed

    Chen, Jane Q; Mori, Hidetoshi; Cardiff, Robert D; Trott, Josephine F; Hovey, Russell C; Hubbard, Neil E; Engelberg, Jesse A; Tepper, Clifford G; Willis, Brandon J; Khan, Imran H; Ravindran, Resmi K; Chan, Szeman R; Schreiber, Robert D; Borowsky, Alexander D

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.

  10. Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans.

    PubMed

    Gunalan, Karthigayan; Lo, Eugenia; Hostetler, Jessica B; Yewhalaw, Delenasaw; Mu, Jianbing; Neafsey, Daniel E; Yan, Guiyun; Miller, Louis H

    2016-05-31

    The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion.

  11. Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

    PubMed Central

    Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

    2015-01-01

    Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

  12. Problem-Solving Test: Tryptophan Operon Mutants

    ERIC Educational Resources Information Center

    Szeberenyi, Jozsef

    2010-01-01

    This paper presents a problem-solving test that deals with the regulation of the "trp" operon of "Escherichia coli." Two mutants of this operon are described: in mutant A, the operator region of the operon carries a point mutation so that it is unable to carry out its function; mutant B expresses a "trp" repressor protein unable to bind…

  13. Optical nulling apparatus and method for testing an optical surface

    NASA Technical Reports Server (NTRS)

    Olczak, Eugene (Inventor); Hannon, John J. (Inventor); Dey, Thomas W. (Inventor); Jensen, Arthur E. (Inventor)

    2008-01-01

    An optical nulling apparatus for testing an optical surface includes an aspheric mirror having a reflecting surface for imaging light near or onto the optical surface under test, where the aspheric mirror is configured to reduce spherical aberration of the optical surface under test. The apparatus includes a light source for emitting light toward the aspheric mirror, the light source longitudinally aligned with the aspheric mirror and the optical surface under test. The aspheric mirror is disposed between the light source and the optical surface under test, and the emitted light is reflected off the reflecting surface of the aspheric mirror and imaged near or onto the optical surface under test. An optical measuring device is disposed between the light source and the aspheric mirror, where light reflected from the optical surface under test enters the optical measuring device. An imaging mirror is disposed longitudinally between the light source and the aspheric mirror, and the imaging mirror is configured to again reflect light, which is first reflected from the reflecting surface of the aspheric mirror, onto the optical surface under test.

  14. Muscular dystrophy in PTFR/cavin-1 null mice

    PubMed Central

    Ding, Shi-Ying; Pilch, Paul F.

    2017-01-01

    ice and humans lacking the caveolae component polymerase I transcription release factor (PTRF, also known as cavin-1) exhibit lipo- and muscular dystrophy. Here we describe the molecular features underlying the muscle phenotype for PTRF/cavin-1 null mice. These animals had a decreased ability to exercise, and exhibited muscle hypertrophy with increased muscle fiber size and muscle mass due, in part, to constitutive activation of the Akt pathway. Their muscles were fibrotic and exhibited impaired membrane integrity accompanied by an apparent compensatory activation of the dystrophin-glycoprotein complex along with elevated expression of proteins involved in muscle repair function. Ptrf deletion also caused decreased mitochondrial function, oxygen consumption, and altered myofiber composition. Thus, in addition to compromised adipocyte-related physiology, the absence of PTRF/cavin-1 in mice caused a unique form of muscular dystrophy with a phenotype similar or identical to that seen in humans lacking this protein. Further understanding of this muscular dystrophy model will provide information relevant to the human situation and guidance for potential therapies. PMID:28289716

  15. Particle Acceleration Due to Coronal Non-null Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Threlfall, James; Neukirch, Thomas; Parnell, Clare Elizabeth

    2017-03-01

    Various topological features, for example magnetic null points and separators, have been inferred as likely sites of magnetic reconnection and particle acceleration in the solar atmosphere. In fact, magnetic reconnection is not constrained to solely take place at or near such topological features and may also take place in the absence of such features. Studies of particle acceleration using non-topological reconnection experiments embedded in the solar atmosphere are uncommon. We aim to investigate and characterise particle behaviour in a model of magnetic reconnection which causes an arcade of solar coronal magnetic field to twist and form an erupting flux rope, crucially in the absence of any common topological features where reconnection is often thought to occur. We use a numerical scheme that evolves the gyro-averaged orbit equations of single electrons and protons in time and space, and simulate the gyromotion of particles in a fully analytical global field model. We observe and discuss how the magnetic and electric fields of the model and the initial conditions of each orbit may lead to acceleration of protons and electrons up to 2 MeV in energy (depending on model parameters). We describe the morphology of time-dependent acceleration and impact sites for each particle species and compare our findings to those recovered by topologically based studies of three-dimensional (3D) reconnection and particle acceleration. We also broadly compare aspects of our findings to general observational features typically seen during two-ribbon flare events.

  16. A maternal Ahr null genotype sensitizes embryos to chemical teratogenesis.

    PubMed

    Thomae, Tami L; Glover, Edward; Bradfield, Christopher A

    2004-07-16

    The aryl hydrocarbon receptor (encoded by the Ahr locus) is a ligand-activated transcription factor that mediates the toxicology and teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). In an effort to understand the role of the maternal compartment in dioxin teratology, we designed a breeding strategy that allowed us to compare the teratogenic response in embryos from Ahr(-/-) (null) and Ahr(+/+) (wild-type) dams. Using this strategy, we demonstrate that embryos from the Ahr(-/-) dams are 5-fold more sensitive to dioxin-induced cleft palate and hydronephrosis as compared with embryos from an Ahr(+/+) dam. Moreover, this increased teratogenic sensitivity extends beyond dioxin, because embryos from Ahr(-/-) dams exhibited a 9-fold increase in their sensitivity to the fetotoxic effects of the glucocorticoid, dexamethasone. In searching for an explanation for this increased sensitivity, we found that more dioxin and dexamethasone reached the embryos from Ahr(-/-) dams as compared with embryos from Ahr(+/+) dams. We propose that increased deposition of teratogens/fetotoxicants to the embryonic compartment is the result of porto-systemic shunting and/or blocked P4501A induction in Ahr(-/-) dams. In addition to demonstrating the importance of maternal AHR in teratogenesis, these data may have implications that reach beyond the mechanism of action of dioxin. In this regard, the Ahr(-/-) mouse may provide a system that allows pharmacological agents and toxicants to be more easily studied in a model where first pass clearance is a significant obstacle.

  17. Magnetic flipping - Reconnection in three dimensions without null points

    NASA Technical Reports Server (NTRS)

    Priest, E. R.; Forbes, T. G.

    1992-01-01

    In three dimensions, magnetic reconnection may take place in a sheared magnetic field at any singular field line, where the nearby field has X-type topology in planes perpendicular to the field line and where an electric field is present parallel to the field line. In the ideal region around the singular line there will, in general, be singularities in the plasma flow and electric field, both at the singular line and at 'magnetic flipping layers', which are remnants of local magnetic separatrices. In the absence of a three-dimensional magnetic neutral point or null point, reconnection of field lines can still occur by a process of magnetic flipping, in which the plasma crosses the flipping layers but the field lines rapidly flip along them by magnetic diffusion. Depending on the boundary conditions, there may be two or four flipping layers which converge on the singular line. A boundary layer analysis of a flipping layer is given, in which the magnetic field parallel to the layer decreases as one crosses it while the plasma pressure (or magnetic pressure associated with the field along the singular line) increases. The width of the flipping layer decreases with distance from the singular line.

  18. Aspects of QCD current algebra on a null plane

    NASA Astrophysics Data System (ADS)

    Beane, S. R.; Hobbs, T. J.

    2016-09-01

    Consequences of QCD current algebra formulated on a light-like hyperplane are derived for the forward scattering of vector and axial-vector currents on an arbitrary hadronic target. It is shown that current algebra gives rise to a special class of sum rules that are direct consequences of the independent chiral symmetry that exists at every point on the two-dimensional transverse plane orthogonal to the lightlike direction. These sum rules are obtained by exploiting the closed, infinite-dimensional algebra satisfied by the transverse moments of null-plane axial-vector and vector charge distributions. In the special case of a nucleon target, this procedure leads to the Adler-Weisberger, Gerasimov-Drell-Hearn, Cabibbo-Radicati and Fubini-Furlan-Rossetti sum rules. Matching to the dispersion-theoretic language which is usually invoked in deriving these sum rules, the moment sum rules are shown to be equivalent to algebraic constraints on forward S-matrix elements in the Regge limit.

  19. Identification of Siglec-1 null individuals infected with HIV-1.

    PubMed

    Martinez-Picado, Javier; McLaren, Paul J; Erkizia, Itziar; Martin, Maureen P; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M; Penugonda, Sudhir; Günthard, Huldrych F; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-08-11

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals.

  20. Identification of Siglec-1 null individuals infected with HIV-1

    PubMed Central

    Martinez-Picado, Javier; McLaren, Paul J.; Erkizia, Itziar; Martin, Maureen P.; Benet, Susana; Rotger, Margalida; Dalmau, Judith; Ouchi, Dan; Wolinsky, Steven M.; Penugonda, Sudhir; Günthard, Huldrych F.; Fellay, Jacques; Carrington, Mary; Izquierdo-Useros, Nuria; Telenti, Amalio

    2016-01-01

    Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) that is found in ∼1% of healthy people. Exome analysis and direct genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo consequences of SIGLEC1 loss-of-function. Cells from these individuals are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo. However, Siglec-1 protein truncation does not have a measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans-infection. Thus, it provides evidence that the classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals. PMID:27510803

  1. Connexin43 null mice reveal that astrocytes express multiple connexins.

    PubMed

    Dermietzel, R; Gao, Y; Scemes, E; Vieira, D; Urban, M; Kremer, M; Bennett, M V; Spray, D C

    2000-04-01

    The gap junction protein connexin43 (Cx43) is the primary component of intercellular channels in cardiac tissue and in astrocytes, the most abundant type of glial cells in the brain. Mice in which the gene for Cx43 is deleted by homologous recombination die at birth, due to profound hypertrophy of the ventricular outflow tract and stenosis of the pulmonary artery. Despite this significant cardiovascular abnormality, brains of connexin43 null [Cx43 (-/-)] animals are shown to be macroscopically normal and to display a pattern of cortical lamination that is not detectably different from wildtype siblings. Presence of Cx40 and Cx45 in brains and astrocytes cultured from both Cx43 (-/-) mice and wildtype littermates was confirmed by RT-PCR, Northern blot analyses and by immunostaining; Cx46 was detected by RT-PCR and Northern blot analyses. Presence of Cx26 in astrocyte cultures was indicated by RT-PCR and by Western blot analysis, although we were unable to resolve whether it was contributed by contaminating cells; Cx30 mRNA was detected by Northern blot in long term (2 weeks) but not fresh cultures of astrocytes. These studies thus reveal that astrocyte gap junctions may be formed of multiple connexins. Presumably, the metabolic and ionic coupling provided by these diverse gap junction types may functionally compensate for the absence of the major astrocyte gap junction protein in Cx43 (-/-) mice, providing whatever intercellular signaling is necessary for brain development and cortical lamination.

  2. In vitro transformation of Li-Fraumeni syndrome fibroblasts by SV40 large T antigen mutants.

    PubMed

    Maclean, K; Rogan, E M; Whitaker, N J; Chang, A C; Rowe, P B; Dalla-Pozza, L; Symonds, G; Reddel, R R

    1994-03-01

    Transfection of SV40 early region DNA into normal human diploid fibroblasts (NHDFs) increases their proliferative potential to a limited extent. We have investigated the roles of the SV40 large T antigen (LTAg) regions responsible for binding to the protein products of the retinoblastoma (Rb) and p53 genes in this temporary escape from senescence. Patients encoding LTAg mutants were transfected into NHDFs and into Li-Fraumeni syndrome (LFS) fibroblasts which are heterozygous wild-type (wt)/null-mutant for p53. A LTAg mutated in the p53-binding region (T402DE) had greatly reduced efficiency of focus formation, and a p110Rb-binding mutant was unable to induce any foci. T402DE-induced NHDF foci senesced at the same time as untransfected cells, but the equivalent LFS foci all had increased proliferative potentials, with the greatest increase being seen in clones that lost the wt p53 allele. One LFS clone expressed the T402DE mutant during focus formation, but later lost both the T402DE DNA and the wt p53 allele. We conclude that SV40-induced focus formation in NHDFs requires the LTAg p110Rb-binding region, and is enhanced by loss of normal p53 function. In contrast, increased proliferative potential is primarily due to loss of p53 function.

  3. Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.

    PubMed

    Di Pietro, Chiara; Marazziti, Daniela; La Sala, Gina; Abbaszadeh, Zeinab; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2017-01-01

    Cellular primary cilia crucially sense and transduce extracellular physicochemical stimuli. Cilium-mediated developmental signaling is tissue and cell type specific. Primary cilia are required for cerebellar differentiation and sonic hedgehog (Shh)-dependent proliferation of neuronal granule precursors. The mammalian G-protein-coupled receptor 37-like 1 is specifically expressed in cerebellar Bergmann glia astrocytes and participates in regulating postnatal cerebellar granule neuron proliferation/differentiation and Bergmann glia and Purkinje neuron maturation. The mouse receptor protein interacts with the patched 1 component of the cilium-associated Shh receptor complex. Mice heterozygous for patched homolog 1 mutations, like heterozygous patched 1 humans, have a higher incidence of Shh subgroup medulloblastoma (MB) and other tumors. Cerebellar cells bearing primary cilia were identified during postnatal development and in adulthood in two mouse strains with altered Shh signaling: a G-protein-coupled receptor 37-like 1 null mutant and an MB-susceptible, heterozygous patched homolog 1 mutant. In addition to granule and Purkinje neurons, primary cilia were also expressed by Bergmann glia astrocytes in both wild-type and mutant animals, from birth to adulthood. Variations in ciliary number and length were related to the different levels of neuronal and glial cell proliferation and maturation, during postnatal cerebellar development. Primary cilia were also detected in pre-neoplastic MB lesions in heterozygous patched homolog 1 mutant mice and they could represent specific markers for the development and analysis of novel cerebellar oncogenic models.

  4. Molecular genetics of Drosophila alpha-actinin: mutant alleles disrupt Z disc integrity and muscle insertions

    PubMed Central

    1990-01-01

    We have isolated a Drosophila melanogaster alpha-actinin gene and partially characterized several mutant alleles. The Drosophila protein sequence is very similar (68% identity) to those of chicken alpha- actinin isoforms, but less closely related (30% identity) to Dictyostelium alpha-actinin. The gene is within subdivision 2C of the X chromosome, coincident with 15 lethal (1)2Cb mutations. At least four alleles, l(1)2Cb1, l(1)2Cb2, l(1)2Cb4, and l(1)2Cb5 are interrupted by rearrangement breakpoints and must be null. In all four cases, hemizygous mutants complete embryogenesis and do not die until the second day of larval growth, signifying that either the role of alpha- actinin in nonmuscle cells is redundant or that a distinct and only distantly related gene encodes the non-muscle isoform. Allelic but less severely affected fliA mutants are apparently due to point mutations, and develop into adults having thoracic muscle abnormalities. EM of mutant muscles reveals that Z discs and myofibrillar attachments are disrupted, whereas epithelial "tendon" cells are less affected. We discuss these phenotypes in the light of presumed in vivo alpha-actinin functions. PMID:2112549

  5. A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal.

    PubMed

    Siggers, Pam; Carré, Gwenn-Aël; Bogani, Debora; Warr, Nick; Wells, Sara; Hilton, Helen; Esapa, Chris; Hajihosseini, Mohammad K; Greenfield, Andy

    2014-01-01

    The secreted molecule fibroblast growth factor 9 (FGF9) plays a critical role in testis determination in the mouse. In embryonic gonadal somatic cells it is required for maintenance of SOX9 expression, a key determinant of Sertoli cell fate. Conditional gene targeting studies have identified FGFR2 as the main gonadal receptor for FGF9 during sex determination. However, such studies can be complicated by inefficient and variable deletion of floxed alleles, depending on the choice of Cre deleter strain. Here, we report a novel, constitutive allele of Fgfr2, hobbyhorse (hob), which was identified in an ENU-based forward genetic screen for novel testis-determining loci. Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser) in the third extracellular immunoglobulin-like domain of FGFR2. Mutant homozygous embryos show severe limb and lung defects and, when on the sensitised C57BL/6J (B6) genetic background, undergo complete XY gonadal sex reversal associated with failure to maintain expression of Sox9. Genetic crosses employing a null mutant of Fgfr2 suggest that Fgr2hob is a hypomorphic allele, affecting both the FGFR2b and FGFR2c splice isoforms of the receptor. We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected.

  6. Measurement of high-departure aspheric surfaces using subaperture stitching with variable null optics

    NASA Astrophysics Data System (ADS)

    Murphy, Paul; DeVries, Gary; Fleig, Jon; Forbes, Gregory; Kulawiec, Andrew; Miladinovic, Dragisha

    2009-08-01

    Aspheric surfaces can provide significant benefits to optical systems, but manufacturing high-precision aspheric surfaces is often limited by the availability of surface metrology. Traditionally, aspheric measurements have required dedicated null correction optics, but the cost, lead time, inflexibility, and calibration difficulty of null optics make aspheres less attractive. In the past three years, we have developed the Subaperture Stitching Interferometer for Aspheres (SSI-A®) to help address this limitation, providing flexible aspheric measurement capability up to 200 waves of aspheric departure from best-fit sphere. Some aspheres, however, have hundreds or even thousands of waves of departure. We have recently developed Variable Optical Null (VONTM) technology that can null much of the aspheric departure in a subaperture. The VON is automatically reconfigurable and is adjusted to nearly null each specific subaperture of an asphere. The VON provides a significant boost in aspheric measurement capability, enabling aspheres with up to 1000 waves of departure to be measured, without the use of null optics that are dedicated to each asphere prescription. We outline the basic principles of subaperture stitching and the Variable Optical Null, demonstrate the extended capability provided by the VON, and present measurement results from our new Aspheric Stitching Interferometer (ASITM).

  7. Measurement of high-departure aspheres using subaperture stitching with the Variable Optical Null (VON)

    NASA Astrophysics Data System (ADS)

    Kulawiec, Andrew; Murphy, Paul; DeMarco, Michael

    2010-10-01

    Aspheric surfaces are proven to provide significant benefits to a wide variety of optical systems, but the ability to produce high-precision aspheric surfaces has historically been limited by the ability (or lack thereof) to measure them. Traditionally, aspheric measurements have required dedicated null optics, but the cost, lead time, and calibration difficulty of using null optics has made the use of aspheres more challenging and less attractive. In the past three years, QED has developed the Subaperture Stitching Interferometer for Aspheres (SSI-A®) to help address this limitation, providing flexible aspheric measurement capability of up to 200 waves of aspheric departure from best-fit sphere. Some aspheres, however, have thousands of waves of departure. We have recently developed Variable Optical Null (VON) technology that can null much of the aspheric departure in a subaperture. The VON is automatically configurable and is adjusted to nearly null each specific subaperture of an asphere. This ability to nearly null a local subaperture of an asphere provides a significant boost in aspheric measurement capability, enabling aspheres with up to 1000 waves of departure to be measured, without the use of dedicated null optics. We outline the basic principles of subaperture stitching and VON technology, demonstrate the extended capability provided by the VON, and present measurement results from the new Aspheric Stitching Interferometer (ASI®).

  8. Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

    PubMed Central

    Carbrey, Jennifer M.; Song, Linhua; Zhou, Yao; Yoshinaga, Masafumi; Rojek, Aleksandra; Wang, Yiding; Liu, Yangjian; Lujan, Heidi L.; DiCarlo, Stephen E.; Nielsen, Søren; Rosen, Barry P.; Agre, Peter; Mukhopadhyay, Rita

    2009-01-01

    Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO2, AQP9-null mice suffer reduced survival rates (LD50, 12 mg/kg) compared with WT mice (LD50, 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10–20 times more arsenic than WT mice. Within hours after NaAsO2 injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only ≈10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity. PMID:19805235

  9. Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

    PubMed

    Sima, Corneliu; Gastfreund, Shoshi; Sun, Chunxiang; Glogauer, Michael

    2014-02-01

    Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

  10. Investigation of nulling and subpulse drifting properties of PSR J1727-2739

    NASA Astrophysics Data System (ADS)

    Wen, Z. G.; Wang, N.; Yuan, J. P.; Yan, W. M.; Manchester, R. N.; Yuen, R.; Gajjar, V.

    2016-08-01

    Aims: We intend to study of the nulling and subpulse drifting in PSR J1727-2739 in detail to investigate its radiation properties. Methods: The observations were carried out on 20 March, 2004 using the Parkes 64-m radio telescope with a central frequency of 1518 MHz. A total of 5568 single pulses were analysed. Results: This pulsar shows well-defined nulls with lengths lasting from 6 to 281 pulses and separated by burst phases ranging from 2 to 133 pulses. We estimate a nulling fraction of around 68%. No emission in the average pulse profile integrated over all null pulses is detected with significance above 3σ. Most transitions from nulls to bursts are within a few pulses, whereas the transitions from bursts to nulls exhibit two patterns of decay; these transitions either decrease gradually or rapidly. In the burst phase, we find that there are two distinct subpulse drift modes with vertical spacing between the drift bands of 9.7 ± 1.6 and 5.2 ± 0.9 pulse periods, while sometimes there is a third mode with no subpulse drifting. Some mode transitions occur within a single burst, while others are separated by nulls. Different modes have different average pulse profiles. Possible physical mechanisms are discussed.

  11. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  12. Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes.

    PubMed

    Yi, Ran; Liu, Bin; Dong, Qi

    2013-06-01

    Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case-control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14-2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37-2.64, P < 0.001), but was not associated with risk of type 1 diabetes (OR = 0.84, 95 % CI 0.66-1.07, P = 0.153). Subgroup analysis by ethnicity further identified the obvious association between GSTM1 null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.

  13. Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

    NASA Astrophysics Data System (ADS)

    Tarr, Lucas A.; Linton, Mark; Leake, James

    2017-03-01

    We perform nonlinear MHD simulations to study the propagation of magnetoacoustic waves from the photosphere to the low corona. We focus on a 2D system with a gravitationally stratified atmosphere and three photospheric concentrations of magnetic flux that produce a magnetic null point with a magnetic dome topology. We find that a single wavepacket introduced at the lower boundary splits into multiple secondary wavepackets. A portion of the packet refracts toward the null owing to the varying Alfvén speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfvén speeds coincide, partially transmit, reflect, and mode-convert between branches of the local dispersion relation. Approximately 15.5% of the wavepacket’s initial energy (E input) converges on the null, mostly as a fast magnetoacoustic wave. Conversion is very efficient: 70% of the energy incident on the null is converted to slow modes propagating away from the null, 7% leaves as a fast wave, and the remaining 23% (0.036E input) is locally dissipated. The acoustic energy leaving the null is strongly concentrated along field lines near each of the null’s four separatrices. The portion of the wavepacket that refracts toward the null, and the amount of current accumulation, depends on the vertical and horizontal wavenumbers and the centroid position of the wavepacket as it crosses the photosphere. Regions that refract toward or away from the null do not simply coincide with regions of open versus closed magnetic field or regions of particular field orientation. We also model wavepacket propagation using a WKB method and find that it agrees qualitatively, though not quantitatively, with the results of the numerical simulation.

  14. Reliability assessment of null allele detection: inconsistencies between and within different methods.

    PubMed

    Dąbrowski, M J; Pilot, M; Kruczyk, M; Żmihorski, M; Umer, H M; Gliwicz, J

    2014-03-01

    Microsatellite loci are widely used in population genetic studies, but the presence of null alleles may lead to biased results. Here, we assessed five methods that indirectly detect null alleles and found large inconsistencies among them. Our analysis was based on 20 microsatellite loci genotyped in a natural population of Microtus oeconomus sampled during 8 years, together with 1200 simulated populations without null alleles, but experiencing bottlenecks of varying duration and intensity, and 120 simulated populations with known null alleles. In the natural population, 29% of positive results were consistent between the methods in pairwise comparisons, and in the simulated data set, this proportion was 14%. The positive results were also inconsistent between different years in the natural population. In the null-allele-free simulated data set, the number of false positives increased with increased bottleneck intensity and duration. We also found a low concordance in null allele detection between the original simulated populations and their 20% random subsets. In the populations simulated to include null alleles, between 22% and 42% of true null alleles remained undetected, which highlighted that detection errors are not restricted to false positives. None of the evaluated methods clearly outperformed the others when both false-positive and false-negative rates were considered. Accepting only the positive results consistent between at least two methods should considerably reduce the false-positive rate, but this approach may increase the false-negative rate. Our study demonstrates the need for novel null allele detection methods that could be reliably applied to natural populations.

  15. Observation of Magnetic Reconnection at a 3D Null Point Associated with a Solar Eruption

    NASA Astrophysics Data System (ADS)

    Sun, J. Q.; Zhang, J.; Yang, K.; Cheng, X.; Ding, M. D.

    2016-10-01

    Magnetic null has long been recognized as a special structure serving as a preferential site for magnetic reconnection (MR). However, the direct observational study of MR at null-points is largely lacking. Here, we show the observations of MR around a magnetic null associated with an eruption that resulted in an M1.7 flare and a coronal mass ejection. The Geostationary Operational Environmental Satellites X-ray profile of the flare exhibited two peaks at ∼02:23 UT and ∼02:40 UT on 2012 November 8, respectively. Based on the imaging observations, we find that the first and also primary X-ray peak was originated from MR in the current sheet (CS) underneath the erupting magnetic flux rope (MFR). On the other hand, the second and also weaker X-ray peak was caused by MR around a null point located above the pre-eruption MFR. The interaction of the null point and the erupting MFR can be described as a two-step process. During the first step, the erupting and fast expanding MFR passed through the null point, resulting in a significant displacement of the magnetic field surrounding the null. During the second step, the displaced magnetic field started to move back, resulting in a converging inflow and subsequently the MR around the null. The null-point reconnection is a different process from the current sheet reconnection in this flare; the latter is the cause of the main peak of the flare, while the former is the cause of the secondary peak of the flare and the conspicuous high-lying cusp structure.

  16. 'True' null allele detection in microsatellite loci: a comparison of methods, assessment of difficulties and survey of possible improvements.

    PubMed

    Dąbrowski, M J; Bornelöv, S; Kruczyk, M; Baltzer, N; Komorowski, J

    2015-05-01

    Null alleles are alleles that for various reasons fail to amplify in a PCR assay. The presence of null alleles in microsatellite data is known to bias the genetic parameter estimates. Thus, efficient detection of null alleles is crucial, but the methods available for indirect null allele detection return inconsistent results. Here, our aim was to compare different methods for null allele detection, to explain their respective performance and to provide improvements. We applied several approaches to identify the 'true' null alleles based on the predictions made by five different methods, used either individually or in combination. First, we introduced simulated 'true' null alleles into 240 population data sets and applied the methods to measure their success in detecting the simulated null alleles. The single best-performing method was ML-NullFreq_frequency. Furthermore, we applied different noise reduction approaches to improve the results. For instance, by combining the results of several methods, we obtained more reliable results than using a single one. Rule-based classification was applied to identify population properties linked to the false discovery rate. Rules obtained from the classifier described which population genetic estimates and loci characteristics were linked to the success of each method. We have shown that by simulating 'true' null alleles into a population data set, we may define a null allele frequency threshold, related to a desired true or false discovery rate. Moreover, using such simulated data sets, the expected null allele homozygote frequency may be estimated independently of the equilibrium state of the population.

  17. Proteus mirabilis mutants defective in swarmer cell differentiation and multicellular behavior.

    PubMed Central

    Belas, R; Erskine, D; Flaherty, D

    1991-01-01

    Proteus mirabilis is a dimorphic bacterium which exists in liquid cultures as a 1.5- to 2.0-microns motile swimmer cell possessing 6 to 10 peritrichous flagella. When swimmer cells are placed on a surface, they differentiate by a combination of events that ultimately produce a swarmer cell. Unlike the swimmer cell, the polyploid swarmer cell is 60 to 80 microns long and possesses hundreds to thousands of surface-induced flagella. These features, combined with multicellular behavior, allow the swarmer cells to move over a surface in a process called swarming. Transposon Tn5 was used to produce P. mirabilis mutants defective in wild-type swarming motility. Two general classes of mutants were found to be defective in swarming. The first class was composed of null mutants that were completely devoid of swarming motility. The majority of nonswarming mutations were the result of defects in the synthesis of flagella or in the ability to rotate the flagella. The remaining nonswarming mutants produced flagella but were defective in surface-induced elongation. Strains in the second general class of mutants, which made up more than 65% of all defects in swarming were motile but were defective in the control and coordination of multicellular swarming. Analysis of consolidation zones produced by such crippled mutants suggested that this pleiotropic phenotype was caused by a defect in the regulation of multicellular behavior. A possible mechanism controlling the cyclic process of differentiation and dediferentiation involved in the swarming behavior of P. mirabilis is discussed. Images PMID:1917860

  18. Dominance relationships among mutant alleles of regulatory gene araC in the Escherichia coli B/R L-arabinose operon.

    PubMed

    Sheppard, D E

    1986-11-01

    The araBAD operon of Escherichia coli B/r is positively and negatively regulated by the araC+ regulatory protein. Mutations in gene araC can result in a variety of different regulatory phenotypes: araC null mutants (those carrying a null allele exhibiting no repressor or activator activity) are unable to achieve operon induction; araC-constitutive (araCc) mutants are partially constitutive, inducible by D-fucose, and resistant to catabolite repression; araCh mutants are hypersensitive to catabolite repression; and araCi mutants are resistant to catabolite repression. Various mutant alleles of gene araC were cloned into a derivative of plasmid pBR322 by in vivo recombination. Various heterozygous araC allelic combinations were constructed by transformation. Analysis of isomerase (araA) specific activity levels under various growth conditions indicated the following dominance relationships with regard to sensitivity to catabolite repression: araCh greater than araC+ greater than (araCc and araCi) greater than araC. It was concluded that the araCh protein may form a repressor complex that is refractory to removal by cyclic AMP receptor protein-cyclic AMP complex. This was interpreted in terms of the known nucleoprotein interactions between ara regulatory proteins and ara regulatory DNA.

  19. Tangential and sagittal curvature from the normals computed by the null screen method in corneal topography

    NASA Astrophysics Data System (ADS)

    Estrada-Molina, Amilcar; Díaz-Uribe, Rufino

    2011-08-01

    A new method for computing the tangential and sagittal curvatures from the normals to a cornea is proposed. The normals are obtained through a Null Screen method from the coordinates of the drops shaped spots at the null screen, the coordinates on a reference approximating surface and the centroids on the image plane. This method assumes that the cornea has rotational symmetry and our derivations will be carried out in the meridional plane that contains the symmetry axis. Experimental results are shown for a calibration spherical surface, using cylindrical null screens with radial point arrays.

  20. Visualization of redundancy resolution for kinematically redundant robots through the Jacobian null space

    NASA Technical Reports Server (NTRS)

    Chen, Yu-Che; Walker, Ian D.; Cheatham, John B., Jr.

    1992-01-01

    We present a unified formulation for the inverse kinematics of redundant arms, based on a special formulation of the null space of the Jacobian. By extending (appropriately re-scaling) previously used null space parameterizations, we obtain, in a unified fashion, the manipulability measure, the null space projector, and particular solutions for the joint velocities. We obtain the minimum norm pseudo-inverse solution as a projection from any particular solution, and the method provides an intuitive visualization of the self-motion. The result is a computationally efficient, consistent approach to computing redundant robot inverse kinematics.

  1. Integrated optics for nulling interferometry in the thermal infrared

    NASA Astrophysics Data System (ADS)

    Barillot, Marc; Barthelemy, Eleonore; Broquin, Jean-Emmanuel; Frayret, Jérôme; Grelin, Jérôme; Hawkins, Gary; Kirschner, Volker; Parent, Gilles; Pradel, Annie; Rossi, Emmanuel; Vigreux, Caroline; Zhang, Shaoqian; Zhang, Xianghua

    2008-07-01

    Modal filtering is based on the capability of single-mode waveguides to transmit only one complex amplitude function to eliminate virtually any perturbation of the interfering wavefronts, thus making very high rejection ratios possible in a nulling interferometer. In the present paper we focus on the progress of Integrated Optics in the thermal infrared [6-20μm] range, one of the two candidate technologies for the fabrication of Modal Filters, together with fiber optics. In conclusion of the European Space Agency's (ESA) "Integrated Optics for Darwin" activity, etched layers of chalcogenide material deposited on chalcogenide glass substrates was selected among four candidates as the technology with the best potential to simultaneously meet the filtering efficiency, absolute and spectral transmission, and beam coupling requirements. ESA's new "Integrated Optics" activity started at mid-2007 with the purpose of improving the technology until compliant prototypes can be manufactured and validated, expectedly by the end of 2009. The present paper aims at introducing the project and the components requirements and functions. The selected materials and preliminary designs, as well as the experimental validation logic and test benches are presented. More details are provided on the progress of the main technology: vacuum deposition in the co-evaporation mode and subsequent etching of chalcogenide layers. In addition, preliminary investigations of an alternative technology based on burying a chalcogenide optical fiber core into a chalcogenide substrate are presented. Specific developments of anti-reflective solutions designed for the mitigation of Fresnel losses at the input and output surface of the components are also introduced.

  2. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

    PubMed Central

    Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP

  3. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

    PubMed

    Soenjaya, Y; Foster, B L; Nociti, F H; Ao, M; Holdsworth, D W; Hunter, G K; Somerman, M J; Goldberg, H A

    2015-09-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the

  4. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1.

    PubMed

    Heinrich, Garrett; Russo, Lucia; Castaneda, Tamara R; Pfeiffer, Verena; Ghadieh, Hilda E; Ghanem, Simona S; Wu, Jieshen; Faulkner, Latrice D; Ergün, Süleyman; McInerney, Marcia F; Hill, Jennifer W; Najjar, Sonia M

    2016-05-20

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice.

  5. Selection of chemotaxis mutants of Dictyostelium discoideum

    PubMed Central

    1987-01-01

    A method has been developed for the efficient selection of chemotaxis mutants of Dictyostelium discoideum. Mutants defective in the chemotactic response to folate could be enriched up to 30-fold in one round of selection using a chamber in which a compartment that contained the chemoattractant was separated by a sandwich of four nitrocellulose filters from a compartment that contained buffer. Mutagenized cells were placed in the center of the filter layer and exposed to the attractant gradient built up between the compartments for a period of 3-4 h. While wild-type cells moved through the filters in a wave towards the compartment that contained attractant, mutant cells remained in the filter to which they were applied. After several repetitions of the selection procedure, mutants defective in chemotaxis made up 10% of the total cell population retained in that filter. Mutants exhibiting three types of alterations were collected: motility mutants with either reduced speed of movement, or altered rates of turning; a single mutant defective in production of the attractant- degrading enzyme, folate deaminase; and mutants with normal motility but reduced chemotactic responsiveness. One mutant showed drastically reduced sensitivity in folate-induced cGMP production. Morphogenetic alterations of mutants defective in folate chemotaxis are described. PMID:3793759

  6. General principles of describing second- and higher-order null points of a potential magnetic field in 3D

    NASA Astrophysics Data System (ADS)

    Lukashenko, A. T.; Veselovsky, I. S.

    2015-12-01

    General principles of describing secondand higher-order null points of a potential magnetic field are formulated. The potential near a second-order null of the general form can be specified by a linear combination of four basic functions, the list of which is presented. Near secondand higher-order null points, field line equations often cannot be integrated analytically; however, in some cases, it is possible to present a qualitative description of the geometry of null vicinities with consideration of the behavior of field lines near rays outgoing from null, at which the field is radial or equals zero.

  7. Adaptive nulling: a new tool for the interfoeromic exo-planet detection

    NASA Technical Reports Server (NTRS)

    Lay, O.; Jeganathan, M.; Peters, R.

    2003-01-01

    This paper describes the need for a compensator that can adaptively correct for mismatches between the optical beamtrains of a Mid-IR nulling interferometer, across the science bandwidth with a range of spectral dependences.

  8. High-resolution adaptive nulling performance for a lightweight agile EHF multiple beam antenna

    NASA Astrophysics Data System (ADS)

    Fenn, A. J.; Johnson, J. R.; Rispin, L. W.; Cummings, W. C.; Potts, B. M.

    The design and experimental performance of a lightweight high-resolution adaptive nulling extremely high-frequency multiple beam antenna (MBA) are addressed. A 127-beam MBA and a four-channel RF nulling network operating over the 43.5-to-45.5-GHz band were used to adaptively null a jammer in anechoic chamber measurements. Lightweight waveguide transmission lines together with ferrite switches were used to select beam ports from the 127-beam MBA. The MBA was designed to provide simultaneous coverage for three communications system users while providing pattern discrimination or nulling of jammers located within 0.1 deg of the user. Cancellation greater than 30 dB when operating in a wideband mode was experimentally demonstrated.

  9. The Visible Nulling Coronagraph--Progress Toward Mission and Technology Development

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Levine, B. Martin; Liu, Duncan; Wallace, J. Kent

    2003-01-01

    This paper describes a space mission for visible direct detection and spectroscopy of Earth like extrasolar planets using a nulling coronagraph instrument behind a moderately sized (approximately 4m) telescope in space. In our design, a 4 beam nulling interferometer is synthesized from the telescope pupil, producing a deep null proportional to theta (sup 4) which is then filtered by a coherent array of single mode fibers to suppress the residual scattered light. With diffraction limited telescope optics and similar quality components in the optical train (lambda/20), suppression of the starlight to 10 (exp -10) is achievable. We describe key features of the basic analysis, show how this effects a space mission design, present latest results of laboratory measurements demonstrating achievable null depth and component development, and discuss future key technical milestones.

  10. Design of null tests for an F/0.8 concave oblate elliptical surface

    NASA Astrophysics Data System (ADS)

    Ding, Xuezhuan; Yang, Bo; Liu, Chenglin; Wang, Xin; Liu, Yinnian

    2010-10-01

    Aspheric surfaces are widely used in aerospace sensing optic instruments. There are numerous reflecting optical system designs that call for oblate elliptical surfaces, such as secondary mirror or tertiary mirror in three mirror anastigmat (TMA). The consequence brought by increase in field of view (FOV) and speed of optical system is the decrease in F/# of aspheric surface which makes its production harder. Due to oblate ellipsoid's stigmatic points are not lined up on the optic axis, null lenses corrector is used more often than the stigmatic null test especially in low F/# aspheric surfaces test. Three types of null lenses tests for an oblate elliptical surface with aperture Φ360mm, F/0.8, conic=0.243 are presented including a new type which is modified by replacing the reference flat and null lens with one lens with reflect surface. Furthermore, sensitivity tolerances for each design are practiced.

  11. Vlasov Fluid stability of a 2-D plasma with a linear magnetic field null

    SciTech Connect

    Kim, J.S.

    1984-01-01

    Vlasov Fluid stability of a 2-dimensional plasma near an O type magnetic null is investigated. Specifically, an elongated Z-pinch is considered, and applied to Field Reversed Configurations at Los Alamos National Laboratory by making a cylindrical approximation of the compact torus. The orbits near an elliptical O type null are found to be very complicated; the orbits are large and some are stochastic. The kinetic corrections to magnetohydrodynamics (MHD) are investigated by evaluating the expectation values of the growth rates of a Vlasov Fluid dispersion functional by using a set of trial functions based on ideal MHD. The dispersion functional involves fluid parts and orbit dependent parts. The latter involves phase integral of two time correlations. The phase integral is replaced by the time integral both for the regular and for the stochastic orbits. Two trial functions are used; one has a large displacement near the null and the other away from the null.

  12. Entropy of a generic null surface from its associated Virasoro algebra

    NASA Astrophysics Data System (ADS)

    Chakraborty, Sumanta; Bhattacharya, Sourav; Padmanabhan, T.

    2016-12-01

    Null surfaces act as one-way membranes, blocking information from those observers who do not cross them (e.g., in the black hole and the Rindler spacetimes) and these observers associate an entropy (and temperature) with the null surface. The black hole entropy can be computed from the central charge of an appropriately defined, local, Virasoro algebra on the horizon. We show that one can extend these ideas to a general class of null surfaces, all of which possess a Virasoro algebra and a central charge, leading to an entropy density (i.e., per unit area) which is just (1 / 4). All the previously known results of associating entropy with horizons arise as special cases of this very general property of null surfaces demonstrated here and we believe this work represents the derivation of the entropy-area law in the most general context. The implications are discussed.

  13. ON THE NATURE OF RECONNECTION AT A SOLAR CORONAL NULL POINT ABOVE A SEPARATRIX DOME

    SciTech Connect

    Pontin, D. I.; Priest, E. R.; Galsgaard, K.

    2013-09-10

    Three-dimensional magnetic null points are ubiquitous in the solar corona and in any generic mixed-polarity magnetic field. We consider magnetic reconnection at an isolated coronal null point whose fan field lines form a dome structure. Using analytical and computational models, we demonstrate several features of spine-fan reconnection at such a null, including the fact that substantial magnetic flux transfer from one region of field line connectivity to another can occur. The flux transfer occurs across the current sheet that forms around the null point during spine-fan reconnection, and there is no separator present. Also, flipping of magnetic field lines takes place in a manner similar to that observed in the quasi-separatrix layer or slip-running reconnection.

  14. Rescue of Aspergillus nidulans severely debilitating null mutations in ESCRT-0, I, II and III genes by inactivation of a salt-tolerance pathway allows examination of ESCRT gene roles in pH signalling.

    PubMed

    Calcagno-Pizarelli, Ana M; Hervás-Aguilar, América; Galindo, Antonio; Abenza, Juan F; Peñalva, Miguel A; Arst, Herbert N

    2011-12-01

    The Aspergillus pal pathway hijacks ESCRT proteins into ambient pH signalling complexes. We show that components of ESCRT-0, ESCRT-I, ESCRT-II and ESCRT-III are nearly essential for growth, precluding assessment of null mutants for pH signalling or trafficking. This severely debilitating effect is rescued by loss-of-function mutations in two cation tolerance genes, one of which, sltA, encodes a transcription factor whose inactivation promotes hypervacuolation. Exploiting a conditional expression sltA allele, we demonstrate that deletion of vps27 (ESCRT-0), vps23 (ESCRT-I), vps36 (ESCRT-II), or vps20 or vps32 (both ESCRT-III) leads to numerous small vacuoles, a phenotype also suppressed by SltA downregulation. This situation contrasts with normal vacuoles and vacuole-associated class E compartments seen in Saccharomyces cerevisiae ESCRT null mutants. Exploiting the suppressor phenotype of sltA(-) mutations, we establish that Vps23, Vps36, Vps20 and Vps32 are essential for pH signalling. Phosphatidylinositol 3-phosphate-recognising protein Vps27 (ESCRT-0) is not, consistent with normal pH signalling in rabB null mutants unable to recruit Vps34 kinase to early endosomes. In contrast to the lack of pH signalling in the absence of Vps20 or Vps32, detectable signalling occurs in the absence of ESCRT-III subunit Vps24. Our data support a model in which certain ESCRT proteins are recruited to the plasma membrane to mediate pH signalling.

  15. Cardiac Characterization of sgca-Null Mice Using High Resolution Echocardiography.

    PubMed

    Fayssoil, Abdallah; Renault, Gilles; Guerchet, Nicolas; Marchiol-Fournigault, Carmen; Fougerousse, Françoise; Richard, Isabelle

    2013-01-01

    Limb-girdle muscular dystrophy 2D (LGMD2D) is an inherited myogenic disorder belonging to the group of muscular dystrophies. Sgca-null mouse is a knock-out model of LGMD2D. Little is known about cardiac phenotype characterization in this model at different ages. We conducted a prospective study to characterize cardiac sgca-null mice phenotype using high resolution Doppler echocardiography at different ages. Conventional echocardiography was performed on anesthetised mice using a Vevo 770 (Visualsonics) with 30 MHz cardiac probe. Wild Type (WT) and sgca-null mice were scanned at 13, 15 and 17 months. From M-mode, we measured interventricular septal (IVS) wall thickness, posterior wall (PW) thickness, and end-left ventricular diameter in systolic and diastolic. From the above parameters, we calculated left ventricular (LV) shortening fraction (SF), LV ejection fraction (EF) and LV mass. At age 13 months, PW diastolic thickness was increased in sgca-null mice (0.89±0.14 mm vs 0.73±0.2 mm; P=0.020) and LV mass was higher in sgca-null mice (LV mass 205.2 mg vs 143 mg; P=0.001). We found also dilation of the LV (LVEDD: 4.84 mm vs 4.29 mm; P=0.019) in sgca-null mice. At age 15 months, dilation of the LV (LVEDD: 4.86 mm vs 4 mm; P=0.05) with an increase of the LV mass (165.7 mg vs 127.12; P=0.03) are found in sgca-null mice. At age 17 months, we found a decrease of the PW thickening (17% vs 30%; P=0.036). This work provides echocardiographic insights for the assessment of pharmaceutical therapies in sgca-null mice.

  16. Cardiac Characterization of sgca-Null Mice Using High Resolution Echocardiography

    PubMed Central

    Fayssoil, Abdallah; Renault, Gilles; Guerchet, Nicolas; Marchiol-Fournigault, Carmen; Fougerousse, Françoise; Richard, Isabelle

    2013-01-01

    Limb-girdle muscular dystrophy 2D (LGMD2D) is an inherited myogenic disorder belonging to the group of muscular dystrophies. Sgca-null mouse is a knock-out model of LGMD2D. Little is known about cardiac phenotype characterization in this model at different ages. We conducted a prospective study to characterize cardiac sgca-null mice phenotype using high resolution Doppler echocardiography at different ages. Conventional echocardiography was performed on anesthetised mice using a Vevo 770 (Visualsonics) with 30 MHz cardiac probe. Wild Type (WT) and sgca-null mice were scanned at 13, 15 and 17 months. From M-mode, we measured interventricular septal (IVS) wall thickness, posterior wall (PW) thickness, and end-left ventricular diameter in systolic and diastolic. From the above parameters, we calculated left ventricular (LV) shortening fraction (SF), LV ejection fraction (EF) and LV mass. At age 13 months, PW diastolic thickness was increased in sgca-null mice (0.89±0.14 mm vs 0.73±0.2 mm; P=0.020) and LV mass was higher in sgca-null mice (LV mass 205.2 mg vs 143 mg; P=0.001). We found also dilation of the LV (LVEDD: 4.84 mm vs 4.29 mm; P=0.019) in sgca-null mice. At age 15 months, dilation of the LV (LVEDD: 4.86 mm vs 4 mm; P=0.05) with an increase of the LV mass (165.7 mg vs 127.12; P=0.03) are found in sgca-null mice. At age 17 months, we found a decrease of the PW thickening (17% vs 30%; P=0.036). This work provides echocardiographic insights for the assessment of pharmaceutical therapies in sgca-null mice. PMID:24416486

  17. Some magnetic null lines of astrophysical interest. II. [in magnetic Ap stars

    NASA Technical Reports Server (NTRS)

    Adelman, S. J.

    1974-01-01

    A list of magnetic null lines from selected spectroscopic analyses is presented for possible use in detailed studies of magnetic Ap stars. The presented data represent an extension of the magnetic null lines whose usefulness Shore and Adelman (1974) have recently demonstrated for the study of the overall physical conditions prevailing in the atmospheres of peculiar A stars and for testing the consequences of the mechanism of selective elemental diffusion.

  18. Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice.

    PubMed

    Martineau, Corine; Martin-Falstrault, Louise; Brissette, Louise; Moreau, Robert

    2014-08-01

    A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender- and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.

  19. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    PubMed

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  20. [Inheritance and phenotype expression of functional and null alleles of aromatic alcohol dehydrogenase (CAD) in diploid wheats].

    PubMed

    Konovalov, A A; Shundrina, I K; Karpova, E V; Nefedov, A A; Goncharov, N P

    2014-11-01

    Functional F and null 0 alleles of the CAD1 (Aadh1) gene, which controls the biosynthesis of aromatic alcohol dehydrogenase, were studied in hybrids of the diploid wheat T. monococcum L. and Triticum sinskajae A.Filat. et Kurk. The gene CAD1 is located in chromosome 5A and is linked with the awnless gene awnS (La) with a recombination frequency of about 32%. Plants with genotypes FF, F0, and 00 were significantly different in the height and mechanical strength of the stalk (culm). The elastic limit of the culm tissues of plants FF was considerably higher than in 00 plants. F0 heterozygotes had intermediate values. The thickness of the wall of the sclerenchyma was thinner in plants with genotype 00. The chemical structure of lignin of plants with the functional CAD allele contained units of a phloroglucinol series missing in the mutant plants. The CAD genotypes had no effect on the relative content of cellulose and lignin in stalks ofdiploid wheat and insignificantly influenced the ratio of H :G : S units in the lignin structure, as well as some components of extractives.

  1. Drosophila atonal fully rescues the phenotype of Math1 null mice: new functions evolve in new cellular contexts

    NASA Technical Reports Server (NTRS)

    Wang, Vincent Y.; Hassan, Bassem A.; Bellen, Hugo J.; Zoghbi, Huda Y.

    2002-01-01

    Many genes share sequence similarity between species, but their properties often change significantly during evolution. For example, the Drosophila genes engrailed and orthodenticle and the onychophoran gene Ultrabithorax only partially substitute for their mouse or Drosophila homologs. We have been analyzing the relationship between atonal (ato) in the fruit fly and its mouse homolog, Math1. In flies, ato acts as a proneural gene that governs the development of chordotonal organs (CHOs), which serve as stretch receptors in the body wall and joints and as auditory organs in the antennae. In the fly CNS, ato is important not for specification but for axonal arborization. Math1, in contrast, is required for the specification of cells in both the CNS and the PNS. Furthermore, Math1 serves a role in the development of secretory lineage cells in the gut, a function that does not parallel any known to be served by ato. We wondered whether ato and Math1 might be more functionally homologous than they appear, so we expressed Math1 in ato mutant flies and ato in Math1 null mice. To our surprise, the two proteins are functionally interchangeable.

  2. Efficient genetic manipulation of the NOD-Rag1-/-IL2RgammaC-null mouse by combining in vitro fertilization and CRISPR/Cas9 technology.

    PubMed

    Li, Feng; Cowley, Dale O; Banner, Debra; Holle, Eric; Zhang, Liguo; Su, Lishan

    2014-06-17

    Humanized mouse models have become increasingly important and widely used in modeling human diseases in biomedical research. Immunodeficient mice such as NOD-Rag1-/-IL2RgammaC-null (NRG) or NOD-SCID-IL2RgammaC-null (NSG) mice are critical for efficient engraftment of human cells or tissues. However, their genetic modification remains challenging due to a lack of embryonic stem cells and difficulty in the collection of timed embryos after superovulation. Here, we report the generation of gene knockout NRG mice by combining in vitro fertilization (IVF) and CRISPR/Cas9 technology. Sufficient numbers of fertilized embryos were produced through IVF, and a high rate of Fah gene targeting was achieved with microinjection of Cas9 mRNA, gRNA and single strand oligonucleotide DNA (ssDNA) into the embryos. The technology paves the way to construct NRG or NSG mutant mice to facilitate new humanized mouse models. The technology can also be readily adapted to introduce mutations in other species such as swine and non-human primates.

  3. FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly.

    PubMed

    Jurak Begonja, Antonija; Hoffmeister, Karin M; Hartwig, John H; Falet, Hervé

    2011-08-25

    Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnA(loxP) PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnA(loxP) PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnA(loxP) PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61(+) platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages.

  4. Regulation of malic enzyme expression and the molecular basis for a cytosolic malic enzyme null mutation

    SciTech Connect

    Brown, M.L.

    1987-01-01

    In order to investigate the basis for the MOD-1 null mutation, a {lambda}gt 11 cDNA library was constructed using mRNA from the livers of induced MOD-1 null mice as a template. A recombinant phage with a 2kb insert was isolated by screening with wild type malic enzyme cDNA probes. The subcloned insert exhibited an atypical (non-wild type) restriction pattern and was subjected to sequence analysis. MOD-1 null malic enzyme cDNA contains an internal, tandemly-duplicated sequence that corresponds to nucleotides 1027-1548 in the coding region of wild type murine malic enzyme cDNA. An open reading frame is retained throughout the duplicated sequences. The discovery of a 522 nucleotide, in-frame duplication accounts for the increased size of MOD-1 null malic enzyme mRNAs. Western immunoblot analysis disclosed that MOD-1 null liver cytosol contains an 82 kDa protein that is recognized by anti malic enzyme antibodies. Under stringent conditions, an anti-sense {sup 32}P-oligonucleotide that spans the abnormal junction between the reiterated sequences hybridized with the 2.5 and 3.6 kb MOD-1 null malic enzyme mRNAs, but failed to form stable complexes with wild type malic enzyme mRNAs.

  5. pyNSMC: A Python Module for Null-Space Monte Carlo Uncertainty Analysis

    NASA Astrophysics Data System (ADS)

    White, J.; Brakefield, L. K.

    2015-12-01

    The null-space monte carlo technique is a non-linear uncertainty analyses technique that is well-suited to high-dimensional inverse problems. While the technique is powerful, the existing workflow for completing null-space monte carlo is cumbersome, requiring the use of multiple commandline utilities, several sets of intermediate files and even a text editor. pyNSMC is an open-source python module that automates the workflow of null-space monte carlo uncertainty analyses. The module is fully compatible with the PEST and PEST++ software suites and leverages existing functionality of pyEMU, a python framework for linear-based uncertainty analyses. pyNSMC greatly simplifies the existing workflow for null-space monte carlo by taking advantage of object oriented design facilities in python. The core of pyNSMC is the ensemble class, which draws and stores realized random vectors and also provides functionality for exporting and visualizing results. By relieving users of the tedium associated with file handling and command line utility execution, pyNSMC instead focuses the user on the important steps and assumptions of null-space monte carlo analysis. Furthermore, pyNSMC facilitates learning through flow charts and results visualization, which are available at many points in the algorithm. The ease-of-use of the pyNSMC workflow is compared to the existing workflow for null-space monte carlo for a synthetic groundwater model with hundreds of estimable parameters.

  6. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

    SciTech Connect

    Takubo, Keiyo . E-mail: keiyot@gmail.com; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio . E-mail: sudato@sc.itc.keio.ac.jp

    2006-12-29

    Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16{sup Ink4a} activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16{sup Ink4a}-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16{sup Ink4a}-mediated senescence.

  7. Design of null lens system for f/0.5 hyperboloid mirror

    NASA Astrophysics Data System (ADS)

    Wang, Zi-wu; Guo, Pei-ji; Chen, Xi; Peng, Ling-jie

    2016-10-01

    The aspherical mirror surface quality testing by using compensation null lens in interferometer is described in this paper. For 310mm, f/0.5 hyperboloid mirror microcrystalline components, based on the theory of aberration compensation, a kind of null lens system which is composed of three pieces of spherical lens is developed. A certain amount of spherical aberration is introduced to the null lens for compensating the deviation of aspheric surface in a normal direction. The design result shows that the primary aberration and the senior aberration are balanced well, the MTF is closed to the diffraction limit and the residual wave aberration (RMS) is less than 0.004λ (λ=0.6328μm). Every indicators of the system meets the requirements of high precision detection of null lens system design. In this paper, the errors caused by the manufacturing, testing and assembling of the null lens system are analyzed. Those errors can be divided into the symmetric error and the asymmetric error. Using the correction method, the influence of the asymmetric error is minimized which seemed bigger than the asymmetric one. Finally, analysis results show that the total residual wave aberration of the system is less than 0.0072λ, which satisfies the requirement of aspheric testing. This null lens system has been applied to aspheric processing.

  8. A gyroscope clock for a null gravitational redshift experiment

    NASA Astrophysics Data System (ADS)

    Walter, Todd

    1994-12-01

    This dissertation describes the analysis and experimental testing of the frequency stability of electrostatically-levitated, superconducting gyroscopes. The tests were conducted on the ground at cryogenic temperatures using a magnetic readout of the gyroscope rotor's spin phase. By achieving fractional frequency stabilities on the order of 3 x 10(exp -11) (or better) over one year it would be possible to perform a test of Local Position Invariance (LPI) to the 10 percent level. LPI states that in local freely falling frames, the outcome of any non-gravitational test is independent of where and when in the universe it is performed. This means that all clocks, independent of the physical principle on which they are based, should exhibit the same gravitational redshift. The experiment proposed in this thesis is intended to compare a gyroscope clock to an atomic clock as they both experience the same time-varying gravitational potential. Since there is expected to be no difference between the two types of clocks, this is a null gravitational redshift experiment. A unique opportunity to perform a gravitational redshift experiment exists in the Gravity Probe B (GPB) program. GPB is a satellite experiment whose purpose is to test two predictions of Einstein's General Theory of Relativity: the geodetic and frame-dragging effects. These effects will be measured by monitoring the precession rates of nearly perfect gyroscopes against the inertial stars. Navigation of the satellite is aided by means of the Global Positioning System (GPS). Thus GPB already has in place nearly all of the essential elements for the proposed clock experiment. These include nearly disturbance-free gyroscopes whose pointing and spin phase can be referenced to the inertial frame of the fixed stars and onboard access to Earth-bound atomic clocks through GPS. The varying gravitational potential is provided by the eccentricity of the Earth's orbit about the Sun. Therefore with very little change to GPB

  9. Targeting ESR1-Mutant Breast Cancer

    DTIC Science & Technology

    2015-09-01

    Award Number: W81XWH-14-1-0360 TITLE: Targeting ESR1- Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Geoffrey L. Greene, Ph.D. CONTRACTING...ADDRESS. 1. REPORT DATE September 2015 2. REPORT TYPE Annual 3. DATES COVERED 1 Sep 2014 - 31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1- Mutant ...approved hormonal therapies and that more potent, selective estrogen receptor degraders (SERDs) will enable complete inhibition of mutant ER signaling and

  10. Targeting ESR1-Mutant Breast Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1- Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1- Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...current FDA approved hormonal therapies and that more potent, selective estrogen receptor degraders (SERDs) will enable complete inhibition of mutant

  11. Electrophysiological study of Drosophila rhodopsin mutants

    PubMed Central

    1986-01-01

    Electrophysiological investigations were carried out on several independently isolated mutants of the ninaE gene, which encodes opsin in R1-6 photoreceptors, and a mutant of the ninaD gene, which is probably important in the formation of the rhodopsin chromophore. In these mutants, the rhodopsin content in R1-6 photoreceptors is reduced by 10(2)-10(6)-fold. Light-induced bumps recorded from even the most severely affected mutants are physiologically normal. Moreover, a detailed noise analysis shows that photoreceptor responses of both a ninaE mutant and a ninaD mutant follow the adapting bump model. Since any extensive rhodopsin-rhodopsin interactions are not likely in these mutants, the above results suggest that such interactions are not needed for the generation and adaptation of light-induced bumps. Mutant bumps are strikingly larger in amplitude than wild-type bumps. This difference is observed both in ninaD and ninaE mutants, which suggests that it is due to severe depletion of rhodopsin content, rather than to any specific alterations in the opsin protein. Lowering or buffering the intracellular calcium concentration by EGTA injection mimics the effects of the mutations on the bump amplitude, but, unlike the mutations, it also affects the latency and kinetics of light responses. PMID:3097245

  12. Identifying representative drug resistant mutants of HIV

    PubMed Central

    2015-01-01

    Background Drug resistance is one of the most important causes for failure of anti-AIDS treatment. During therapy, multiple mutations accumulate in the HIV genome, eventually rendering the drugs ineffective in blocking replication of the mutant virus. The huge number of possible mutants precludes experimental analysis to explore the molecular mechanisms of resistance and develop improved antiviral drugs. Results In order to solve this problem, we have developed a new algorithm to reveal the most representative mutants from the whole drug resistant mutant database based on our newly proposed unified protein sequence and 3D structure encoding method. Mean shift clustering and multiple regression analysis were applied on genotype-resistance data for mutants of HIV protease and reverse transcriptase. This approach successfully chooses less than 100 mutants with the highest resistance to each drug out of about 10K in the whole database. When considering high level resistance to multiple drugs, the numbers reduce to one or two representative mutants. Conclusion This approach for predicting the most representative mutants for each drug has major importance for experimental verification since the results provide a small number of representative sequences, which will be amenable for in vitro testing and characterization of the expressed mutant proteins. PMID:26678327

  13. Root hair-specific disruption of cellulose and xyloglucan in AtCSLD3 mutants, and factors affecting the post-rupture resumption of mutant root hair growth.

    PubMed

    Galway, Moira E; Eng, Ryan C; Schiefelbein, John W; Wasteneys, Geoffrey O

    2011-05-01

    The glycosyl transferase encoded by the cellulose synthase-like gene CSLD3/KJK/RHD7 (At3g03050) is required for cell wall integrity during root hair formation in Arabidopsis thaliana but it remains unclear whether it contributes to the synthesis of cellulose or hemicellulose. We identified two new alleles, root hair-defective (rhd) 7-1 and rhd7-4, which affect the C-terminal end of the encoded protein. Like root hairs in the previously characterized kjk-2 putative null mutant, rhd7-1 and rhd7-4 hairs rupture before tip growth but, depending on the growth medium and temperature, hairs are able to survive rupture and initiate tip growth, indicating that these alleles retain some function. At 21°C, the rhd7 tip-growing root hairs continued to rupture but at 5ºC, rupture was inhibited, resulting in long, wild type-like root hairs. At both temperatures, the expression of another root hair-specific CSLD gene, CSLD2, was increased in the rhd7-4 mutant but reduced in the kjk-2 mutant, suggesting that CSLD2 expression is CSLD3-dependent, and that CSLD2 could partially compensate for CSLD3 defects to prevent rupture at 5°C. Using a fluorescent brightener (FB 28) to detect cell wall (1 → 4)-β-glucans (primarily cellulose) and CCRC-M1 antibody to detect fucosylated xyloglucans revealed a patchy distribution of both in the mutant root hair cell walls. Cell wall thickness varied, and immunogold electron microscopy indicated that xyloglucan distribution was altered throughout the root hair cell walls. These cell wall defects indicate that CSLD3 is required for the normal organization of both cellulose and xyloglucan in root hair cell walls.

  14. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation

    PubMed Central

    Elf, Shannon; Abdelfattah, Nouran S.; Chen, Edwin; Perales-Patón, Javier; Rosen, Emily A.; Ko, Amy; Peisker, Fabian; Florescu, Natalie; Giannini, Silvia; Wolach, Ofir; Morgan, Elizabeth A.; Tothova, Zuzana; Losman, Julie-Aurore; Schneider, Rebekka K.; Al-Shahrour, Fatima; Mullally, Ann

    2016-01-01

    Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN) but the mechanism by which mutant CALR is oncogenic remains unclear. Here, we demonstrate that expression of mutant CALR alone is sufficient to engender MPN in mice and recapitulates the disease phenotype of CALR-mutant MPN patients. We further show that the thrombopoietin receptor, MPL is required for mutant CALR-driven transformation through JAK-STAT pathway activation, thus rendering mutant CALR-transformed hematopoietic cells sensitive to JAK2 inhibition. Finally, we demonstrate that the oncogenicity of mutant CALR is dependent on the positive electrostatic charge of the C-terminus of the mutant protein, which is necessary for physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel paradigm of cancer pathogenesis and reveal how CALR mutations induce MPN. PMID:26951227

  15. Biofilm formation ability of Salmonella enterica serovar Typhimurium acrAB mutants.

    PubMed

    Schlisselberg, Dov B; Kler, Edna; Kisluk, Guy; Shachar, Dina; Yaron, Sima

    2015-10-01

    Recent studies offer contradictory findings about the role of multidrug efflux pumps in bacterial biofilm development. Thus, the aim of this study was to investigate the involvement of the AcrAB efflux pump in biofilm formation by investigating the ability of AcrB and AcrAB null mutants of Salmonella enterica serovar Typhimurium to produce biofilms. Three models were used to compare the ability of S. Typhimurium wild-type and its mutants to form biofilms: formation of biofilm on polystyrene surfaces; production of biofilm (mat model) on the air/liquid interface; and expression of curli and cellulose on Congo red-supplemented agar plates. All three investigated genotypes formed biofilms with similar characteristics. However, upon exposure to chloramphenicol, formation of biofilms on solid surfaces as well as the production of curli were either reduced or were delayed more significantly in both mutants, whilst there was no visible effect on pellicle formation. It can be concluded that when no selective pressure is applied, S. Typhimurium is able to produce biofilms even when the AcrAB efflux pumps are inactivated, implying that the use of efflux pump inhibitors to prevent biofilm formation is not a general solution and that combined treatments might be more efficient. Other factors that affect the ability to produce biofilms depending on efflux pump activity are yet to be identified.

  16. Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice

    PubMed Central

    Petit, Fabrice G.; Deng, Chuxia; Jamin, Soazik P.

    2016-01-01

    Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct. PMID:27194944

  17. Hepatic effects of a methionine-choline-deficient diet in hepatocyte RXR{alpha}-null mice

    SciTech Connect

    Gyamfi, Maxwell Afari; Tanaka, Yuji; He Lin; Klaassen, Curtis D.; Wan, Y.-J.Y.

    2009-01-15

    Retinoid X receptor-{alpha} (RXR{alpha}) is an obligate partner for several nuclear hormone receptors that regulate important physiological processes in the liver. In this study the impact of hepatocyte RXR{alpha} deficiency on methionine and choline deficient (MCD) diet-induced steatosis, oxidative stress, inflammation, and hepatic transporters gene expression were examined. The mRNA of sterol regulatory element-binding protein (SREBP)-regulated genes, important for lipid synthesis, were not altered in wild type (WT) mice, but were increased 2.0- to 5.4-fold in hepatocyte RXR{alpha}-null (H-RXR{alpha}-null) mice fed a MCD diet for 14 days. Furthermore, hepatic mRNAs and proteins essential for fatty acid {beta}-oxidation were not altered in WT mice, but were decreased in the MCD diet-fed H-RXR{alpha}-null mice, resulting in increased hepatic free fatty acid levels. Cyp2e1 enzyme activity and lipid peroxide levels were induced only in MCD-fed WT mice. In contrast, hepatic mRNA levels of pro-inflammatory factors were increased only in H-RXR{alpha}-null mice fed the MCD diet. Hepatic uptake transporters Oatp1a1 and Oatp1b2 mRNA levels were decreased in WT mice fed the MCD diet, whereas the efflux transporter Mrp4 was increased. However, in the H-RXR{alpha}-null mice, the MCD diet only moderately decreased Oatp1a1 and induced both Oatp1a4 and Mrp4 gene expression. Whereas the MCD diet increased serum bile acid levels and alkaline phosphatase activity in both WT and H-RXR{alpha}-null mice, serum ALT levels were induced (2.9-fold) only in the H-RXR{alpha}-null mice. In conclusion, these data suggest a critical role for RXR{alpha} in hepatic fatty acid homeostasis and protection against MCD-induced hepatocyte injury.

  18. The atherogenic Scarb1 null mouse model shows a high bone mass phenotype.

    PubMed

    Martineau, Corine; Martin-Falstrault, Louise; Brissette, Louise; Moreau, Robert

    2014-01-01

    Scavenger receptor class B, type I (SR-BI), the Scarb1 gene product, is a receptor associated with cholesteryl ester uptake from high-density lipoproteins (HDL), which drives cholesterol movement from peripheral tissues toward the liver for excretion, and, consequently, Scarb1 null mice are prone to atherosclerosis. Because studies have linked atherosclerosis incidence with osteoporosis, we characterized the bone metabolism in these mice. Bone morphometry was assessed through microcomputed tomography and histology. Marrow stromal cells (MSCs) were used to characterize influence of endogenous SR-BI in cell functions. Total and HDL-associated cholesterol in null mice were increased by 32-60%, correlating with its role in lipoprotein metabolism. Distal metaphyses from 2- and 4-mo-old null mice showed correspondingly 46 and 37% higher bone volume fraction associated with a higher number of trabeculae. Histomorphometric analyses in 2-mo-old null male mice revealed 1.42-fold greater osteoblast surface, 1.37-fold higher percent mineralizing surface, and 1.69-fold enhanced bone formation rate. In vitro assays for MSCs from null mice revealed 37% higher proliferation rate, 48% more alkaline phosphatase activity, 70% greater mineralization potential and a 2-fold osterix (Sp7) expression, yet a 0.5-fold decrease in caveolin-1 (Cav1) expression. Selective uptake levels of HDL-associated cholesteryl oleate and estradiol were similar between MSC from wild-type and Scarb1 null mice, suggesting that its contribution to this process is not its main role in these cells. However, Scarb1 knockout stunted the HDL-dependent regulation of Cav1 genic expression. Scarb1 null mice are not prone to osteoporosis but show higher bone mass associated with enhanced bone formation.

  19. Influence of choice of null network on small-world parameters of structural correlation networks.

    PubMed

    Hosseini, S M Hadi; Kesler, Shelli R

    2013-01-01

    In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

  20. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    PubMed

    Sengle, Gerhard; Carlberg, Valerie; Tufa, Sara F; Charbonneau, Noe L; Smaldone, Silvia; Carlson, Eric J; Ramirez, Francesco; Keene, Douglas R; Sakai, Lynn Y

    2015-06-01

    Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can

  1. Effects of Local Heart Irradiation in a Glutathione S-Transferase Alpha 4-Null Mouse Model.

    PubMed

    Boerma, Marjan; Singh, Preeti; Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Singh, Sharda P

    2015-06-01

    Glutathione S-transferase alpha 4 (GSTA4-4) is one of the enzymes responsible for the removal of 4-hydroxynonenal (4-HNE), an electrophilic product of lipid peroxidation in cellular membranes during oxidative stress. 4-HNE is a direct activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor with many target genes encoding antioxidant and anti-electrophile enzymes. We have previously shown that Gsta4-null mice on a 129/Sv background exhibited increased activity of Nrf2 in the heart. Here we examined the sensitivity of this Gsta4-null mouse model towards cardiac function and structure loss due to local heart irradiation. Male Gsta4-null and wild-type mice were exposed to a single X-ray dose of 18 Gy to the heart. Six months after irradiation, immunohistochemical staining for respiratory complexes 2 and 5 indicated that radiation exposure had caused most pronounced alterations in mitochondrial morphology in Gsta4-null mice. On the other hand, wild-type mice showed a decline in cardiac function and an increase in plasma levels of troponin-I, while no such changes were observed in Gsta4-null mice. Radiation-induced Nrf2-target gene expression only in Gsta4-null mice. In conclusion, although loss of GSTA4-4 led to enhanced susceptibility of cardiac mitochondria to radiation-induced loss of morphology, cardiac function was preserved in Gsta4-null mice. We propose that this protection against cardiac function loss may occur, at least in part, by upregulation of the Nrf2 pathway.

  2. Secreted Protein Acidic and Rich in Cysteine (SPARC)-Null Mice Exhibit More Uniform Outflow

    PubMed Central

    Swaminathan, Swarup S.; Oh, Dong-Jin; Kang, Min Hyung; Ren, Ruiyi; Jin, Rui; Gong, Haiyan; Rhee, Douglas J.

    2013-01-01

    Purpose. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) in many tissues and is highly expressed in trabecular meshwork (TM). SPARC-null mice have a 15% to 20% decrease in intraocular pressure (IOP) compared to wild-type (WT) mice. We hypothesized that mouse aqueous outflow is segmental, and that transgenic deletion of SPARC causes a more uniform pattern that correlates with IOP and TM morphology. Methods. Eyes of C57BL6-SV129 WT and SPARC-null mice were injected with fluorescent microbeads, which were also passively exposed to freshly enucleated eyes. Confocal and electron microscopy were performed. Percentage effective filtration length (PEFL) was calculated as PEFL = FL/TL × 100%, where TL = total length and FL = filtration length. IOP was measured by rebound tonometry. Results. Passive microbead affinity for WT and SPARC-null ECM did not differ. Segmental flow was observed in the mouse eye. SPARC-null mice had a 23% decrease in IOP. PEFL increased in SPARC-null (70.61 ± 11.36%) versus WT mice (54.68 ± 9.95%, P < 0.005; n = 11 pairs), and PEFL and IOP were negatively correlated (R2 = 0.72, n = 10 pairs). Morphologically, TM of high-tracer regions had increased separation between beams compared to low-tracer regions. Collagen fibril diameter decreased in SPARC-null (28.272 nm) versus WT tissue (34.961 nm, P < 0.0005; n = 3 pairs). Conclusions. Aqueous outflow in mice is segmental. SPARC-null mice demonstrated a more uniform outflow pattern and decreased collagen fibril diameter. Areas of high flow had less compact juxtacanalicular connective tissue ECM, and IOP was inversely correlated with PEFL. Our data show a correlation between morphology, aqueous outflow, and IOP, indicating a modulatory role of SPARC in IOP regulation. PMID:23422826

  3. Enhancers of Conidiation Mutants in Aspergillus Nidulans

    PubMed Central

    Gems, D. H.; Clutterbuck, A. J.

    1994-01-01

    Mutants at a number of loci, designated sthenyo, have been isolated as enhancers of the oligoconidial mutations at the medA locus. Two loci have been mapped: sthA on linkage group I, and sthB on linkage group V. Two probable alleles have been identified at each locus but two further mutants were unlinked to either sthA or sthB. Neither sthA nor sthB mutants have conspicuous effects on morphology on their own, nor could the sthA1 sthB2 double mutant be distinguished from wild type. Mutants at both loci also interact with the temperature-sensitive brlA42 mutant at the permissive temperature to give a phenotype described as ``Abacoid.'' sthA1 also induces a slight modification of the phenotype of an abaA mutant. We conclude that sthenyo genes act mainly at the phialide stage of conidiation. We also describe the isolation of new medA mutants arising spontaneously as outgrowths on brlA42 colonies. PMID:8056325

  4. Regulation of Mutant p53 Protein Expression.

    PubMed

    Vijayakumaran, Reshma; Tan, Kah Hin; Miranda, Panimaya Jeffreena; Haupt, Sue; Haupt, Ygal

    2015-01-01

    For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type (wt) counterpart. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. While wt p53 returns to basal level following recovery from stress, mutant p53 remains stable. In part, this can be explained in mutant p53-expressing cells by the lack of an auto-regulatory loop with Mdm2 and other negative regulators, which are pivotal for wt p53 regulation. Further, additional protective mechanisms are acquired by mutant p53, largely mediated by the co-chaperones and their paralogs, the stress-induced heat shock proteins. Consequently, mutant p53 is accumulated in cancer cells in response to chronic stress and this accumulation is critical for its oncogenic gain of functions (GOF). Building on the extensive knowledge regarding wt p53, the regulation of mutant p53 is unraveling. In this review, we describe the current understanding on the major levels at which mutant p53 is regulated. These include the regulation of p53 protein levels by microRNA and by enzymes controlling p53 proteasomal degradation.

  5. A halotolerant mutant of Saccharomyces cerevisiae.

    PubMed Central

    Gaxiola, R; Corona, M; Zinker, S

    1996-01-01

    FRD, a nuclear and dominant spontaneous mutant of Saccharomyces cerevisiae capable of growing in up to 2 M NaCl, was isolated. Compared with parental cells, the mutant cells have a lower intracellular Na+/K+ ratio, shorter generation times in the presence of 1 M NaCl, and alterations in gene expression. PMID:8631691

  6. crl mutants of Saccharomyces cerevisiae resemble both mutants affecting general control of amino acid biosynthesis and omnipotent translational suppressor mutants.

    PubMed

    McCusker, J H; Haber, J E

    1988-06-01

    Cyocloheximide resistant lethal (crl) mutants of Saccharomyces cerevisiae, defining 22 unlinked complementation groups, are unable to grow at 37 degrees. They are also highly pleiotropic at their permissive temperature of 25 degrees. The mutants are all unable to arrest at the G1 stage of the cell cycle when grown to stationary phase or when starved for a single amino acid, though they do arrest at G1 when deprived of all nitrogen. The crl mutants are also hypersensitive to various amino acid analogs and to 3-aminotriazole. These mutants also "tighten" leaky auxotrophic mutations that permit wild-type cells to grow in the absence of the appropriate amino acid. All of these phenotypes are also exhibited by gcn mutants affecting general control of amino acid biosynthesis. In addition, the crl mutants are all hypersensitive to hygromycin B, an aminoglycoside antibiotic that stimulates translational misreading. The crl mutations also suppress one nonsense mutation which is phenotypically suppressed by hygromycin B. Many crl mutants are also osmotically sensitive. These are phenotypes which the crl mutations have in common with previously isolated omnipotent suppressors. We suggest that the the crl mutations all affect the fidelity of protein translation.

  7. Low frequency of filaggrin null mutations in Croatia and their relation with allergic diseases.

    PubMed

    Sabolić Pipinić, I; Varnai, V M; Turk, R; Breljak, D; Kezić, S; Macan, J

    2013-06-01

    Filaggrin gene (FLG) null mutations are considered associated with atopic dermatitis. This study was conducted to determine the prevalence of FLG null mutations R501X, 2282del4, R2447X and S3247X in the Croatian population and their role in the occurrence of allergic diseases including atopic dermatitis, allergic rhinitis, asthma and allergic contact dermatitis (ACD). Study enrolled 440 freshmen with defined allergic diseases by means of both present symptoms in International Study of Asthma and Allergies in Childhood questionnaire (relevant respiratory and/or skin symptoms) and markers of allergic sensitization (positive skin prick and/or patch test). FLG null mutations were successfully genotyped in 423 students of which 11 (2.6%) were carriers of FLG null mutation: 1/423 (0.2%) was heterozygous for R501X and 10/423 (2.4%) were heterozygous for 2282del4. No carriers of R2447X and S3247X mutations were identified. In wild-type FLG carriers (412 subjects), atopic dermatitis was present in 45 (11%), allergic rhinitis in 70 (17%) and allergic asthma in 29 (7%) students. Twenty-five of 393 (7%) patch-tested wild-type FLG carriers had ACD. Among 11 FLG null mutation carriers, four had one or more allergic diseases, and five had reported skin symptoms without defined allergic sensitization (positive skin prick test and/or patch test). FLG null mutations were not confirmed as a predictor of analysed allergic diseases, but were confirmed as an independent predictor of skin symptoms (OR 17.19, 95% CI 3.41-86.6, P < 0.001). Our results in general indicate a low frequency of FLG null mutations in the studied Croatian population supporting a theory of a latitude-dependent distribution of FGL null mutations in Europe, with a decreasing north-south gradient of R501X and 2282del4 mutation frequency. The relation between FLG null mutations and skin disorders was confirmed.

  8. In vitro analysis of the glucose-transport system in GLUT4-null skeletal muscle.

    PubMed Central

    Ryder, J W; Kawano, Y; Chibalin, A V; Rincón, J; Tsao, T S; Stenbit, A E; Combatsiaris, T; Yang, J; Holman, G D; Charron, M J; Zierath, J R

    1999-01-01

    We have characterized the glucose-transport system in soleus muscle from female GLUT4-null mice to determine whether GLUT1, 3 or 5 account for insulin-stimulated glucose-transport activity. Insulin increased 2-deoxyglucose uptake 2.8- and 2.1-fold in soleus muscle from wild-type and GLUT4-null mice, respectively. Cytochalasin B, an inhibitor of GLUT1- and GLUT4-mediated glucose transport, inhibited insulin-stimulated 2-deoxyglucose uptake by >95% in wild-type and GLUT4-null soleus muscle. Addition of 35 mM fructose to the incubation media was without effect on insulin-stimulated 3-O-methylglucose transport activity in soleus muscle from either genotype, whereas 35 mM glucose inhibited insulin-stimulated (20 nM) 3-O-methylglucose transport by 65% in wild-type and 99% in GLUT4-null mice. We utilized the 2-N-4-1-(1-azi-2,2,2-triflu oroethyl)benzoyl-1, 3-bis(D-mannose-4-yloxy)-2-propylamine (ATB-BMPA) exofacial photolabel to determine if increased cell-surface GLUT1 or GLUT4 content accounted for insulin-stimulated glucose transport in GLUT4-null muscle. In wild-type soleus muscle, cell-surface GLUT4 content was increased by 2.8-fold under insulin-stimulated conditions and this increase corresponded to the increase in 2-deoxyglucose uptake. No detectable cell-surface GLUT4 was observed in soleus muscle from female GLUT4-null mice under either basal or insulin-stimulated conditions. Basal cell-surface GLUT1 content was similar between wild-type and GLUT4-null mice, with no further increase noted in either genotype with insulin exposure. Neither GLUT3 nor GLUT5 appeared to account for insulin-stimulated glucose-transport activity in wild-type or GLUT4-null muscle. In conclusion, insulin-stimulated glucose-transport activity in female GLUT4-null soleus muscle is mediated by a facilitative transport process that is glucose- and cytochalasin B-inhibitable, but which is not labelled strongly by ATB-BMPA. PMID:10455018

  9. Magnetic nulls in three-dimensional kinetic simulations of space plasmas

    NASA Astrophysics Data System (ADS)

    Olshevsky, Vyacheslav; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni

    2016-04-01

    We present a survey of magnetic nulls and associated energy dissipation in different three-dimensional kinetic particle-in-cell simulations of space plasmas. The configurations under study include: a traditional Harris current sheet and current sheets with asymmetric density distribution, dipolar and quadrupolar planetary magnetospheres, lunar magnetic anomalies, and decaying turbulence. Nulls are detected in the simulation snapshots by the topological degree method. In all runs except the quadrupolar magnetospere the dominating majority of nulls are of spiral topological type. When supported by strong currents, these nulls indicate the regions of strong energy dissipation. Dissipation, often accompanied by the changes in magnetic topology, is caused by plasma instabilities in the current channels or on their interfaces. Radial nulls show less activity, they can be created or destroyed in pairs, via topological bifurcations. Although such events demonstrate energy release, they are rather rare and short-living. An important implication of our study to observations is that magnetic topology should not be considered independently of other plasma properties such as currents.

  10. Vacuum Nuller Testbed (VNT) Performance, Characterization and Null Control: Progress Report

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

    2011-01-01

    Herein we report on the development. sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled. segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be Hown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies. and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). Tbe VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(sup 8), 10(sup 9) and ideally 10(sup 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

  11. Current Structure and Nonideal Behavior at Magnetic Null Points in the Turbulent Magnetosheath

    NASA Technical Reports Server (NTRS)

    Wendel, D. E.; Adrian, M. L.

    2013-01-01

    The Poincaré index indicates that the Cluster spacecraft tetrahedron entraps a number of 3-D magnetic nulls during an encounter with the turbulent magnetosheath. Previous researchers have found evidence for reconnection at one of the many filamentary current layers observed by Cluster in this region. We find that many of the entrained nulls are also associated with strong currents. We dissect the current structure of a pair of spiral nulls that may be topologically connected. At both nulls, we find a strong current along the spine, accompanied by a somewhat more modest current perpendicular to the spine that tilts the fan toward the axis of the spine. The current along the fan is comparable to the that along the spine. At least one of the nulls manifests a rotational flow pattern in the fan plane that is consistent with torsional spine reconnection as predicted by theory. These results emphasize the importance of examining the magnetic topology in interpreting the nature of currents and reconnection in 3-D turbulence.

  12. Steady state reconnection at a single 3D magnetic null point

    NASA Astrophysics Data System (ADS)

    Galsgaard, K.; Pontin, D. I.

    2011-05-01

    Aims: We systematically stress a rotationally symmetric 3D magnetic null point by advecting the opposite footpoints of the spine axis in opposite directions. This stress eventually concentrates in the vicinity of the null point, thereby forming a local current sheet through which magnetic reconnection takes place. The aim is to look for a steady state evolution of the current sheet dynamics, which may provide scaling relations for various characteristic parameters of the system. Methods: The evolution is followed by solving numerically the non-ideal MHD equations in a Cartesian domain. The null point is embedded in an initially constant density and temperature plasma. Results: It is shown that a quasi-steady reconnection process can be set up at a 3D null by continuous shear driving. It appears that a true steady state is unlikely to be realised because the current layer tends to grow until it is restricted by the geometry of the computational domain and the imposed driving profile. However, ratios between characteristic quantities clearly settle after some time to stable values, so that the evolution is quasi-steady. The experiments show a number of scaling relations, but they do not provide a clear consensus for extending to lower magnetic resistivity or faster driving velocities. More investigations are needed to fully clarify the properties of current sheets at magnetic null points.

  13. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our contrast assessment and the development, sensing and control of the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraphy (VNC) for exoplanet detection and characterization. Tbe VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center has an established effort to develop VNC technologies, and an incremental sequence of testbeds to advance this approach and its critical technologies. We discuss the development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(exp 8), 10(exp 9) and ideally 10(exp 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the laboratory results, optical configuration, critical technologies and the null sensing and control approach.

  14. Time asymmetric spacetimes near null and spatial infinity: I. Expansions of developments of conformally flat data

    NASA Astrophysics Data System (ADS)

    Valiente Kroon, Juan Antonio

    2004-12-01

    The conformal Einstein equations and the representation of spatial infinity as a cylinder introduced by Friedrich are used to analyse the behaviour of the gravitational field near null and spatial infinity for the development of data which are asymptotically Euclidean, conformally flat and time asymmetric. Our analysis allows for initial data whose second fundamental form is more general than the one given by the standard Bowen York ansatz. The conformal Einstein equations imply, upon evaluation on the cylinder at spatial infinity, a hierarchy of transport equations which can be used to calculate asymptotic expansions for the gravitational field in a recursive way. It is found that the solutions to these transport equations develop logarithmic divergences at the critical sets where null infinity meets spatial infinity. Associated with these, there is a series of quantities expressible in terms of the initial data (obstructions), which if zero, preclude the appearance of some of the logarithmic divergences. The obstructions are, in general, time asymmetric. That is, the obstructions at the intersection of future null infinity with spatial infinity are in general different from those obtained at the intersection of past null infinity with spatial infinity. The latter allows for the possibility of having spacetimes where future and past null infinity have different degrees of smoothness. Finally, it is shown that if both sets of obstructions vanish up to a certain order, then the initial data have to be asymptotically Schwarzschildean in a certain sense.

  15. A Null Space Control of Two Wheels Driven Mobile Manipulator Using Passivity Theory

    NASA Astrophysics Data System (ADS)

    Shibata, Tsuyoshi; Murakami, Toshiyuki

    This paper describes a control strategy of null space motion of a two wheels driven mobile manipulator. Recently, robot is utilized in various industrial fields and it is preferable for the robot manipulator to have multiple degrees of freedom motion. Several studies of kinematics for null space motion have been proposed. However stability analysis of null space motion is not enough. Furthermore, these approaches apply to stable systems, but they do not apply unstable systems. Then, in this research, base of manipulator equips with two wheels driven mobile robot. This robot is called two wheels driven mobile manipulator, which becomes unstable system. In the proposed approach, a control design of null space uses passivity based stabilizing. A proposed controller is decided so that closed-loop system of robot dynamics satisfies passivity. This is passivity based control. Then, control strategy is that stabilizing of the robot system applies to work space observer based approach and null space control while keeping end-effector position. The validity of the proposed approach is verified by simulations and experiments of two wheels driven mobile manipulator.

  16. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge.

    PubMed

    Cho, Joo-Youn; Matsubara, Tsutomu; Kang, Dong Wook; Ahn, Sung-Hoon; Krausz, Kristopher W; Idle, Jeffrey R; Luecke, Hans; Gonzalez, Frank J

    2010-05-01

    Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.

  17. Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart

    PubMed Central

    Beneš, Helen; Vuong, Mai K.; Boerma, Marjan; McElhanon, Kevin E.; Siegel, Eric R.; Singh, Sharda P.

    2013-01-01

    4-hydroxynonenal (4-HNE) mediates many pathological effects of oxidative and electrophilic stress and signals to activate cytoprotective gene expression regulated by NF-E2-related factor 2 (Nrf2). By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene. Gsta4-null mice exhibited no cardiac phenotype under normal conditions and no difference in cardiac 4-HNE level as compared to wild-type (WT) mice. We hypothesized that the Nrf2 pathway might contribute an important compensatory mechanism to remove excess cardiac 4-HNE in Gsta4-null mice. Cardiac nuclear extracts from Gsta4-null mice exhibited significantly higher Nrf2 binding to antioxidant-response elements (AREs). We also observed responses in critical Nrf2 target gene products: elevated Sod2, Cat, and Akr1b7 mRNA levels and significant increases in both cardiac anti-oxidant and anti-electrophile enzyme activities. Gsta4-null mice were less sensitive and maintained normal cardiac function following chronic doxorubicin (DOX) treatment, known to increase cardiac 4-HNE levels. Hence, in the absence of GSTA4-4 to modulate both physiological and pathological 4-HNE levels, the adaptive Nrf2 pathway may be primed to contribute to a preconditioned cardiac phenotype in the Gsta4-null mouse. PMID:23690225

  18. Teleparallelism as a universal connection on null hypersurfaces in general relativity

    NASA Technical Reports Server (NTRS)

    Mazur, P. O.; Sokolowski, L. M.

    1986-01-01

    It is shown that a close relationship between the inner geometry of a null hypersurface N3 and the Newman-Penrose (NP) (1962, 1963) spin coefficient formalism exists. Projecting the null complex NP tetrad onto N3, two triads of basis vectors in N3 are obtained. The inner geometry of N3 is based on the assumption that these vectors are parallelly transported along the surface; this gives rise to the teleparallel connection as a metric nonsymmetric affine connection. The gauge freedom for the choice of the basis triads is given by the isotropy subgroup of the local Lorentz group leaving invariant the direction of the null generators of N3, and teleparallelism is determined by the equivalence class of the basis triads with respect to the global gauge group. Nine of the twelve NP coefficients are identified as the triad components of the torsion and the second fundamental form of N3. The resulting generalized Gauss-Codazzi equations are identical to nine of the NP equations, i.e., to the half of the Ricci identities. This result gives a geometrical meaning to the entire formalism. Finally a general proof of Penrose's theorem that the shear of the null generators of N3 is the only initial null datum for a gravitational field on N3 is presented.

  19. Spacetime characterizations of Λ-vacuum metrics with a null Killing 2-form

    NASA Astrophysics Data System (ADS)

    Mars, Marc; Senovilla, José M. M.

    2016-10-01

    An exhaustive list of four-dimensional Λ-vacuum spacetimes admitting a Killing vector ξ whose self-dual Killing two-form {{ F }}μ ν is null is obtained assuming that the self-dual Weyl tensor is proportional to the tensor product of {{ F }}μ ν by itself. Our analysis complements previous results (Mars 1999 Class Quantum Grav. 16 2507-23 Mars and Senovilla 2015 Ann. H. Poincaré 16 1509-50) concerning the case with non-null {{ F }}μ ν . We analyze both cases with Λ vanishing or not. In the latter case we prove that {{Λ }}\\lt 0 must hold necessarily, and we find a characterization of the Einstein spacetimes conformal to pp-waves. In the former case we obtain spacetime characterizations of vacuum plane waves and of the stationary vacuum Brinkmann spacetimes. At the light of the full set of results, old and new, we reformulate the case with non-null {{ F }}μ ν and {{Λ }}=0. We finally present a table collecting the results for both null, and non-null, {{ F }}μ ν .

  20. Brucella abortus Cyclic β-1,2-Glucan Mutants Have Reduced Virulence in Mice and Are Defective in Intracellular Replication in HeLa Cells

    PubMed Central

    Briones, Gabriel; Iñón de Iannino, Nora; Roset, Mara; Vigliocco, Ana; Paulo, Patricia Silva; Ugalde, Rodolfo A.

    2001-01-01

    Null cyclic β-1,2-glucan synthetase mutants (cgs mutants) were obtained from Brucella abortus virulent strain 2308 and from B. abortus attenuated vaccinal strain S19. Both mutants show greater sensitivity to surfactants like deoxycholic acid, sodium dodecyl sulfate, and Zwittergent than the parental strains, suggesting cell surface alterations. Although not to the same extent, both mutants display reduced virulence in mice and defective intracellular multiplication in HeLa cells. The B. abortus S19 cgs mutant was completely cleared from the spleens of mice after 4 weeks, while the 2308 mutant showed a 1.5-log reduction of the number of brucellae isolated from the spleens after 12 weeks. These results suggest that cyclic β-1,2-glucan plays an important role in the residual virulence of the attenuated B. abortus S19 strain. Although the cgs mutant was cleared from the spleens earlier than the wild-type parental strain (B. abortus S19) and produced less inflammatory response, its ability to confer protection against the virulent strain B. abortus 2308 was fully retained. Equivalent levels of induction of spleen gamma interferon mRNA and anti-lipopolysaccharide (LPS) of immunoglobulin G2a (IgG2a) subtype antibodies were observed in mice injected with B. abortus S19 or the cgs mutant. However, the titer of anti-LPS antibodies of the IgG1 subtype induced by the cgs mutant was lower than that observed with the parental S19 strain, thus suggesting that the cgs mutant induces a relatively exclusive Th1 response. PMID:11401996

  1. Characterization of SSIIIa-deficient mutants of rice: the function of SSIIIa and pleiotropic effects by SSIIIa deficiency in the rice endosperm.

    PubMed

    Fujita, Naoko; Yoshida, Mayumi; Kondo, Tomonori; Saito, Kaori; Utsumi, Yoshinori; Tokunaga, Takashi; Nishi, Aiko; Satoh, Hikaru; Park, Jin-Hee; Jane, Jay-Lin; Miyao, Akio; Hirochika, Hirohiko; Nakamura, Yasunori

    2007-08-01

    Starch synthase IIIa (SSIIIa)-deficient rice (Oryza sativa) mutants were generated using retrotransposon insertion and chemical mutagenesis. The lowest migrating SS activity bands on glycogen-containing native polyacrylamide gel, which were identified to be those for SSIIIa, were completely absent in these mutants, indicating that they are SSIIIa null mutants. The amylopectin B(2) to B(4) chains with degree of polymerization (DP) >/= 30 and the M(r) of amylopectin in the mutant were reduced to about 60% and 70% of the wild-type values, respectively, suggesting that SSIIIa plays an important part in the elongation of amylopectin B(2) to B(4) chains. Chains with DP 6 to 9 and DP 16 to 19 decreased while chains with DP 10 to 15 and DP 20 to 25 increased in the mutants amylopectin. These changes in the SSIIIa mutants are almost opposite images of those of SSI-deficient rice mutant and were caused by 1.3- to 1.7-fold increase of the amount of SSI in the mutants endosperm. Furthermore, the amylose content and the extralong chains (DP >/= 500) of amylopectin were increased by 1.3- and 12-fold, respectively. These changes in the composition in the mutants starch were caused by 1.4- to 1.7-fold increase in amounts of granules-bound starch synthase (GBSSI). The starch granules of the mutants were smaller with round shape, and were less crystalline. Thus, deficiency in SSIIIa, the second major SS isozyme in developing rice endosperm affected the structure of amylopectin, amylase content, and physicochemical properties of starch granules in two ways: directly by the SSIIIa deficiency itself and indirectly by the enhancement of both SSI and GBSSI gene transcripts.

  2. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-08-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both -/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress.

  3. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome

    PubMed Central

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-01-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both −/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress. PMID:24769161

  4. A Mycobacterium tuberculosis cytochrome bd oxidase mutant is hypersensitive to bedaquiline.

    PubMed

    Berney, Michael; Hartman, Travis E; Jacobs, William R

    2014-07-15

    The new medicinal compound bedaquiline (BDQ) kills Mycobacterium tuberculosis by inhibiting F1Fo-ATP synthase. BDQ is bacteriostatic for 4 to 7 days and kills relatively slowly compared to other frontline tuberculosis (TB) drugs. Here we show that killing with BDQ can be improved significantly by inhibiting cytochrome bd oxidase, a non-proton-pumping terminal oxidase. BDQ was instantly bactericidal against a cytochrome bd oxidase null mutant of M. tuberculosis, and the rate of killing was increased by more than 50%. We propose that this exclusively bacterial enzyme should be a high-priority target for new drug discovery. Importance: A major drawback of current TB chemotherapy is its long duration. New drug regimens with rapid killing kinetics are desperately needed. Our study demonstrates that inhibition of a nonessential bacterial enzyme greatly improves the efficacy of the latest TB drug bedaquiline and emphasizes that screening for compounds with synergistic killing mechanisms is a promising strategy.

  5. Endonuclease IV (nfo) mutant of Escherichia coli.

    PubMed Central

    Cunningham, R P; Saporito, S M; Spitzer, S G; Weiss, B

    1986-01-01

    A cloned gene, designated nfo, caused overproduction of an EDTA-resistant endonuclease specific for apurinic-apyrimidinic sites in DNA. The sedimentation coefficient of the enzyme was similar to that of endonuclease IV. An insertion mutation was constructed in vitro and transferred from a plasmid to the Escherichia coli chromosome. nfo mutants had an increased sensitivity to the alkylating agents methyl methanesulfonate and mitomycin C and to the oxidants tert-butyl hydroperoxide and bleomycin. The nfo mutation enhanced the killing of xth (exonuclease III) mutants by methyl methanesulfonate, H2O2, tert-butyl hydroperoxide, and gamma rays, and it enhanced their mutability by methyl methanesulfonate. It also increased the temperature sensitivity of an xth dut (dUTPase) mutant that is defective in the repair of uracil-containing DNA. These results are consistent with earlier findings that endonuclease IV and exonuclease III both cleave DNA 5' to an apurinic-apyrimidinic site and that exonuclease III is more active. However, nfo mutants were more sensitive to tert-butyl hydroperoxide and to bleomycin than were xth mutants, suggesting that endonuclease IV might recognize some lesions that exonuclease III does not. The mutants displayed no marked increase in sensitivity to 254-nm UV radiation, and the addition of an nth (endonuclease III) mutation to nfo or nfo xth mutants did not significantly increase their sensitivity to any of the agents tested. Images PMID:2430946

  6. Anti-optic-null medium: Achieving the optic-null medium effect by enclosing an air region with relatively low-anisotropy media

    NASA Astrophysics Data System (ADS)

    Sun, Fei; Liu, Yichao; He, Sailing

    2016-07-01

    A so-called anti-optic-null medium (anti-ONM), which can be utilized to cancel the optic-null medium (ONM) and create many novel optical illusions, is introduced and designed by transformation optics (TO). Optical separation illusions can be achieved with an anti-ONM. With the help of the anti-ONM, we can achieve the same optical illusions where ONM is required via a shelled structure filled with low anisotropic medium, which is easier to realize for some novel optical devices designed by TO and optical surface transformation. The special function of the anti-ONM will lead to a new way to design optical devices or simplify the material requirements. Overlapping illusions, and wave-front reshapers are designed to demonstrate the function of the proposed method.

  7. Arabidopsis KINETOCHORE NULL2 Is an Upstream Component for Centromeric Histone H3 Variant cenH3 Deposition at Centromeres[W

    PubMed Central

    Lermontova, Inna; Kuhlmann, Markus; Friedel, Swetlana; Rutten, Twan; Heckmann, Stefan; Sandmann, Michael; Demidov, Dmitri; Schubert, Veit; Schubert, Ingo

    2013-01-01

    The centromeric histone H3 variant cenH3 is an essential centromeric protein required for assembly, maintenance, and proper function of kinetochores during mitosis and meiosis. We identified a KINETOCHORE NULL2 (KNL2) homolog in Arabidopsis thaliana and uncovered features of its role in cenH3 loading at centromeres. We show that Arabidopsis KNL2 colocalizes with cenH3 and is associated with centromeres during all stages of the mitotic cell cycle, except from metaphase to mid-anaphase. KNL2 is regulated by the proteasome degradation pathway. The KNL2 promoter is mainly active in meristematic tissues, similar to the cenH3 promoter. A knockout mutant for KNL2 shows a reduced level of cenH3 expression and reduced amount of cenH3 protein at chromocenters of meristematic nuclei, anaphase bridges during mitosis, micronuclei in pollen tetrads, and 30% seed abortion. Moreover, knl2 mutant plants display reduced expression of suppressor of variegation 3-9 homologs2, 4, and 9 and reduced DNA methylation, suggesting an impact of KNL2 on the epigenetic environment for centromere maintenance. PMID:24014547

  8. Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1.

    PubMed

    Hurlock, Edward C; Bose, Mitali; Pierce, Ganon; Joho, Rolf H

    2009-12-16

    The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded by Kcnc genes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxic Kcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereas Kcnc3-mutant mice additionally lacking one Kcnc1 allele were partially rescued. Here, we report mice lacking all Kcnc1 and Kcnc3 alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. As Kcnc1, but not Kcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking just Kcnc3 is hypermetria, while gait ataxia emerges when additionally Kcnc1 alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning.

  9. Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains

    SciTech Connect

    Willing, M.C.; Deschenes, S.P.; Roberts, E.J.

    1996-10-01

    Nonsense and frameshift mutations, which predict premature termination of translation, often cause a dramatic reduction in the amount of transcript from the mutant allele (nonsense-mediated mRNA decay). In some genes, these mutations also influence RNA splicing and induce skipping of the exon that contains the nonsense codon. To begin to dissect how premature termination alters the metabolism of RNA from the COL1A1 gene, we studied nonsense and frameshift mutations distributed over exons 11-49 of the gene. These mutations were originally identified in 10 unrelated families with osteogenesis imperfecta (OI) type I. We observed marked reduction in steady-state amounts of mRNA from the mutant allele in both total cellular and nuclear RNA extracts of cells from affected individuals, suggesting that nonsense-mediated decay of COL1A1 RNA is a nuclear phenomenon. Position of the mutation within the gene did not influence this observation. None of the mutations induced skipping of either the exon containing the mutation or, for the frameshifts, the downstream exons with the new termination sites. Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type I. 42 refs., 6 figs., 1 tab.

  10. Analysis of defects on the slopes on a parabolic trough solar collector with null-screens

    NASA Astrophysics Data System (ADS)

    Campos-García, Manuel; Huerta-Carranza, Oliver; Díaz-Uribe, Rufino; Moreno-Oliva, Víctor I.

    2015-09-01

    The null-screen method has been used to test aspheric surfaces, among them the surface of a parabolic trough solar collector (PTSC). This geometrical method measures the slope of the test surface and by a numerical integration procedure the shape of the test surface can be obtained. In this work, through some numerical simulations sinusoidal deformations with different amplitudes and spatial periods are introduced on PTSC surfaces. Then, an analysis of the deformations of the reflected images of a null-screen by the PTSC surface due to defects on the surface is performed. This procedure allows to validate the kind and magnitude of the surface deformations that can be measured with the proposed method. Also, an analysis of the advantages and limitations of the null-screen testing method will be discussed.

  11. Planet detection and spectroscopy in visible light with a single aperture telescope and a nulling coronagraph

    NASA Technical Reports Server (NTRS)

    Shao, Michael; Serabyn, Eugene; Levine, Bruce Martin; Beichman, Charles; Liu, Duncan; Martin, Stefan; Orton, Glen; Mennesson, Bertrand; Morgan, Rhonda; Velusamy, Thangasamy; Wallace, J. Kent; Unwin, Stephen

    2003-01-01

    This talk describes a new concept for visible direct detection of Earth like extra solar planets using a nulling coronagraph instrument behind a 4m telescope in space. In the baseline design, a 4 beam nulling interferometer is synthesized from the telescope pupil, producing a very deep theta^4null which is then filtered by a coherent array of single mode fibers to suppress the residual scattered light. With perfect optics, the stellar leakage is less than 1e-11 of the starlight at the location of the planet. With diffraction limited telescope optics (lambda/20), suppression of the starlight to 1e-10 is possible. The concept is described along with the key advantages over more traditional approaches such as apodized aperture telescopes and Lyot type coronagraphs.

  12. Mind the Gap: Exploring the Physics of Null Points Using Unconventional Coordinate Systems

    NASA Astrophysics Data System (ADS)

    Shanahan, Brendan; Dudson, Ben; Avino, Fabio; Leddy, Jarrod; Hill, Peter; Furno, Ivo

    2015-11-01

    Simulations of instabilities and turbulence in X-point configurations are challenging due to the limitations of field-aligned coordinate systems: X-point dynamics are often interpolated from flux surfaces, which could exclude relevant physics. Here we explore the physics of null regions in multiple geometries using unconventional coordinate systems in BOUT++. Specifically, we have investigated the physics of blob propagation and compared with experimental measurements within the TORPEX device, indicating an increase in inertially limited filament propagation in the null region caused by longer connection lengths. The null point dynamics of filaments crossing the separatrix in tokamak geometry will also be presented using a novel field-aligned coordinate system, with applications to ELM and blob theory. Finally, recent work on implementation and applicability of the Flux Coordinate Independent (FCI) approach to complex magnetic geometry modelling will be discussed.

  13. Maxwell, Yang-Mills, Weyl and eikonal fields defined by any null shear-free congruence

    NASA Astrophysics Data System (ADS)

    Kassandrov, Vladimir V.; Rizcallah, Joseph A.

    We show that (specifically scaled) equations of shear-free null geodesic congruences on the Minkowski space-time possess intrinsic self-dual, restricted gauge and algebraic structures. The complex eikonal, Weyl 2-spinor, SL(2, ℂ) Yang-Mills and complex Maxwell fields, the latter produced by integer-valued electric charges (“elementary” for the Kerr-like congruences), can all be explicitly associated with any shear-free null geodesic congruence. Using twistor variables, we derive the general solution of the equations of the shear-free null geodesic congruence (as a modification of the Kerr theorem) and analyze the corresponding “particle-like” field distributions, with bounded singularities of the associated physical fields. These can be obtained in a straightforward algebraic way and exhibit nontrivial collective dynamics simulating physical interactions.

  14. High performance testbed for four-beam infrared interferometric nulling and exoplanet detection.

    PubMed

    Martin, Stefan; Booth, Andrew; Liewer, Kurt; Raouf, Nasrat; Loya, Frank; Tang, Hong

    2012-06-10

    Technology development for a space-based infrared nulling interferometer capable of earthlike exoplanet detection and characterization started in earnest in the last 10 years. At the Jet Propulsion Laboratory, the planet detection testbed was developed to demonstrate the principal components of the beam combiner train for a high performance four-beam nulling interferometer. Early in the development of the testbed, the importance of "instability noise" for nulling interferometer sensitivity was recognized, and the four-beam testbed would produce this noise, allowing investigation of methods for mitigating this noise source. The testbed contains the required features of a four-beam combiner for a space interferometer and performs at a level matching that needed for the space mission. This paper describes in detail the design, functions, and controls of the testbed.

  15. Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants.

    PubMed

    Hurlock, Edward C; McMahon, Anne; Joho, Rolf H

    2008-04-30

    The fast-activating/deactivating voltage-gated potassium channel Kv3.3 (Kcnc3) is expressed in various neuronal cell types involved in motor function, including cerebellar Purkinje cells. Spinocerebellar ataxia type 13 (SCA13) patients carrying dominant-negative mutations in Kcnc3 and Kcnc3-null mutant mice both display motor incoordination, suggested in mice by increased lateral deviation while ambulating and slips on a narrow beam. Motor skill learning, however, is spared. Mice lacking Kcnc3 also exhibit muscle twitches. In addition to broadened spikes, recordings of Kcnc3-null Purkinje cells revealed fewer spikelets in complex spikes and a lower intraburst frequency. Targeted reexpression of Kv3.3 channels exclusively in Purkinje cells in Kcnc3-null mice as well as in mice also heterozygous for Kv3.1 sufficed to restore simple spike brevity along with normal complex spikes and to rescue specifically coordination. Therefore, spike parameters requiring Kv3.3 function in Purkinje cells are involved in the ataxic null phenotype and motor coordination, but not motor learning.

  16. Salmonella typhimurium mutants lacking NAD pyrophosphatase.

    PubMed Central

    Park, U E; Roth, J R; Olivera, B M

    1988-01-01

    NAD can serve as both a purine and a pyridine source for Salmonella typhimurium. Exogenous NAD is rapidly broken down into nicotinamide mononucleotide and AMP by an NAD pyrophosphatase, the first step in the pathway for the assimilation of exogenous NAD. We isolated and characterized mutants of S. typhimurium lacking NAD pyrophosphatase activity; such mutants were identified by their failure to use exogenous NAD as a purine source. These mutants carry mutations that map at a new locus, designated pnuE, between 86 and 87 min on the Salmonella chromosome. PMID:2841298

  17. Genetic requirements for high constitutive SOS expression in recA730 mutants of Escherichia coli.

    PubMed

    Vlašić, Ignacija; Šimatović, Ana; Brčić-Kostić, Krunoslav

    2011-09-01

    The RecA protein in its functional state is in complex with single-stranded DNA, i.e., in the form of a RecA filament. In SOS induction, the RecA filament functions as a coprotease, enabling the autodigestion of the LexA repressor. The RecA filament can be formed by different mechanisms, but all of them require three enzymatic activities essential for the processing of DNA double-stranded ends. These are helicase, 5'-3' exonuclease, and RecA loading onto single-stranded DNA (ssDNA). In some mutants, the SOS response can be expressed constitutively during the process of normal DNA metabolism. The RecA730 mutant protein is able to form the RecA filament without the help of RecBCD and RecFOR mediators since it better competes with the single-strand binding (SSB) protein for ssDNA. As a consequence, the recA730 mutants show high constitutive SOS expression. In the study described in this paper, we studied the genetic requirements for constitutive SOS expression in recA730 mutants. Using a β-galactosidase assay, we showed that the constitutive SOS response in recA730 mutants exhibits different requirements in different backgrounds. In a wild-type background, the constitutive SOS response is partially dependent on RecBCD function. In a recB1080 background (the recB1080 mutation retains only helicase), constitutive SOS expression is partially dependent on RecBCD helicase function and is strongly dependent on RecJ nuclease. Finally, in a recB-null background, the constitutive SOS expression of the recA730 mutant is dependent on the RecJ nuclease. Our results emphasize the importance of the 5'-3' exonuclease for high constitutive SOS expression in recA730 mutants and show that RecBCD function can further enhance the excellent intrinsic abilities of the RecA730 protein in vivo.

  18. Mutant generation in vertebrate model organisms by TILLING.

    PubMed

    Winkler, Sylke; Gscheidel, Nicola; Brand, Michael

    2011-01-01

    TILLING (Targeting Induced Local Lesions IN Genomes) is a popular reverse genetic approach that has been successfully applied in several genetic model organisms such as zebrafish, rat, Drosophila, Arabidopsis, or medaka. In contrast to classical targeted knockout technologies that work in mice by directly targeting a gene of interest, TILLING follows an indirect strategy. The first step of the TILLING pipeline is the generation of a TILLING library that consists of large numbers of mutagenized individuals. In a second step, these individuals are screened for mutations in any gene of interest. Screening is performed by PCR amplification of specific exons from each individual of a library followed by mutation detection. This could be done, for example, by direct re-sequencing of PCR fragments or alternatively, by CEL1 endonuclease-mediated mutation discovery. Individuals carrying potentially deleterious point mutations are isolated from the library and mutant lines are established. TILLING allows the identification of a whole range of point mutations, covering nonsense, splice site, and missense mutations in only one screening round, because the generation of mutations by mutagenesis as well as the screening tools is not biased. Potential knockout mutations are initially the mutations of choice, but TILLING screens can also be used to isolate allelic series of point mutations ranging from complete null phenotypes to hypomorphic or even dominant-negative or conditional alleles. These allelic series can be helpful for a comprehensive functional analysis of a gene of interest. TILLING is applicable to any kind of genetically tractable model organism, as long as this model organism is amenable to chemical mutagenesis, and genomic sequence information for a gene of interest is available. This chapter describes the design and pipeline of a TILLING facility as we are currently operating it for zebrafish in Dresden. Protocols for mutation detection by direct re

  19. Improving accuracy in the MPM method using a null space filter

    NASA Astrophysics Data System (ADS)

    Gritton, Chris; Berzins, Martin

    2017-01-01

    The material point method (MPM) has been very successful in providing solutions to many challenging problems involving large deformations. Nevertheless there are some important issues that remain to be resolved with regard to its analysis. One key challenge applies to both MPM and particle-in-cell (PIC) methods and arises from the difference between the number of particles and the number of the nodal grid points to which the particles are mapped. This difference between the number of particles and the number of grid points gives rise to a non-trivial null space of the linear operator that maps particle values onto nodal grid point values. In other words, there are non-zero particle values that when mapped to the grid point nodes result in a zero value there. Moreover, when the nodal values at the grid points are mapped back to particles, part of those particle values may be in that same null space. Given positive mapping weights from particles to nodes such null space values are oscillatory in nature. While this problem has been observed almost since the beginning of PIC methods there are still elements of it that are problematical today as well as methods that transcend it. The null space may be viewed as being connected to the ringing instability identified by Brackbill for PIC methods. It will be shown that it is possible to remove these null space values from the solution using a null space filter. This filter improves the accuracy of the MPM methods using an approach that is based upon a local singular value decomposition (SVD) calculation. This local SVD approach is compared against the global SVD approach previously considered by the authors and to a recent MPM method by Zhang and colleagues.

  20. Stimulation of Sigma-1 Receptor Ameliorates Depressive-like Behaviors in CaMKIV Null Mice.

    PubMed

    Moriguchi, Shigeki; Sakagami, Hiroyuki; Yabuki, Yasushi; Sasaki, Yuzuru; Izumi, Hisanao; Zhang, Chen; Han, Feng; Fukunaga, Kohji

    2015-12-01

    Sigma-1 receptor (Sig-1R) is a molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to the mitochondria. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) null mice exhibit depressive-like behaviors and impaired neurogenesis as assessed by bromodeoxyuridine (BrdU) incorporation into newborn cells of the hippocampal dentate gyrus (DG). Here, we demonstrate that chronic stimulation of Sig-1R by treatment with the agonist SA4503 or the SSRI fluvoxamine for 14 days improves depressive-like behaviors in CaMKIV null mice. By contrast, treatment with paroxetine, which lacks affinity for Sig-1R, did not alter these behaviors. Reduced numbers of BrdU-positive cells and decreased brain-derived neurotrophic factor (BDNF) mRNA expression and protein kinase B (Akt; Ser-473) phosphorylation seen in the DG of CaMKIV null mice were significantly rescued by chronic Sig-1R stimulation. Interestingly, reduced ATP production observed in the DG of CaMKIV null mice was improved by chronic Sig-1R stimulation. Such stimulation also improved hippocampal long-term potentiation (LTP) induction and maintenance, which are impaired in the DG of CaMKIV null mice. LTP rescue was closely associated with both increases in calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and GluA1 (Ser-831) phosphorylation. Taken together, Sig-1R stimulation by SA4503 or fluvoxamine treatment increased hippocampal neurogenesis, which is closely associated with amelioration of depressive-like behaviors in CaMKIV null mice.

  1. Bending amplitude - a new quantitative assay of C. elegans locomotion: identification of phenotypes for mutants in genes encoding muscle focal adhesion components.

    PubMed

    Nahabedian, John F; Qadota, Hiroshi; Stirman, Jeffrey N; Lu, Hang; Benian, Guy M

    2012-01-01

    The nematode Caenorhabditis elegans uses striated muscle in its body wall for locomotion. The myofilament lattice is organized such that all the thin filament attachment structures (dense bodies, analogous to Z-disks) and thick filament organizing centers (M-lines) are attached to the muscle cell membrane. Thus, the force of muscle contraction is transmitted through these structures and allows locomotion of the worm. Dense bodies and M-lines are compositionally similar to focal adhesions and costameres, and are based on integrin and associated proteins. Null mutants for many of the newly discovered dense body and M-line proteins do not have obvious locomotion defects when observed casually, or when assayed by counting the number of times a worm moves back and forth in liquid. We hypothesized that many of these proteins, located as they are in muscle focal adhesions, function in force transmission, but we had not used an appropriate or sufficiently sensitive assay to reveal this function. Recently, we have developed a new quantitative assay of C. elegans locomotion that measures the maximum bending amplitude of an adult worm as it moves backwards. The assay had been used to reveal locomotion defects for null mutants of genes encoding ATN-1 (α-actinin) and PKN-1 (protein kinase N). Here, we describe the details of this method, and apply it to 21 loss of function mutants in 17 additional genes, most of which encode components of muscle attachment structures. As compared to wild type, mutants in 11 genes were found to have less ability to bend, and mutants in one gene were found to have greater ability to bend. Loss of function mutants for eight proteins had been reported to have normal locomotion (ZYX-1 (zyxin), ALP-1 (Enigma), DIM-1, SCPL-1), or locomotion that was not previously investigated (FRG-1 (FRG1), KIN-32 (focal adhesion kinase), LIM-8), or had only slightly decreased locomotion (PFN-3 (profilin)).

  2. The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice.

    PubMed

    Shu, Cindy; Smith, Susan M; Melrose, James

    2016-06-01

    This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg2(∆3-/∆3-) perlecan exon 3 null mouse skin. Despite its obvious importance in skin repair and tissue homeostasis no definitive studies have immunolocalised TGF-β1 in skin in WT or Hspg2(∆3-/∆3-) perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg2(∆3-/∆3-) mice were fixed in neutral buffered formalin, paraffin embedded and 4 μm sections stained with Mayers haematoxylin and eosin (H & E). TGF-β1 was immunolocalised using a rabbit polyclonal antibody, heat retrieval and the Envision NovaRED detection system. Immunolocalisation of TGF-β1 differed markedly in C57BL/6 and Hspg2(∆3-/∆3-) mouse skin, ablation of exon 3 of Hspg2 resulted in a very severe reduction in the deposition of TGF-β1 in skin 3-12 weeks postnatally. The reduced deposition of TGF-β1 observed in the present study would be expected to impact detrimentally on the remodelling and healing capacity of skin in mutant mice compounding on the poor wound-healing properties already reported for perlecan exon 3 null mice due to an inability to signal with FGF-2 and promote angiogenic repair processes. TGF-β1 also has cell mediated effects in tissue homeostasis and matrix stabilisation a reduction in TGF-β1 deposition would therefore be expected to detrimentally impact on skin homeostasis in the perlecan mutant mice.

  3. Design approaches and parameters for magnetically levitated transport systems. [Null flux suspension (Maglev)

    SciTech Connect

    Danby, G.T.; Powell, J.R.

    1988-01-01

    Mechanically levitated transport system approaches are assessed with regard to thrust power needs, track cost, suspension stability, and safety. The null flux suspension appears as the favored approach, having the least thrust power requirements, highest stability, and lowest amount of track material. Various null flux configurations are described together with their operating parameters. The Linear Synchronous Motor (LSM) propulsion system is also described for propelling the suspended vehicles. Cryogenics and superconductivity aspects are discussed and the effect of high T/sub c/ superconductors evaluated. 13 refs., 16 figs., 2 tabs.

  4. Wound Healing Characteristics of ICAM-1 Null Mice Devoid of All Isoforms of ICAM-1

    PubMed Central

    Gay, Andre N.; Mushin, Oren P.; Lazar, David A.; Naik-Mathuria, Bindi J.; Yu, Ling; Gobin, Andre; Smith, C. Wayne; Olutoye, Oluyinka O.

    2011-01-01

    Background Intercellular Adhesion Molecule-1 (ICAM-1) permits leukocyte-endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM-1 knockout mice have been used to understand this molecule’s role in wound-healing, but expressed spliced isoforms of ICAM-1 may have impacted results. We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM-1 isoforms. Methods Full-thickness 8-mm wounds were created on C57/BL6 wild-type (n=24) and ICAM-1 null (n=24) mice. Wound area was calculated using daily photographs. Histologic samples were harvested on post-operative Days 1,3,7, and 14. Wound margins were evaluated for mRNA expression of 13 inflammatory cytokines. A separate group of wild-type and ICAM-1 null mice (n=24) received full-thickness incisions with tensiometry measured at Day 14. Separately, complete blood counts were measured in unwounded wild-type (n=4) and ICAM-1 null mice (n=4). Results Wound-closure was significantly delayed in ICAM-1 null mice through Day 7 by gross and histologic measurement. mRNA expression of VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds demonstrated higher stiffness upon Day 14 tensiometry compared to the wild-type (1880 ± 926 kPa vs. 478 ± 117 kPa;p<0.01), and had higher counts of white blood cells (10,009 vs. 5,720 cells/microliter,p<0.05), neutrophils (2,130 vs. 630 cells/microliter,p<0.01), and lymphocytes (7,130 vs. 4,740 cells/microliter, p<0.05). Conclusions ICAM-1 null mice demonstrate delayed wound-healing and decreased wound elasticity compared to wild-type controls. This lag, however, was less than observed in earlier membrane-bound ICAM-1 knockouts, suggesting that other ICAM-1 isoforms may promote delayed wound-healing. PMID:21872884

  5. A Fortran code for null geodesic solutions in the Lemaître-Tolman-Bondi spacetime

    NASA Astrophysics Data System (ADS)

    Ribeiro, Marcelo B.

    2002-10-01

    This paper describes the Fortran 77 code SIMU, version 1.1, designed for numerical simulations of observational relations along the past null geodesic in the Lemaître-Tolman-Bondi (LTB) spacetime. SIMU aims at finding scale invariant solutions of the average density, but due to its full modularity it can be easily adapted to any application which requires LTB's null geodesic solutions. In version 1.1 the numerical output can be read by the GNUPLOT plotting package to produce a fully graphical output, although other plotting routines can be easily adapted. Details of the code's subroutines are discussed, and an example of its output is shown.

  6. Collision between variably polarized plane gravitational wave and a shell of null matter

    NASA Astrophysics Data System (ADS)

    Feinstein, Alexander; Senovilla, Josém. M.

    1989-06-01

    We construct a solution to the Einstein field equations which describes the collision between a variably polarized gravitational wave and a shell of null dust. Depending on the choice of the parameters the variably polarized wave can have an arbitrarily smooth wavefront. The shell of null dust is followed by a constantly polarized plane gravitational wave. Also Grupo de Física Teórica, Departamento de Física, Ingeniería y Radiología Médica, Facultad de Ciencias, Universidad de Salamanca, 37008 Salamanca, Spain.

  7. Exo-zodi detection capability of the Ground-Based European Nulling Interferometry Experiment (GENIE) instrument.

    PubMed

    Wallner, Oswald; Flatscher, Reinhold; Ergenzinger, Klaus

    2006-06-20

    The Ground-Based European Nulling Interferometry Experiment (GENIE) is intended as an Earth-based precursor for the European Darwin mission that will prepare the Darwin science program and demonstrate the required technology at system level. We propose a compact nulling interferometer design consisting of a two-telescope aperture configuration, an optional split-pupil add-on, and only four active control loops for counteracting environmentally induced disturbances. We show by simulation that the proposed instrument is able to detect, within a few minutes of observation time, exo-zodiacal dust clouds around Sunlike stars at 20 parsecs that are 20 times stronger than the local zodiacal dust cloud density.

  8. Extending the scanning angle of a phased array antenna by using a null-space medium

    PubMed Central

    Sun, Fei; He, Sailing

    2014-01-01

    By introducing a columnar null-space region as the reference space, we design a radome that can extend the scanning angle of a phased array antenna (PAA) by a predetermined relationship (e.g. a linear relationship between the incident angle and steered output angle can be achieved). After some approximation, we only need two homogeneous materials to construct the proposed radome layer by layer. This kind of medium is called a null-space medium, which has been studied and fabricated for realizing hyper-lenses and some other devices. Numerical simulations verify the performance of our radome. PMID:25355198

  9. Corneal topography with conical null-screen for non-symmetric aspheric corneas

    NASA Astrophysics Data System (ADS)

    Armengol-Cruz, Victor de Emanuel; Osorio-Infante, Arturo I.; Campos-García, Manuel; Cossio-Guerrero, Cesar; Díaz-Uribe, José Rufino

    2016-09-01

    In this work, we will present some improvements to the conical null-screen based corneal topographer, for testing aspheric surfaces without rotational symmetry. We present the formulae to design the conical null-screen in such a way that the image on the CCD is a perfect array of spots; departures from this geometry are due to deformation or misalignment of the surface. Additionally, we will explain how to improve the algorithms to find the normals of corneal surface. Finally, we will evaluate the topography of a spherical surface.

  10. Petrology of the Cangas de Onis and nulles regolith breccias Implications for parent body history

    NASA Technical Reports Server (NTRS)

    Williams, C. V.; Rubin, A. E.; Keil, K.; San Miguel, A.

    1985-01-01

    The present study of the Cangas de Onis and Nulles H chondrite regolith breccias indicates that the minerals in the matrices and equilibrated clasts have essentially the same compositional distributions, so that much of the material in the castic matrix would have to have been derived from the impact comminution of clats. The apparently exclusive occurrence of H6 clasts in Cangas de Onis, and H4 clasts in Nulles, suggests that, at the locations where these breccias formed, the regolith predominantly consisted of H6 and H4 material, respectively.

  11. Null tests for oblate spheroids. [aspheric surfaces in reflecting optical system designs

    NASA Technical Reports Server (NTRS)

    Rodgers, J. M.; Parks, R. E.

    1984-01-01

    In most real cases requiring simple null optics, the optical path difference cannot be reduced to zero but can be kept at a fractional wavelength level so that interferometric data reduction can be used to account for the residual error. In other cases, computer-generated holograms may be used to obtain apparently straight fringes when the desired surface is obtained. Two examples, one involving an f/2.5 concave oblate spheroid and the other a Paul-Baker secondary, are examined. It is shown that although the null tests are not generally perfect, the residual error is small and the tests are simple.

  12. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    PubMed

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis.

  13. Organic Anion Transporting Polypeptide 1a1 Null Mice Are Sensitive to Cholestatic Liver Injury

    PubMed Central

    Zhang, Youcai; Csanaky, Iván L.; Cheng, Xingguo; Lehman-McKeeman, Lois D.; Klaassen, Curtis D.

    2012-01-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na+-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance–associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. PMID:22461449

  14. Causality and entropic arguments pointing to a null Big Bag hypersurface

    NASA Astrophysics Data System (ADS)

    Minguzzi, E.

    2011-09-01

    I propose a causality argument in order to solve the homogeneity (horizon) problem and the entropy problem of cosmology. The solution is based on the replacement of the spacelike Big Bang boundary with a null boundary behind which stays a chronology violating region. This solution requires a tilting of the light cones near the null boundary and thus it is based more on the behavior of the light cones and hence on causality than on the behavior of the scale factor (expansion). The connection of this picture with Augustine of Hippo famous philosophical discussion on time and creation is mentioned.

  15. The Segmented Aperture Interferometric Nulling Testbed (SAINT) I: overview and air-side system description

    NASA Astrophysics Data System (ADS)

    Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Ballard, Marlin; Bolcar, Matthew R.; Bolognese, Jeff; Clampin, Mark; Dogoda, Peter; Dworzanski, Daniel; Helmbrecht, Michael A.; Koca, Corina; Shiri, Ron

    2016-07-01

    This work presents an overview of the Segmented Aperture Interferometric Nulling Testbed (SAINT), a project that will pair an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC). SAINT will incorporate the VNC's demonstrated wavefront sensing and control system to refine and quantify end-to-end high-contrast starlight suppression performance. This pathfinder testbed will be used as a tool to study and refine approaches to mitigating instabilities and complex diffraction expected from future large segmented aperture telescopes.

  16. Noncolocated Time-Reversal MUSIC: High-SNR Distribution of Null Spectrum

    NASA Astrophysics Data System (ADS)

    Ciuonzo, Domenico; Rossi, Pierluigi Salvo

    2017-04-01

    We derive the asymptotic distribution of the null spectrum of the well-known Multiple Signal Classification (MUSIC) in its computational Time-Reversal (TR) form. The result pertains to a single-frequency non-colocated multistatic scenario and several TR-MUSIC variants are here investigated. The analysis builds upon the 1st-order perturbation of the singular value decomposition and allows a simple characterization of null-spectrum moments (up to the 2nd order). This enables a comparison in terms of spectrums stability. Finally, a numerical analysis is provided to confirm the theoretical findings.

  17. Deep nulling of laser light with a single-mode-fiber beam combiner.

    PubMed

    Haguenauer, Pierre; Serabyn, Eugene

    2006-04-20

    The detection of faint companions to bright stars requires the development of very-high-contrast-ratio detection techniques such as nulling interferometry. Here we present, to our knowledge, the first experimental test of a novel beam-combination method, which is based on coupling the light at the center of a dual-aperture interference pattern into a single-mode fiber. Using such a "fiber nuller" approach, a visible He-Ne laser has been stably nulled to as low as 1.3x10(-6), thus validating the approach.

  18. An efficient algorithm for antenna synthesis updating following null-constraint changes

    NASA Astrophysics Data System (ADS)

    Magdy, M. A.; Paoloni, F. J.; Cheah, J. Y. C.

    1985-08-01

    The procedure to maximize the array signal to noise ratio with null constraints involves an optimization problem that can be solved efficiently using a modified Cholesky decomposition (UD) technique. Following changes in the main lobe and/or null positions, the optimal element weight vector can be updated without the need for a new complete matrix inversion. Some properties of the UD technique can be utilized such that the updating algorithm reprocesses only a part of the unit triangular matrix U. Proper ordering of matrix entries can minimize the dimension of the updated part.

  19. A Review of Phase-Only Sidelobe Nulling Investigations at RADC (Rome Air Development Center).

    DTIC Science & Technology

    1985-08-01

    IC.ntno ,1 reon nir-. ’I0P0ITAd Ident~y by blocknonbI FIEL GRUP SB G Linear Arrays-, Pattern Synthesis, 093 10 Phase-Only Weight Control,. Adaptive Nulling...Obtaining the phase perturbations that satisfy the null equations (1) subject 4. to minimizing the objective function F, given by Eq. (2), is a nonlinear...dnum) 0 m 1, 2. M , N even n=l (N-)/2 an cos(on ++ + d )+ a m 1, 2, M nflI N odd and the objective function , Eq. (2), as N/2 c 8 sin2 n , N evenF = 8

  20. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction.

    PubMed

    Park, Jeehye; Kim, Sung Yun; Cha, Guang-Ho; Lee, Sung Bae; Kim, Sunhong; Chung, Jongkyeong

    2005-11-21

    DJ-1 is linked to an early-onset autosomal recessive Parkinson's disease (PD) characterized primarily by selective loss of dopaminergic (DA) neurons, which results in motor disturbances. However, our understanding on how mutations in DJ-1 are related to PD is unclear. Here, we isolated the DJ-1 orthologue, DJ-1beta, in Drosophila and characterized its expression and loss-of-function mutants. We observed its strongest expression in the adult stage of development and ubiquitous expression in the larval brain. Our homozygous mutants showed severe defects in locomotor ability without loss of DA neurons, consistent with the previous mice DJ-1 mutant studies ([Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., et al., 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-496.]; [Kim, R.H., Smith, P.D., Aleyasin, H., Hayley, S., Mount, M.P., Pownall, S., Wakeham, A., You-Ten, A.J., Kalia, S.K., Horne, P., Westaway, D., Lozano, A.M., Anisman, H., Park, D.S., Mak, T.W., 2005. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. USA 102, 5215-5220.]; [Chen, L., Cagniard, B., Mathews, T., Jones, S., Koh, H.C., Ding, Y., Carvey, P.M., Ling, Z., Kang, U.J., Zhuang, X., 2005. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 280, 21418-21426.]). The locomotor activity of DJ-1beta mutants was further decreased by paraquat-induced oxidative stress. Moreover, we found that Drosophila DJ-1 is prominently localized in mitochondria, suggesting that DJ-1 functions as a protector against oxidative stress in mitochondria.

  1. A Novel Mouse Fgfr2 Mutant, Hobbyhorse (hob), Exhibits Complete XY Gonadal Sex Reversal

    PubMed Central

    Siggers, Pam; Carré, Gwenn-Aël; Bogani, Debora; Warr, Nick; Wells, Sara; Hilton, Helen; Esapa, Chris; Hajihosseini, Mohammad K.; Greenfield, Andy

    2014-01-01

    The secreted molecule fibroblast growth factor 9 (FGF9) plays a critical role in testis determination in the mouse. In embryonic gonadal somatic cells it is required for maintenance of SOX9 expression, a key determinant of Sertoli cell fate. Conditional gene targeting studies have identified FGFR2 as the main gonadal receptor for FGF9 during sex determination. However, such studies can be complicated by inefficient and variable deletion of floxed alleles, depending on the choice of Cre deleter strain. Here, we report a novel, constitutive allele of Fgfr2, hobbyhorse (hob), which was identified in an ENU-based forward genetic screen for novel testis-determining loci. Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser) in the third extracellular immunoglobulin-like domain of FGFR2. Mutant homozygous embryos show severe limb and lung defects and, when on the sensitised C57BL/6J (B6) genetic background, undergo complete XY gonadal sex reversal associated with failure to maintain expression of Sox9. Genetic crosses employing a null mutant of Fgfr2 suggest that Fgr2hob is a hypomorphic allele, affecting both the FGFR2b and FGFR2c splice isoforms of the receptor. We exploited the consistent phenotype of this constitutive mutant by analysing MAPK signalling at the sex-determining stage of gonad development, but no significant abnormalities in mutant embryos were detected. PMID:24956260

  2. Differential protein stability of EGFR mutants determines responsiveness to tyrosine kinase inhibitors

    PubMed Central

    Ray, Paramita; Tan, Yee Sun; Somnay, Vishal; Mehta, Ranjit; Sitto, Merna; Ahsan, Aarif; Nyati, Shyam; Naughton, John P.; Bridges, Alexander; Zhao, Lili; Rehemtulla, Alnawaz; Lawrence, Theodore S.; Ray, Dipankar; Nyati, Mukesh K.

    2016-01-01

    Non-small cell lung cancer (NSCLC) patients carrying specific EGFR kinase activating mutations (L858R, delE746-A750) respond well to tyrosine kinase inhibitors (TKIs). However, drug resistance develops within a year. In about 50% of such patients, acquired drug resistance is attributed to the enrichment of a constitutively active point mutation within the EGFR kinase domain (T790M). To date, differential drug-binding and altered ATP affinities by EGFR mutants have been shown to be responsible for differential TKI response. As it has been reported that EGFR stability plays a role in the survival of EGFR driven cancers, we hypothesized that differential TKI-induced receptor degradation between the sensitive L858R and delE746-A750 and the resistant T790M may also play a role in drug responsiveness. To explore this, we have utilized an EGFR-null CHO overexpression system as well as NSCLC cell lines expressing various EGFR mutants and determined the effects of erlotinib treatment. We found that erlotinib inhibits EGFR phosphorylation in both TKI sensitive and resistant cells, but the protein half-lives of L858R and delE746-A750 were significantly shorter than L858R/T790M. Third generation EGFR kinase inhibitor (AZD9291) inhibits the growth of L858R/T790M-EGFR driven cells and also induces EGFR degradation. Erlotinib treatment induced polyubiquitination and proteasomal degradation, primarily in a c-CBL-independent manner, in TKI sensitive L858R and delE746-A750 mutants when compared to the L858R/T790M mutant, which correlated with drug sensitivity. These data suggest an additional mechanism of TKI resistance, and we postulate that agents that degrade L858R/T790M-EGFR protein may overcome TKI resistance. PMID:27612423

  3. Characterization of rag1 mutant zebrafish leukocytes

    PubMed Central

    Petrie-Hanson, Lora; Hohn, Claudia; Hanson, Larry

    2009-01-01

    Background Zebrafish may prove to be one of the best vertebrate models for innate immunology. These fish have sophisticated immune components, yet rely heavily on innate immune mechanisms. Thus, the development and characterization of mutant and/or knock out zebrafish are critical to help define immune cell and immune gene functions in the zebrafish model. The use of Severe Combined Immunodeficient (SCID) and recombination activation gene 1 and 2 mutant mice has allowed the investigation of the specific contribution of innate defenses in many infectious diseases. Similar zebrafish mutants are now being used in biomedical and fish immunology related research. This report describes the leukocyte populations in a unique model, recombination activation gene 1-/- mutant zebrafish (rag1 mutants). Results Differential counts of peripheral blood leukocytes (PBL) showed that rag1 mutants had significantly decreased lymphocyte-like cell populations (34.7%) compared to wild-types (70.5%), and significantly increased granulocyte populations (52.7%) compared to wild-types (17.6%). Monocyte/macrophage populations were similar between mutants and wild-types, 12.6% and 11.3%, respectively. Differential leukocyte counts of rag1 mutant kidney hematopoietic tissue showed a significantly reduced lymphocyte-like cell population (8%), a significantly increased myelomonocyte population (57%), 34.8% precursor cells, and 0.2% thrombocytes, while wild-type hematopoietic kidney tissue showed 29.4% lymphocytes/lymphocyte-like cells, 36.4% myelomonocytes, 33.8% precursors and 0.5% thrombocytes. Flow cytometric analyses of kidney hematopoietic tissue revealed three leukocyte populations. Population A was monocytes and granulocytes and comprised 34.7% of the gated cells in rag1 mutants and 17.6% in wild-types. Population B consisted of hematopoietic precursors, and comprised 50% of the gated cells for rag1 mutants and 53% for wild-types. Population C consisted of lymphocytes and lymphocyte

  4. Characteristics of Agrobacterium tumefaciens auxotrophic mutant infectivity.

    PubMed

    Lippincott, B B; Lippincott, J A

    1966-10-01

    Lippincott, Barbara B. (Northwestern University, Evanston, Ill.), and James A. Lippincott. Characteristics of Agrobacterium tumefaciens auxotrophic mutant infectivity. J. Bacteriol. 92:937-945. 166.-Mutants of Agrobacterium tumefaciens auxotrophic for adenine, methionine, or asparagine are less infectious than the wild-type strain B6 from which they were derived and show increased infectivity on pinto bean leaves when the specific compounds required for growth of the mutants are added to the infected leaf. Reversion to a prototrophic form of nutrition is accompanied by increased infectivity. Tumors initiated by these auxotrophic mutants are shown to arise only at large wound sites where nutritional conditions may be less restricting. The data indicate that, after inoculation, the bacteria pass through a phase in which host-supplied nutrients are utilized for the production of one or more factors necessary for successful tumor initiation.

  5. Mutant IDH1 and thrombosis in gliomas.

    PubMed

    Unruh, Dusten; Schwarze, Steven R; Khoury, Laith; Thomas, Cheddhi; Wu, Meijing; Chen, Li; Chen, Rui; Liu, Yinxing; Schwartz, Margaret A; Amidei, Christina; Kumthekar, Priya; Benjamin, Carolina G; Song, Kristine; Dawson, Caleb; Rispoli, Joanne M; Fatterpekar, Girish; Golfinos, John G; Kondziolka, Douglas; Karajannis, Matthias; Pacione, Donato; Zagzag, David; McIntyre, Thomas; Snuderl, Matija; Horbinski, Craig

    2016-12-01

    Mutant isocitrate dehydrogenase 1 (IDH1) is common in gliomas, and produces D-2-hydroxyglutarate (D-2-HG). The full effects of IDH1 mutations on glioma biology and tumor microenvironment are unknown. We analyzed a discovery cohort of 169 World Health Organization (WHO) grade II-IV gliomas, followed by a validation cohort of 148 cases, for IDH1 mutations, intratumoral microthrombi, and venous thromboemboli (VTE). 430 gliomas from The Cancer Genome Atlas were analyzed for mRNAs associated with coagulation, and 95 gliomas in a tissue microarray were assessed for tissue factor (TF) protein. In vitro and in vivo assays evaluated platelet aggregation and clotting time in the presence of mutant IDH1 or D-2-HG. VTE occurred in 26-30 % of patients with wild-type IDH1 gliomas, but not in patients with mutant IDH1 gliomas (0 %). IDH1 mutation status was the most powerful predictive marker for VTE, independent of variables such as GBM diagnosis and prolonged hospital stay. Microthrombi were far less common within mutant IDH1 gliomas regardless of WHO grade (85-90 % in wild-type versus 2-6 % in mutant), and were an independent predictor of IDH1 wild-type status. Among all 35 coagulation-associated genes, F3 mRNA, encoding TF, showed the strongest inverse relationship with IDH1 mutations. Mutant IDH1 gliomas had F3 gene promoter hypermethylation, with lower TF protein expression. D-2-HG rapidly inhibited platelet aggregation and blood clotting via a novel calcium-dependent, methylation-independent mechanism. Mutant IDH1 glioma engraftment in mice significantly prolonged bleeding time. Our data suggest that mutant IDH1 has potent antithrombotic activity within gliomas and throughout the peripheral circulation. These findings have implications for the pathologic evaluation of gliomas, the effect of altered isocitrate metabolism on tumor microenvironment, and risk assessment of glioma patients for VTE.

  6. Plastidic phosphoglucomutase and ADP-glucose pyrophosphorylase mutants impair starch synthesis in rice pollen grains and cause male sterility

    PubMed Central

    Lee, Sang-Kyu; Eom, Joon-Seob; Hwang, Seon-Kap; Shin, Dongjin; An, Gynheung; Okita, Thomas W.; Jeon, Jong-Seong

    2016-01-01

    To elucidate the starch synthesis pathway and the role of this reserve in rice pollen, we characterized mutations in the plastidic phosphoglucomutase, OspPGM, and the plastidic large subunit of ADP-glucose (ADP-Glc) pyrophosphorylase, OsAGPL4. Both genes were up-regulated in maturing pollen, a stage when starch begins to accumulate. Progeny analysis of self-pollinated heterozygous lines carrying the OspPGM mutant alleles, osppgm-1 and osppgm-2, or the OsAGPL4 mutant allele, osagpl4-1, as well as reciprocal crosses between the wild type (WT) and heterozygotes revealed that loss of OspPGM or OsAGPL4 caused male sterility, with the former condition rescued by the introduction of the WT OspPGM gene. While iodine staining and transmission electron microscopy analyses of pollen grains from homozygous osppgm-1 lines produced by anther culture confirmed the starch null phenotype, pollen from homozygous osagpl4 mutant lines, osagpl4-2 and osagpl4-3, generated by the CRISPR/Cas system, accumulated small amounts of starch which were sufficient to produce viable seed. Such osagpl4 mutant pollen, however, was unable to compete against WT pollen successfully, validating the important role of this reserve in fertilization. Our results demonstrate that starch is mainly polymerized from ADP-Glc synthesized from plastidic hexose phosphates in rice pollen and that starch is an essential requirement for successful fertilization in rice. PMID:27588462

  7. Plastidic phosphoglucomutase and ADP-glucose pyrophosphorylase mutants impair starch synthesis in rice pollen grains and cause male sterility.

    PubMed

    Lee, Sang-Kyu; Eom, Joon-Seob; Hwang, Seon-Kap; Shin, Dongjin; An, Gynheung; Okita, Thomas W; Jeon, Jong-Seong

    2016-10-01

    To elucidate the starch synthesis pathway and the role of this reserve in rice pollen, we characterized mutations in the plastidic phosphoglucomutase, OspPGM, and the plastidic large subunit of ADP-glucose (ADP-Glc) pyrophosphorylase, OsAGPL4 Both genes were up-regulated in maturing pollen, a stage when starch begins to accumulate. Progeny analysis of self-pollinated heterozygous lines carrying the OspPGM mutant alleles, osppgm-1 and osppgm-2, or the OsAGPL4 mutant allele, osagpl4-1, as well as reciprocal crosses between the wild type (WT) and heterozygotes revealed that loss of OspPGM or OsAGPL4 caused male sterility, with the former condition rescued by the introduction of the WT OspPGM gene. While iodine staining and transmission electron microscopy analyses of pollen grains from homozygous osppgm-1 lines produced by anther culture confirmed the starch null phenotype, pollen from homozygous osagpl4 mutant lines, osagpl4-2 and osagpl4-3, generated by the CRISPR/Cas system, accumulated small amounts of starch which were sufficient to produce viable seed. Such osagpl4 mutant pollen, however, was unable to compete against WT pollen successfully, validating the important role of this reserve in fertilization. Our results demonstrate that starch is mainly polymerized from ADP-Glc synthesized from plastidic hexose phosphates in rice pollen and that starch is an essential requirement for successful fertilization in rice.

  8. Specific loss of apoptotic but not cell-cycle arrest function in a human tumor derived p53 mutant.

    PubMed Central

    Rowan, S; Ludwig, R L; Haupt, Y; Bates, S; Lu, X; Oren, M; Vousden, K H

    1996-01-01

    The p53 tumor-suppressor gene product is frequently inactivated in malignancies by point mutation. Although most tumor-derived p53 mutants show loss of sequence specific transcriptional activation, some mutants have been identified which retain this activity. One such mutant, p53175P, is defective for the suppression of transformation in rodent cells, despite retaining the ability to suppress the growth of p53-null human cells. We now demonstrate that p53175P can induce a cell-cycle arrest in appropriate cell types but shows loss of apoptotic function. Our results therefore support a direct role of p53 transcriptional activation in mediating a cell-cycle arrest and demonstrate that such activity is not sufficient for the full apoptotic response. These data suggest that either p53 can induce apoptosis through a transcriptionally independent mechanism, a function lost by p53175P, or that this mutant has specifically lost the ability to activate genes which contribute to cell death, despite activation of genes responsible for the G1 arrest. This dissociation of the cell-cycle arrest and apoptotic activities of p53 indicates that inactivation of p53 apoptotic function without concomitant loss of growth inhibition can suffice to relieve p53-dependent tumor-suppression in vivo and thereby contribute to tumor development. Images PMID:8631304

  9. Immediate-early regulatory gene mutants define different stages in the establishment and reactivation of herpes simplex virus latency.

    PubMed Central

    Leib, D A; Coen, D M; Bogard, C L; Hicks, K A; Yager, D R; Knipe, D M; Tyler, K L; Schaffer, P A

    1989-01-01

    Using nonsense and deletion mutants of herpes simplex virus type 1, we investigated the roles of three immediate-early proteins (ICP4, ICP27 and ICP0) in the establishment and reactivation of ganglionic latency in a mouse ocular model. DNA hybridization, superinfection-rescue, and cocultivation techniques provided quantitative data that distinguished between the failure of a virus to establish latency in the ganglion and its failure to reactivate. Null mutants with lesions in the genes for ICP4 and ICP27 did not replicate in the eye or in ganglia and failed to establish reactivatable latent infections. Three ICP0 deletion mutants which could replicate in the eye and ganglia varied in their ability to establish and reactivate from the latent state, demonstrating that ICP0 plays a role both in the establishment and the reactivation of latency. The use of viral mutants and a variety of stage-specific assays allowed us to better define the stages in the establishment and reactivation of herpes simplex virus type 1 latency. Images PMID:2536101

  10. Altered Mitochondrial Respiration and Other Features of Mitochondrial Function in Parkin-Mutant Fibroblasts from Parkinson's Disease Patients

    PubMed Central

    Swart, Chrisna; van der Westhuizen, Francois; van Dyk, Hayley; van der Merwe, Lize; van der Merwe, Celia; Loos, Ben; Carr, Jonathan; Kinnear, Craig; Bardien, Soraya

    2016-01-01

    Mutations in the parkin gene are the most common cause of early-onset Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, is involved in respiratory chain function, mitophagy, and mitochondrial dynamics. Human cellular models with parkin null mutations are particularly valuable for investigating the mitochondrial functions of parkin. However, published results reporting on patient-derived parkin-mutant fibroblasts have been inconsistent. This study aimed to functionally compare parkin-mutant fibroblasts from PD patients with wild-type control fibroblasts using a variety of assays to gain a better understanding of the role of mitochondrial dysfunction in PD. To this end, dermal fibroblasts were obtained from three PD patients with homozygous whole exon deletions in parkin and three unaffected controls. Assays of mitochondrial respiration, mitochondrial network integrity, mitochondrial membrane potential, and cell growth were performed as informative markers of mitochondrial function. Surprisingly, it was found that mitochondrial respiratory rates were markedly higher in the parkin-mutant fibroblasts compared to control fibroblasts (p = 0.0093), while exhibiting more fragmented mitochondrial networks (p = 0.0304). Moreover, cell growth of the parkin-mutant fibroblasts was significantly higher than that of controls (p = 0.0001). These unanticipated findings are suggestive of a compensatory mechanism to preserve mitochondrial function and quality control in the absence of parkin in fibroblasts, which warrants further investigation. PMID:27034887

  11. Isolation and characterization of unusual gin mutants.

    PubMed Central

    Klippel, A; Cloppenborg, K; Kahmann, R

    1988-01-01

    Site-specific inversion of the G segment in phage Mu DNA is promoted by two proteins, the DNA invertase Gin and the host factor FIS. Recombination occurs if the recombination sites (IR) are arranged as inverted repeats and a recombinational enhancer sequence is present in cis. Intermolecular reactions as well as deletions between direct repeats of the IRs rarely occur. Making use of a fis- mutant of Escherichia coli we have devised a scheme to isolate gin mutants that have a FIS independent phenotype. This mutant phenotype is caused by single amino acid changes at five different positions of gin. The mutant proteins display a whole set of new properties in vivo: they promote inversions, deletions and intermolecular recombination in an enhancer- and FIS-independent manner. The mutants differ in recombination activity. The most active mutant protein was analysed in vitro. The loss of site orientation specificity was accompanied with the ability to recombine even linear substrates. We discuss these results in connection with the role of the enhancer and FIS protein in the wild-type situation. Images PMID:2974801

  12. Quantitative Analysis of Triple Mutant Genetic Interactions

    PubMed Central

    Braberg, Hannes; Alexander, Richard; Shales, Michael; Xu, Jiewei; Franks-Skiba, Kathleen E.; Wu, Qiuqin; Haber, James E.; Krogan, Nevan J.

    2014-01-01

    The quantitative analysis of genetic interactions between pairs of gene mutations has proven effective for characterizing cellular functions but can miss important interactions for functionally redundant genes. To address this limitation, we have developed an approach termed Triple Mutant Analysis (TMA). The procedure relies on a query strain that contains two deletions in a pair of redundant or otherwise related genes, that is crossed against a panel of candidate deletion strains to isolate triple mutants and measure their growth. A central feature of TMA is to interrogate mutants that are synthetically sick when two other genes are deleted but interact minimally with either single deletion. This approach has been valuable for discovering genes that restore critical functions when the principle actors are deleted. TMA has also uncovered double mutant combinations that produce severe defects because a third protein becomes deregulated and acts in a deleterious fashion, and it has revealed functional differences between proteins presumed to act together. The protocol is optimized for Singer ROTOR pinning robots, takes 3 weeks to complete, and measures interactions for up to 30 double mutants against a library of 1536 single mutants. PMID:25010907

  13. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

    PubMed Central

    Lambert, Laura J.; Challa, Anil K.; Niu, Aidi; Zhou, Lihua; Tucholski, Janusz; Johnson, Maria S.; Nagy, Tim R.; Eberhardt, Alan W.; Estep, Patrick N.; Kesterson, Robert A.

    2016-01-01

    ABSTRACT Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance testing (ITT), microcomputed tomography (µCT), and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research. PMID:27483347

  14. Characterization of pullulanase (PUL)-deficient mutants of rice (Oryza sativa L.) and the function of PUL on starch biosynthesis in the developing rice endosperm

    PubMed Central

    Fujita, Naoko; Toyosawa, Yoshiko; Utsumi, Yoshinori; Higuchi, Toshiyuki; Hanashiro, Isao; Ikegami, Akira; Akuzawa, Sayuri; Yoshida, Mayumi; Mori, Akiko; Inomata, Kotaro; Itoh, Rumiko; Miyao, Akio; Hirochika, Hirohiko; Satoh, Hikaru; Nakamura, Yasunori

    2009-01-01

    Rice (Oryza sativa) allelic sugary1 (sug1) mutants defective in isoamylase 1 (ISA1) accumulate varying levels of starch and phytoglycogen in their endosperm, and the activity of a pullulanase-type of a debranching enzyme (PUL) was found to correlate closely with the severity of the sug1 phenotype. Thus, three PUL-deficient mutants were generated to investigate the function of PUL in starch biosynthesis. The reduction of PUL activity had no pleiotropic effects on the other enzymes involved in starch biosynthesis. The short chains (DP ≤13) of amylopectin in PUL mutants were increased compared with that of the wild type, but the extent of the changes was much smaller than that of sug1 mutants. The α-glucan composition [amylose, amylopectin, water-soluble polysaccharide (WSP)] and the structure of the starch components (amylose and amylopectin) of the PUL mutants were essentially the same, although the average chain length of the B2-3 chains of amylopectin in the PUL mutant was ∼3 residues longer than that of the wild type. The double mutants between the PUL-null and mild sug1 mutants still retained starch in the outer layer of endosperm tissue, while the amounts of WSP and short chains (DP ≤7) of amylopectin were higher than those of the sug1 mutant; this indicates that the PUL function partially overlaps with that of ISA1 and its deficiency has a much smaller effect on the synthesis of amylopectin than ISA1 deficiency and the variation of the sug1 phenotype is not significantly dependent on the PUL activities. PMID:19190097

  15. Ca2+ release in muscle fibers expressing R4892W and G4896V type 1 ryanodine receptor disease mutants.

    PubMed

    Lefebvre, Romain; Legrand, Claude; Groom, Linda; Dirksen, Robert T; Jacquemond, Vincent

    2013-01-01

    The large and rapidly increasing number of potentially pathological mutants in the type 1 ryanodine receptor (RyR1) prompts the need to characterize their effects on voltage-activated sarcoplasmic reticulum (SR) Ca(2+) release in skeletal muscle. Here we evaluated the function of the R4892W and G4896V RyR1 mutants, both associated with central core disease (CCD) in humans, in myotubes and in adult muscle fibers. For both mutants expressed in RyR1-null (dyspedic) myotubes, voltage-gated Ca(2+) release was absent following homotypic expression and only partially restored following heterotypic expression with wild-type (WT) RyR1. In muscle fibers from adult WT mice, both mutants were expressed in restricted regions of the fibers with a pattern consistent with triadic localization. Voltage-clamp-activated confocal Ca(2+) signals showed that fiber regions endowed with G4896V-RyR1s exhibited an ∼30% reduction in the peak rate of SR Ca(2+) release, with no significant change in SR Ca(2+) content. Immunostaining revealed no associated change in the expression of either α1S subunit (Cav1.1) of the dihydropyridine receptor (DHPR) or type 1 sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA1), indicating that the reduced Ca(2+) release resulted from defective RyR1 function. Interestingly, in spite of robust localized junctional expression, the R4892W mutant did not affect SR Ca(2+) release in adult muscle fibers, consistent with a low functional penetrance of this particular CCD-associated mutant.

  16. Numerical Study of the Gravitational and Electromagnetic Waves on the Null Cone

    NASA Astrophysics Data System (ADS)

    Babiuc, Maria

    2015-04-01

    The numerical calculation of the Einstein-Maxwell equations in a characteristic framework has not been done numerically before and is expected to shed new light on nonlinear phenomena like null memory. The main objective of this study is the analytical and numerical modeling of the of gravitational and electromagnetic radiation in a fully general relativistic framework, as it propagates on the null cone to null infinity, with no simplifications due to assumed symmetries. Moreover, the global interaction between the gravitational and electromagnetic radiation will be closely monitored, in order to reveal the electromagnetic radiation memory induced by the gravitational field. The numerical approach used, called the ``Cauchy-characteristic extraction'' method, is the most precise method for the computation of gravitational waveforms at infinite distance from a world-tube that encloses the source. The analytical and numerical models presented here will be implemented in the PittNull code, and the experience gained will be disseminated, in order to facilitate new standalone characteristic codes.This will lead to more insight on the interaction between gravitational and electromagnetic fields, and even point to new effects.

  17. Active optics null test system based on a liquid crystal programmable spatial light modulator

    SciTech Connect

    Ares, Miguel; Royo, Santiago; Sergievskaya, Irina; Riu, Jordi

    2010-11-10

    We present an active null test system adapted to test lenses and wavefronts with complex shapes and strong local deformations. This system provides greater flexibility than conventional static null tests that match only a precisely positioned, individual wavefront. The system is based on a cylindrical Shack-Hartmann wavefront sensor, a commercial liquid crystal programmable phase modulator (PPM), which acts as the active null corrector, enabling the compensation of large strokes with high fidelity in a single iteration, and a spatial filter to remove unmodulated light when steep phase changes are compensated. We have evaluated the PPM's phase response at 635 nm and checked its performance by measuring its capability to generate different amounts of defocus aberration, finding root mean squared errors below {lambda}/18 for spherical wavefronts with peak-to-valley heights of up to 78.7{lambda}, which stands as the limit from which diffractive artifacts created by the PPM have been found to be critical under no spatial filtering. Results of a null test for a complex lens (an ophthalmic customized progressive addition lens) are presented and discussed.

  18. Design of a single flat null-screen for testing a parabolic trough solar collector

    NASA Astrophysics Data System (ADS)

    Moreno-Oliva, Víctor Iván; Campos-García, Manuel; Román-Hernández, Edwin; Santiago-Alvarado, Agustín

    2014-11-01

    We present a null-screen design for testing the shape quality of the reflecting surface of a parabolic trough solar collector (PTSC). This technique is inexpensive, the whole surface is tested at once, and it is easy to implement. For this, we propose the design of a flat null-screen perpendicular to the optical axis of the PTSC in such a way that it allows testing of the full aperture; we compute the caustic associated with the reflected light rays on the desired surface and analyze the parameters that determine the null-screen dimensions. Additionally, we perform a numerical simulation to analyze the accuracy of the method by introducing random displacement errors into the measured data. Accuracies >0.35 mrad were found to evaluate the quality of surfaces with this method. The errors in the determination of the coordinates of the centroids of the reflected images must be measured with an accuracy >0.5 pixels, and the errors in the coordinates of the spots of the null-screen must be <0.5 mm.

  19. Active optics null test system based on a liquid crystal programmable spatial light modulator.

    PubMed

    Ares, Miguel; Royo, Santiago; Sergievskaya, Irina; Riu, Jordi

    2010-11-10

    We present an active null test system adapted to test lenses and wavefronts with complex shapes and strong local deformations. This system provides greater flexibility than conventional static null tests that match only a precisely positioned, individual wavefront. The system is based on a cylindrical Shack-Hartmann wavefront sensor, a commercial liquid crystal programmable phase modulator (PPM), which acts as the active null corrector, enabling the compensation of large strokes with high fidelity in a single iteration, and a spatial filter to remove unmodulated light when steep phase changes are compensated. We have evaluated the PPM's phase response at 635 nm and checked its performance by measuring its capability to generate different amounts of defocus aberration, finding root mean squared errors below λ/18 for spherical wavefronts with peak-to-valley heights of up to 78.7λ, which stands as the limit from which diffractive artifacts created by the PPM have been found to be critical under no spatial filtering. Results of a null test for a complex lens (an ophthalmic customized progressive addition lens) are presented and discussed.

  20. A Communication Researchers' Guide to Null Hypothesis Significance Testing and Alternatives

    ERIC Educational Resources Information Center

    Levine, Timothy R.; Weber, Rene; Park, Hee Sun; Hullett, Craig R.

    2008-01-01

    This paper offers a practical guide to use null hypotheses significance testing and its alternatives. The focus is on improving the quality of statistical inference in quantitative communication research. More consistent reporting of descriptive statistics, estimates of effect size, confidence intervals around effect sizes, and increasing the…

  1. A Critical Assessment of Null Hypothesis Significance Testing in Quantitative Communication Research

    ERIC Educational Resources Information Center

    Levine, Timothy R.; Weber, Rene; Hullett, Craig; Park, Hee Sun; Lindsey, Lisa L. Massi

    2008-01-01

    Null hypothesis significance testing (NHST) is the most widely accepted and frequently used approach to statistical inference in quantitative communication research. NHST, however, is highly controversial, and several serious problems with the approach have been identified. This paper reviews NHST and the controversy surrounding it. Commonly…

  2. A Game Theoretic Power Control Algorithm with Sequential Subchannel Nulling for Wireless Networks

    NASA Astrophysics Data System (ADS)

    Park, Jae Cheol; Kim, Yun Hee; Hong, Een Kee; Song, Iickho

    Based on game theory, a distributed power control algorithm with sequential subchannel nulling is proposed for ad-hoc networks. It is shown that the proposed method, by sharing subchannels appropriately according to the interference profiles, can reduce the power consumption of the network while satisfying the target rate of each link.

  3. An Argument Framework for the Application of Null Hypothesis Statistical Testing in Support of Research

    ERIC Educational Resources Information Center

    LeMire, Steven D.

    2010-01-01

    This paper proposes an argument framework for the teaching of null hypothesis statistical testing and its application in support of research. Elements of the Toulmin (1958) model of argument are used to illustrate the use of p values and Type I and Type II error rates in support of claims about statistical parameters and subject matter research…

  4. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal planeregion extending from 14 D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. TheVNC is a hybrid interferometriccoronagraphic approach for exoplanet science. It operates with high Lyot stopefficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential futureNASA flight telescopes. NASAGoddard Space Flight Center (GSFC) has a well-established effort to develop the VNCand its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and itsenabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry tounprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a W configurationto accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters.We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, criticaltechnologies and null sensing and control.

  5. A Range-Null Hypothesis Approach for Testing DIF under the Rasch Model

    ERIC Educational Resources Information Center

    Wells, Craig S.; Cohen, Allan S.; Patton, Jeffrey

    2009-01-01

    A primary concern with testing differential item functioning (DIF) using a traditional point-null hypothesis is that a statistically significant result does not imply that the magnitude of DIF is of practical interest. Similarly, for a given sample size, a non-significant result does not allow the researcher to conclude the item is free of DIF. To…

  6. Mixture of normal distributions in multivariate null intercept measurement error model.

    PubMed

    Aoki, Reiko; Pinto Júnior, Dorival Leão; Achcar, Jorge Alberto; Bolfarine, Heleno

    2006-01-01

    In this paper we propose the use of a multivariate null intercept measurement error model, where the true unobserved value of the covariate follows a mixture of two normal distributions. The proposed model is applied to a dental clinical trial presented in Hadgu and Koch (1999). A Bayesian approach is considered and a Gibbs Sampler is used to perform the computations.

  7. A novel mutation at the JK locus causing Jk null phenotype in a Chinese family.

    PubMed

    Meng, Yan; Zhou, Xueyan; Li, Yang; Zhao, Dan; Liang, Shuyuan; Zhao, Xuejian; Yang, Baoxue

    2005-12-01

    Urea transporters are a group of proteins that facilitate urea movement across biological membranes. Kidd blood group (Jk antigen) and urea transporter of human erythrocytes are carried by the same protein UT-B. To investigate the molecular basis of the Jk null phenotype in the Chinese population, blood samples from Chinese individuals were screened using the 2 mol/L urea solution hemolysis test. Urea and water permeability of erythrocytes membrane was measured by stopped-flow light scattering. Genomic DNA was extracted from lymphocytes. UT-B gene of JKnnu's family was analyzed using genomic PCR by primers designed to cover sequences of all exons and exon-intron boundaries in human UT-B gene. One Jk null subject was found from twenty thousand screened Chinese individuals, and it was confirmed that this individual did not express the erythrocyte urea transporter. Genomic sequence analysis of the Jk null individual showed that there were two point mutations, G-->C, which is novel, and G-->A, at the 3'-acceptor splice site (AG) of intron 5 of UT-B gene. Exon 6 is spliced out in the UT-B transcript due to either of these mutations. Water permeability in Jk null erythrocytes (Pf, -0.00037 cm/s) was significantly lower than that in normal erythrocytes (Pf, -0.00062 cm/s) after HgCl2 incubation, providing evidence for UT-B facilitated water transport in human erythrocytes.

  8. Better Statistics for Better Decisions: Rejecting Null Hypotheses Statistical Tests in Favor of Replication Statistics

    ERIC Educational Resources Information Center

    Sanabria, Federico; Killeen, Peter R.

    2007-01-01

    Despite being under challenge for the past 50 years, null hypothesis significance testing (NHST) remains dominant in the scientific field for want of viable alternatives. NHST, along with its significance level "p," is inadequate for most of the uses to which it is put, a flaw that is of particular interest to educational practitioners…

  9. Experimental progress in deep and broadband infrared nulling for TPF-I

    NASA Technical Reports Server (NTRS)

    Wallace, J. Kent; Bartos, Randall; Gappinger, Robert; Loya, Frank; Moser, Steve; Negron, John

    2005-01-01

    Our activities are focused upon the experimental demonstration of deep nulling in the mid-IR over a wide bandpass. Specifically, our near-term goal is demonstrating a contrast of 10^-6 at 10 um with a 25% spectral bandwidth.

  10. Nitrosative stress elicited by nNOSµ delocalization inhibits muscle force in dystrophin-null mice.

    PubMed

    Li, Dejia; Yue, Yongping; Lai, Yi; Hakim, Chady H; Duan, Dongsheng

    2011-01-01

    The mechanism of force reduction is not completely understood in Duchenne muscular dystrophy (DMD), a dystrophin-deficient lethal disease. Nitric oxide regulates muscle force. Interestingly, neuronal nitric oxide synthase µ (nNOSµ), a major source of muscle nitric oxide, is lost from the sarcolemma in DMD muscle. We hypothesize that nNOSµ delocalization contributes to force reduction in DMD. To test this hypothesis, we generated dystrophin/nNOSµ double knockout mice. Genetic elimination of nNOSµ significantly enhanced force in dystrophin-null mice. Pharmacological inhibition of nNOS yielded similar results. To further test our hypothesis, we studied δ-sarcoglycan-null mice, a model of limb-girdle muscular dystrophy. These mice had minimal sarcolemmal nNOSµ delocalization and muscle force was less compromised. Annihilation of nNOSµ did not improve their force either. To determine whether nNOSµ delocalization itself inhibited force, we corrected muscle disease in dystrophin-null mice with micro-dystrophins that either restored or did not restore sarcolemmal nNOSµ. Similar muscle force was obtained irrespective of nNOSµ localization. Additional studies suggest that nNOSµ delocalization selectively inhibits muscle force in dystrophin-null mice via nitrosative stress. In summary, we have demonstrated for the first time that nitrosative stress elicited by nNOSµ delocalization is an important mechanism underlying force loss in DMD.

  11. Incisional wound healing in transforming growth factor-beta1 null mice.

    PubMed

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B

    2000-01-01

    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  12. ELECTRIC CURRENT FILAMENTATION AT A NON-POTENTIAL MAGNETIC NULL-POINT DUE TO PRESSURE PERTURBATION

    SciTech Connect

    Jelínek, P.; Karlický, M.; Murawski, K.

    2015-10-20

    An increase of electric current densities due to filamentation is an important process in any flare. We show that the pressure perturbation, followed by an entropy wave, triggers such a filamentation in the non-potential magnetic null-point. In the two-dimensional (2D), non-potential magnetic null-point, we generate the entropy wave by a negative or positive pressure pulse that is launched initially. Then, we study its evolution under the influence of the gravity field. We solve the full set of 2D time dependent, ideal magnetohydrodynamic equations numerically, making use of the FLASH code. The negative pulse leads to an entropy wave with a plasma density greater than in the ambient atmosphere and thus this wave falls down in the solar atmosphere, attracted by the gravity force. In the case of the positive pressure pulse, the plasma becomes evacuated and the entropy wave propagates upward. However, in both cases, owing to the Rayleigh–Taylor instability, the electric current in a non-potential magnetic null-point is rapidly filamented and at some locations the electric current density is strongly enhanced in comparison to its initial value. Using numerical simulations, we find that entropy waves initiated either by positive or negative pulses result in an increase of electric current densities close to the magnetic null-point and thus the energy accumulated here can be released as nanoflares or even flares.

  13. Fabrication tolerant chalcogenide mid-infrared multimode interference coupler design with applications for Bracewell nulling interferometry.

    PubMed

    Goldsmith, Harry-Dean Kenchington; Cvetojevic, Nick; Ireland, Michael; Madden, Stephen

    2017-02-20

    Understanding exoplanet formation and finding potentially habitable exoplanets is vital to an enhanced understanding of the universe. The use of nulling interferometry to strongly attenuate the central star's light provides the opportunity to see objects closer to the star than ever before. Given that exoplanets are usually warm, the 4 µm Mid-Infrared region is advantageous for such observations. The key performance parameters for a nulling interferometer are the extinction ratio it can attain and how well that is maintained across the operational bandwidth. Both parameters depend on the design and fabrication accuracy of the subcomponents and their wavelength dependence. Via detailed simulation it is shown in this paper that a planar chalcogenide photonic chip, consisting of three highly fabrication tolerant multimode interference couplers, can exceed an extinction ratio of 60 dB in double nulling operation and up to 40 dB for a single nulling operation across a wavelength window of 3.9 to 4.2 µm. This provides a beam combiner with sufficient performance, in theory, to image exoplanets.

  14. Stable deep nulling in polychromatic unpolarized light with multiaxial beam combination.

    PubMed

    Buisset, Christophe; Rejeaunier, Xavier; Rabbia, Yves; Barillot, Marc

    2007-11-10

    In the context of the space-based nulling mission ESA-Darwin, Thales Alenia Space has developed a nulling breadboard for the European Space Agency (ESA): the multiaperture imaging interferometer (MAII) to demonstrate deep and stable nulling and to investigate various subsystems of the ESA-Darwin interferometer. Recently, we have extended our investigations to the multiaxial beam combination. This combination scheme presents many advantages: simplicity, compactness, and a high coupling efficiency for a three-beam combination. The near-infrared (lambda approximately 1.55 microm) MAII breadboard has been upgraded to the multiaxial beam combination. Polarization and stability issues have been thoroughly investigated. We report on the recent results we have obtained with the multiaxial configuration of MAII in unpolarized light with a relative spectral bandwidth of 5%: nulling ratios of mean value N=1.7 x 10(-5), stable over 1 h with a standard deviation sigma( N )=5.7 x 10(-7). These results indicate that the multiaxial beam combination has the potential to meet Darwin requirements.

  15. What Are Null Hypotheses? The Reasoning Linking Scientific and Statistical Hypothesis Testing

    ERIC Educational Resources Information Center

    Lawson, Anton E.

    2008-01-01

    We should dispense with use of the confusing term "null hypothesis" in educational research reports. To explain why the term should be dropped, the nature of, and relationship between, scientific and statistical hypothesis testing is clarified by explication of (a) the scientific reasoning used by Gregor Mendel in testing specific…

  16. Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

    SciTech Connect

    Kubiznak, David; Frolov, Valeri P.; Connell, Patrick; Krtous, Pavel

    2009-01-15

    In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a nondegenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4, 5, 6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.

  17. Virtual interferometer calibration method of a non-null interferometer for freeform surface measurements.

    PubMed

    Hao, Qun; Wang, Shaopu; Hu, Yao; Cheng, Hanglin; Chen, Meng; Li, Tengfei

    2016-12-10

    Non-null interferometry is a prospective method for aspheric and freeform surface measurements because of its potential versatility over null interferometry. Due to the existence of the retrace error, non-null testing usually has the drawbacks of low accuracy and inconvenient alignment of the surface under test (SUT). In this paper, a calibration method for freeform SUT in a non-null interferometer is introduced. This method calibrates the position and attitude of the SUT in a virtual interferometer with an optimization algorithm, and no accurate adjustment mechanism is required to adjust the SUT in the real interferometer. An application of this method in the digital moiré interferometric technique (DMIT) is presented. The retrace error and the influence of the alignment error can be removed after calibration. Experimental results indicate that with this calibration method, the DMIT can achieve a measurement repeatability of λ/20 (PV) when the freeform SUT has obvious alignment error. This is adequate for most aspheric and freeform surface measurements, especially when the vibration cannot be isolated completely and the freeform SUT is not easy to align.

  18. Interpretation of Chinese Overt and Null Embedded Arguments by English-Speaking Learners

    ERIC Educational Resources Information Center

    Zhao, Lucy Xia

    2012-01-01

    It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese…

  19. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome.

    PubMed

    Asaka, Yukiko; Jugloff, Denis G M; Zhang, Liang; Eubanks, James H; Fitzsimonds, Reiko Maki

    2006-01-01

    Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in the gene encoding the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Here we demonstrate that the Mecp2-null mouse model of Rett syndrome shows an age-dependent impairment in hippocampal CA1 long-term potentiation induced by tetanic or theta-burst stimulation. Long-term depression induced by repetitive low-frequency stimulation is also absent in behaviorally symptomatic Mecp2-null mice. Immunoblot analyses from behaviorally symptomatic Mecp2-null mice reveal altered expression of N-methyl-d-aspartate receptor subunits NR2A and NR2B. Presynaptic function is also affected, as demonstrated by a significant reduction in paired-pulse facilitation. Interestingly, the properties of basal neurotransmission are normal in the Mecp2-null mice, consistent with our observations that the levels of expression of synaptic and cytoskeletal proteins, including glutamate receptor subunits GluR1 and GluR2, PSD95, synaptophysin-1, synaptobrevin-2, synaptotagmin-1, MAP2, betaIII-tubulin and NF200, are not significantly altered. Together, these data provide the first evidence that the loss of Mecp2 expression is accompanied by age-dependent alterations in excitatory synaptic plasticity that are likely to contribute to the cognitive and functional deficits underlying Rett syndrome.

  20. Dmp1 Null Mice Develop a Unique Osteoarthritis-like Phenotype

    PubMed Central

    Zhang, Qi; Lin, Shuxian; Liu, Ying; Yuan, Baozhi; Harris, Steph E; Feng, Jian Q.

    2016-01-01

    Patients with hypophosphatemia rickets (including DMP1 mutations) develop severe osteoarthritis (OA), although the mechanism is largely unknown. In this study, we first identified the expression of DMP1 in hypertrophic chondrocytes using immunohistochemistry (IHC) and X-gal analysis of Dmp1-knockout-lacZ-knockin heterozygous mice. Next, we characterized the OA-like phenotype in Dmp1 null mice from 7-week-old to one-year-old using multiple techniques, including X-ray, micro-CT, H&E staining, Goldner staining, scanning electronic microscopy, IHC assays, etc. We found a classical OA-like phenotype in Dmp1 null mice such as articular cartilage degradation, osteophyte formation, and subchondral osteosclerosis. These Dmp1 null mice also developed unique pathological changes, including a biphasic change in their articular cartilage from the initial expansion of hypertrophic chondrocytes at the age of 1-month to a quick diminished articular cartilage layer at the age of 3-months. Further, these null mice displayed severe enlarged knees and poorly formed bone with an expanded osteoid area. To address whether DMP1 plays a direct role in the articular cartilage, we deleted Dmp1 specifically in hypertrophic chondrocytes by crossing the Dmp1-loxP mice with Col X Cre mice. Interestingly, these conditional knockout mice didn't display notable defects in either the articular cartilage or the growth plate. Because of the hypophosphatemia remained in the entire life span of the Dmp1 null mice, we also investigated whether a high phosphate diet would improve the OA-like phenotype. A 8-week treatment of a high phosphate diet significantly rescued the OA-like defect in Dmp1 null mice, supporting the critical role of phosphate homeostasis in maintaining the healthy joint morphology and function. Taken together, this study demonstrates a unique OA-like phenotype in Dmp1 null mice, but a lack of the direct impact of DMP1 on chondrogenesis. Instead, the regulation of phosphate homeostasis

  1. Dmp1 Null Mice Develop a Unique Osteoarthritis-like Phenotype.

    PubMed

    Zhang, Qi; Lin, Shuxian; Liu, Ying; Yuan, Baozhi; Harris, Steph E; Feng, Jian Q

    2016-01-01

    Patients with hypophosphatemia rickets (including DMP1 mutations) develop severe osteoarthritis (OA), although the mechanism is largely unknown. In this study, we first identified the expression of DMP1 in hypertrophic chondrocytes using immunohistochemistry (IHC) and X-gal analysis of Dmp1-knockout-lacZ-knockin heterozygous mice. Next, we characterized the OA-like phenotype in Dmp1 null mice from 7-week-old to one-year-old using multiple techniques, including X-ray, micro-CT, H&E staining, Goldner staining, scanning electronic microscopy, IHC assays, etc. We found a classical OA-like phenotype in Dmp1 null mice such as articular cartilage degradation, osteophyte formation, and subchondral osteosclerosis. These Dmp1 null mice also developed unique pathological changes, including a biphasic change in their articular cartilage from the initial expansion of hypertrophic chondrocytes at the age of 1-month to a quick diminished articular cartilage layer at the age of 3-months. Further, these null mice displayed severe enlarged knees and poorly formed bone with an expanded osteoid area. To address whether DMP1 plays a direct role in the articular cartilage, we deleted Dmp1 specifically in hypertrophic chondrocytes by crossing the Dmp1-loxP mice with Col X Cre mice. Interestingly, these conditional knockout mice didn't display notable defects in either the articular cartilage or the growth plate. Because of the hypophosphatemia remained in the entire life span of the Dmp1 null mice, we also investigated whether a high phosphate diet would improve the OA-like phenotype. A 8-week treatment of a high phosphate diet significantly rescued the OA-like defect in Dmp1 null mice, supporting the critical role of phosphate homeostasis in maintaining the healthy joint morphology and function. Taken together, this study demonstrates a unique OA-like phenotype in Dmp1 null mice, but a lack of the direct impact of DMP1 on chondrogenesis. Instead, the regulation of phosphate homeostasis

  2. THE NATURE OF FLARE RIBBONS IN CORONAL NULL-POINT TOPOLOGY

    SciTech Connect

    Masson, S.; Aulanier, G.; Pariat, E.; Schrijver, C. J.

    2009-07-20

    Flare ribbons are commonly attributed to the low-altitude impact, along the footprints of separatrices or quasi-separatrix layers (QSLs), of particle beams accelerated through magnetic reconnection. If reconnection occurs at a three-dimensional coronal magnetic null point, the footprint of the dome-shaped fan surface would map a closed circular ribbon. This paper addresses the following issues: does the entire circular ribbon brighten simultaneously, as expected because all fan field lines pass through the null point? And since the spine separatrices are singular field lines, do spine-related ribbons look like compact kernels? What can we learn from these observations about current sheet formation and magnetic reconnection in a null-point topology? The present study addresses these questions by analyzing Transition Region and Coronal Explorer and Solar and Heliospheric Observatory/Michelson Doppler Imager observations of a confined flare presenting a circular ribbon. Using a potential field extrapolation, we linked the circular shape of the ribbon with the photospheric mapping of the fan field lines originating from a coronal null point. Observations show that the flare ribbon outlining the fan lines brightens sequentially along the counterclockwise direction and that the spine-related ribbons are elongated. Using the potential field extrapolation as initial condition, we conduct a low-{beta} resistive magnetohydrodynamics simulation of this observed event. We drive the coronal evolution by line-tied diverging boundary motions, so as to emulate the observed photospheric flow pattern associated with some magnetic flux emergence. The numerical analysis allows us to explain several observed features of the confined flare. The vorticity induced in the fan by the prescribed motions causes the spines to tear apart along the fan. This leads to formation of a thin current sheet and induces null-point reconnection. We also find that the null point and its associated

  3. SOLAR CYCLE VARIATIONS OF CORONAL NULL POINTS: IMPLICATIONS FOR THE MAGNETIC BREAKOUT MODEL OF CORONAL MASS EJECTIONS

    SciTech Connect

    Cook, G. R.; Mackay, D. H.; Nandy, Dibyendu E-mail: duncan@mcs.st-and.ac.u

    2009-10-20

    In this paper, we investigate the solar cycle variation of coronal null points and magnetic breakout configurations in spherical geometry, using a combination of magnetic flux transport and potential field source surface models. Within the simulations, a total of 2843 coronal null points and breakout configurations are found over two solar cycles. It is found that the number of coronal nulls present at any time varies cyclically throughout the solar cycle, in phase with the flux emergence rate. At cycle maximum, peak values of 15-17 coronal nulls per day are found. No significant variation in the number of nulls is found from the rising to the declining phase. This indicates that the magnetic breakout model is applicable throughout both phases of the solar cycle. In addition, it is shown that when the simulations are used to construct synoptic data sets, such as those produced by Kitt Peak, the number of coronal nulls drops by a factor of 1/6. The vast majority of the coronal nulls are found to lie above the active latitudes and are the result of the complex nature of the underlying active region fields. Only 8% of the coronal nulls are found to be connected to the global dipole. Another interesting feature is that 18% of coronal nulls are found to lie above the equator due to cross-equatorial interactions between bipoles lying in the northern and southern hemispheres. As the majority of coronal nulls form above active latitudes, their average radial extent is found to be in the low corona below 1.25 R {sub sun} (175, 000 km above the photosphere). Through considering the underlying photospheric flux, it is found that 71% of coronal nulls are produced though quadrupolar flux distributions resulting from bipoles in the same hemisphere interacting. When the number of coronal nulls present in each rotation is compared to the number of bipoles emerging, a wide scatter is found. The ratio of coronal nulls to emerging bipoles is found to be approximately 1/3. Overall

  4. maLPA1-null mice as an endophenotype of anxious depression.

    PubMed

    Moreno-Fernández, R D; Pérez-Martín, M; Castilla-Ortega, E; Rosell Del Valle, C; García-Fernández, M I; Chun, J; Estivill-Torrús, G; Rodríguez de Fonseca, F; Santín, L J; Pedraza, C

    2017-04-04

    Anxious depression is a prevalent disease with devastating consequences and a poor prognosis. Nevertheless, the neurobiological mechanisms underlying this mood disorder remain poorly characterized. The LPA1 receptor is one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts as an intracellular signalling molecule. The loss of this receptor induces anxiety and several behavioural and neurobiological changes that have been strongly associated with depression. In this study, we sought to investigate the involvement of the LPA1 receptor in mood. We first examined hedonic and despair-like behaviours in wild-type and maLPA1 receptor null mice. Owing to the behavioural response exhibited by the maLPA1-null mice, the panic-like reaction was assessed. In addition, c-Fos expression was evaluated as a measure of the functional activity, followed by interregional correlation matrices to establish the brain map of functional activation. maLPA1-null mice exhibited anhedonia, agitation and increased stress reactivity, behaviours that are strongly associated with the psychopathological endophenotype of depression with anxiety features. Furthermore, the functional brain maps differed between the genotypes. The maLPA1-null mice showed increased limbic-system activation, similar to that observed in depressive patients. Antidepressant treatment induced behavioural improvements and functional brain normalisation. Finally, based on validity criteria, maLPA1-null mice are proposed as an animal model of anxious depression. Here, for we believe the first time, we have identified a possible relationship between the LPA1 receptor and anxious depression, shedding light on the unknown neurobiological basis of this subtype of depression and providing an opportunity to explore new therapeutic targets for the treatment of mood disorders, especially for the anxious subtype of depression.

  5. Molecular identification of rare FY*Null and FY*X alleles in Caucasian thalassemic family from Sardinia.

    PubMed

    Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

    2015-10-01

    Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping.

  6. Partial suppression of the respiratory defect of qrs1/her2 glutamyl-tRNA amidotransferase mutants by overexpression of the mitochondrial pentatricopeptide Msc6p.

    PubMed

    Moda, Bruno S; Ferreira-Júnior, José Ribamar; Barros, Mario H

    2016-08-01

    Recently, a large body of evidences indicates the existence in the mitochondrial matrix of foci that contain different proteins involved in mitochondrial RNA metabolism. Some of these proteins have a pentatricopeptide repeat motif that constitutes their RNA-binding structures. Here we report that MSC6, a mitochondrial pentatricopeptide protein of unknown function, is a multi copy suppressor of mutations in QRS1/HER2 a component of the trimeric complex that catalyzes the transamidation of glutamyl-tRNAQ to glutaminyl-tRNAQ. This is an essential step in mitochondrial translation because of the lack of a specific mitochondrial aminoacyl glutaminyl-tRNA synthetase. MSC6 over-expression did not abolish translation of an aberrant variant form of Cox2p detected in QRS1/HER2 mutants, arguing against a suppression mechanism that bypasses Qrs1p function. A slight decrement of the mitochondrial translation capacity as well as diminished growth on respiratory carbon sources media for respiratory activity was observed in the msc6 null mutant. Additionally, the msc6 null mutant did not display any impairment in RNA transcription, processing or turnover. We concluded that Msc6p is a mitochondrial matrix protein and further studies are required to indicate the specific function of Msc6p in mitochondrial translation.

  7. A NADP-glutamate dehydrogenase mutant of the petit-negative yeast Kluyveromyces lactis uses the glutamine synthetase-glutamate synthase pathway for glutamate biosynthesis.

    PubMed

    Valenzuela, L; Guzmán-León, S; Coria, R; Ramírez, J; Aranda, C; González, A

    1995-10-01

    The activities of the enzymes involved in ammonium assimilation and glutamate biosynthesis were determined in wild-type and NADP-glutamate dehydrogenase (GDH) null mutant strains of Kluyveromyces lactis. The specific NADP-GDH activity from K. lactis was fivefold lower than that found in Saccharomyces cerevisiae. The glutamine synthetase (GS) and glutamate synthase (GOGAT) activities were similar to those reported in S. cerevisiae. The NADP-GDH null mutant was obtained by transforming the uraA strain MD2/1 with a linearized integrative yeast vector harbouring a 390 bp fragment of the NADP-GDH structural gene. This mutant grew as well as the parent strain on ammonium, but showed GS and GOGAT activities higher that those found in the wild-type strain, implying that the GS-GOGAT pathway could play a leading role in glutamate biosynthesis in K. lactis. Southern blotting analysis of K. lactis chromosomes separated by contour-clamped homogeneous electric field electrophoresis, indicated that the NADP-GDH structural gene is localized on chromosome VI.

  8. Timed conditional null of connexin26 in mice reveals temporary requirements of connexin26 in key cochlear developmental events before the onset of hearing.

    PubMed

    Chang, Qing; Tang, Wenxue; Kim, Yeunjung; Lin, Xi

    2015-01-01

    Mutations in the Gjb2 gene, which encodes a gap junction protein connexin26 (Cx26), are the most prevalent form of hereditary deafness in humans and represent about half of non-syndromic congenital deafness cases in many ethnic populations. Cochlear potassium (K+) recycling in mature cochlea is required for normal hearing. It is thought that gap junctions are essential for K+ recycling and that Gjb2 mutations cause Gjb2-associated deafness by disrupting K+ recycling in mature cochlea. Here we present evidence showing that Gjb2 is required for normal development of the neonatal organ of Corti prior to the onset of the hearing in mice. In the conditional Gjb2 null (cCx26 null) mice, ribbon synapses in inner hair cells remained poorly developed, the afferent type I fibers failed to finish the refinement process to form convergent innervation to individual inner hair cells. The spontaneous depolarizing activities in the supporting cells, which normally diminish in the wild type cochleae after postnatal day 8 (P8), remained strong in the cochlea after P8 in the mutant mice. Furthermore, the deafness phenotype was readily generated only if the Cx26 expression in the organ of Corti was significantly reduced before P6. Similar amount of Cx26 reduction in more mature cochleae had a much weaker effect in damaging the hearing sensitivity. Our findings indicated that Cx26 plays essential roles in the maturation process of the organ of Corti prior to the establishment of high K+ in the endolymph and the onset of hearing. These results suggest that successful treatment of Cx26 deafness requires early intervention before the cochlea fully matures.

  9. Characterization of shrunken endosperm mutants in barley.

    PubMed

    Ma, Jian; Jiang, Qian-Tao; Wei, Long; Wang, Ji-Rui; Chen, Guo-Yue; Liu, Ya-Xi; Li, Wei; Wei, Yu-Ming; Liu, Chunji; Zheng, You-Liang

    2014-04-10

    Despite numerous studies on shrunken endosperm mutants caused by either maternal tissues (seg) or kernel per se (sex) in barley, the molecular mechanism for all of the eight seg mutants (seg1-seg8) and some sex mutants is yet to be uncovered. In this study, we determined the amylose content, characterized granule-binding proteins, analyzed the expression of key genes involved in starch synthesis, and examined starch granule structure of both normal (Bowman and Morex) and shrunken endosperm (seg1, seg3, seg4a, seg4b, seg5, seg6, seg7, and sex1) barley accessions. Our results showed that amylose contents of shrunken endosperm mutants ranged from 8.9% (seg4a) to 25.8% (seg1). SDS-PAGE analysis revealed that 87 kDa proteins corresponding to the starch branching enzyme II (SBEII) and starch synthase II (SSII) were not present in seg1, seg3, seg6, and seg7 mutants. Real-time quantitative PCR (RT-qPCR) analysis indicated that waxy expression levels of seg1, seg3, seg6, and seg7 mutants decreased in varying degrees to lower levels until 27 days after anthesis (DAA) after reaching the peak at 15-21 DAA, which differed from the pattern of normal barley accessions. Further characterization of waxy alleles revealed 7 non-synonymous single nucleotide polymorphisms (SNPs) in the coding sequences and 16 SNPs and 8 indels in the promoter sequences of the mutants. Results from starch granule by scanning electron microscopy (SEM) indicated that, in comparison with normal barley accessions, seg4a, seg4b, and sex1 had fewer starch granules per grain; seg3 and seg6 had less small B-type granules; some large A-type granules in seg7 had a hollow surface. These results improve our understanding about effects of seg and sex mutants on starch biosynthesis and granule structure during endosperm development and provide information for identification of key genes responsible for these shrunken endosperm mutants.

  10. Peripheral and site-specific CD4(+) CD28(null) T cells from rheumatoid arthritis patients show distinct characteristics.

    PubMed

    Pieper, J; Johansson, S; Snir, O; Linton, L; Rieck, M; Buckner, J H; Winqvist, O; van Vollenhoven, R; Malmström, V

    2014-02-01

    Proinflammatory CD4(+) CD28(null) T cells are frequently found in the circulation of patients with rheumatoid arthritis (RA), but are less common in the rheumatic joint. In the present study, we sought to identify functional differences between CD4(+) CD28(null) T cells from blood and synovial fluid in comparison with conventional CD28-expressing CD4(+) T cells. Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments. Circulating CD4(+) CD28(null) T cells were significantly more hypomethylated in the CNS-1 region of the IFNG locus than conventional CD4(+) CD28(+) T cells and produced higher levels of both IFN-γ and TNF after TCR cross-linking. CD4(+) CD28(null) T cells from the site of inflammation expressed significantly more CXCR3 and CCR6 compared to their counterparts in blood. While IL-17A production could hardly be detected in CD4(+) CD28(null) cells from the blood, a significant production was observed in CD4(+) CD28(null) T cells from synovial fluid. CD4(+) CD28(null) T cells were not only found to differ from conventional CD4(+) CD28(+) T cells in the circulation, but we could also demonstrate that synovial CD4(+) CD28(null) T cells showed additional effector functions (IL-17 coproduction) as compared to the same subset in peripheral blood, suggesting an active role for these cells in the perpetuation of inflammation in the subset of patients having a CD28(null) population.

  11. CD4⁺CD28null T lymphocytes resemble CD8⁺CD28null T lymphocytes in their responses to IL-15 and IL-21 in HIV-infected patients.

    PubMed

    Echeverría, Ainara; Moro-García, Marco A; Asensi, Víctor; Cartón, José A; López-Larrea, Carlos; Alonso-Arias, Rebeca

    2015-09-01

    HIV-infected individuals suffer from accelerated immunologic aging. One of the most prominent changes during T lymphocyte aging is the accumulation of CD28(null) T lymphocytes, mainly CD8(+) but also CD4(+) T lymphocytes. Enhancing the functional properties of these cells may be important because they provide antigen-specific defense against chronic infections. The objective of this study was to compare the responses of CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes from HIV-infected patients to the immunomodulatory effects of cytokines IL-15 and IL-21. We quantified the frequencies of CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes in peripheral blood from 110 consecutive, HIV-infected patients and 25 healthy controls. Patients showed increased frequencies of CD4(+)CD28(null) and CD8(+)CD28(null). Both subsets were positively correlated to each other and showed an inverse correlation with the absolute counts of CD4(+) T lymphocytes. Higher frequencies of HIV-specific and CMV-specific cells were found in CD28(null) than in CD28(+) T lymphocytes. Activation of STAT5 by IL-15 and STAT3 by IL-21 was higher in CD28(null) compared with CD28(+) T lymphocytes. Proliferation, expression of CD69, and IFN-γ production in CD28(null) T lymphocytes were increased after treatment with IL-15, and IL-21 potentiated most of those effects. Nevertheless, IL-21 alone reduced IFN-γ production in response to anti-CD3 stimulation but increased CD28 expression, even counteracting the inhibitory effect of IL-15. Intracytoplasmic stores of granzyme B and perforin were increased by IL-15, whereas IL-21 and simultaneous treatment with the 2 cytokines also significantly enhanced degranulation in CD4(+)CD28(null) and CD8(+)CD28(null) T lymphocytes. IL-15 and IL-21 could have a role in enhancing the effector response of CD28(null) T lymphocytes against their specific chronic antigens in HIV-infected patients.

  12. Phanerochaete mutants with enhanced ligninolytic activity

    SciTech Connect

    Kakar, S.N.; Perez, A.; Gonzales, J.

    1993-06-01

    In addition to lignin, the white rot fungus Phanerochaete chrysosporium has the ability to degrade a wide spectrum of recalcitrant organopollutants in soils and aqueous media. Although some of the organic compounds are degraded under nonligninolytic conditions, most are degraded under ligninolytic conditions with the involvement of the extracellular enzymes, lignin peroxidases, and manganese-dependent peroxidases, which are produced as secondary metabolites triggered by conditions of nutrient starvation (e.g., nitrogen limitation). The fungus and its enzymes can thus provide alternative technologies for bioremediation, biopulping, biobleaching, and other industrial applications. The efficiency and effectiveness of the fungus can be enhanced by increasing production and secretion of the important enzymes in large quantities and as primary metabolites under enriched conditions. One way this can be achieved is through isolation of mutants that are deregulated or are hyperproducers or supersecretors of key enzymes under enriched conditions. Through ultraviolet-light and gamma-rays mutagenesis we have i