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Sample records for orotic aciduria reveals

  1. Hereditary orotic aciduria with epilepsy and without megaloblastic anemia.

    PubMed

    Grohmann, Karina; Lauffer, Heinz; Lauenstein, Peter; Hoffmann, Georg F; Seidlitz, Günter

    2015-04-01

    Hereditary orotic aciduria is a rare metabolic disease that results from a defect of uridine-5-monophosphate synthase (UMPS). In affected patients, main clinical symptoms are a markedly increased urinary excretion of orotic acid combined with megaloblastic anemia. This report describes a new case of UMPS deficiency without megaloblastic anemia but with epilepsy. PMID:25757096

  2. [Chronic hyperammonemia with orotic aciduria: evidence of pyrimidine pathway stimulation (author's transl)].

    PubMed

    Beaudry, M A; Letarte, J; Collu, R; Leboeuf, G; Ducharme, J R; Melancon, S B; Dallairf, L

    1975-03-01

    We have investigated a 3 year old girl with mental and physical retardation, chronic hyperammonemia and orotic aciduria. Plsma glutamine, alanine and proline concentrations were high. Alanine was present in her urine. She excreted only half the urea of control subjects on a similar protein intake. Raising protein intake induced NH4 intoxication with convulsion. Orotic aciduria was present (max: 693 mg/day) and was related to NH4 levels. Red blood cell orotate phosphoribosyl transferase and orotidine decarboxylase activieé were normal, eliminating congenital orotic aciduria, with induction of activity seen on repeated assay during protein load (form 1.37 to 7.5 nmole/109 RBC/hr). Blood ammonia rose with ornithine load, while ornithine levels were twice that of controls. Citrulline was normally metabolized. Although lacking liver assay, we have provided evidence of partial ornithine carbamyl transferase deficiency. The importance of orotic aciduria for ammonia detoxication in partial OCT deficiency is shown, and its possible effect on liver lipoprotein synthesis discussed. Our investigation also confirmed that OCT activity is not present in normal leukocytes rendering them useless for OCT deficiency diagnosis.

  3. Quantitation of orotic acid in urine using isotope dilution-selected ion gas chromatography-mass spectrometry.

    PubMed

    Chen, Jie; Bennett, Michael J

    2010-01-01

    The measurement of urinary orotic acid excretion is an important test for establishing a diagnosis of hereditary orotic aciduria, a genetic defect of pyrimidine biosynthesis. Measurement of secondary urinary orotic acid elevation is also an important clinical test for the differential diagnosis of hyperammonemia due to some of the primary disorders of the urea cycle including ornithine transcarbamylase (OTC) deficiency, and the hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome. Low levels of orotic acid are observed in carbamylphosphate synthetase (CPS) defects. This method utilizes a stable-isotope labeled internal standard (1, 3-(15)N-orotic acid), which is added to the standards, controls, and patient samples prior to extraction. Interference from urea is removed by incubation of samples with urease and the orotic acid is derivatized by trimethylsilylation. Quantitation is made against an eight-point standard curve using specific selected ions from both the labeled and unlabeled orotic acid. PMID:20077096

  4. Metabolic supplementation with orotic acid and magnesium orotate.

    PubMed

    Rosenfeldt, F L

    1998-09-01

    Orotic acid (OA), a naturally occurring substance, is a key intermediate in the biosynthetic pathway of pyrimidines. Previous investigations in the heart suggest that orotate can protect recently infarcted hearts against a further ischemic stress and may be beneficial in certain types of experimental cardiomyopathy. At the Hamburg symposium on magnesium orotate, a number of studies of this form of metabolic supplementation were presented that indicate orotic acid and its magnesium salt have a modest beneficial effect on the myocardium under conditions of stress ranging from myocardial infarction to severe physical exercise. The following conclusions can be drawn: (1) Orotic acid can improve the energy status of the recently infarcted myocardium (rat hearts). (2) Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream, which in turn augments depleted myocardial pyrimidines and purines (rat heart). (3) Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats). (4) Magnesium orotate may reduce the severity of chronic myocardial dysfunction and structural damage in cardiomyopathy (cardiomyopathic hamsters). (5) Magnesium orotate may improve exercise tolerance in patients with coronary artery disease and in trained athletes (humans). (6) Magnesium orotate has only a weak inotropic effect, if any, on normal hearts (rats). (7) Further clinical testing is indicated to determine if the effects described could be of significant clinical benefit in the treatment of heart disease. PMID:9794088

  5. Development of an assay to simultaneously measure orotic acid, amino acids, and acylcarnitines in dried blood spots

    PubMed Central

    Held, Patrice K.; Haynes, Christopher A.; De Jesús, Víctor R.; Baker, Mei W.

    2016-01-01

    Background Orotic aciduria in the presence of hyperammonemia is a key indicator for a defect in the urea cycle, specifically ornithine transcarbamylase (OTC) deficiency. Current newborn screening (NBS) protocols can detect several defects of the urea cycle, but screening for OTC deficiency remains a challenge due to the lack of a suitable assay. The purpose of this study was to develop a high-throughput assay to measure orotic acid in dried blood spot (DBS) specimens as an indicator for urea cycle dysfunction, which can be readily incorporated into routine NBS. Methods Orotic acid was extracted from DBS punches and analyzed using flow-injection analysis tandem mass spectrometry (FIA–MS/MS) with negative-mode ionization, requiring <2 min/sample run time. This method was then multiplexed into a conventional newborn screening assay for analysis of amino acids, acylcarnitines, and orotic acid. Results We describe 2 assays which can quantify orotic acid in DBS: a stand-alone method and a combined method for analysis of orotic acid, amino acids, and acylcarnitines. Both methods demonstrated orotic acid recovery of 75–85% at multiple levels of enrichment. Precision was also comparable to traditional FIA–MS/MS methods. Analysis of residual presumptively normal NBS specimens demonstrated a 5:1 signal to noise ratio and the average concentration of orotic acid was approximately 1.2 μmol/l. The concentration of amino acids and acylcarnitines as measured by the combined method showed no significant differences when compared to the conventional newborn screening assay. In addition, retrospective analysis of confirmed patients and presumptively normal newborn screening specimens suggests potential for the methods to identify patients with OTC deficiency, as well as other urea cycle defects. Conclusion The assays described here quantify orotic acid in DBS using a simple extraction and FIA–MS/MS analysis procedures that can be implemented into current NBS protocols. PMID

  6. Cytosinium orotate dihydrate.

    PubMed

    Portalone, Gustavo

    2013-01-01

    The title compound, C4H6N3O(+)·C5H3N2O4(-)·2H2O or Cyt(+)·Or(-)·2H2O, was synthesized by a reaction between cytosine (4-amino-2-hy-droxy-pyrimidine, Cyt) and orotic acid (2,4-dihy-droxy-6-carb-oxy-pyrimidine, Or) in aqueous solution. The two ions are joined by two N(+)-H⋯O(-) (±)-(CAHB) hydrogen bonds, forming a dimer with graph-set motif R2(2)(8). In the crystal, the ion pairs of the asymmetric unit are joined by four N-H⋯O inter-actions to adjacent dimers, forming hydrogen-bonded rings with R2(2)(8) graph-set motif in a two-dimensional network. The formation of the three-dimensional array is facilitated by water mol-ecules, which act as bridges between structural sub-units linked in R3(2)(8) and R3(2)(7) hydrogen-bonded rings. The orotate anion is essentially planar, as the dihedral angle between the planes defined by the carboxylate group and the uracil fragment is 4.0 (4)°. PMID:23476396

  7. Cytosinium orotate dihydrate

    PubMed Central

    Portalone, Gustavo

    2013-01-01

    The title compound, C4H6N3O+·C5H3N2O4 −·2H2O or Cyt+·Or−·2H2O, was synthesized by a reaction between cytosine (4-amino-2-hy­droxy­pyrimidine, Cyt) and orotic acid (2,4-dihy­droxy-6-carb­oxy­pyrimidine, Or) in aqueous solution. The two ions are joined by two N+—H⋯O− (±)-(CAHB) hydrogen bonds, forming a dimer with graph-set motif R 2 2(8). In the crystal, the ion pairs of the asymmetric unit are joined by four N—H⋯O inter­actions to adjacent dimers, forming hydrogen-bonded rings with R 2 2(8) graph-set motif in a two-dimensional network. The formation of the three-dimensional array is facilitated by water mol­ecules, which act as bridges between structural sub-units linked in R 3 2(8) and R 3 2(7) hydrogen-bonded rings. The orotate anion is essentially planar, as the dihedral angle between the planes defined by the carboxylate group and the uracil fragment is 4.0 (4)°. PMID:23476396

  8. Genetics Home Reference: 2-hydroxyglutaric aciduria

    MedlinePlus

    ... Climb National Information Centre for Metabolic Diseases (UK) Organic Acidemia Association: D-2 Hydroxyglutaric Aciduria Organic Acidemia Association: L-2 Hydroxyglutaric Aciduria Resource List ...

  9. Orotic acid content of infant formulas.

    PubMed

    Durschlag, R P; Robinson, J L

    1980-10-01

    The orotic acid content of four commercially available infant formulas has been examined. Enfamil contains 118 microgram orotic acid per milliliter as fed, Similac 98, SMA 27, and Isomil less than 1 microgram/ml. As expressed relative to total solids, these formulas contain less than 0.1% orotic acid. Since consumption of 1% orotic acid does not lead to a fatty liver in any species examined other than the rat and 0.1% orotic acid fails to induce statistically significant hepatic changes in the rat, it is suggested that orotic acid at the level found in these formulas is not likely to pose a health hazard to the infants consuming them.

  10. Milder clinical course of Type IV 3-methylglutaconic aciduria due to a novel mutation in TMEM70.

    PubMed

    Shchelochkov, Oleg A; Li, Fang-Yuan; Wang, Jing; Zhan, Hongli; Towbin, Jeffrey A; Jefferies, John Lynn; Wong, Lee-Jun; Scaglia, Fernando

    2010-01-01

    Mitochondrial disorders are a large and genetically heterogeneous group of disorders posing a significant diagnostic challenge. Only approximately 10-20% of patients have identifiable alterations in their mitochondrial DNA (mtDNA). The remaining ~80-90% of affected patients likely harbor mutations in nuclear genes, most of which are still poorly characterized, and therefore not amenable to efficient screening using currently available molecular methods. Here we present a patient, who has been followed since birth after presenting with neonatal hyperammonemia, lactic acidosis, Reye-like syndrome episodes, and ventricular tachyarrhythmia. Initial biochemical work-up revealed hyperalaninemia, normal plasma glutamine, mild orotic aciduria and significant amounts of urinary 3-methylglutaconic (3-MGC) and 3-methylglutaric (3-MGA) acids. Muscle biopsy demonstrated the presence of ragged-red fibers and non-specific structural abnormalities of mitochondria. The activities of respiratory chain enzymes (complexes I-IV) showed no deficiency. Mutational analysis of the entire mitochondrial genome did not reveal deleterious point mutations or large deletions. Long-term follow-up was significant for a later-onset hypertrophic cardiomyopathy, muscle weakness, and exercise intolerance. Although she had frequent episodes of Reye-like episodes in infancy and early childhood, mostly triggered by illnesses, these symptoms improved significantly with the onset of puberty. In the light of recent reports linking cases of type IV 3-methylglutaconic aciduria (3-MGCA) and hypertrophic cardiomyopathy to mutations in TMEM70, we proceeded with sequencing analysis of this gene. We identified one previously reported splice site mutation, c.317-2A>G and a novel mutation c.494G>A (p.G165D) in an evolutionarily conserved region predicted to be deleterious. This variant was not identified in 100 chromosomes of healthy control subjects and 200 chromosomes of patients with cardiomyopathies. Western

  11. Glutaric aciduria type I associated with learning disability.

    PubMed

    Patil, Neela; Shinde, Santosh; Karande, Sunil; Kulkarni, Madhuri

    2004-10-01

    The authors report a 7-year-8-months-old boy with glutaric aciduria type I who had associated dyslexia, dysgraphia and dyscalculia. The diagnosis of glutaric aciduria type I was confirmed on the basis of characteristic neuroimaging and biochemical findings. Axial T1-weighted magnetic resonance imaging scan of the brain showed fronto-temporal atrophy, open opercula and bat-wing dilatation of the sylvian fissures. Axial T[2]-weighted and FLAIR imaging showed hyperintense signal abnormality in both putamen and in the fronto-parietal deep white matter. Urinary aminoacidogram by thin layer chromatography revealed a generalized aminoaciduria. Urinary organic acid analysis by gas chromatography- mass spectroscopy revealed a marked excretion of glutaric acid. Psychoeducational testing was used to diagnose the learning disability. We postulate that the accumulation of glutaric acid and other metabolites was responsible for the child developing the associated learning disability. PMID:15531849

  12. Orotic acid quantification in dried blood spots and biological fluids by hydrophilic interaction liquid chromatography tandem mass spectrometry.

    PubMed

    D'Apolito, Oceania; Garofalo, Daniela; Paglia, Giuseppe; Zuppaldi, Alfredo; Corso, Gaetano

    2010-03-01

    Orotic acid (ORA) is an intermediate metabolite in the pathway of pyrimidine nucleotides; its urinary excretion is useful to diagnose the hereditary orotic aciduria and some hyperammonemic inherited defects of urea cycle enzymes and amino acid transporters. ORA analysis is based on stable isotope dilution by GC-MS or LC-MS/MS methods. We developed a fast assay that measures the ORA in dried blood spots (DBS), plasma and urine using hydrophilic interaction LC-MS/MS. Within- and between-day analytical imprecision (CV%) of three quality control levels, in plasma, DBS and urine, ranged from 0.8 to 14.1%, while the inaccuracy ranged from -13.5 to 9.4%. In healthy children (n=20), ORA concentrations were less than 0.69 microM in plasma, less than 0.82 microM in DBS and from 0.2 to 1.4 mmol/mol of creatinine in urine. A patient with citrullinemia showed ORA levels of 133 microM in plasma and 39 microM in DBS. A patient with hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome presented a urinary ORA level of 9.1 mmol/mol of creatinine. The method is potentially able to discriminate affected patients from reference subjects; the clinical validation should be expanded on a higher number of patients. PMID:20209505

  13. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats.

    PubMed Central

    Smith, D F

    1976-01-01

    1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion. PMID:1260219

  14. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats.

    PubMed

    Smith, D F

    1976-04-01

    1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion. PMID:1260219

  15. Fungal metabolic model for type I 3-methylglutaconic aciduria.

    PubMed

    Rodríguez, José M; Ruíz-Sala, Pedro; Ugarte, Magdalena; Peñalva, Miguel A

    2004-07-30

    Aspergillus nidulans catabolizes Leu to acetyl-CoA and acetoacetate through a pathway homologous to that used by humans. Fungal hlyA encodes a bifunctional polypeptide comprising the last two enzymes in this pathway, 3-methylglutaconyl-CoA hydratase and 3-hydroxy-3-methylglutaryl-CoA lyase. hlyA transcription is specifically induced by Leu. A Delta hlyA mutation removing the complete 3-methylglutaconyl-CoA hydratase C-terminal domain prevents growth on Leu but not on lactose or other amino acids and, in agreement with the predicted enzyme function, leads to Leu-dependent accumulation of 3-methylglutaconic acid in the culture supernatant. These data represent a formal demonstration in vivo of the specific involvement of 3-methylglutaconyl-CoA hydratase in Leu catabolism. Type I 3-methylglutaconic aciduria patients deficient in 3-methylglutaconyl-CoA hydratase show urinary excretion of 3-methylglutaconic acid and, in contrast to the other three types of methylglutaconic acidurias, 3-hydroxyisovaleric acid excretion. Gas chromatography-mass spectrometry analysis revealed an accumulation of both diagnostic compounds in Delta hlyA culture supernatants, illustrating that the metabolic consequences of equivalent inborn errors of metabolism are conserved from fungi to humans. Using our fungal type I 3-methylglutaconic aciduria model, we show that metabolites accumulating in the deficient strain are toxic, although less so than those accumulating in a Delta mccB strain deficient for the upstream enzyme 3-methylcrotonyl-CoA carboxylase. Diagnostic metabolite accumulation is Leu concentration-dependent, in agreement with the ability of Leu intake restriction to reduce the levels of offending metabolites. Delta mccB and Delta hlyA mutations show additive Leu toxicities. The double mutant accumulates 3-methylglutaconic acid, which can therefore be synthesized through 3-methylcrotonyl-CoA carboxylase-dependent and -independent reactions.

  16. D-2-hydroxyglutaric aciduria: case report and biochemical studies.

    PubMed

    Chalmers, R A; Lawson, A M; Watts, R W; Tavill, A S; Kamerling, J P; Hey, E; Ogilvie, D

    1980-01-01

    A patient with protein-losing gastroenteropathy and egg allergy has been shown to have a previously unrecognized organic aciduria, D-2-hydroxyglutaric aciduria. The observations made are consistent with an inherited metabolic disorder in the catabolism of 5-aminolaevulinate possibly due to deficient activity of a specific D-2-hydroxyglutarate dehydrogenase.

  17. L-2-hydroxyglutaric aciduria in two female Yorkshire terriers.

    PubMed

    Sanchez-Masian, Daniel F; Artuch, Rafael; Mascort, Joan; Jakobs, Corlenis; Salomons, Gajja; Zamora, Angeles; Casado, Mercedes; Fernandez, Matilde; Recio, Alfredo; Lujan, Alejandro

    2012-01-01

    Two female Yorkshire terrier puppies were presented with generalized tonic-clonic seizures and ataxia. MRI revealed bilaterally symmetrical, diffuse regions of gray matter hyperintensity on T2-weighted and fluid-attenuated inversion recovery sequences. Urinary organic acids were quantified by gas chromatography-mass spectroscopy and were consistent with a diagnosis of L-2-hydroxyglutaric aciduria (L2HGA). The L2HGDH gene encodes for the enzyme L-2-hydroxyglutarate dehydrogenase, which helps break down L-2-hydroxyglutaric acid. In both puppies described in this report, a homozygous mutation at the translation initiation codon of the homolog canine L2HGDH gene was detected (c.1A>G; p.Met1?), confirming the diagnosis of L2HGA at the DNA level. Canine L2HGA is caused by more than one mutation of L2HGDH, as reported in humans.

  18. Lithium orotate in the treatment of alcoholism and related conditions.

    PubMed

    Sartori, H E

    1986-01-01

    The subjects were 42 alcoholic patients (33 males and 9 females) who were treated with lithium orotate during an alcohol rehabilitation program in a private clinical setting for at least six months. They derive from a total number of 105 patients who received this treatment initially, while the remainder discontinued the treatment within six months. The data were collected from a private practice record and the follow-up varied between six months and 10 years. The 42 patients studied displayed a multitude of complaints in addition to chronic alcoholism. These included liver dysfunction, seizure disorders, headaches, hyperthyroidism, affective disorders. Meniere's syndrome, liver and lung cancers. Thirty-six of the 42 patients studied had been hospitalized at least once for the management of their alcoholism. Lithium orotate was given, 150 mg daily, with a diet low in simple carbohydrates and containing moderate amounts of protein and fat. In addition, calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and supportive measures were instituted, if required. Lithium orotate proved useful as the main pharmacologic agent for the treatment of alcoholism. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. Lithium orotate therapy was safe and the adverse side effects noted were minor, i.e., eight patients developed muscle weakness, loss of appetite or mild apathy. For these patients, the symptoms subsided when the daily dose was given 4 to 5 times weekly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3718672

  19. Accumulation of Pyrimidine Intermediate Orotate Decreases Virulence Factor Production in Pseudomonas aeruginosa.

    PubMed

    Niazy, Abdurahman; Hughes, Lee E

    2015-08-01

    The impact of orotate accumulation in the medically important bacterium Pseudomonas aeruginosa was studied by deleting pyrE, the gene encoding orotate phosphoribosyltransferase and responsible for converting orotate into orotate monophosphate within the de novo pyrimidine synthesis pathway. The pyrE mutant accumulated orotate and exhibited decreased production of hemolysin, casein protease, and elastase. Feeding orotate at a concentration of 51.25 μM to the wild type, PAO1, likewise decreased production of these factors except for hemolysin, which was not affected. A significant increase in the pigments pyocyanin and pyoverdin was also observed. Pyocyanin increase in the pyrE mutant was heightened when the mutant was supplemented with orotate. Although pyoverdin production in the wild-type PAO1 was unaffected by orotate supplementation, a decrease in the mutant's production was observed when supplemented with orotate. These results indicate a significant reduction in virulence factor production in the pyrE mutant and reduction in some virulence factors in the wild type when supplemented with orotate. PMID:25917504

  20. Structure of Plasmodium falciparum orotate phosphoribosyltransferase with autologous inhibitory protein–protein interactions

    SciTech Connect

    Kumar, Shiva; Krishnamoorthy, Kalyanaraman; Mudeppa, Devaraja G.; Rathod, Pradipsinh K.

    2015-04-21

    P. falciparum orotate phosphoribosyltransferase, a potential target for antimalarial drugs and a conduit for prodrugs, crystallized as a structure with eight molecules per asymmetric unit that included some unique parasite-specific auto-inhibitory interactions between catalytic dimers. The most severe form of malaria is caused by the obligate parasite Plasmodium falciparum. Orotate phosphoribosyltransferase (OPRTase) is the fifth enzyme in the de novo pyrimidine-synthesis pathway in the parasite, which lacks salvage pathways. Among all of the malaria de novo pyrimidine-biosynthesis enzymes, the structure of P. falciparum OPRTase (PfOPRTase) was the only one unavailable until now. PfOPRTase that could be crystallized was obtained after some low-complexity sequences were removed. Four catalytic dimers were seen in the asymmetic unit (a total of eight polypeptides). In addition to revealing unique amino acids in the PfOPRTase active sites, asymmetric dimers in the larger structure pointed to novel parasite-specific protein–protein interactions that occlude the catalytic active sites. The latter could potentially modulate PfOPRTase activity in parasites and possibly provide new insights for blocking PfOPRTase functions.

  1. Avoidance reaction of painful stimulation of another rat: effect of methylglucamine orotate.

    PubMed

    Wetzel, W; Simonov, P V

    1978-10-01

    An avoidance reaction to painful stimulation of another animal was developed in rats. Two hundred twenty-five mg/kg methylglucamine orotate was injected intraperitoneally each day, 1 hr before the training session. The orotate treated rats showed an accelerated development of the avoidance reaction during 5 days of training. Depending on the experimental conditions, extinction of the reaction was delayed in orotate treated rats, compared to saline controls. The results from these experiments, using neither footshock punishment nor food reward as reinforcement, give further evidence for the improvement of long term memory by orotic acid. PMID:733825

  2. [Complex heterogeneity phenotypes and genotypes of glutaric aciduria type 1].

    PubMed

    Wang, Qiao; Yang, Yan-Ling

    2016-05-01

    Glutaric aciduria type 1 is a rare autosomal recessive disorder. GCDH gene mutations cause glutaryl-CoA dehydrogenase deficiency and accumulation of glutaric acid and 3-hydroxyglutaric acid, resulting in damage of striatum and other brain nucleus and neurodegeneration. Patients with glutaric aciduria type 1 present with complex heterogeneous phenotypes and genotypes. The symptoms are extremely variable. The ages of the clinical onset of the patients range from the fetus period to adulthood. The patients with mild glutaric aciduria type 1 are almost asymptomatic before onset, however, severe glutaric aciduria type 1 may cause death or disability due to acute encephalopathy. Acute metabolic crisis in patients with underlying glutaric aciduria type 1 is often triggered by febrile illnesses, trauma, hunger, high-protein foods and vaccination during a vulnerable period of brain development in infancy or early childhood. The early-onset patients usually have a poor prognosis. Urinary organic acids analysis, blood acylcarnitines analysis and GCDH study are important for the diagnosis of this disorder. Neonatal screening is essential for the early diagnosis and the improvement of prognosis. PMID:27165598

  3. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate.

    PubMed

    Smith, D F; Schou, M

    1979-03-01

    A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients. PMID:34690

  4. The mechanistic study of Leishmania major dihydro-orotate dehydrogenase based on steady- and pre-steady-state kinetic analysis.

    PubMed

    Reis, Renata A G; Ferreira, Patricia; Medina, Milagros; Nonato, M Cristina

    2016-03-01

    Leishmania major dihydro-orotate dehydrogenase (DHODHLm) has been considered as a potential therapeutic target against leishmaniasis. DHODHLm, a member of class 1A DHODH, oxidizes dihydro-orotate (DHO) to orotate (ORO) during pyrimidine biosynthesis using fumarate (FUM) as the oxidizing substrate. In the present study, the chemistry of reduction and reoxidation of the flavin mononucleotide (FMN) cofactor in DHODHLm was examined by steady- and pre-steady state kinetics under both aerobic and anaerobic environments. Our results provide for the first time the experimental evidence of co-operative behaviour in class 1A DHODH regulated by DHO binding and reveal that the initial reductive flavin half-reaction follows a mechanism with two steps. The first step is consistent with FMN reduction and shows a hyperbolic dependence on the DHO concentration with a limiting rate (kred) of 110±6 s(-1) and a K(DHO) d of 180±27 μM. Dissociation of the reduced flavin-ORO complex corresponds to the second step, with a limiting rate of 6 s(-1). In the oxidative half-reaction, the oxygen-sensitive reoxidation of the reduced FMN cofactor of DHODHLm by FUM exhibited a hyperbolic saturation profile dependent on FUM concentration allowing estimation of K(FUM) d and the limiting rate (kreox) of 258±53 μM and 35±2 s(-1), respectively. Comparison between steady- and pre-steady-state parameters together with studies of interaction for DHODHLm with both ORO and succinate (SUC), suggests that ORO release is the rate-limiting step in overall catalysis. Our results provide evidence of mechanistic differences between class 1A and class 2 individual half-reactions to be exploited for the development of selective inhibitors. PMID:26656485

  5. [Course of the progression of experimentally induced arteriosclerotic vessel wall changes after treatment with magnesium orotate] .

    PubMed

    Jellinek, H; Takács, E

    2000-12-01

    There are some experimental and clinical results regarding blood vessel protective properties of magnesium orotate (CAS 27067-77-2) till now. The goal of the present investigation was to verify the therapeutical efficacy of magnesium orotate vs. its singular components in cholesterol fed rabbits. Besides, the blood-lipid concentrations (LDL as risk factor for atherosclerosis and HDL as negative risk factor) were analyzed in relation to pathomorphological changes in the aortic blood vessel wall. The results of our experiments in New Zealand rabbits support the assumption that orotic acid and especially magnesium orotate influence the lipid level and/or the LDL/HDL-quotient in a favorable way and that they decrease the interaction between monocytes/macrophages and the endothelium of the blood vessels. Consequently, the plaque formation will be decreased in a clinically relevant manner.

  6. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate.

    PubMed

    Kling, M A; Manowitz, P; Pollack, I W

    1978-06-01

    Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations. PMID:26768

  7. Clinical and neuropathological picture of ethylmalonic aciduria - diagnostic dilemma.

    PubMed

    Jamroz, Ewa; Paprocka, Justyna; Adamek, Dariusz; Pytel, Justyna; Szczechowska, Katarzyna; Grabska, Natalia; Malec, Michalina; Głuszkiewicz, Ewa; Daab, Michał; Wodołażski, Anatolij

    2011-01-01

    Increased ethylmalonic acid (EMA) in urine is a non-specific finding, and is observed in a number of inborn errors of metabolism, as well as in individuals who carry one of two common polymorphisms identified in the SCAD coding region. The authors present an 8-month-old girl with a suspicion of neuroinfection, although the clinical presentation led to diagnosis of ethylmalonic aciduria. From the neuropathological point of view the most remarkable changes were observed in the brain cortex, which was diffusely damaged practically in all regions of the brain. Of note, the most severe destruction was observed in the deepest regions of the sulci. The cortex of the affected regions showed no normal stratification and its structure was almost totally replaced by a form of "granulation tissue" with a markedly increased number of capillaries. To the authors' knowledge this is the first clinical report of ethylmalonic aciduria with brain autopsy findings.

  8. Elevated urinary excretion of orotic acid in sheep caused by intraruminal infusion of sodium propionate.

    PubMed

    Bödeker, D; Martens, H

    1992-06-01

    1. The effect of sodium propionate on urinary excretion of orotic acid was investigated. 2. Solutions containing sodium propionate or NaCl, 750 mM/day each, were continuously infused into the rumen for 10 days. 3. During NaCl infusion, an urinary orotic acid excretion of 290 +/- 80 micrograms/day was noted. The intraruminal infusion of sodium propionate raised the concentration of propionic acid in the rumen fluid from 14.0 +/- 0.9 to 26.9 +/- 1.9 mM. 4. During this experimental period the excretion of orotic acid via urine significantly increased to 492 +/- 30 micrograms/day. Parameters of nitrogen balance were not altered by propionate. 5. It is suggested that the site of propionate action in intact sheep is in the pyrimidine synthesis pathway.

  9. A global outer-rise/outer-trench-slope (OR/OTS) earthquake study

    NASA Astrophysics Data System (ADS)

    Wartman, J. M.; Kita, S.; Kirby, S. H.; Choy, G. L.

    2009-12-01

    Using improved seismic, bathymetric, satellite gravity and other geophysical data, we investigated the seismicity patterns and focal mechanisms of earthquakes in oceanic lithosphere off the trenches of the world that are large enough to be well recorded at teleseismic distances. A number of prominent trends are apparent, some of which have been previously recognized based on more limited data [1], and some of which are largely new [2-5]: (1) The largest events and the highest seismicity rates tend to occur where Mesozoic incoming plates are subducting at high rates (e.g., those in the western Pacific and the Banda segment of Indonesia). The largest events are predominantly shallow normal faulting (SNF) earthquakes. Less common are reverse-faulting (RF) events that tend to be deeper and to be present along with SNF events where nearby seamounts, seamount chains and other volcanic features are subducting [Seno and Yamanaka, 1996]. Blooms of SNF OR/OTS events usually occur just after and seaward of great interplate thrust (IPT) earthquakes but are far less common after smaller IPT events. (2) Plates subducting at slow rates (<20 mm/a) often show sparse OR/OTS seismicity. It is unclear if such low activity is a long-term feature of these systems or is a consequence of the long return times of great IPT earthquakes (e.g., the sparse OR/OTS seismicity before the 26 December 2004 M9.2 Sumatra earthquake and many subsequent OR/OTS events). (3) OR/OTS shocks are generally sparse or absent where incoming plates are very young (<20 Ma) (e.g., Cascadia, southern Mexico, Nankai, and South Shetlands). (4) Subducting plates of intermediate age (20 to about 65 Ma) display a diversity of focal mechanisms and seismicity patterns. In the Philippines, NE Indonesia, and Melanesia, bands of reverse faulting events occur at or near the trench and SNF earthquakes are restricted to OR/OTS sites further from the trench. (5) Clustering of OR/OTS events of all types commonly occurs where

  10. Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*

    PubMed Central

    Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

    2013-01-01

    The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5′-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5′-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

  11. Molecular basis of 3-hydroxy-3-methylglutaric aciduria.

    PubMed

    Pie, J; Casals, N; Puisac, B; Hegardt, F G

    2003-12-01

    3-Hydroxy-3-methylglutaric aciduria is a human autosomal recessive metabolic disorder that usually appears within the first year of life. The causes of this aciduria are lethal mutations in the gene encoding for 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL). HL is a mitochondrial matrix enzyme that catalyzes the last step of ketogenesis and leucine catabolism. This gene has been mapped to chromosome 1 at locus 1pter-p33 and its genomic organisation comprises 9 exons whose sizes vary between 64-678 bp. The human cDNA sequence was reported in 1993 with the first genetic study of two Acadian-French Canadian siblings. To date, 24 mutations in 36 patients have been described; most of them are single-base substitutions causing amino acid replacements and a variety of splicing defects. In the population studied two mutations appear predominant: g.122GA (8 patients and 15 alleles) frequent in Saudi Arabia, and g.109GT (6 patients and 12 alleles), prevalent in Spain. At least seven mutations are clustered in the second half of exon 2 affecting aminoacids E37, R41 and D42 and conforming a possible hot spot. The genotype-phenotype correlation is difficult to establish since the probands received different treatments, and the onset of an acute episode frequently depends on external factors such as fasting or acute illness. PMID:15164951

  12. Argininosuccinic aciduria: prenatal studies in a family at risk.

    PubMed Central

    Fleisher, L D; Rassin, D K; Desnick, R J; Salwen, H R; Rogers, P; Bean, M; Gaull, G E

    1979-01-01

    We have monitored two successive pregnancies in a family which we found to be at risk for argininosuccinic aciduria. We measured argininosuccinic acid (ASA) concentrations in amniotic fluid and utilized an indirect assay of ASA lyase activity in cultured amniotic fluid cells. The assay procedure is based on the uptake of 14C from [14C]citrulline and of [3H]leucine into protein. ASA was easily measured in amniotic fluid from the first fetus at risk, whereas none was detectable in control fluids. Amniotic fluid cells cultured from this fetus had only 5.5% of control ASA lyase activity. The pregnancy was terminated, and hepatic ASA lyase activity in the fetus was shown to be about 1.3% of control values. In addition, eight fetal tissues were analyzed for ASA, and all had significant accumulation. ASA was not detected in amniotic fluid from the second fetus at risk, and ASA lyase activity in cultured cells was 80% of control activity. Enzymatic analysis of erythrocyte lysate confirmed the diagnosis of an unaffected child (ASA lyase = 46% of control) and indicated heterozygosity. Thus, we provide further evidence that argininosuccinic aciduria can be diagnosed successfully in utero by indirect assay of ASA lyase activity in cultured amniotic fluid cells. In addition, high amniotic fluid ASA concentrations provide strong adjunctive evidence for such a prenatal determination, and may prove to be sufficient for diagnosis. PMID:484552

  13. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria.

    PubMed

    Kranendijk, Martijn; Struys, Eduard A; van Schaftingen, Emile; Gibson, K Michael; Kanhai, Warsha A; van der Knaap, Marjo S; Amiel, Jeanne; Buist, Neil R; Das, Anibh M; de Klerk, Johannis B; Feigenbaum, Annette S; Grange, Dorothy K; Hofstede, Floris C; Holme, Elisabeth; Kirk, Edwin P; Korman, Stanley H; Morava, Eva; Morris, Andrew; Smeitink, Jan; Sukhai, Rám N; Vallance, Hilary; Jakobs, Cornelis; Salomons, Gajja S

    2010-10-15

    Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer. PMID:20847235

  14. Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1

    PubMed Central

    Yakob, Yusnita; Abdul Azize, Nor Azimah; Md Yunus, Zabedah; Huey Yin, Leong; Mohd Khalid, Mohd Khairul Nizam; Lock Hock, Ngu

    2016-01-01

    Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.

  15. Congenital defect in intracellular cobalamin metabolism resulting in homocystinuria and methylmalonic aciduria. II. Biochemical investigations.

    PubMed

    Baumgartner, E R; Wick, H; Linnell, J C; Gaull, G E; Bachmann, C; Steinmann, B

    1979-01-01

    Biochemical investigations are reported in an infant with methylmalonic aciduria and homocystinuria who died at 4 months of age. Postmortem analysis of liver obtained 2 weeks after the child was treated with vitamin B12 revealed deficient activity of both cobalamin dependent enzymes: N5-methyltetrahydrofolate: homocysteine methyltransferase (requiring Me-Cbl), and methylmalonyl CoA mutase (requiring Ado-Cbl). MMA-CoA mutase activity could be restored to normal in vitro by added Ado-Cbl, but MeTHF-HCy transferase activity was not significantly enhanced by addition of Me-Cbl. Though the serum total cobalamin was normal, total cobalamin in liver and kidney was abnormally low. In the kidney Me-Cbl and Ado-Cbl were disproportionally decreased whereas in the liver only Ado-Cbl was significantly reduced. This suggests that at least some of the CN-Cbl administered was converted to the coenzymes in liver which would explain the reduction of MMA- and HCy-excretion during therapy. The results show 1. that this infant suffered from a congenital defect in one of the steps of intracellular cobalamin metabolism or transport common to the synthesis of both coenzymes, 2. that life-long treatment with vitamin B12 (OH-Cbl) may be of value in similar cases, particularly if given early in the course of the disease. PMID:43301

  16. Chronic intermittent form of isovaleric aciduria in a 2-year-old boy

    PubMed Central

    Cho, Jin Min; Lee, Beom Hee; Kim, Gu-Hwan; Kim, Yoo-Mi; Choi, Jin-Ho

    2013-01-01

    Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as an acute episode of fulminant metabolic acidosis, which may lead to coma or death, or later as a "chronic intermittent form" that is associated with developmental delays, with or without recurrent acidotic episodes during periods of stress, such as infections. Here, we report the case of a 2-year old boy with IVA who presented with the chronic intermittent form. He was admitted to Asan Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis, hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and markedly increased urine isovalerylglycine concentration were noted. Sequence analysis of the IVD gene in the patient revealed the novel compound mutations-a missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del (p.Ile361fs*11). Following stabilization during the acute phase, the patient has remained in a stable condition on a low-leucine diet. PMID:24019846

  17. Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1

    PubMed Central

    Yakob, Yusnita; Abdul Azize, Nor Azimah; Md Yunus, Zabedah; Huey Yin, Leong; Mohd Khalid, Mohd Khairul Nizam; Lock Hock, Ngu

    2016-01-01

    Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome. PMID:27672653

  18. Methylmalonic Aciduria Secondary to Selective Cobalamin Malabsorption in a Yorkshire Terrier.

    PubMed

    McLauchlan, Gerard; McLaughlin, Angela; Sewell, Adrian C; Bell, Rory

    2015-01-01

    An 8 wk old male Yorkshire terrier was presented with a 2 wk history of recurrent hypoglycemia, lethargy, and seizures. Investigations revealed a marked increase in blood ammonia, low serum cobalamin, and increased levels of urinary methylmalonic acid (MMA) excretion. No liver vascular abnormality was detected. The patient was diagnosed with methylmalonic aciduria due to cobalamin malabsorption. The patient responded well to parenteral cobalamin administration, and the urinary MMA levels normalized rapidly following instigation of treatment. Due to the suspected hereditary nature of selective cobalamin deficiency, one sibling of this dog was screened and found to be normal. This is the first reported case of MMA secondary to hypocobalaminemia in Yorkshire terriers, and the second report of this disease in a dog in the United Kingdom. Given the fact that clinical signs of MMA are similar to those seen in dogs with portosystemic shunts and that Yorkshire terriers are predisposed to liver vascular abnormalities, this case report adds important clinical information to the current available literature.

  19. Riboflavin-responsive glutaric aciduria type II presenting as a leukodystrophy.

    PubMed

    Uziel, G; Garavaglia, B; Ciceri, E; Moroni, I; Rimoldi, M

    1995-11-01

    The clinical phenotype of multiple acyl-CoA dehydrogenase deficiency in infancy is characterized by recurrent episodes of hypoketotic hypoglycemia and lipid storage myopathy. Brain damage has been described only as a consequence of severe and protracted hypoglycemia. We describe a child who experienced normal physical and psychomotor development until the age of 3 years, who then developed progressive intention tremors, dysarthria, ataxia, and spastic tetraparesis. Episodes of acute metabolic distress were never observed. Magnetic resonance imaging disclosed abnormal signals within the white matter of the brain and cerebellum, suggesting leukodystrophy. Gas chromatography/mass spectrometry analysis revealed abnormally high levels of glutaric acid, dicarboxylic acids, and glycine derivatives in urine. Riboflavin therapy was initiated at 4 years of age, when the patient had already lost control of trunk and head posture. Consistent improvement rapidly occurred after riboflavin supplementation. Glutaric aciduria type II may cause brain damage, in spite of the absence of acute metabolic distress, and should be considered in the differential diagnosis of leukodystrophies. PMID:8771170

  20. Transition metal(II) complexes of vitamin B13 with monodentate orotate(1-) ligands

    NASA Astrophysics Data System (ADS)

    Köse, Dursun Ali; Zümreoglu-Karan, Birgül; Şahin, Onur; Büyükgüngör, Orhan

    2006-05-01

    The formation of bisorotate(1-) complexes of the type [M(C 5H 3N 2O 4) 2(H 2O) 4]· nH 2O (M=Co, Ni, Zn and n=2, 4) was achieved by the reaction of ammonium orotate with the corresponding M(II) ions. The crystal structure of [Co(C 5H 3N 2O 4) 2(H 2O) 4]·2H 2O was determined by single crystal X-ray diffraction analysis. Each Co(II) ion in the monomeric Co(C 5H 3N 2O 4) 2(H 2O) 4 units adapts a slightly distorted octahedral geometry comprised of two monodentate orotate anions and four H 2O ligands. Columnar packing of pyrimidine rings along the c axis leads to the formation of layers that propagate parallel to the b axis and the adjacent layers are linked by hydrogen bonds forming a 3D lattice. Complexes of nickel and zinc were assumed to contain monodentate bound orotate ligands as well on the basis of physical and spectroscopic data.

  1. Orotate phosphoribosyl transferase MoPyr5 is involved in uridine 5'-phosphate synthesis and pathogenesis of Magnaporthe oryzae.

    PubMed

    Qi, Zhongqiang; Liu, Muxing; Dong, Yanhan; Yang, Jie; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

    2016-04-01

    Orotate phosphoribosyl transferase (OPRTase) plays an important role in de novo and salvage pathways of nucleotide synthesis and is widely used as a screening marker in genetic transformation. However, the function of OPRTase in plant pathogens remains unclear. In this study, we characterized an ortholog of Saccharomyces cerevisiae Ura5, the OPRTase MoPyr5, from the rice blast fungus Magnaporthe oryzae. Targeted gene disruption revealed that MoPyr5 is required for mycelial growth, appressorial turgor pressure and penetration into plant tissues, invasive hyphal growth, and pathogenicity. Interestingly, the ∆Mopyr5 mutant is also involved in mycelial surface hydrophobicity. Exogenous uridine 5'-phosphate (UMP) restored vegetative growth and rescued the defect in pathogenicity on detached barley and rice leaf sheath. Collectively, our results show that MoPyr5 is an OPRTase for UMP biosynthesis in M. oryzae and indicate that UTP biosynthesis is closely linked with vegetative growth, cell wall integrity, and pathogenicity of fungus. Our results also suggest that UMP biosynthesis would be a good target for the development of novel fungicides against M. oryzae. PMID:26810198

  2. Causes of and diagnostic approach to methylmalonic acidurias.

    PubMed

    Fowler, B; Leonard, J V; Baumgartner, M R

    2008-06-01

    Several mutant genetic classes that cause isolated methylmalonic acidurias (MMAuria) are known based on biochemical, enzymatic and genetic complementation analysis. The mut(0) and mut(-) defects result from deficiency of MMCoA mutase apoenzyme which requires adenosyl-cobalamin (Ado-Cbl) as coenzyme. The cblA, cblB and the variant 2 form of cblD complementation groups are linked to processes unique to Ado-Cbl synthesis. The cblC, cblD and cblF complementation groups are associated with defective methyl-cobalamin synthesis as well. Mutations in the genes associated with most of these defects have been described. Recently a few patients have been described with mild MMAuria associated with mutations of the MMCoA epimerase gene or with neurological symptoms due to SUCL mutations. A comprehensive diagnostic approach involves investigations at the level of metabolites, genetic complementation analysis and enzymatic studies, and finally mutation analysis. MMA levels in urine range from 10-20 mmol/mol creatinine in mild disturbances of MMA metabolism to over 20000 mmol/mol creatinine in severe MMCoA mutase deficiency, but show considerable overlap and are of limited value for differential diagnosis. The underlying defect in isolated MMAuria can be characterized in cultured skin fibroblasts using several assays, e.g. conversion of propionate to succinate, specific activity of MMCoA, cobalamin adenosyltransferase assay, cellular uptake of CN-[(57)Co] cobalamin and its conversion to cobalamin coenzymes and complementation analysis. The reliable characterization of patients with isolated MMAuria pinpoints the correct gene for mutation analysis. Reliable classification of these patients is essential for ongoing and future prospective studies on treatment and outcome. PMID:18563633

  3. Dynamic Changes of Striatal and Extrastriatal Abnormalities in Glutaric Aciduria Type I

    ERIC Educational Resources Information Center

    Harting, Inga; Neumaier-Probst, Eva; Seitz, Angelika; Maier, Esther M.; Assmann, Birgit; Baric, Ivo; Troncoso, Monica; Muhlhausen, Chris; Zschocke, Johannes; Boy, Nikolas P. S.; Hoffmann, Georg F.; Garbade, Sven F.; Kolker, Stefan

    2009-01-01

    In glutaric aciduria type I, an autosomal recessive disease of mitochondrial lysine, hydroxylysine and tryptophan catabolism, striatal lesions are characteristically induced by acute encephalopathic crises during a finite period of brain development (age 3-36 months). The frequency of striatal injury is significantly less in patients diagnosed as…

  4. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

  5. Molecular and biochemical alterations in tubular epithelial cells of patients with isolated methylmalonic aciduria.

    PubMed

    Ruppert, T; Schumann, A; Gröne, H J; Okun, J G; Kölker, S; Morath, M A; Sauer, S W

    2015-12-15

    Methylmalonic acidurias (MMAurias) are a group of inherited disorders in the catabolism of branched-chain amino acids, odd-chain fatty acids and cholesterol caused by complete or partial deficiency of methylmalonyl-CoA mutase (mut(0) and mut(-) subtype respectively) and by defects in the metabolism of its cofactor 5'-deoxyadenosylcobalamin (cblA, cblB or cblD variant 2 type). A long-term complication found in patients with mut(0) and cblB variant is chronic tubulointerstitial nephritis. The underlying pathomechanism has remained unknown. We established an in vitro model of tubular epithelial cells from patient urine (hTEC; 9 controls, 5 mut(0), 1 cblB). In all human tubular epithelial cell (hTEC) lines we found specific tubular markers (AQP1, UMOD, AQP2). Patient cells showed disturbance of energy metabolism in glycolysis, mitochondrial respiratory chain and Krebs cycle in concert with increased reactive oxygen species (ROS) formation. Electron micrographs indicated increased autophagosome production and endoplasmic reticulum stress, which was supported by positive acridine orange staining and elevated levels of LC3 II, P62 and pIRE1. Screening mTOR signaling revealed a release of inhibition of autophagy. Patient hTEC produced and secreted elevated amounts of the pro-inflammatory cytokine IL8, which was highly correlated with the acridine orange staining. Summarizing, hTEC of MMAuria patients are characterized by disturbed energy metabolism and ROS production that lead to increased autophagy and IL8 secretion. PMID:26420839

  6. 33 CFR 334.1420 - Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. 334.1420 Section 334.1420... AND RESTRICTED AREA REGULATIONS § 334.1420 Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. (a) The danger zone. The waters within an area delineated by...

  7. 33 CFR 334.1420 - Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. 334.1420 Section 334.1420... AND RESTRICTED AREA REGULATIONS § 334.1420 Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. (a) The danger zone. The waters within an area delineated by...

  8. 33 CFR 334.1420 - Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. 334.1420 Section 334.1420... AND RESTRICTED AREA REGULATIONS § 334.1420 Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. (a) The danger zone. The waters within an area delineated by...

  9. 33 CFR 334.1420 - Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. 334.1420 Section 334.1420... AND RESTRICTED AREA REGULATIONS § 334.1420 Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. (a) The danger zone. The waters within an area delineated by...

  10. Neurodegeneration and chronic renal failure in methylmalonic aciduria--a pathophysiological approach.

    PubMed

    Morath, M A; Okun, J G; Müller, I B; Sauer, S W; Hörster, F; Hoffmann, G F; Kölker, S

    2008-02-01

    In the last decades the survival of patients with methylmalonic aciduria has been improved. However, the overall outcome of affected patients remains disappointing. The disease course is often complicated by acute life-threatening metabolic crises, which can result in multiple organ failure or even death, resembling primary defects of mitochondrial energy metabolism. Biochemical abnormalities during metabolic derangement, such as metabolic acidosis, ketonaemia/ketonuria, lactic acidosis, hypoglycaemia and hyperammonaemia, suggest mitochondrial dysfunction. In addition, long-term complications such as chronic renal failure and neurological disease are frequently found. Neuropathophysiological studies have focused on various effects caused by accumulation of putatively toxic organic acids, the so-called 'toxic metabolite' hypothesis. In previous studies, methylmalonate (MMA) has been considered as the major neurotoxin in methylmalonic aciduria, whereas more recent studies have highlighted a synergistic inhibition of mitochondrial energy metabolism (pyruvate dehydrogenase complex, tricarboxylic acid cycle, respiratory chain, mitochondrial salvage pathway of deoxyribonucleoside triphosphate (dNTP)) induced by propionyl-CoA, 2-methylcitrate and MMA as the key pathomechanism of inherited disorders of propionate metabolism. Intracerebral accumulation of toxic metabolites ('trapping' hypothesis') is considered a biochemical risk factor for neurodegeneration. Secondary effects of mitochondrial dysfunction, such as oxidative stress and impaired mtDNA homeostasis, contribute to pathogenesis of these disorders. The underlying pathomechanisms of chronic renal insufficiency in methylmalonic acidurias are not yet understood. We hypothesize that renal and cerebral pathomechanisms share some similarities, such as an involvement of dicarboxylic acid transport. This review aims to give a comprehensive overview on recent pathomechanistic concepts for methylmalonic acidurias.

  11. Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

    PubMed

    Saheki, T; Mori, K; Kobayashi, K; Horiuchi, M; Shige, T; Obara, T; Suzuki, S; Mori, M; Yamamura, K

    1995-01-25

    We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

  12. 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated strains of Candida albicans.

    PubMed

    Wellington, Melanie; Kabir, M Anaul; Rustchenko, Elena

    2006-01-01

    We previously reported the occurrence of chromosome alterations in a Candida albicans prototrophic strain 3153A treated with 5-fluoro-orotic acid (5-FOA). In this study we investigated the mutagenic properties of 5-FOA with two derivatives of C. albicans strain CAF4-2 (ura3/ura3), each containing an ectopic copy of URA3 gene (ura3/ ura3 URA3) on a different chromosome. As expected, after the ura3/ura3 URA3 constructs were applied to 5-FOA containing solid medium, the "pop-outs" that lost URA3 appeared. However most of the "pop-outs" acquired various chromosome alterations. Thus constructs exposed to 5-FOA should be examined for chromosome alterations or the use of 5-FOA should be avoided. PMID:17040068

  13. Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

    PubMed Central

    2016-01-01

    Orotic acid (OTA) is reported to exist in the anhydrous (AH), monohydrate (Hy1), and dimethyl sulfoxide monosolvate (SDMSO) forms. In this study we investigate the (de)hydration/desolvation behavior, aiming at an understanding of the elusive structural features of anhydrous OTA by a combination of experimental and computational techniques, namely, thermal analytical methods, gravimetric moisture (de)sorption studies, water activity measurements, X-ray powder diffraction, spectroscopy (vibrational, solid-state NMR), crystal energy landscape, and chemical shift calculations. The Hy1 is a highly stable hydrate, which dissociates above 135 °C and loses only a small part of the water when stored over desiccants (25 °C) for more than one year. In Hy1, orotic acid and water molecules are linked by strong hydrogen bonds in nearly perfectly planar arranged stacked layers. The layers are spaced by 3.1 Å and not linked via hydrogen bonds. Upon dehydration the X-ray powder diffraction and solid-state NMR peaks become broader, indicating some disorder in the anhydrous form. The Hy1 stacking reflection (122) is maintained, suggesting that the OTA molecules are still arranged in stacked layers in the dehydration product. Desolvation of SDMSO, a nonlayer structure, results in the same AH phase as observed upon dehydrating Hy1. Depending on the desolvation conditions, different levels of order–disorder of layers present in anhydrous OTA are observed, which is also suggested by the computed low energy crystal structures. These structures provide models for stacking faults as intergrowth of different layers is possible. The variability in anhydrate crystals is of practical concern as it affects the moisture dependent stability of AH with respect to hydration. PMID:26741914

  14. Structural Properties, Order-Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms.

    PubMed

    Braun, Doris E; Nartowski, Karol P; Khimyak, Yaroslav Z; Morris, Kenneth R; Byrn, Stephen R; Griesser, Ulrich J

    2016-03-01

    Orotic acid (OTA) is reported to exist in the anhydrous (AH), monohydrate (Hy1), and dimethyl sulfoxide monosolvate (SDMSO) forms. In this study we investigate the (de)hydration/desolvation behavior, aiming at an understanding of the elusive structural features of anhydrous OTA by a combination of experimental and computational techniques, namely, thermal analytical methods, gravimetric moisture (de)sorption studies, water activity measurements, X-ray powder diffraction, spectroscopy (vibrational, solid-state NMR), crystal energy landscape, and chemical shift calculations. The Hy1 is a highly stable hydrate, which dissociates above 135 °C and loses only a small part of the water when stored over desiccants (25 °C) for more than one year. In Hy1, orotic acid and water molecules are linked by strong hydrogen bonds in nearly perfectly planar arranged stacked layers. The layers are spaced by 3.1 Å and not linked via hydrogen bonds. Upon dehydration the X-ray powder diffraction and solid-state NMR peaks become broader, indicating some disorder in the anhydrous form. The Hy1 stacking reflection (122) is maintained, suggesting that the OTA molecules are still arranged in stacked layers in the dehydration product. Desolvation of SDMSO, a nonlayer structure, results in the same AH phase as observed upon dehydrating Hy1. Depending on the desolvation conditions, different levels of order-disorder of layers present in anhydrous OTA are observed, which is also suggested by the computed low energy crystal structures. These structures provide models for stacking faults as intergrowth of different layers is possible. The variability in anhydrate crystals is of practical concern as it affects the moisture dependent stability of AH with respect to hydration. PMID:26741914

  15. A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian.

    PubMed

    Higginbottom, M C; Sweetman, L; Nyhan, W L

    1978-08-17

    We studied a six-month-old infant with severe megaloblastic anemia, coma and hyperpigmentation of the extremities. He was found to have methylmalonic aciduria (79 mumol per milligram of creatinine) and homocystinuria (0.85 mumol per milligram of creatinine). Additional biochemical abnormalities included cystathioninuria, glycinuria, methylcitric aciduria, 3-hydroxypropionic aciduria and formic aciduria. The concentration of vitamin B12 in the serum was 20 pg per milliliter. This severe nutritional deficiency was a consequence of inadequate intake, for the infant was exclusively breast-fed by a strictly vegetarian mother who manifested methylmalonic aciduria. Our observations emphasize the importance of educating strict vegetarians about the deficiency of vitamin B12 in their diets and the importance of vitamin B12 supplementation.

  16. Investigation of vital pathogenic target orotate phosphoribosyltransferases (OPRTase) from Thermus thermophilus HB8: Phylogenetic and molecular modeling approach.

    PubMed

    Surekha, Kanagarajan; Prabhu, Damodharan; Richard, Mariadasse; Nachiappan, Mutharasappan; Biswal, Jayashree; Jeyakanthan, Jeyaraman

    2016-06-01

    Biosynthesis pathways of pyrimidine and purine are shown to play an important role in regular cellular activities. The biosynthesis can occur either through de novo or salvage pathways based on the requirement of the cell. The pyrimidine biosynthesis pathway has been linked to several disorders and various autoimmune diseases. Orotate phosphoribosyl transferase (OPRTase) is an important enzyme which catalyzes the conversion of orotate to orotate monophosphate in the fifth step of pyrimidine biosynthesis. Phylogenetic analysis of 228 OPRTase sequences shows the distribution of proteins across different living forms of life. High structural similarities between Thermusthermophilus and other organisms kindled us to concentrate on OPRTase as an anti-pathogenic target. In this study, a homology model of OPRTase was constructed using 2P1Z as a template. About 100 ns molecular dynamics simulation was performed to investigate the conformational stability and dynamic patterns of the protein. The amino acid residues (Met1, Asp2, Glu43, Ala44, Glu47, Lys51, Ala157 and Leu158) lining in the binding site were predicted using SiteMap. Further, structure based virtual screening was performed on the predicted binding site using ChemBridge, Asinex, Binding, NCI, TosLab and Zinc databases. Compounds retrieved from the screening collections were manually clustered. The resultant protein-ligand complexes were subjected to molecular dynamics simulations, which further validates the binding modes of the hits. The study may provide better insight for designing potent anti-pathogenic agent. PMID:26861612

  17. Di-, tri-, tetranuclear clusters and polymeric cadmium compounds: Syntheses, structures and fluorescent properties with various linking fashions and high stability of orotates under the condition of strong bases

    SciTech Connect

    Li Xing; Bing Yue; Zha Meiqin; Wang Dongjie; Han Lei; Cao Rong

    2011-08-15

    Assembly reactions of orotic acid (H{sub 3}dtpc ) and CdCl{sub 2}.2.5H{sub 2}O or CdSO{sub 4}.8H{sub 2}O yielded four new cadmium compounds {l_brace}[Cd(H{sub 2}dtpc)(phen)(H{sub 2}O){sub 2}].(H{sub 2}dtpc).4H{sub 2}O{r_brace}{sub 2} (1: solution reaction, pH=4-5, in addition of phen), [Cd{sub 3}(dtpc){sub 2}(phen){sub 5}].13H{sub 2}O (2: hydrothermal reaction, initial pH=14, final pH=7.5), [Cd(Hdtpc)(H{sub 2}O){sub 3}]{sub 4} (3: solution reaction, initial pH=6.5, final pH=6.0), {l_brace}[Cd(Hdtpc)(phen)(H{sub 2}O)].H{sub 2}O{r_brace}{sub n} (4: hydrothermal reaction, initial pH=8; final pH=6.5), respectively. Compounds 1-4 have been characterized by IR, thermogravimetric analyses (TGA), photoluminescence analyses, single-crystal and powder X-ray diffraction (PXRD). Compound 1 is a binuclear, 2 is a trinuclear, 3 is a tetranuclear structure, and 4 possesses one-dimensional chain framework, respectively, in which the orotate ligands show seven different linking fashions in 1-4. The orotate ligands as trivalence anions are observed in the formation of orotate-compounds, in which the orotates show high stability under the extreme condition of strong basic solution, high temperature and pressure. - Graphical abstract: Assembly of orotic acid and Cd(II) salts result in four new compounds under different reaction conditions, the compounds possess strong photoluminescence emissions and high thermal stability. Highlights: > Four Cd-compounds were prepared from orotic acid under different crystallization systems. > The orotates as trivalence anions displayed high stability under extremely conditions. > The orotates displayed various connection modes in the compounds. > The strong photoluminescence emissions have been observed in the compounds.

  18. Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

    PubMed

    Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

    2015-01-01

    Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

  19. Infantile mitochondrial DNA depletion syndrome associated with methylmalonic aciduria and 3-methylcrotonyl-CoA and propionyl-CoA carboxylase deficiencies in two unrelated patients: a new phenotype of mtDNA depletion syndrome.

    PubMed

    Yano, S; Li, L; Le, T P; Moseley, K; Guedalia, A; Lee, J; Gonzalez, I; Boles, R G

    2003-01-01

    Mitochondrial DNA (mtDNA) depletion refers to a quantitative defect in mtDNA and is heterogeneous with regard to causal genotypes and the associated clinical phenotypes. We report two unrelated infants with mtDNA depletion. A diagnosis of methylmalonic aciduria was initially raised in both on the basis of high urine methylmalonic acid and related organic acids and elevated propionylcarnitine and methylmalonylcarnitine. Carboxylase assay with skin fibroblasts revealed low propionyl-CoA and 3-methylcrotonyl-CoA carboxylase and normal pyruvate carboxylase activities. Quantitative Southern blot analysis of mitochondrial and nuclear DNA with muscle tissues revealed the patients' mtDNA to be depleted to 24% and 39% of normal controls. Our two patients showed multiple mitochondrial dysfunction including respiratory chain defects and deficiencies in the two nuclear DNA encoded carboxylases resulting in abnormal urine organic acids. To our knowledge, there is no obvious connection between the defective pathways other than their mitochondrial locations. These two cases may represent a new entity of mitochondrial disease that might be due to a defective common mechanism, such as assembly, maintenance and transport, affecting various mitochondrial enzymes and functions. Mitochondrial depletion should be considered in infants with atypical organic aciduria that may resemblemethylmalonicaciduria, propionicacidaemia, or 3-methylcrotonyl-CoA carboxylase deficiency.

  20. 33 CFR 334.1420 - Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... AND RESTRICTED AREA REGULATIONS § 334.1420 Pacific Ocean off Orote Point, Apra Harbor, Island of Guam, Marianas Islands; small arms firing range. (a) The danger zone. The waters within an area delineated by a....2″ 13°24′51.2″ 144°36′31.9″ 13°25′28.7″ 144°37′59.1″ 13°25′43.2″ 144°38′09.5″ (b) The...

  1. Orotate phosphoribosyltransferase is overexpressed in malignant pleural mesothelioma: Dramatically responds one case in high OPRT expression

    PubMed Central

    Hamamoto, Yoichiro; Takeoka, Shinjiro; Mouri, Atsuto; Fukusumi, Munehisa; Wakuda, Kazushige; Ibe, Tatsuya; Honma, Chie; Arimoto, Yoshihito; Yamada, Kazuaki; Wagatsuma, Miyuki; Tashiro, Akito; Kamoshida, Shingo; Kamimura, Mitsuhiro

    2016-01-01

    ABSTRACT Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases Results: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM. PMID:27274438

  2. A Mouse Model of L-2-Hydroxyglutaric Aciduria, a Disorder of Metabolite Repair

    PubMed Central

    Rzem, Rim; Achouri, Younes; Marbaix, Etienne; Schakman, Olivier; Wiame, Elsa; Marie, Sandrine; Gailly, Philippe; Vincent, Marie-Françoise; Veiga-da-Cunha, Maria; Van Schaftingen, Emile

    2015-01-01

    The purpose of the present work was to progress in our understanding of the pathophysiology of L-2-hydroxyglutaric aciduria, due to a defect in L-2-hydroxyglutarate dehydrogenase, by creating and studying a mouse model of this disease. L-2-hydroxyglutarate dehydrogenase-deficient mice (l2hgdh-/-) accumulated L-2-hydroxyglutarate in tissues, most particularly in brain and testis, where the concentration reached ≈ 3.5 μmol/g. Male mice showed a 30% higher excretion of L-2-hydroxyglutarate compared to female mice, supporting that this dicarboxylic acid is partially made in males by lactate dehydrogenase C, a poorly specific form of this enzyme exclusively expressed in testes. Involvement of mitochondrial malate dehydrogenase in the formation of L-2-hydroxyglutarate was supported by the commensurate decrease in the formation of this dicarboxylic acid when down-regulating this enzyme in mouse l2hgdh-/- embryonic fibroblasts. The concentration of lysine and arginine was markedly increased in the brain of l2hgdh-/- adult mice. Saccharopine was depleted and glutamine was decreased by ≈ 40%. Lysine-α-ketoglutarate reductase, which converts lysine to saccharopine, was inhibited by L-2-hydroxyglutarate with a Ki of ≈ 0.8 mM. As low but significant activities of the bifunctional enzyme lysine-α-ketoglutarate reductase/saccharopine dehydrogenase were found in brain, these findings suggest that the classical lysine degradation pathway also operates in brain and is inhibited by the high concentrations of L-2-hydroxyglutarate found in l2hgdh-/- mice. Pathological analysis of the brain showed significant spongiosis. The vacuolar lesions mostly affected oligodendrocytes and myelin sheats, as in other dicarboxylic acidurias, suggesting that the pathophysiology of this model of leukodystrophy may involve irreversible pumping of a dicarboxylate in oligodendrocytes. Neurobehavioral testing indicated that the mice mostly suffered from a deficit in learning capacity. In

  3. A mouse model of L-2-hydroxyglutaric aciduria, a disorder of metabolite repair.

    PubMed

    Rzem, Rim; Achouri, Younes; Marbaix, Etienne; Schakman, Olivier; Wiame, Elsa; Marie, Sandrine; Gailly, Philippe; Vincent, Marie-Françoise; Veiga-da-Cunha, Maria; Van Schaftingen, Emile

    2015-01-01

    The purpose of the present work was to progress in our understanding of the pathophysiology of L-2-hydroxyglutaric aciduria, due to a defect in L-2-hydroxyglutarate dehydrogenase, by creating and studying a mouse model of this disease. L-2-hydroxyglutarate dehydrogenase-deficient mice (l2hgdh-/-) accumulated L-2-hydroxyglutarate in tissues, most particularly in brain and testis, where the concentration reached ≈ 3.5 μmol/g. Male mice showed a 30% higher excretion of L-2-hydroxyglutarate compared to female mice, supporting that this dicarboxylic acid is partially made in males by lactate dehydrogenase C, a poorly specific form of this enzyme exclusively expressed in testes. Involvement of mitochondrial malate dehydrogenase in the formation of L-2-hydroxyglutarate was supported by the commensurate decrease in the formation of this dicarboxylic acid when down-regulating this enzyme in mouse l2hgdh-/- embryonic fibroblasts. The concentration of lysine and arginine was markedly increased in the brain of l2hgdh-/- adult mice. Saccharopine was depleted and glutamine was decreased by ≈ 40%. Lysine-α-ketoglutarate reductase, which converts lysine to saccharopine, was inhibited by L-2-hydroxyglutarate with a Ki of ≈ 0.8 mM. As low but significant activities of the bifunctional enzyme lysine-α-ketoglutarate reductase/saccharopine dehydrogenase were found in brain, these findings suggest that the classical lysine degradation pathway also operates in brain and is inhibited by the high concentrations of L-2-hydroxyglutarate found in l2hgdh-/- mice. Pathological analysis of the brain showed significant spongiosis. The vacuolar lesions mostly affected oligodendrocytes and myelin sheats, as in other dicarboxylic acidurias, suggesting that the pathophysiology of this model of leukodystrophy may involve irreversible pumping of a dicarboxylate in oligodendrocytes. Neurobehavioral testing indicated that the mice mostly suffered from a deficit in learning capacity. In

  4. Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

    PubMed

    Stojiljkovic, M; Klaassen, K; Djordjevic, M; Sarajlija, A; Brasil, S; Kecman, B; Grkovic, S; Kostic, J; Rodriguez-Pombo, P; Desviat, L R; Pavlovic, S; Perez, B

    2016-09-01

    Specific mitochondrial enzymatic deficiencies in the catabolism of branched-chain amino acids cause methylmalonic aciduria (MMA), propionic acidemia (PA) and maple syrup urine disease (MSUD). Disease-causing mutations were identified in nine unrelated branched-chain organic acidurias (BCOA) patients. We detected eight previously described mutations: p.Asn219Tyr, p.Arg369His p.Val553Glyfs*17 in MUT, p.Thr198Serfs*6 in MMAA, p.Ile144_Leu181del in PCCB, p.Gly288Valfs*11, p.Tyr438Asn in BCKDHA and p.Ala137Val in BCKDHB gene. Interestingly, we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants. Aberrant enzymes p.Leu549Pro MUT, p.Leu641Pro MUT and p.Tyr206Cys PCCB did not show residual activity in activity assays. In addition, activity of MUT enzymes was not rescued in the presence of vitamin B12 precursor in vitro which was in accordance with non-responsiveness or partial responsiveness of patients to vitamin B12 therapy. Our study brings the first molecular genetic data and detailed phenotypic characteristics for MMA, PA and MSUD patients for Serbia and the whole South-Eastern European region. Therefore, our study contributes to the better understanding of molecular landscape of BCOA in Europe and to general knowledge on genotype-phenotype correlation for these rare diseases. PMID:26830710

  5. Insights into the mechanism of oxidation of dihydroorotate to orotate catalysed by human class 2 dihydroorotate dehydrogenase: a QM/MM free energy study.

    PubMed

    Alves, Cláudio Nahum; Silva, José Rogério A; Roitberg, Adrian E

    2015-07-21

    The dihydroorotate dehydrogenase (DHOD) enzyme catalyzes the unique redox reaction in the de novo pyrimidine biosynthesis pathway. In this reaction, the oxidation of dihydroorotate (DHO) to orotate (OA) and reduction of the flavin mononucleotide (FMN) cofactor is catalysed by DHOD. The class 2 DHOD, to which the human enzyme belongs, was experimentally shown to follow a stepwise mechanism but the data did not allow the determination of the order of bond-breaking in a stepwise oxidation of DHO. The goal of this study is to understand the reaction mechanism at the molecular level of class 2 DHOD, which may aid in the design of inhibitors that selectively impact the activity of only certain members of the enzyme family. In this paper, the catalytic mechanism of oxidation of DHO to OA in human DHOD was studied using a hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) approach and Molecular Dynamics (MD) simulations. The free energy barriers calculated reveal that the mechanism in human DHOD occurs via a stepwise reaction pathway. In the first step, a proton is abstracted from the C5 of DHO to the deprotonated Ser215 side chain. Whereas, in the second step, the transfer of the hydride or hydride equivalent from the C6 of DHO to the N5 of FMN, where free energy barrier calculated by the DFT/MM level is 10.84 kcal mol(-1). Finally, a residual decomposition analysis was carried out in order to elucidate the influence of the catalytic region residues during DHO oxidation.

  6. Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse model

    SciTech Connect

    Buck, Nicole E.; Pennell, Samuel D.; Wood, Leonie R.; Pitt, James J.; Allen, Katrina J.; Peters, Heidi L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Fetal cells were transplanted into a methylmalonic acid mouse model. Black-Right-Pointing-Pointer Cell engraftment was detected in liver, spleen and bone marrow. Black-Right-Pointing-Pointer Biochemical disease correction was measured in blood samples. Black-Right-Pointing-Pointer A double dose of 5 million cells (1 week apart) proved more effective. Black-Right-Pointing-Pointer Higher levels of engraftment may be required for greater disease correction. -- Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 {+-} 156 (sham transplanted) to 338 {+-} 157 {mu}mol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 {+-} 4 (sham transplanted) to 5.3 {+-} 1.9 {mu}mol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may

  7. Type III 3-Methylglutaconic Aciduria (Optic Atrophy Plus Syndrome, or Costeff Optic Atrophy Syndrome): Identification of the OPA3 Gene and Its Founder Mutation in Iraqi Jews

    PubMed Central

    Anikster, Yair; Kleta, Robert; Shaag, Avraham; Gahl, William A.; Elpeleg, Orly

    2001-01-01

    Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) is a neuro-ophthalmologic syndrome that consists of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased. The disorder has been reported in ∼40 patients of Iraqi Jewish origin, allowing the mapping of the disease to chromosome 19q13.2-q13.3, by linkage analysis. To isolate the causative gene, OPA3, we sequenced four genes within the critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype. The FLJ22187-cDNA clone, which we identified as the OPA3 gene, consists of two exons and encodes a peptide of 179 amino acid residues. Northern blot analysis revealed a primary transcript of ∼5.0 kb that was ubiquitously expressed, most prominently in skeletal muscle and kidney. Within the brain, the cerebral cortex, the medulla, the cerebellum, and the frontal lobe, compared to other parts of the brain, had slightly increased expression. The intronic G→C mutation abolished mRNA expression in fibroblasts from affected patients and was detected in 8 of 85 anonymous Israeli individuals of Iraqi Jewish origin. Milder mutations in OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurological abnormalities. PMID:11668429

  8. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

    PubMed

    Wortmann, Saskia B; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B; Gersting, Søren W; Muntau, Ania C; Rakovic, Aleksandar; Renkema, G Herma; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Rubio-Gozalbo, M Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N; Vaz, Frédéric M; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A A P; de Brouwer, Arjan P M; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A

    2015-02-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria.

  9. Novel Mouse Models of Methylmalonic Aciduria Recapitulate Phenotypic Traits with a Genetic Dosage Effect.

    PubMed

    Forny, Patrick; Schumann, Anke; Mustedanagic, Merima; Mathis, Déborah; Wulf, Marie-Angela; Nägele, Nadine; Langhans, Claus-Dieter; Zhakupova, Assem; Heeren, Joerg; Scheja, Ludger; Fingerhut, Ralph; Peters, Heidi L; Hornemann, Thorsten; Thony, Beat; Kölker, Stefan; Burda, Patricie; Froese, D Sean; Devuyst, Olivier; Baumgartner, Matthias R

    2016-09-23

    Methylmalonic aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the newborn period with failure to thrive and metabolic crisis leading to coma or even death. Survivors remain at risk of metabolic decompensations and severe long term complications, notably renal failure and neurological impairment. We generated clinically relevant mouse models of MMAuria using a constitutive Mut knock-in (KI) allele based on the p.Met700Lys patient mutation, used homozygously (KI/KI) or combined with a knockout allele (KO/KI), to study biochemical and clinical MMAuria disease aspects. Transgenic Mut(ki/ki) and Mut(ko/ki) mice survive post-weaning, show failure to thrive, and show increased methylmalonic acid, propionylcarnitine, odd chain fatty acids, and sphingoid bases, a new potential biomarker of MMAuria. Consistent with genetic dosage, Mut(ko/ki) mice have lower Mut activity, are smaller, and show higher metabolite levels than Mut(ki/ki) mice. Further, Mut(ko/ki) mice exhibit manifestations of kidney and brain damage, including increased plasma urea, impaired diuresis, elevated biomarkers, and changes in brain weight. On a high protein diet, mutant mice display disease exacerbation, including elevated blood ammonia, and catastrophic weight loss, which, in Mut(ki/ki) mice, is rescued by hydroxocobalamin treatment. This study expands knowledge of MMAuria, introduces the discovery of new biomarkers, and constitutes the first in vivo proof of principle of cobalamin treatment in mut-type MMAuria.

  10. Novel Mouse Models of Methylmalonic Aciduria Recapitulate Phenotypic Traits with a Genetic Dosage Effect.

    PubMed

    Forny, Patrick; Schumann, Anke; Mustedanagic, Merima; Mathis, Déborah; Wulf, Marie-Angela; Nägele, Nadine; Langhans, Claus-Dieter; Zhakupova, Assem; Heeren, Joerg; Scheja, Ludger; Fingerhut, Ralph; Peters, Heidi L; Hornemann, Thorsten; Thony, Beat; Kölker, Stefan; Burda, Patricie; Froese, D Sean; Devuyst, Olivier; Baumgartner, Matthias R

    2016-09-23

    Methylmalonic aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the newborn period with failure to thrive and metabolic crisis leading to coma or even death. Survivors remain at risk of metabolic decompensations and severe long term complications, notably renal failure and neurological impairment. We generated clinically relevant mouse models of MMAuria using a constitutive Mut knock-in (KI) allele based on the p.Met700Lys patient mutation, used homozygously (KI/KI) or combined with a knockout allele (KO/KI), to study biochemical and clinical MMAuria disease aspects. Transgenic Mut(ki/ki) and Mut(ko/ki) mice survive post-weaning, show failure to thrive, and show increased methylmalonic acid, propionylcarnitine, odd chain fatty acids, and sphingoid bases, a new potential biomarker of MMAuria. Consistent with genetic dosage, Mut(ko/ki) mice have lower Mut activity, are smaller, and show higher metabolite levels than Mut(ki/ki) mice. Further, Mut(ko/ki) mice exhibit manifestations of kidney and brain damage, including increased plasma urea, impaired diuresis, elevated biomarkers, and changes in brain weight. On a high protein diet, mutant mice display disease exacerbation, including elevated blood ammonia, and catastrophic weight loss, which, in Mut(ki/ki) mice, is rescued by hydroxocobalamin treatment. This study expands knowledge of MMAuria, introduces the discovery of new biomarkers, and constitutes the first in vivo proof of principle of cobalamin treatment in mut-type MMAuria. PMID:27519416

  11. CLPB Mutations Cause 3-Methylglutaconic Aciduria, Progressive Brain Atrophy, Intellectual Disability, Congenital Neutropenia, Cataracts, Movement Disorder

    PubMed Central

    Wortmann, Saskia B.; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B.; Gersting, Søren W.; Muntau, Ania C.; Rakovic, Aleksandar; Renkema, G. Herma; Rodenburg, Richard J.; Strom, Tim M.; Meitinger, Thomas; Rubio-Gozalbo, M. Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H.; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N.; Vaz, Frédéric M.; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A.A.P.; de Brouwer, Arjan P.M.; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A.

    2015-01-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. PMID:25597510

  12. Effects of fatty liver induced by niacin-free diet with orotic acid on the metabolism of tryptophan to niacin in rats.

    PubMed

    Fukuwatari, Tsutomu; Morikawa, Yuko; Sugimoto, Etsuro; Shibata, Katsumi

    2002-06-01

    The effects of dietary orotic acid on the metabolism of tryptophan to niacin in weaning rats was investigated. The rats were fed with a niacin-free, 20% casein diet containing 0% (control diet) or 1% orotic acid diet (test diet) for 29 d. Retardation of growth, development of fatty liver, and enlargement of liver were observed in the test group in comparison with the control group. The concentrations of NAD and NADP in liver significantly decreased, while these in blood did not decrease compared to the control group. The formation of the upper metabolites of tryptophan to niacin such as anthranilic acid, kynurenic acid, and 3-hydroxyanthranilic acid were not affected, but the quinolinic acid and beyond, such as nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, were significantly reduced by the administration of orotic acid. Therefore, the conversion ratio of tryptophan to niacin significantly decreased in the test group in comparison with the control group.

  13. Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type

    PubMed Central

    Jorge-Finnigan, Ana; Brasil, Sandra; Underhaug, Jarl; Ruíz-Sala, Pedro; Merinero, Begoña; Banerjee, Ruma; Desviat, Lourdes R.; Ugarte, Magdalena; Martinez, Aurora; Pérez, Belén

    2013-01-01

    Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene. This encodes the enzyme ATP:cob(I)alamin adenosyltransferase (ATR), which converts reduced cob(I)alamin to an active adenosylcobalamin cofactor. We recently reported the presence of destabilizing pathogenic mutations that retain some residual ATR activity. The aim of the present study was to seek pharmacological chaperones as a tailored therapy for stabilizing the ATR protein. High-throughput ligand screening of over 2000 compounds was performed; six were found to enhance the thermal stability of purified recombinant ATR. Further studies using a well-established bacterial system in which the recombinant ATR protein was expressed in the presence of these six compounds, showed them all to increase the stability of the wild-type ATR and the p.Ile96Thr mutant proteins. Compound V (N-{[(4-chlorophenyl)carbamothioyl]amino}-2-phenylacetamide) significantly increased this stability and did not act as an inhibitor of the purified protein. Importantly, compound V increased the activity of ATR in patient-derived fibroblasts harboring the destabilizing p.Ile96Thr mutation in a hemizygous state to within control range. When cobalamin was coadministrated with compound V, mutant ATR activity further improved. Oral administration of low doses of compound V to C57BL/6J mice for 12 days, led to increase in steady-state levels of ATR protein in liver and brain (disease-relevant organs). These results hold promise for the clinical use of pharmacological chaperones in MMA cblB type patients harboring chaperone-responsive mutations. PMID:23674520

  14. Orotate phosphoribosyltransferase from baker's yeast: I. Kinetic analysis, chemical modification, and proton NMR spectroscopy of the enzyme substrate complex. II. Amino acid analysis and NMR spectroscopy of the protein

    SciTech Connect

    Strauss, R.S.

    1986-01-01

    Kinetic analysis of the effect of pH on the reversible reaction catalyzed by orotate phosphoribosyltransferase (OPRTase) from Baker's yeast revealed that different amino acid residues may enable the enzyme-catalyzed reactions to proceed in the forward and reverse directions, respectively. For the forward reaction, there appear to be at least two critical amino acid residues (pK's 4.6 and 7.1) which must be in a deprotonated state to reach a maximum activity near pH 8 which is maintained through pH 9.5. For the reverse reaction, maximum activity is reached near pH 7 (pK's at 5.4) and then the activity decreases at higher pH (pK's at 7.9 and possibly above 9). A theoretical proton NMR spectrum was generated for OPRTase, based on its amino acid composition. The spectrum thus produced has a similar number of major peaks to that of the actual spectrum taken at 300 MHz. Spectra collected at various pH values between 8 and 5, were consistent with the maintenance of the gross conformational structure of the enzyme over that pH range.

  15. Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.

    PubMed

    Kanabus, Marta; Shahni, Rojeen; Saldanha, José W; Murphy, Elaine; Plagnol, Vincent; Hoff, William Van't; Heales, Simon; Rahman, Shamima

    2015-03-01

    Whole exome sequencing was used to investigate the genetic cause of mitochondrial disease in two siblings with a syndrome of congenital lamellar cataracts associated with nephrocalcinosis, medullary cysts and 3-methylglutaconic aciduria. Autosomal recessive inheritance in a gene encoding a mitochondrially targeted protein was assumed; the only variants which satisfied these criteria were c.1882C>T (p.Arg628Cys) and c.1915G>A (p.Glu639Lys) in the CLPB gene, encoding a heat shock protein/chaperonin responsible for disaggregating mitochondrial and cytosolic proteins. Functional studies, including quantitative PCR (qPCR) and Western blot, support pathogenicity of these mutations. Furthermore, molecular modelling suggests that the mutations disrupt interactions between subunits so that the CLPB hexamer cannot form or is unstable, thus impairing its role as a protein disaggregase. We conclude that accumulation of protein aggregates underlies the development of cataracts and nephrocalcinosis in CLPB deficiency, which is a novel genetic cause of 3-methylglutaconic aciduria. A common mitochondrial cause for 3-methylglutaconic aciduria appears to be disruption of the architecture of the mitochondrial membranes, as in Barth syndrome (tafazzin deficiency), Sengers syndrome (acylglycerol kinase deficiency) and MEGDEL syndrome (impaired remodelling of the mitochondrial membrane lipids because of SERAC1 mutations). We now propose that perturbation of the mitochondrial membranes by abnormal protein aggregates leads to 3-methylglutaconic aciduria in CLPB deficiency.

  16. Profile of polychlorinated biphenyls in the brown alga Padina sanctae-crucis along the Orote dump coastline, Orote Peninsula, Western Guam.

    PubMed

    Schaible, Brian Christopher

    2010-01-01

    The purpose of this study was to determine whether the brown seaweed Padina sanctae-crucis might be used as a biomonitor organism to determine the location, distribution, and type of polychlorinated biphenyls (PCB) present along a contaminated tropical coastline. Polychlorinated biphenyls were detected in P. sanctae-crucis collected from near-shore waters along a 4-km stretch of coastline. The profile of PCB levels from samples obtained at 13 sites along the coastline demonstrated a positive concentration gradient as sample locations progressed toward the dump site. Sample locations nearest the dump site revealed PCB levels twofold higher than background levels for P. sanctae-crucis. Chromatograms of samples obtained nearest the dump site indicated a similarity to the Aroclor 1260 fingerprint. The P. sanctae-crucis frond trimmings used for laboratory analysis were approximately 3-5 wk old. This study was conducted 8 mo following the completion of the removal actions at the dump site. Data suggest a release of Aroclor 1260 into the marine environment approximately 7 mo following the completion of removal actions at the dump site.

  17. Orotic Acid Decarboxylation in Water and Nonpolar Solvents: a Potential Role For Desolvation in the Action Of OMP Decarboxylase†

    PubMed Central

    Lewis, Charles A.; Wolfenden, Richard

    2009-01-01

    OMP decarboxylase (ODCase) generates a very large rate enhancement without the assistance of metals or other cofactors. The uncatalyzed decarboxylation of 1-methylorotate in water is shown to involve the monoanion, although uncharged 1-methylorotic acid is decarboxylated at a similar rate. To measure the extent to which the rate of the nonenzymatic decarboxylation of orotate derivatives might be enhanced by their removal from solvent water, the 1-phosphoribosyl moiety of OMP was replaced by 1-substituents that would allow it to enter less polar solvents. When the tetrabuytlyammonium salt of 1-cyclohexylorotate was transferred from water to a series of dipolar aprotic solvents, its rate of decarboxylation increased markedly, varying with the relative ability of each solvent to release the substrate in the ground state from stabilization by solvent water acting as a proton donor. These findings are consistent with the view that separation of the substrate from solvent water may contribute, at least to a limited extent, to the rate enhancement produced by ODCase. This enzyme's active site, like that of another cofactorless enzyme recently shown to produce a rate enhancement of similar magnitude (uroporphyrinogen decarboxylase), is equipped with an ammonium group positioned in such a way as to balance the electrostatic charge of the carboxylate group of the substrate and later supply a proton to the incipient carbanion in a relatively waterless environment. PMID:19678695

  18. Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects

    PubMed Central

    Lee, Soo-Yun; Kim, Jung-Ryul; Jung, Jin Ah; Huh, Wooseong; Bahng, Mi Young; Ko, Jae-Wook

    2015-01-01

    A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg. PMID:26082611

  19. Bioequivalence evaluation of two amlodipine salts, besylate and orotate, each in a fixed-dose combination with olmesartan in healthy subjects.

    PubMed

    Lee, Soo-Yun; Kim, Jung-Ryul; Jung, Jin Ah; Huh, Wooseong; Bahng, Mi Young; Ko, Jae-Wook

    2015-01-01

    A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg.

  20. Mechanism of the Orotidine 5’-Monophosphate Decarboxylase-Catalyzed Reaction: Importance of Residues in the Orotate Binding Site†

    PubMed Central

    Iiams, Vanessa; Desai, Bijoy J.; Fedorov, Alexander A.; Fedorov, Elena V.; Almo, Steven C.; Gerlt, John A.

    2011-01-01

    The reaction catalyzed by orotidine 5’-monophosphate decarboxylase (OMPDC) is accompanied by exceptional values for the rate enhancement [kcat/knon = 7.1 × 1016] and catalytic proficiency [(kcat/KM)/knon = 4.8 × 1022 M−1]. Although a stabilized vinyl carbanion/carbene intermediate is located on the reaction coordinate, the structural strategies by which the reduction in the activation energy barrier is realized remain incompletely understood. This laboratory recently reported that “substrate destabilization” by Asp 70 in the OMPDC from Methanothermobacter thermoautotrophicus (MtOMPDC) lowers the activation energy barrier by ~5 kcal/mol (contributing ~2.7 × 103 to the rate enhancement) [K. K. Chan, B. M. Wood, A. A. Fedorov, E. V. Fedorov, H. J. Imker, T. L. Amyes, J. P. Richard, S. C. Almo, and J. A. Gerlt (2009) Biochemistry 48, 5518–31]. We now report that substitutions of hydrophobic residues in a pocket proximal to the carboxylate group of the substrate (Ile 96, Leu 123, and Val 155) with neutral hydrophilic residues decrease the value of kcat by as much as 400-fold but have minimal effect on the value of kex for exchange of H6 of the FUMP product analog with solvent deuterium; we hypothesize that this pocket destabilizes the substrate by preventing hydration of the substrate carboxylate group. We also report that substitutions for Ser 127 that is proximal to O4 of the orotate ring decrease the value of kcat/KM, with the S127P substitution that eliminates hydrogen-bonding interactions with O4 producing a 2.5 × 106-fold reduction in the value of kcat/KM; this effect is consistent with delocalization of the negative charge of the carbanionic intermediate on O4 to produce an anionic carbene intermediate and thereby provide a structural strategy for stabilization of the intermediate. These observations provide additional information on the identities of the active site residues that contribute to the rate enhancement and, therefore, insights into the

  1. C6-C10-dicarboxylic aciduria: biochemical considerations in relation to diagnosis of beta-oxidation defects.

    PubMed

    Gregersen, N; Kølvraa, S; Mortensen, P B; Rasmussen, K

    1982-01-01

    By means of gas chromatographic methods substantial amounts of the C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, have been found in the urine from children with unexplained attacks of lethargy and hypotonia, presumably related to episodes of fever and/or insufficient food intake. The course have once been fatal and is often characterized by severe hypoglycemia without ketonuria. Systematic gas chromatographic/mass spectrometric determinations of selected organic acid metabolites in the urine, together with enzymatic measurements in fibroblasts and clinical data from 4 patients of this category, have shown that the biochemical basis of this syndrome can be inborn errors of the beta-oxidation of fatty acids, localized to the medium-chain acyl-CoA dehydrogenation system. The biosynthesis of adipic, suberic and sebacic acids was studied using ketotic rats as the model, since ketosis in rats and humans is accompanied by excessive urinary excretion of adipic and suberic acids. A probable pathway for the production of the three dicarboxylic acids was found to be an initial omega-oxidation of the medium-chain C10-C14-monocarboxylic acids followed by beta-oxidation of the resulting medium-chain dicarboxylic acids. It is argued that the source of the omega-oxidizable monocarboxylic acids in ketosis most probably is the fat deposites, and it is speculated that the patients with beta-oxidation defects supplement this source with beta-oxidation intermediate medium-chain monocarboxylic acids, accumulated as a result of the defect. The ratio between the excreted amounts of adipic acid and sebacic acid in the urine from the patients with beta-oxidation defects is less than 50. This is in contrast to the ratio in urine from ketotic patients, where it is greater than 100. Adipic acid/sebacic acid ratio-measured by means of a gas chromatographic analysis-is therefore suggested as a tool in the diagnosis of dicarboxylic acidurias. Based on the clinical picture and

  2. Refractory focal epilepsy in a patient with methylmalonic aciduria: case report on positive and long-lasting effect of rufinamide.

    PubMed

    von Stülpnagel, C; Leichsenring, M; Müller, A; Staudt, M; Kluger, G

    2011-02-01

    We report on a 5-year-old boy with methylmalonic aciduria, an autosomal recessive inborn error of metabolism leading to accumulation of methylmalonic-CoA and thereby causing intoxication with leading symptoms of hyperammonaemia and metabolic acidosis. Hyperammonemia itself causes brain oedema. In our patient, this led to a vast metabolic stroke of the left hemisphere and subsequent pharmacoresistant epilepsy. Guided by his main seizures--drop attacks--the orphan drug rufinamide (RUF) was introduced as "off-label use" and led to freedom of drop attacks and tonic-clonic seizures over a period of 14 months as well as normalisation of the electroencephalogramm. Only once during an episode of fever and diarrhoea with reduced level of RUF did some provoked seizures with focal complex semiology for the time period of infection occur. In the 16 months follow-up, the patient also improved in his development, showing a more stable gait with the hemiparesis and understanding more complex sentences. PMID:21547865

  3. A Korean patient with glutaric aciduria type 1 with a novel mutation in the glutaryl CoA dehydrogenase gene.

    PubMed

    Kim, Hee Su; Yu, Hee Joon; Lee, Jeehun; Park, Hyung-Doo; Kim, Ji Hye; Shin, Hyung-Jin; Jin, Dong Kyu; Lee, Munhyang

    2014-01-01

    Mutations in the glutaryl-CoA dehydrogenase gene can result in Glutaric aciduria type 1(GA 1) by accumulation of glutaric acid, 3-hydroxyglutaric acid (3-OH-GA), and glutarylcarnitine (C5DC). GA 1 is characterized by macrocephaly, subdural hemorrhage (SDH), and dystonic movement disorder after acute encephalopathic crisis. We report a Korean patient with GA1 and a novel mutation. A 16-month-old boy presented with SDH, macrocephaly, and developmental delay. In the neurologic examination, the patient had mild axial hypotonia, but otherwise normal neurologic functions. The brain MRI showed large amounts of bilateral SDH and high signal intensity in both basal ganglia and thalamus. Metabolic screening tests detected highly elevated urinary GA levels but 3-OH-glutaric acid was normal. C5DC was 0.94 μM/L (reference range < 0.3 μM/L). The patient had compound heterozygous mutations of the GCDH gene: p.Arg257Gln (c.770G>A) and p.Cys308Arg (c.922T>C). p.Cys308Arg is a novel mutation; reports of p.Arg257Gln were also rare both in Caucasians and Asian populations. In summary, we hereby report one Korean patient with GA1 with clinical, biochemical, and radiologic characteristics confirmed by genetic analysis. PMID:24795062

  4. Anesthetic management of comprehensive dental restoration in a child with glutaric aciduria type 1 using volatile sevoflurane.

    PubMed

    Teng, Wei-Nung; Lin, Su-Man; Niu, Dau-Ming; Kuo, Yi-Min; Chan, Kwok-Hon; Sung, Chun-Sung

    2014-10-01

    Glutaric aciduria type 1 (GA1) is a rare, inherited mitochondrial disorder that results from deficiency of mitochondrial glutaryl-CoA dehydrogenase. Most patients develop neurological dysfunction early in life, which leads to severe disabilities. We present a 37-month-old girl with GA1 manifested as macrocephaly and hypotonia who received comprehensive dental restoration surgery under general anesthesia with sevoflurane. She was placed on specialized fluid management during a preoperative fasting period and anesthesia was administered without complications. All the physiological parameters, including glucose and lactate blood levels and arterial blood gas were carefully monitored and maintained within normal range perioperatively. Strategies for anesthetic management should include prevention of pulmonary aspiration, dehydration, hyperthermia and catabolic state, adequate analgesia to minimize surgical stress, and avoidance of prolonged neuromuscular blockade. We administered general anesthesia with sevoflurane uneventfully, which was well tolerated by our patient with GA1. Additionally, communication with a pediatric geneticist and surgeons should be undertaken to formulate a comprehensive anesthetic strategy in these patients.

  5. Plasmid pCS1966, a new selection/counterselection tool for lactic acid bacterium strain construction based on the oroP gene, encoding an orotate transporter from Lactococcus lactis.

    PubMed

    Solem, Christian; Defoor, Els; Jensen, Peter Ruhdal; Martinussen, Jan

    2008-08-01

    In this paper we describe the new selection/counterselection vector pCS1966, which is suitable for both sequence-specific integration based on homologous recombination and integration in a bacteriophage attachment site. This plasmid harbors oroP, which encodes a dedicated orotate transporter, and can replicate only in Escherichia coli. Selection for integration is performed primarily by resistance to erythromycin; alternatively, the ability to utilize orotate as a pyrimidine source in a pyrimidine auxotrophic mutant could be utilized. Besides allowing the cell to utilize orotate, the transporter renders the cell sensitive to 5-fluoroorotate. This sensitivity is used to select for loss of the plasmid. When expressed from its own promoter, oroP was toxic to E. coli, whereas in Lactococcus lactis the level of expression of oroP from a chromosomal copy was too low to confer 5-fluoroorotate sensitivity. In order to obtain a plasmid that confers 5-fluoroorotate sensitivity when it is integrated into the chromosome of L. lactis and at the same time can be stably maintained in E. coli, the expression of the oroP gene was controlled from a synthetic promoter conferring these traits. To demonstrate its use, a number of L. lactis strains expressing triosephosphate isomerase (tpiA) at different levels were constructed.

  6. Neurodevelopmental profiles of children with glutaric aciduria type I diagnosed by newborn screening: a follow-up case series.

    PubMed

    Brown, Amy; Crowe, Louise; Beauchamp, Miriam H; Anderson, Vicki; Boneh, Avihu

    2015-01-01

    Glutaric aciduria type I (GA-I) is an inherited metabolic disorder that may lead to severe motor disorder and cognitive impairment. GA-I is now included in the newborn screening programme in many countries as early detection allows for prompt treatment and effectively reduces the risk of poor developmental outcome. Information regarding the long-term neurodevelopmental outcome of children with GA-I treated early is sparse.We recruited children with a confirmed diagnosis of GA-I diagnosed via newborn screening, treated in our centre and >3 years of age (n = 6). Children were assessed at two time points using a comprehensive neuropsychological test battery. Four of these had been the subject of a previous report. All participants were male, 3-6 years at the initial assessment and 6-12 years of age at the follow-up assessment.Fine motor skills were below average in all patients. Speech, which was affected in all four patients reported previously, improved following speech therapy. IQ scores remained generally stable within the normal range. Executive functioning was average to high average in four patients. Behaviour, as assessed through parental questionnaires, was problematic in two patients. Compounding factors included child neglect, family history of autism and multiple admissions to hospital (n = 1 in each).GA-I affects fine motor skills and speech, regardless of early treatment, but not IQ scores. Patients with GA-I should be referred for assessment and appropriate early intervention. Further research is needed to correlate specific neuropsychological deficits with neuroimaging.

  7. Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families.

    PubMed

    Sass, Jörn Oliver; Gemperle-Britschgi, Corinne; Tarailo-Graovac, Maja; Patel, Nisha; Walter, Melanie; Jordanova, Albena; Alfadhel, Majid; Barić, Ivo; Çoker, Mahmut; Damli-Huber, Aynur; Faqeih, Eissa Ali; García Segarra, Nuria; Geraghty, Michael T; Jåtun, Bjørn Magne; Kalkan Uçar, Sema; Kriewitz, Merten; Rauchenzauner, Markus; Bilić, Karmen; Tournev, Ivailo; Till, Claudia; Sayson, Bryan; Beumer, Daniel; Ye, Cynthia Xin; Zhang, Lin-Hua; Vallance, Hilary; Alkuraya, Fowzan S; van Karnebeek, Clara D M

    2016-09-01

    Primary 5-oxoprolinuria (pyroglutamic aciduria) is caused by a genetic defect in the γ-glutamyl cycle, affecting either glutathione synthetase or 5-oxoprolinase. While several dozens of patients with glutathione synthetase deficiency have been reported, with hemolytic anemia representing the clinical key feature, 5-oxoprolinase deficiency due to OPLAH mutations is less frequent and so far has not attracted much attention. This has prompted us to investigate the clinical phenotype as well as the underlying genotype in patients from 14 families of various ethnic backgrounds who underwent diagnostic mutation analysis following the detection of 5-oxoprolinuria. In all patients with 5-oxoprolinuria studied, bi-allelic mutations in OPLAH were indicated. An autosomal recessive mode of inheritance for 5-oxoprolinase deficiency is further supported by the identification of a single mutation in all 9/14 parent sample sets investigated (except for the father of one patient whose result suggests homozygosity), and the absence of 5-oxoprolinuria in all tested heterozygotes. It is remarkable, that all 20 mutations identified were novel and private to the respective families. Clinical features were highly variable and in several sib pairs, did not segregate with 5-oxoprolinuria. Although a pathogenic role of 5-oxoprolinase deficiency remains possible, this is not supported by our findings. Additional patient ascertainment and long-term follow-up is needed to establish the benign nature of this inborn error of metabolism. It is important that all symptomatic patients with persistently elevated levels of 5-oxoproline and no obvious explanation are investigated for the genetic etiology.

  8. Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families.

    PubMed

    Sass, Jörn Oliver; Gemperle-Britschgi, Corinne; Tarailo-Graovac, Maja; Patel, Nisha; Walter, Melanie; Jordanova, Albena; Alfadhel, Majid; Barić, Ivo; Çoker, Mahmut; Damli-Huber, Aynur; Faqeih, Eissa Ali; García Segarra, Nuria; Geraghty, Michael T; Jåtun, Bjørn Magne; Kalkan Uçar, Sema; Kriewitz, Merten; Rauchenzauner, Markus; Bilić, Karmen; Tournev, Ivailo; Till, Claudia; Sayson, Bryan; Beumer, Daniel; Ye, Cynthia Xin; Zhang, Lin-Hua; Vallance, Hilary; Alkuraya, Fowzan S; van Karnebeek, Clara D M

    2016-09-01

    Primary 5-oxoprolinuria (pyroglutamic aciduria) is caused by a genetic defect in the γ-glutamyl cycle, affecting either glutathione synthetase or 5-oxoprolinase. While several dozens of patients with glutathione synthetase deficiency have been reported, with hemolytic anemia representing the clinical key feature, 5-oxoprolinase deficiency due to OPLAH mutations is less frequent and so far has not attracted much attention. This has prompted us to investigate the clinical phenotype as well as the underlying genotype in patients from 14 families of various ethnic backgrounds who underwent diagnostic mutation analysis following the detection of 5-oxoprolinuria. In all patients with 5-oxoprolinuria studied, bi-allelic mutations in OPLAH were indicated. An autosomal recessive mode of inheritance for 5-oxoprolinase deficiency is further supported by the identification of a single mutation in all 9/14 parent sample sets investigated (except for the father of one patient whose result suggests homozygosity), and the absence of 5-oxoprolinuria in all tested heterozygotes. It is remarkable, that all 20 mutations identified were novel and private to the respective families. Clinical features were highly variable and in several sib pairs, did not segregate with 5-oxoprolinuria. Although a pathogenic role of 5-oxoprolinase deficiency remains possible, this is not supported by our findings. Additional patient ascertainment and long-term follow-up is needed to establish the benign nature of this inborn error of metabolism. It is important that all symptomatic patients with persistently elevated levels of 5-oxoproline and no obvious explanation are investigated for the genetic etiology. PMID:27477828

  9. Multiple Acyl-CoA Dehydrogenation Deficiency (Glutaric Aciduria Type II) with a Novel Mutation of Electron Transfer Flavoprotein-Dehydrogenase in a Cat.

    PubMed

    Wakitani, Shoichi; Torisu, Shidow; Yoshino, Taiki; Hattanda, Kazuhisa; Yamato, Osamu; Tasaki, Ryuji; Fujita, Haruo; Nishino, Koichiro

    2014-01-01

    Multiple acyl-CoA dehydrogenation deficiency (MADD; also known as glutaric aciduria type II) is a human autosomal recessive disease classified as one of the mitochondrial fatty-acid oxidation disorders. MADD is caused by a defect in the electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH) molecule, but as yet, inherited MADD has not been reported in animals. Here we present the first report of MADD in a cat. The affected animal presented with symptoms characteristic of MADD including hypoglycemia, hyperammonemia, vomiting, diagnostic organic aciduria, and accumulation of medium- and long-chain fatty acids in plasma. Treatment with riboflavin and L-carnitine ameliorated the symptoms. To detect the gene mutation responsible for MADD in this case, we determined the complete cDNA sequences of feline ETFα, ETFβ, and ETFDH. Finally, we identified the feline patient-specific mutation, c.692T>G (p.F231C) in ETFDH. The affected animal only carries mutant alleles of ETFDH. p.F231 in feline ETFDH is completely conserved in eukaryotes, and is located on the apical surface of ETFDH, receiving electrons from ETF. This study thus identified the mutation strongly suspected to have been the cause of MADD in this cat. PMID:24142280

  10. Next generation sequencing of patients with mut methylmalonic aciduria: Validation of somatic cell studies and identification of 16 novel mutations.

    PubMed

    Chu, Jordan; Pupavac, Mihaela; Watkins, David; Tian, Xia; Feng, Yanming; Chen, Stella; Fenter, Remington; Zhang, Victor W; Wang, Jing; Wong, Lee-Jun; Rosenblatt, David S

    2016-08-01

    Mutations in the MUT gene, which encodes the mitochondrial enzyme methylmalonyl-CoA mutase, are responsible for the mut form of methylmalonic aciduria (MMA). In this study, a next generation sequencing (NGS) based gene panel was used to analyze 53 patients that had been diagnosed with mut MMA by somatic cell complementation analysis. A total of 54 different mutations in MUT were identified in 48 patients; 16 novel mutations were identified, including 1 initiation site mutation (c.2T>C [p.M1?]), 1 missense mutation (c.566A>T [p.N189I]), 2 nonsense mutations (c.129G>A [p.W43*] and c.1975C>T [p.Q659*]), 2 mutations affecting splice sites (c.753+3A>G and c.754-2A>G), 8 small insertions, deletions, and duplications (c.29dupT [p.L10Ffs*39], c.55dupG [p.V19Gfs*30], c.631_633delGAG [p.E211del], c.795_796insT [p.M266Yfs*7], c.1061delCinsGGA [p.S354Wfs*20], c.1065_1068dupATGG [p.S357Mfs*5], c.1181dupT [p.L394Ffs*30], c.1240delG [p.E414Kfs*17]), a large insertion (c.146_147ins279), and a large deletion involving exon 13. Phenotypic rescue and cDNA analysis were used to confirm that the c.146_147ins279 and c.631_633delGAG mutations were associated with the decreased methylmalonyl-CoA mutase function observed in the patient fibroblasts. In five patients, the NGS panel did not confirm the diagnosis made by complementation analysis. One of these patients was found to carry 2 novel mutations (c.433G > A [p.E145K] and c.511A>C [p.N171H]) in the SUCLG1 gene. PMID:27233228

  11. Radioautographic visualization of differences in the pattern of (/sup 3/H)uridine and (/sup 3/H)orotic acid incorporation into the RNA of migrating columnar cells in the rat small intestine

    SciTech Connect

    Uddin, M.; Altmann, G.G.; Leblond, C.P.

    1984-05-01

    The epithelium of rat small intestine was radioautographed to examine whether RNA is synthesized by the salvage pathway as shown after (/sup 3/H)uridine injection or by the de novo pathway as shown after (/sup 3/H)orotic acid injection. The two modes of RNA synthesis were thus investigated during the migration of columnar cells from crypt base to villus top, and the rate of synthesis was assessed by counting silver grains over the nucleolus and nucleoplasm at six levels along the duodenal epithelium - that is, in the base, mid, and top regions of the crypts and in the base, mid, and top regions of the villi. Concomitant biochemical analyses established that, after injection of either (5-/sup 3/H)uridine or (5-/sup 3/H)orotic acid: (a) buffered glutaraldehyde fixative was as effective as perchloric acid or trichloroacetic acid in insolubilizing the nucleic acids of rat small intestine; (b) a major fraction of the nucleic acid label was in RNA, that is, 91% after (/sup 3/H)uridine and 72% after (/sup 3/H)orotic acid, with the rest in DNA; and (c) a substantial fraction of the RNA label was in poly A/sup +/ RNA (presumed to be messenger RNA). In radioautographs of duodenum prepared after (/sup 3/H)uridine injection, the count of silver grains was high over nucleolus and nucleoplasm in crypt base cells and gradually decreased at the upper levels up to the villus base. In the rest of the villus, the grain count over the nucleolus was negligible, while over the nucleoplasm it was low but significant.

  12. The M405V allele of the glutaryl-CoA dehydrogenase gene is an important marker for glutaric aciduria type I (GA-I) low excretors.

    PubMed

    Schillaci, Lori-Anne P; Greene, Carol L; Strovel, Erin; Rispoli-Joines, Jessica; Spector, Elaine; Woontner, Michael; Scharer, Gunter; Enns, Gregory M; Gallagher, Renata; Zinn, Arthur B; McCandless, Shawn E; Hoppel, Charles L; Goodman, Stephen I; Bedoyan, Jirair K

    2016-09-01

    Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria resulting from a functional deficiency of glutaryl-CoA dehydrogenase, encoded by GCDH. Two clinically indistinguishable diagnostic subgroups of GA-I are known; low and high excretors (LEs and HEs, respectively). Early medical and dietary interventions can result in significantly better outcomes and improved quality of life for patients with GA-I. We report on nine cases of GA-I LE patients all sharing the M405V allele with two cases missed by newborn screening (NBS) using tandem mass spectrometry (MS/MS). We describe a novel case with the known pathogenic M405V variant and a novel V133L variant, and present updated and previously unreported clinical, biochemical, functional and molecular data on eight other patients all sharing the M405V allele. Three of the nine patients are of African American ancestry, with two as siblings. GCDH activity was assayed in six of the nine patients and varied from 4 to 25% of the control mean. We support the use of urine glutarylcarnitine as a biochemical marker of GA-I by demonstrating that glutarylcarnitine is efficiently cleared by the kidney (50-90%) and that plasma and urine glutarylcarnitine follow a linear relationship. We report the allele frequencies for three known GA-I LE GCDH variants (M405V, V400M and R227P) and note that both the M405V and V400M variants are significantly more common in the population of African ancestry compared to the general population. This report highlights the M405V allele as another important molecular marker in patients with the GA-I LE phenotype. Therefore, the incorporation into newborn screening of molecular screening for the M405V and V400M variants in conjunction with MS/MS could help identify asymptomatic at-risk GA-I LE patients that could potentially be missed by current NBS programs.

  13. Ammonium accumulation is a primary effect of 2-methylcitrate exposure in an in vitro model for brain damage in methylmalonic aciduria.

    PubMed

    Cudré-Cung, Hong-Phuc; Zavadakova, Petra; do Vale-Pereira, Sónia; Remacle, Noémie; Henry, Hugues; Ivanisevic, Julijana; Tavel, Denise; Braissant, Olivier; Ballhausen, Diana

    2016-09-01

    Using 3D organotypic rat brain cell cultures in aggregates we recently identified 2-methylcitrate (2-MCA) as the main toxic metabolite for developing brain cells in methylmalonic aciduria. Exposure to 2-MCA triggered morphological changes and apoptosis of brain cells. This was accompanied by increased ammonium and decreased glutamine levels. However, the sequence and causal relationship between these phenomena remained unclear. To understand the sequence and time course of pathogenic events, we exposed 3D rat brain cell aggregates to different concentrations of 2-MCA (0.1, 0.33 and 1.0mM) from day in vitro (DIV) 11 to 14. Aggregates were harvested at different time points from DIV 12 to 19. We compared the effects of a single dose of 1mM 2-MCA administered on DIV 11 to the effects of repeated doses of 1mM 2-MCA. Pan-caspase inhibitors Z-VAD FMK or Q-VD-OPh were used to block apoptosis. Ammonium accumulation in the culture medium started within few hours after the first 2-MCA exposure. Morphological changes of the developing brain cells were already visible after 17h. The highest rate of cleaved caspase-3 was observed after 72h. A dose-response relationship was observed for all effects. Surprisingly, a single dose of 1mM 2-MCA was sufficient to induce all of the biochemical and morphological changes in this model. 2-MCA-induced ammonium accumulation and morphological changes were not prevented by concomitant treatment of the cultures with pan-caspase inhibitors Z-VAD FMK or Q-VD-OPh: ammonium increased rapidly after a single 1mM 2-MCA administration even after apoptosis blockade. We conclude that following exposure to 2-MCA, ammonium production in brain cell cultures is an early phenomenon, preceding cell degeneration and apoptosis, and may actually be the cause of the other changes observed. The fact that a single dose of 1mM 2-MCA is sufficient to induce deleterious effects over several days highlights the potential damaging effects of even short-lasting metabolic

  14. Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation.

    PubMed

    Colak, Gozde; Pougovkina, Olga; Dai, Lunzhi; Tan, Minjia; Te Brinke, Heleen; Huang, He; Cheng, Zhongyi; Park, Jeongsoon; Wan, Xuelian; Liu, Xiaojing; Yue, Wyatt W; Wanders, Ronald J A; Locasale, Jason W; Lombard, David B; de Boer, Vincent C J; Zhao, Yingming

    2015-11-01

    The protein substrates of sirtuin 5-regulated lysine malonylation (Kmal) remain unknown, hindering its functional analysis. In this study, we carried out proteomic screening, which identified 4042 Kmal sites on 1426 proteins in mouse liver and 4943 Kmal sites on 1822 proteins in human fibroblasts. Increased malonyl-CoA levels in malonyl-CoA decarboxylase (MCD)-deficient cells induces Kmal levels in substrate proteins. We identified 461 Kmal sites showing more than a 2-fold increase in response to MCD deficiency as well as 1452 Kmal sites detected only in MCD-/- fibroblast but not MCD+/+ cells, suggesting a pathogenic role of Kmal in MCD deficiency. Cells with increased lysine malonylation displayed impaired mitochondrial function and fatty acid oxidation, suggesting that lysine malonylation plays a role in pathophysiology of malonic aciduria. Our study establishes an association between Kmal and a genetic disease and offers a rich resource for elucidating the contribution of the Kmal pathway and malonyl-CoA to cellular physiology and human diseases. PMID:26320211

  15. Nucleic acid labeling with ( sup 3 H)orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

    SciTech Connect

    Jakobsson, B.; el Hag, I.A.; Andersson, M.; Christensson, P.I.; Stenram, U. )

    1990-09-01

    Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of (3H)orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes.

  16. Genetics Home Reference: argininosuccinic aciduria

    MedlinePlus

    ... belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occur ... by the body, to make a compound called urea that is excreted by the kidneys. In argininosuccinic ...

  17. Revealing Mercury

    NASA Astrophysics Data System (ADS)

    Prockter, L. M.; Solomon, S. C.; Head, J. W.; Watters, T. R.; Murchie, S. L.; Robinson, M. S.; Chapman, C. R.; McNutt, R. L.

    2009-04-01

    The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft, developed under NASA's Discovery Program, launched in August 2004. En route to insertion into orbit about Mercury in 2011, MESSENGER flies by Mercury three times. The first and second of these encounters were accomplished in January and October of 2008. These flybys viewed portions of Mercury's surface that were not observed by Mariner 10 during its reconnaissance of somewhat less than half of the planet in 1974-1975. All MESSENGER instruments operated during each flyby and returned a wealth of new data. Many of the new observations were focused on the planet's geology, including monochrome imaging at resolutions as high as 100 m/pixel, multispectral imaging in 11 filters at resolutions as high as 500 m/pixel, laser altimetry tracks extending over several thousands of kilometers, and high-resolution spectral measurements of several types of terrain. Here we present an overview of the first inferences on the global geology of Mercury from the MESSENGER observations. Whereas evidence for volcanism was equivocal from Mariner 10 data, the new MESSENGER images and altimetry provide compelling evidence that volcanism was widespread and protracted on Mercury. Color imaging reveals three common spectral units on the surface: a higher-reflectance, relatively red material occurring as a distinct class of smooth plains, typically with distinct embayment relationships interpreted to indicate volcanic emplacement; a lower-reflectance, relatively blue material typically excavated by impact craters and therefore inferred to be more common at depth; and a spectrally intermediate terrain that constitutes much of the uppermost crust. Three more minor spectral units are also seen: fresh crater ejecta, reddish material associated with rimless depressions interpreted to be volcanic centers, and high-reflectance deposits seen in some crater floors. Preliminary measurements of crater size

  18. Carbanions from Decarboxylation of Orotate Analogues: Stability and Mechanistic Implications

    PubMed Central

    Yeoh, Fong Ying; Cuasito, Roxanne R.; Capule, Christina C.; Wong, Freeman M.; Wu, Weiming

    2009-01-01

    The pKa’s of the 6–CH groups of 1,3-dimethyluracil, N-methyl-2-pyridone, and N-methyl-4-pyridone were determined through their reactions with bases derived from carbon acids with known pKa and the reactions of their corresponding carbanions with the carbon acids. No correlation between the stability of the carbanions and the rate of decarboxylation of corresponding carboxylic acids was found. PMID:17400276

  19. How Are Preferences Revealed?

    PubMed

    Beshears, John; Choi, James J; Laibson, David; Madrian, Brigitte C

    2008-08-01

    Revealed preferences are tastes that rationalize an economic agent's observed actions. Normative preferences represent the agent's actual interests. It sometimes makes sense to assume that revealed preferences are identical to normative preferences. But there are many cases where this assumption is violated. We identify five factors that increase the likelihood of a disparity between revealed preferences and normative preferences: passive choice, complexity, limited personal experience, third-party marketing, and intertemporal choice. We then discuss six approaches that jointly contribute to the identification of normative preferences: structural estimation, active decisions, asymptotic choice, aggregated revealed preferences, reported preferences, and informed preferences. Each of these approaches uses consumer behavior to infer some property of normative preferences without equating revealed and normative preferences. We illustrate these issues with evidence from savings and investment outcomes. PMID:24761048

  20. How Are Preferences Revealed?

    PubMed Central

    Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

    2009-01-01

    Revealed preferences are tastes that rationalize an economic agent’s observed actions. Normative preferences represent the agent’s actual interests. It sometimes makes sense to assume that revealed preferences are identical to normative preferences. But there are many cases where this assumption is violated. We identify five factors that increase the likelihood of a disparity between revealed preferences and normative preferences: passive choice, complexity, limited personal experience, third-party marketing, and intertemporal choice. We then discuss six approaches that jointly contribute to the identification of normative preferences: structural estimation, active decisions, asymptotic choice, aggregated revealed preferences, reported preferences, and informed preferences. Each of these approaches uses consumer behavior to infer some property of normative preferences without equating revealed and normative preferences. We illustrate these issues with evidence from savings and investment outcomes. PMID:24761048

  1. Genetics Home Reference: combined malonic and methylmalonic aciduria

    MedlinePlus

    ... plays a role in the formation (synthesis) of fatty acids. Fatty acids are building blocks used to make fats (lipids). ... malonyl-CoA, which is the first step of fatty acid synthesis in cellular structures called mitochondria . Based on ...

  2. [Sweet syndrome revealing leukemia].

    PubMed

    Elleuch, E; Hammami, B; Smaoui, F; Maaloul, I; Turki, H; Elloumi, M; Ben Jemaa, M

    2011-09-01

    Sweet syndrome is a neutrophilic dermatosis that can lead to various inflammatory and neoplastic pathologies. We report a case of Sweet syndrome revealing acute leukemia at a 13-year-old girl, who had no history of illness. The diagnosis was made in spite of atypical skin lesions and was confirmed by the skin biopsy and the bone marrow examination. In spite of corticosteroid therapy and chemotherapy, the patient died. Sweet syndrome's diagnosis requires an exhaustive etiologic survey. If there is no evidence of underlying disease, patients must be regularly monitored.

  3. The Universe Revealed

    NASA Astrophysics Data System (ADS)

    Spence, Pam

    1998-10-01

    The Universe is a bewildering place to the uninitiated. The concepts and theories that govern space seem complex and often contradictory. The Universe Revealed provides the keys to unlocking the wonders of the cosmos. Elegantly written and lavishly illustrated, it begins with the Sun and stretches through our solar system into deepest space. Lucid prose, written by many of the people who have shaped our current thinking on space, and spectacular photographs make the physics of the Universe accessible and provide a solid background for understanding the most recent astronomical discoveries. Covering the most intriguing features of the cosmos, the topics discussed range from the Earth and global warming to cosmic collisions and the size of the Universe. Major sections examine the Solar System, stars, galaxies, cosmology, and the observational techniques used by astronomers, both amateur and professional. The Universe Revealed represents the collaboration of internationally renowned experts in astronomy and cosmology, with contributions from authors including David Malin, F. Duccio Macchetto, Iain Nicholson, Neil Bone, Ian Ridpath, Seth Shostak, Mike Lancaster, Steve Miller, Ken Croswell, Geoff McNamara, and Steven Young. This extraordinary blend of astronomy, astrophysics, and cosmology, will appeal to amateur and armchair astronomers alike.

  4. Gusev's Rim Revealed

    NASA Technical Reports Server (NTRS)

    2004-01-01

    NASA's Mars Exploration Rover Spirit took this panoramic camera image on sol 91 (April 5, 2004). Spirit is looking to the southeast, and through the martian haze has captured the rim of Gusev Crater approximately 80 kilometers (49.7 miles) away on the horizon.

    The right side of this image reveals the portion of the crater edge that descends into the mouth of Ma'adim Vallis, a channel that opens into Gusev Crater. Spirit is currently traveling toward the informally named 'Columbia Hills,' which lie to the left of the region pictured here.

    This image is similar to a panoramic camera image taken on sol 68, but Gusev's ridge is more visible here because the atmospheric dust caused by winter dust storms has settled. Scientists expect to get even clearer images than this one in upcoming sols.

    This image has been modified to make the crater rim more visible.

  5. The Climate Revealed

    NASA Astrophysics Data System (ADS)

    Burroughs, William

    1999-10-01

    El Niño, La Niña, global warming--terms that crop up frequently in current media coverage of anomalous weather conditions: a spring thaw in January in New York City...a snowstorm in Bakersfield, California...winterlike temperatures in Miami. Such phenomena as these and reports of devastating droughts, floods, and storms around the world bring home the fact of how deeply climate affects our daily lives--and of our inability to control the consequences of climatic events. Extraordinarily timely, The Climate Revealed explores the human-climate "relationship" in all its fascinating complexity. Packed with 250 beautiful, full-color photographs, the volume travels the globe to provide a detailed portrait of individual climate zones from the polar icecaps to the fiercest deserts. The expert and highly accessible text uncovers the essential elements--earth, air, fire and water--that make up the world's various climates. William Burroughs reveals the dramatic discoveries and techniques of historians and archaeologists in their search to understand climates of the past. In the book's conclusion he considers the future and presents every facet of the current environmental debate. With its detailed coverage of the past, present, and future, this marvelous work is essential reading for all those who want to understand one of the most critical facets of life, climate. William Burroughs is a well known and successful science author who has written four books on the weather including Does the Weather Really Matter? (1997), Weather Cycles: Real or Imaginary (1992), and Watching the World's Weather (1991), all published by Cambridge University Press.

  6. Revealing cosmic rotation

    NASA Astrophysics Data System (ADS)

    Yadav, Amit P. S.; Shimon, Meir; Keating, Brian G.

    2012-10-01

    Cosmological Birefringence, a rotation of the polarization plane of radiation coming to us from distant astrophysical sources, may reveal parity violation in either the electromagnetic or gravitational sectors of the fundamental interactions in nature. Until only recently this phenomenon could be probed with only radio observations or observations at UV wavelengths. Recently, there is a substantial effort to constrain such nonstandard models using observations of the rotation of the polarization plane of cosmic microwave background (CMB) radiation. This can be done via measurements of the B-modes of the CMB or by measuring its TB and EB correlations which vanish in the standard model. In this paper we show that EB correlations-based estimator is the best for upcoming polarization experiments. The EB-based estimator surpasses other estimators because it has the smallest noise and of all the estimators is least affected by systematics. Current polarimeters are optimized for the detection of B-mode polarization from either primordial gravitational waves or by large-scale structures via gravitational lensing. In the paper we also study the optimization of CMB experiments for the detection of cosmological birefringence, in the presence of instrumental systematics, which by themselves are capable of producing EB correlations, potentially mimicking cosmological birefringence.

  7. Titan Casts Revealing Shadow

    NASA Astrophysics Data System (ADS)

    2004-05-01

    A rare celestial event was captured by NASA's Chandra X-ray Observatory as Titan -- Saturn's largest moon and the only moon in the Solar System with a thick atmosphere -- crossed in front of the X-ray bright Crab Nebula. The X-ray shadow cast by Titan allowed astronomers to make the first X-ray measurement of the extent of its atmosphere. On January 5, 2003, Titan transited the Crab Nebula, the remnant of a supernova explosion that was observed to occur in the year 1054. Although Saturn and Titan pass within a few degrees of the Crab Nebula every 30 years, they rarely pass directly in front of it. "This may have been the first transit of the Crab Nebula by Titan since the birth of the Crab Nebula," said Koji Mori of Pennsylvania State University in University Park, and lead author on an Astrophysical Journal paper describing these results. "The next similar conjunction will take place in the year 2267, so this was truly a once in a lifetime event." Animation of Titan's Shadow on Crab Nebula Animation of Titan's Shadow on Crab Nebula Chandra's observation revealed that the diameter of the X-ray shadow cast by Titan was larger than the diameter of its solid surface. The difference in diameters gives a measurement of about 550 miles (880 kilometers) for the height of the X-ray absorbing region of Titan's atmosphere. The extent of the upper atmosphere is consistent with, or slightly (10-15%) larger, than that implied by Voyager I observations made at radio, infrared, and ultraviolet wavelengths in 1980. "Saturn was about 5% closer to the Sun in 2003, so increased solar heating of Titan may account for some of this atmospheric expansion," said Hiroshi Tsunemi of Osaka University in Japan, one of the coauthors on the paper. The X-ray brightness and extent of the Crab Nebula made it possible to study the tiny X-ray shadow cast by Titan during its transit. By using Chandra to precisely track Titan's position, astronomers were able to measure a shadow one arcsecond in

  8. Revealing the Beast Within

    NASA Astrophysics Data System (ADS)

    2003-07-01

    Deeply Embedded Massive Stellar Clusters Discovered in Milky Way Powerhouse Summary Peering into a giant molecular cloud in the Milky Way galaxy - known as W49 - astronomers from the European Southern Observatory (ESO) have discovered a whole new population of very massive newborn stars . This research is being presented today at the International Astronomical Union's 25th General Assembly held in Sydney, Australia, by ESO-scientist João Alves. With the help of infrared images obtained during a period of excellent observing conditions with the ESO 3.5-m New Technology Telescope (NTT) at the La Silla Observatory (Chile), the astronomers looked deep into this molecular cloud and discovered four massive stellar clusters, with hot and energetic stars as massive as 120 solar masses. The exceedingly strong radiation from the stars in the largest of these clusters is "powering" a 20 light-year diameter region of mostly ionized hydrogen gas (a "giant HII region"). W49 is one of the most energetic regions of star formation in the Milky Way. With the present discovery, the true sources of the enormous energy have now been revealed for the first time, finally bringing to an end some decades of astronomical speculations and hypotheses. PR Photo 21a/03 : Colour Composite of W49A (NTT+SOFI). PR Photo 21b/03 : Radio and Near-Infrared Composite of W49A Giant molecular clouds Stars form predominantly inside Giant Molecular Clouds which populate our Galaxy, the Milky Way. One of the most prominent of these is W49 , which has a mass of a million solar masses. It is located some 37,000 light-years away and is the most luminous star-forming region known in our home galaxy: its luminosity is several million times the luminosity of our Sun. A smaller region within this cloud is denoted W49A - this is one of the strongest radio-emitting areas known in the Galaxy . Massive stars are excessive in all ways. Compared to their smaller and ligther brethren, they form at an Olympic speed and

  9. Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency.

    PubMed

    Kühne, T; Bubl, R; Baumgartner, R

    1991-01-01

    We present a 9-month-old exclusively breast-fed baby of a strict vegetarian mother who had excluded all animal proteins from her diet. The patient's symptoms included dystrophy, weakness, muscular atrophy, loss of tendon reflexes, psychomotor regression and haematological abnormalities. Biochemical investigations revealed severe methylmalonic aciduria and homocystinuria in the patient, slight methylmalonic aciduria in the mother and low concentrations of serum vitamin B12 in both patient and mother.

  10. Maternal vegan diet causing a serious infantile neurological disorder due to vitamin B12 deficiency.

    PubMed

    Kühne, T; Bubl, R; Baumgartner, R

    1991-01-01

    We present a 9-month-old exclusively breast-fed baby of a strict vegetarian mother who had excluded all animal proteins from her diet. The patient's symptoms included dystrophy, weakness, muscular atrophy, loss of tendon reflexes, psychomotor regression and haematological abnormalities. Biochemical investigations revealed severe methylmalonic aciduria and homocystinuria in the patient, slight methylmalonic aciduria in the mother and low concentrations of serum vitamin B12 in both patient and mother. PMID:2044594

  11. Two Unique Glioma Subtypes Revealed.

    PubMed

    Poh, Alissa

    2016-04-01

    A comprehensive analysis of 1,122 diffuse glioma samples from The Cancer Genome Atlas has revealed two new subtypes of this common brain cancer, with molecular and clinical features that diverge from the norm. The study findings also support the use of DNA methylation profiles to improve glioma classification and treatment.

  12. Electrocardiograph abnormalities revealed during laparoscopy.

    PubMed

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner.

  13. Pharmacophore Modeling for Anti-Chagas Drug Design Using the Fragment Molecular Orbital Method

    PubMed Central

    Ohno, Kazuki; Orita, Masaya; Inoue, Masayuki; Shiba, Tomoo; Harada, Shigeharu; Honma, Teruki; Balogun, Emmanuel Oluwadare; da Rocha, Josmar Rodrigues; Montanari, Carlos Alberto; Kita, Kiyoshi; Sekijima, Masakazu

    2015-01-01

    Background Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate derivatives. Methodology/Principal Findings Intermolecular interactions in the complexes of TcDHODH with orotate, oxonate, and 43 orotate derivatives were analyzed by FMO calculation at the MP2/6-31G level. The results indicated that the orotate moiety, which is the base fragment of these compounds, interacts with the Lys43, Asn67, and Asn194 residues of TcDHODH and the cofactor flavin mononucleotide (FMN), whereas functional groups introduced at the orotate 5-position strongly interact with the Lys214 residue. Conclusions/Significance FMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs. PMID:25961853

  14. Archimedes: Accelerator Reveals Ancient Text

    SciTech Connect

    Bergmann, Uwe

    2004-02-24

    Archimedes (287-212 BC), who is famous for shouting 'Eureka' (I found it) is considered one of the most brilliant thinkers of all times. The 10th-century parchment document known as the 'Archimedes Palimpsest' is the unique source for two of the great Greek's treatises. Some of the writings, hidden under gold forgeries, have recently been revealed at the Stanford Synchrotron Radiation Laboratory at SLAC. An intense x-ray beam produced in a particle accelerator causes the iron in original ink, which has been partly erased and covered, to send out a fluorescence glow. A detector records the signal and a digital image showing the ancient writings is produced. Please join us in this fascinating journey of a 1,000-year-old parchment from its origin in the Mediterranean city of Constantinople to a particle accelerator in Menlo Park.

  15. Revealing ontological commitments by magic.

    PubMed

    Griffiths, Thomas L

    2015-03-01

    Considering the appeal of different magical transformations exposes some systematic asymmetries. For example, it is more interesting to transform a vase into a rose than a rose into a vase. An experiment in which people judged how interesting they found different magic tricks showed that these asymmetries reflect the direction a transformation moves in an ontological hierarchy: transformations in the direction of animacy and intelligence are favored over the opposite. A second and third experiment demonstrated that judgments of the plausibility of machines that perform the same transformations do not show the same asymmetries, but judgments of the interestingness of such machines do. A formal argument relates this sense of interestingness to evidence for an alternative to our current physical theory, with magic tricks being a particularly pure source of such evidence. These results suggest that people's intuitions about magic tricks can reveal the ontological commitments that underlie human cognition.

  16. Plan competitions reveal entrepreneurial talent

    SciTech Connect

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  17. [Abdominal cystic tumor revealing lymphangioleiomyomatosis].

    PubMed

    Barbier, L; Ebbo, M; Andrac-Meyer, L; Schneilitz, N; Le Treut, Y-P; Reynaud-Gaubert, M; Hardwigsen, J

    2009-02-01

    We report the case of a 39 year-old woman with many years of intermittent abdominal pain who was found to have cystic masses evocative of cystic lymphangioma involving the posterior mediastinal and retroperitoneum. Worsening abdominal pain led to a recommendation for laparoscopic unroofing and decompression of the cysts. During the postoperative period, hemorrhagic shock required reintervention with excision of the tumoral mass. Pathologic examination revealed lymphangioleiomyomatosis (LAM). On the 15th postoperative day, the patient developed a chylopneumothorax which required prolonged chest tube drainage. The presence of multiple polycystic lesions in the pulmonary parenchyma supported the diagnosis of diffuse LAM with primary extrapulmonary presentation. This diagnosis should be considered preoperatively since it modifies the treatment: a complete excision of the cystic lesions seems to be necessary in order to prevent bleeding and lymphatic extravasation.

  18. Erosion and what it Reveals

    NASA Technical Reports Server (NTRS)

    2003-01-01

    [figure removed for brevity, see original site]

    Released 20 November 2003

    This image is located near the boundary between Syrtis Major and Isidis Planitia. The top of the image shows rough material that has eroded away from the lower portion of the image, revealing an underlying surface that has many small craters. It also reveals an ancient flow lobe that is barely discernable, crossing the southern part of the image (this flow lobe is much easier to see as a smooth region in the context image).

    Image information: VIS instrument. Latitude 16.4, Longitude 77.9 East (282.1 West). 19 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  19. Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases.

    PubMed

    Yamada, Kazuhiro; Gherasim, Carmen; Banerjee, Ruma; Koutmos, Markos

    2015-12-01

    In mammals, B12 (or cobalamin) is an essential cofactor required by methionine synthase and methylmalonyl-CoA mutase. A complex intracellular pathway supports the assimilation of cobalamin into its active cofactor forms and delivery to its target enzymes. MMADHC (the methylmalonic aciduria and homocystinuria type D protein), commonly referred to as CblD, is a key chaperone involved in intracellular cobalamin trafficking, and mutations in CblD cause methylmalonic aciduria and/or homocystinuria. Herein, we report the first crystal structure of the globular C-terminal domain of human CblD, which is sufficient for its interaction with MMADHC (the methylmalonic aciduria and homocystinuria type C protein), or CblC, and for supporting the cytoplasmic cobalamin trafficking pathway. CblD contains an α+β fold that is structurally reminiscent of the nitro-FMN reductase superfamily. Two of the closest structural relatives of CblD are CblC, a multifunctional enzyme important for cobalamin trafficking, and the activation domain of methionine synthase. CblD, CblC, and the activation domain of methionine synthase share several distinguishing features and, together with two recently described corrinoid-dependent reductive dehalogenases, constitute a new subclass within the nitro-FMN reductase superfamily. We demonstrate that CblD enhances oxidation of cob(II)alamin bound to CblC and that disease-causing mutations in CblD impair the kinetics of this reaction. The striking structural similarity of CblD to CblC, believed to be contiguous in the cobalamin trafficking pathway, suggests the co-option of molecular mimicry as a strategy for achieving its function.

  20. Hubble Images Reveal Jupiter's Auroras

    NASA Technical Reports Server (NTRS)

    1996-01-01

    These images, taken by the Hubble Space Telescope, reveal changes in Jupiter's auroral emissions and how small auroral spots just outside the emission rings are linked to the planet's volcanic moon, Io. The images represent the most sensitive and sharply-detailed views ever taken of Jovian auroras.

    The top panel pinpoints the effects of emissions from Io, which is about the size of Earth's moon. The black-and-white image on the left, taken in visible light, shows how Io and Jupiter are linked by an invisible electrical current of charged particles called a 'flux tube.' The particles - ejected from Io (the bright spot on Jupiter's right) by volcanic eruptions - flow along Jupiter's magnetic field lines, which thread through Io, to the planet's north and south magnetic poles. This image also shows the belts of clouds surrounding Jupiter as well as the Great Red Spot.

    The black-and-white image on the right, taken in ultraviolet light about 15 minutes later, shows Jupiter's auroral emissions at the north and south poles. Just outside these emissions are the auroral spots. Called 'footprints,' the spots are created when the particles in Io's 'flux tube' reach Jupiter's upper atmosphere and interact with hydrogen gas, making it fluoresce. In this image, Io is not observable because it is faint in the ultraviolet.

    The two ultraviolet images at the bottom of the picture show how the auroral emissions change in brightness and structure as Jupiter rotates. These false-color images also reveal how the magnetic field is offset from Jupiter's spin axis by 10 to 15 degrees. In the right image, the north auroral emission is rising over the left limb; the south auroral oval is beginning to set. The image on the left, obtained on a different date, shows a full view of the north aurora, with a strong emission inside the main auroral oval.

    The images were taken by the telescope's Wide Field and Planetary Camera 2 between May 1994 and September 1995.

    This image and

  1. Satellites reveal Antarctic mass imbalance

    NASA Astrophysics Data System (ADS)

    Shepherd, A.

    2004-05-01

    Satellite radar observations have revealed a widespread mass imbalance in western Antarctica and rapid thinning of ice shelves at the Antarctic Peninsula. The former shows grounded ice retreat in a region previously considered unstable to such events, and the latter illuminates an ongoing debate as to the mechanism through which ice shelves have disintegrated over the past decade. Both measurements inform us as to the present state of balance of the cryosphere and its interactions with the southern oceans. Since 1992, the Amundsen Sea sector of the West Antarctic Ice Sheet has lost 39 cubic kilometers of its volume each year due to an imbalance between snow accumulation and ice discharge. A flow disturbance is responsible for removing the majority of that ice from the trunks of the Pine Island, Thwaites and Smith glacier drainage systems, raising global sea level by over 1 mm during the past decade alone. The coincidence of rapid ice thinning at the Amundsen Coast and warm circumpolar deep water intrusion in Pine Island Bay, coupled with a ~ 50 cubic kilometre annual freshening of the Ross Sea Gyre downstream, makes ocean melting an attractive proposition for the origin of the regional disturbance. At the same time, the Larsen Ice Shelf surface has lowered by up to 0.27 m per year, in tandem with a period of atmospheric warming and ice shelf collapse. The lowering cannot be explained by increased summer melt-water production alone, and must reflect a loss of basal ice through melting. Ocean temperature measurements close to the ice shelf barrier support this conclusion, making enhanced basal ice melting a likely factor linking the regional climate warming and the successive disintegration of sections of the Larsen Ice Shelf.

  2. A New Mouse Model of Mild Ornithine Transcarbamylase Deficiency (spf-j) Displays Cerebral Amino Acid Perturbations at Baseline and upon Systemic Immune Activation

    PubMed Central

    Tarasenko, Tatyana N.; Rosas, Odrick R.; Singh, Larry N.; Kristaponis, Kara; Vernon, Hilary; McGuire, Peter J.

    2015-01-01

    Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans. PMID:25647322

  3. Focus groups reveal consumer ambivalence.

    PubMed

    1983-01-01

    According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

  4. [Cholangitis revealing an intrahepatic Osler's disease].

    PubMed

    Asma, Kochlef; Dalila, Gargouri; Olfa, Bousnina; Malika, Romani; Afef, Kilani; Najet, BelHadg; Jamel, Kharrat; Abdeljabbar, Gorbel; Sarra, Shili; Chiraz, Jemli; Mohamed, Habib Daghfous; Slim, Khlifi; Anis, Ben Maamer; Abdelmajid, Letaïef

    2005-08-01

    Osler Weber Rendu Disease is an hereditary haemorrhagic télangectasia habitually revealed by reccurent bleeding (epistaxis). Hepatic involvement in Osler disease is found in 8 to 31%, manifested by cholestasis. We report an original observation of a cholangitis revealing Osler disease.

  5. REVEAL: Software Documentation and Platform Migration

    NASA Technical Reports Server (NTRS)

    Wilson, Michael A.; Veibell, Victoir T.; Freudinger, Lawrence C.

    2008-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA s Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This report specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as a final report for that internship. The topics discussed include: the documentation of REVEAL source code; the migration of REVEAL to other platforms; and an end-to-end field test that successfully validates the efforts.

  6. Revealing advantage in a quantum network

    NASA Astrophysics Data System (ADS)

    Mukherjee, Kaushiki; Paul, Biswajit; Sarkar, Debasis

    2016-07-01

    The assumption of source independence was used to reveal nonlocal (apart from standard Bell-CHSH scenario) nature of correlations generated in entanglement swapping experiments. In this work, we have discussed the various utilities of this assumption to reveal nonlocality (via generation of nonbilocal correlations) and thereby exploiting quantumness under lesser requirements compared to some standard means of doing the same. We have also provided with a set of sufficient criteria, imposed on the states (produced by the sources) under which source independence can reveal nonbilocal nature of correlations in a quantum network.

  7. Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital.

    PubMed

    Humphreys, Benjamin D; Forman, John P; Zandi-Nejad, Kambiz; Bazari, Hasan; Seifter, Julian; Magee, Colm C

    2005-07-01

    A rare cause of high anion gap acidosis is 5-oxoproline (pyroglutamic acid), an organic acid intermediate of the gamma-glutamyl cycle. Acetaminophen and several other drugs have been implicated in the development of transient 5-oxoprolinemia in adults. We report the case of a patient with lymphoma who was admitted for salvage chemotherapy. The patient subsequently developed fever and neutropenia and was administered 20.8 g of acetaminophen during 10 days. During this time, anion gap increased from 14 to 30 mEq/L (14 to 30 mmol/L) and altered mental status developed. After usual causes of high anion gap acidosis were ruled out, a screen for urine organic acids showed 5-oxoproline levels elevated at 58-fold greater than normal values. Predisposing factors in this case included renal dysfunction and sepsis. Clinicians need to be aware of this unusual cause of anion gap acidosis because it may be more common than expected, early discontinuation of the offending agent is therapeutic, and administration of N -acetylcysteine could be beneficial.

  8. Metabolic biology of 3-methylglutaconic acid-uria: a new perspective

    PubMed Central

    Su, Betty; Ryan, Robert O.

    2014-01-01

    Summary Over the past twenty-five years a growing number of distinct syndromes / mutations associated with compromised mitochondrial function have been identified that share a common feature: urinary excretion of 3-methylglutaconic acid (3MGA). In the leucine degradation pathway, carboxylation of 3-methylcrotonyl CoA leads to formation of 3-methylglutaconyl CoA while 3-methylglutaconyl CoA hydratase converts this metabolite to 3-hydroxy-3-methylglutaryl CoA (HMG CoA). In “primary” 3MGA-uria, mutations in the hydratase are directly responsible for the accumulation of 3MGA. On the other hand, in all “secondary” 3MGA-urias, no defect in leucine catabolism exists and the metabolic origin of 3MGA is unknown. Herein, a path to 3MGA from mitochondrial acetyl CoA is proposed. The pathway is initiated when syndrome-associated mutations / DNA deletions result in decreased Krebs cycle flux. When this occurs, acetoacetyl CoA thiolase condenses two acetyl CoA into acetoacetyl CoA plus CoASH. Subsequently, HMG CoA synthase 2 converts acetoacetyl CoA and acetyl CoA to HMG CoA. Under syndrome-specific metabolic conditions, 3-methylglutaconyl CoA hydratase converts HMG CoA into 3-methylglutaconyl CoA in a reverse reaction of the leucine degradation pathway. This metabolite fails to proceed further up the leucine degradation pathway owing to the kinetic properties of 3-methylcrotonyl CoA carboxylase. Instead, hydrolysis of the CoA moiety of 3-methylglutaconyl CoA generates 3MGA, which appears in urine. If experimentally confirmed, this pathway provides an explanation for the occurrence of 3MGA in multiple disorders associated with compromised mitochondrial function. PMID:24407466

  9. Metabolic biology of 3-methylglutaconic acid-uria: a new perspective.

    PubMed

    Su, Betty; Ryan, Robert O

    2014-05-01

    Over the past 25 years a growing number of distinct syndromes/mutations associated with compromised mitochondrial function have been identified that share a common feature: urinary excretion of 3-methylglutaconic acid (3MGA). In the leucine degradation pathway, carboxylation of 3-methylcrotonyl CoA leads to formation of 3-methylglutaconyl CoA while 3-methylglutaconyl CoA hydratase converts this metabolite to 3-hydroxy-3-methylglutaryl CoA (HMG CoA). In "primary" 3MGA-uria, mutations in the hydratase are directly responsible for the accumulation of 3MGA. On the other hand, in all "secondary" 3MGA-urias, no defect in leucine catabolism exists and the metabolic origin of 3MGA is unknown. Herein, a path to 3MGA from mitochondrial acetyl CoA is proposed. The pathway is initiated when syndrome-associated mutations/DNA deletions result in decreased Krebs cycle flux. When this occurs, acetoacetyl CoA thiolase condenses two acetyl CoA into acetoacetyl CoA plus CoASH. Subsequently, HMG CoA synthase 2 converts acetoacetyl CoA and acetyl CoA to HMG CoA. Under syndrome-specific metabolic conditions, 3-methylglutaconyl CoA hydratase converts HMG CoA into 3-methylglutaconyl CoA in a reverse reaction of the leucine degradation pathway. This metabolite fails to proceed further up the leucine degradation pathway owing to the kinetic properties of 3-methylcrotonyl CoA carboxylase. Instead, hydrolysis of the CoA moiety of 3-methylglutaconyl CoA generates 3MGA, which appears in urine. If experimentally confirmed, this pathway provides an explanation for the occurrence of 3MGA in multiple disorders associated with compromised mitochondrial function.

  10. The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome.

    PubMed

    Sofer, S; Schweiger, A; Blumkin, L; Yahalom, G; Anikster, Y; Lev, D; Ben-Zeev, B; Lerman-Sagie, T; Hassin-Baer, S

    2015-04-01

    Costeff syndrome is a rare genetic neuro-ophthalmological syndrome consisting of early-onset bilateral optic atrophy along with a progressive complex motor disorder with elevated levels of urinary 3-methylglutaconic acid and 3-methylglutaric acid. While borderline to mild cognitive deficits have been considered to be common in patients with this syndrome, a comprehensive cognitive assessment has never been performed. The aim of the current study was to explore the cognitive profile associated with Costeff syndrome. Sixteen adult patients diagnosed with Costeff syndrome were administered a neuropsychological test battery that was composed of standardized verbal tests adapted for the blind. General intelligence ranged from average to borderline, with a group mean consistent with intact general cognitive functioning (VIQmean  = 85, z = -1) in the low-average range of the general population. The auditory immediate and delayed memory indexes were in the average range and were significantly higher than the general cognitive functioning, whereas the working memory index was significantly lower than the general cognitive functioning. Adult patients with Costeff syndrome have intact global cognition and learning abilities and strong auditory memory performance. © 2015 Wiley Periodicals, Inc. PMID:25657044

  11. Mitochondrial dysfunction and organic aciduria in five patients carrying mutations in the Ras-MAPK pathway

    PubMed Central

    Kleefstra, Tjitske; Wortmann, Saskia B; Rodenburg, Richard J T; Bongers, Ernie M H F; Hadzsiev, Kinga; Noordam, Cees; van den Heuvel, Lambert P; Nillesen, Willy M; Hollody, Katalin; Gillessen-Kaesbach, Gabrielle; Lammens, Martin; Smeitink, Jan A M; van der Burgt, Ineke; Morava, Eva

    2011-01-01

    Various syndromes of the Ras-mitogen-activated protein kinase (MAPK) pathway, including the Noonan, Cardio-Facio-Cutaneous, LEOPARD and Costello syndromes, share the common features of craniofacial dysmorphisms, heart defect and short stature. In a subgroup of patients, severe muscle hypotonia, central nervous system involvement and failure to thrive occur as well. In this study we report on five children diagnosed initially with classic metabolic and clinical symptoms of an oxidative phosphorylation disorder. Later in the course of the disease, the children presented with characteristic features of Ras-MAPK pathway-related syndromes, leading to the reevaluation of the initial diagnosis. In the five patients, in addition to the oxidative phosphorylation disorder, disease-causing mutations were detected in the Ras-MAPK pathway. Three of the patients also carried a second, mitochondrial genetic alteration, which was asymptomatically present in their healthy relatives. Did we miss the correct diagnosis in the first place or is mitochondrial dysfunction directly related to Ras-MAPK pathway defects? The Ras-MAPK pathway is known to have various targets, including proteins in the mitochondrial membrane influencing mitochondrial morphology and dynamics. Prospective screening of 18 patients with various Ras-MAPK pathway defects detected biochemical signs of disturbed oxidative phosphorylation in three additional children. We concluded that only a specific, metabolically vulnerable sub-population of patients with Ras-MAPK pathway mutations presents with mitochondrial dysfunction and a more severe, early-onset disease. We postulate that patients with Ras-MAPK mutations have an increased susceptibility, but a second metabolic hit is needed to cause the clinical manifestation of mitochondrial dysfunction. PMID:21063443

  12. Hiding personal information reveals the worst

    PubMed Central

    John, Leslie K.; Barasz, Kate; Norton, Michael I.

    2016-01-01

    Seven experiments explore people’s decisions to share or withhold personal information, and the wisdom of such decisions. When people choose not to reveal information—to be “hiders”—they are judged negatively by others (experiment 1). These negative judgments emerge when hiding is volitional (experiments 2A and 2B) and are driven by decreases in trustworthiness engendered by decisions to hide (experiments 3A and 3B). Moreover, hiders do not intuit these negative consequences: given the choice to withhold or reveal unsavory information, people often choose to withhold, but observers rate those who reveal even questionable behavior more positively (experiments 4A and 4B). The negative impact of hiding holds whether opting not to disclose unflattering (drug use, poor grades, and sexually transmitted diseases) or flattering (blood donations) information, and across decisions ranging from whom to date to whom to hire. When faced with decisions about disclosure, decision-makers should be aware not just of the risk of revealing, but of what hiding reveals. PMID:26755591

  13. REVEAL: Software Documentation and Platform Migration

    NASA Technical Reports Server (NTRS)

    Wilson, Michael A.; Veibell, Victoir T.

    2011-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA's Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This presentation specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as an overview of the content of the final report for that internship.

  14. Systemic lupus erythematous revealed by cytomegalovirus infection

    PubMed Central

    Amel, Rezgui; Monia, Karmani; Anis, Mzabi; Fatma, Ben Fredj; Chadia, Laouani

    2016-01-01

    Cytomegalovirus (CMV) infection have been described as exacerbing systemic lupus erythematous (SLE). The role of CMV in starting off SLE remains object of debate. We report a severe presentation of SLE revealed by CMV infection with hemophogocytic syndrome. A 22 old women without a history of systemic disease developed a cutaneous eruption with fever and myalgia persistant for 2 weeks. Laboratory studies revealed a CMV serology supporting acute CMV infection, with positive antinuclear antidody, anti ds DNA, elevated liver functions tests, pancytopenia. Further exams revealed an hemophagocytic syndrome and a lupus nephritis. While receiving antiviral and corticosteroid therapy, the patient developed seizures related to a cerebral vasculitis. The outcome was favorable when intravenous immunoglobulins were associated. This observation showed that CMV infection in patients with SLE is often serious and difficult to diagnose and to treat, especially when SLE is not yet recognized. So we suggest all patients with recent SLE have routine testing for CMV immunity. PMID:27800096

  15. Eye Movements Reveal Dynamics of Task Control

    ERIC Educational Resources Information Center

    Mayr, Ulrich; Kuhns, David; Rieter, Miranda

    2013-01-01

    With the goal to determine the cognitive architecture that underlies flexible changes of control settings, we assessed within-trial and across-trial dynamics of attentional selection by tracking of eye movements in the context of a cued task-switching paradigm. Within-trial dynamics revealed a switch-induced, discrete delay in onset of…

  16. The cattle genome reveals its secrets

    PubMed Central

    Burt, David W

    2009-01-01

    The domesticated cow is the latest farm animal to have its genome sequenced and deciphered. The members of the Bovine Genome Consortium have published a series of papers on the assembly and what the sequence reveals so far about the biology of this ruminant and the consequences of its domestication. PMID:19439025

  17. Revealing a Child's Pathology: Physicians' Experiences

    ERIC Educational Resources Information Center

    Scelles, Regine; Aubert-Godard, Anne; Gargiulo, Marcela; Avant, Monique; Gortais, Jean

    2010-01-01

    In this study, 12 physicians and 12 care-givers were interviewed using semi-structured interviews. We explored physicians' experiences when they revealed a diagnosis. We also tried to understand which family members the physician was thinking of, with whom they identified themselves, and their first choice of the person to whom they prefer to…

  18. Open chromatin reveals the functional maize genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Every cellular process mediated through nuclear DNA must contend with chromatin. As results from ENCODE show, open chromatin assays can efficiently integrate across diverse regulatory elements, revealing functional non-coding genome. In this study, we use a MNase hypersensitivity assay to discover o...

  19. Nucleolar organization as revealed in cell spreads.

    PubMed

    Ghosh, S; Paweletz, N

    1996-07-01

    The nucleolar organization has been studied in spreads of cells either untreated or treated with hypotonic salt solution for different periods. A network corresponding to the nucleolonema becomes evident with progressive hypotonic treatment. The network reveals units comparable to the rDNA transcriptional units in length and is associated with tufts of fibrils and granules. Spread preparations from cycloheximide treated cells reveal a thread-like axis and often 'Christmas tree'-like configurations within these units. Spacers joining the units can also be detected. It is supposed that the transcriptional units move outwards with their transcriptional products where the processing takes place. In loose nucleoli, this network forms the nucleolonema, which remains associated with the granules, the processed transcriptional products. In compact nucleoli the network is obliterated by the granules and they form the major component of the nucleoli. Such organization represents all the events in the transcription and processing of ribosomal RNA.

  20. What Eye Movements Reveal about Deaf Readers

    PubMed Central

    Bélanger, Nathalie N.; Rayner, Keith

    2014-01-01

    Levels of illiteracy in the deaf populations around the world have been extremely high for decades and much higher than the illiteracy levels found in the general population. Research has mostly focused on deaf readers’ difficulties rather than on their strengths, which can then inform reading education. Deaf readers are a unique population. They process language and the world surrounding them mostly via the visual channel and this greatly affects how they read or might learn to read. The study of eye movements in reading provides highly sophisticated information about how words and sentences are processed and our research with deaf readers reveals the importance of their uniqueness. PMID:26594098

  1. Infections Revealing Complement Deficiency in Adults

    PubMed Central

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  2. Changes in Pluto's Atmosphere Revealed by Occultations

    NASA Astrophysics Data System (ADS)

    Sicardy, Bruno; Widemann, Thomas; Lellouch, Emmanuel; Veillet, Christian; Colas, Francois; Roques, Francoise; Beisker, Wolfgang; Kretlow, Mike; Cuillandre, Jean-Charles; Hainaut, Olivier

    After the discovery and study of Pluto's tenuous atmosphere in 1985 and 1988 with stellar occultations 14 years were necessary before two other occultations by the planet could be observed on 20 July 2002 and 21 August 2002 from Northern Chile with a portable telescope and from CFHT in Hawaii respectively. These occultations reveal drastric changes in Pluto's nitrogen atmosphere whose pressure increased by a factor two or more since 1988. In spite of an increasing distance to the Sun (and a correlated decrease of solar energy input at Pluto) this increase can be explained by the fact that Pluto's south pole went from permanent darkness to permanent illumination between 1988 and 2002. This might cause the sublimation of the south polar cap and the increase of pressure which could go on till 2015 according to current nitrogen cycle models. Furthermore we detect temperature contrasts between the polar and the equatorial regions probed on Pluto possibly caused by different diurnally averaged insolations at those locations. Finally spikes observed in the light curves reveal a dynamical activity in Pluto's atmosphere.

  3. Interior Evolution of Ceres Revealed by Dawn

    NASA Astrophysics Data System (ADS)

    Raymond, Carol A.; Park, Ryan S.; Konopliv, Alex S.; Bland, Michael T.; Marchi, Simone; Castillo-Rogez, Julie C.; McCord, Thomas B.; Jaumann, Ralf; Russell, Christopher T.; Prettyman, Thomas H.

    2015-11-01

    Dawn's exploration of Ceres has revealed its geophysical characteristics, informing the processes that have shaped it. Dawn has determined the average diameter of Ceres to be 940 km, smaller than the previously estimated 975 km [1]. This implies a density of 2160 kg/m3, indicating that Ceres is less differentiated than predicted [2]. The low-degree gravity field is consistent with the body being in hydrostatic equilibrium and the magnitude of J2 implies some central condensation. Ceres' entire surface is cratered, implying the lack of a thick (10's of km) water ice layer at the surface. Variability in Ceres' crater morphology indicates that the near-surface layer has variable strength and rheology, likely due to heterogeneity in the near-surface mixture of rock, ice and salt. The lack of a number of expected large impact basins on Ceres can be interpreted to be the result of viscous relaxation, resurfacing or a combination of both. These data provide insights into Ceres' thermal evolution and mechanical properties, which appear to be unique to this warm, icy body.[1] Thomas, P. C., et al., Differentiation of the asteroid Ceres as revealed by its shape, Nature, 437, 224-226, 2005; [2] McCord et al., Ceres: Its Origin, Evolution and Structure and Dawn's Potential Contribution, Space Sci Rev DOI 10.1007/s11214-010-9729-9, 2011.

  4. Mammalian phylogeny reveals recent diversification rate shifts.

    PubMed

    Stadler, Tanja

    2011-04-12

    Phylogenetic trees of present-day species allow investigation of the rate of evolution that led to the present-day diversity. A recent analysis of the mammalian phylogeny challenged the view of explosive mammalian evolution after the Cretaceous-Tertiary (K/T) boundary (65 Mya). However, due to lack of appropriate methods, the diversification (speciation minus extinction) rates in the more recent past of mammalian evolution could not be determined. In this paper, I provide a method that reveals that the tempo of mammalian evolution did not change until ∼ 33 Mya. This constant period was followed by a peak of diversification rates between 33 and 30 Mya. Thereafter, diversification rates remained high and constant until 8.55 Mya. Diversification rates declined significantly at 8.55 and 3.35 Mya. Investigation of mammalian subgroups (marsupials, placentals, and the six largest placental subgroups) reveals that the diversification rate peak at 33-30 Mya is mainly driven by rodents, cetartiodactyla, and marsupials. The recent diversification rate decrease is significant for all analyzed subgroups but eulipotyphla, cetartiodactyla, and primates. My likelihood approach is not limited to mammalian evolution. It provides a robust framework to infer diversification rate changes and mass extinction events in phylogenies, reconstructed from, e.g., present-day species or virus data. In particular, the method is very robust toward noise and uncertainty in the phylogeny and can account for incomplete taxon sampling. PMID:21444816

  5. [Pneumothorax revealed by postoperative computed tomography].

    PubMed

    Ikeda, Shizuka; Katori, Kiyoshi; Fujimoto, Minoru; Nitahara, Keiichi; Higa, Kazuo

    2005-11-01

    We report a case of pneumothorax revealed by postoperative computed tomography. A 39-year-old obese woman (height 153 cm, weight 70 kg) with fractures of the radius, ulna, clavicle, and femur in a traffic accident, was scheduled for osteosynthesis. Anesthesia was induced with thiopental and maintained with 50% nitrous oxide in oxygen and sevoflurane. The Spo2 decreased from 99% to 94% during the surgery. Bilateral chest sounds were symmetrical. The Spo2 increased to 100% after discontinuation of nitrous oxide. Pneumothorax was not evident on a postoperative chest X-ray, but computed tomography of the chest demonstrated right-sided pneumothorax. An ECG electrode had overlapped the fractured rib on the preoperative chest X-ray.

  6. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    SciTech Connect

    Warren, Jeffrey; Bilheux, Hassina Z; Kang, Misun; Voisin, Sophie; Cheng, Chu-Lin; Horita, Jusuke; Perfect, Edmund

    2013-01-01

    Many terrestrial ecosystem processes are constrained by water availability and transport within the soil. Knowledge of plant water fluxes is thus critical for assessing mechanistic processes linked to biogeochemical cycles, yet resolution of root structure and xylem water transport dynamics has been a particularly daunting task for the ecologist. Through neutron imaging, we demonstrate the ability to non-invasively monitor individual root functionality and water fluxes within Zea mays L. (maize) and Panicum virgatum L. (switchgrass) seedlings growing in a sandy medium. Root structure and growth were readily imaged by neutron radiography and neutron computed tomography. Seedlings were irrigated with water or deuterium oxide and imaged through time as a growth lamp was cycled on to alter leaf demand for water. Sub-millimeter scale resolution reveals timing and magnitudes of root water uptake, redistribution within the roots, and root-shoot hydraulic linkages, relationships not well characterized by other techniques.

  7. Protein Vivisection Reveals Elusive Intermediates in Folding

    SciTech Connect

    Zheng, Zhongzhou; Sosnick, Tobin R.

    2010-05-25

    Although most folding intermediates escape detection, their characterization is crucial to the elucidation of folding mechanisms. Here, we outline a powerful strategy to populate partially unfolded intermediates: A buried aliphatic residue is substituted with a charged residue (e.g., Leu {yields} Glu{sup -}) to destabilize and unfold a specific region of the protein. We applied this strategy to ubiquitin, reversibly trapping a folding intermediate in which the {beta}5-strand is unfolded. The intermediate refolds to a native-like structure upon charge neutralization under mildly acidic conditions. Characterization of the trapped intermediate using NMR and hydrogen exchange methods identifies a second folding intermediate and reveals the order and free energies of the two major folding events on the native side of the rate-limiting step. This general strategy may be combined with other methods and have broad applications in the study of protein folding and other reactions that require trapping of high-energy states.

  8. Protein vivisection reveals elusive intermediates in folding.

    PubMed

    Zheng, Zhongzhou; Sosnick, Tobin R

    2010-04-01

    Although most folding intermediates escape detection, their characterization is crucial to the elucidation of folding mechanisms. Here, we outline a powerful strategy to populate partially unfolded intermediates: A buried aliphatic residue is substituted with a charged residue (e.g., Leu-->Glu(-)) to destabilize and unfold a specific region of the protein. We applied this strategy to ubiquitin, reversibly trapping a folding intermediate in which the beta5-strand is unfolded. The intermediate refolds to a native-like structure upon charge neutralization under mildly acidic conditions. Characterization of the trapped intermediate using NMR and hydrogen exchange methods identifies a second folding intermediate and reveals the order and free energies of the two major folding events on the native side of the rate-limiting step. This general strategy may be combined with other methods and have broad applications in the study of protein folding and other reactions that require trapping of high-energy states.

  9. Can Clustering in Genotype Space Reveal "Niches"?

    PubMed

    D'Andrea, Rafael; Ostling, Annette

    2016-01-01

    Community ecology lacks the success enjoyed by population genetics to quantify the relative roles played by deterministic and stochastic processes. It has been proposed that clustered patterns of abundance in genotype space provide evidence of selection in microbial communities, since no such clustering would arise in the absence of selection. We critique this test for its unrealistic null hypothesis. We show mathematically and with simulations that point mutations alone lead to clustering in genotype space by causing correlations between abundances of similar genotypes. We also show potential deviations from the mutation-only pattern caused by immigration from a source pool. Clustered patterns in genotype space may still be revealing of selection if analyzed quantitatively but only if neutral and selective regimes can be distinguished once mutation and immigration are included in the null model.

  10. Social patterns revealed through random matrix theory

    NASA Astrophysics Data System (ADS)

    Sarkar, Camellia; Jalan, Sarika

    2014-11-01

    Despite the tremendous advancements in the field of network theory, very few studies have taken weights in the interactions into consideration that emerge naturally in all real-world systems. Using random matrix analysis of a weighted social network, we demonstrate the profound impact of weights in interactions on emerging structural properties. The analysis reveals that randomness existing in particular time frame affects the decisions of individuals rendering them more freedom of choice in situations of financial security. While the structural organization of networks remains the same throughout all datasets, random matrix theory provides insight into the interaction pattern of individuals of the society in situations of crisis. It has also been contemplated that individual accountability in terms of weighted interactions remains as a key to success unless segregation of tasks comes into play.

  11. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  12. Open chromatin reveals the functional maize genome

    PubMed Central

    Rodgers-Melnick, Eli; Vera, Daniel L.; Bass, Hank W.

    2016-01-01

    Cellular processes mediated through nuclear DNA must contend with chromatin. Chromatin structural assays can efficiently integrate information across diverse regulatory elements, revealing the functional noncoding genome. In this study, we use a differential nuclease sensitivity assay based on micrococcal nuclease (MNase) digestion to discover open chromatin regions in the maize genome. We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks. Although MNase HS regions map to less than 1% of the genome, they consistently explain a remarkably large amount (∼40%) of heritable phenotypic variance in diverse complex traits. MNase HS regions are therefore on par with coding sequences as annotations that demarcate the functional parts of the maize genome. These results imply that less than 3% of the maize genome (coding and MNase HS regions) may give rise to the overwhelming majority of phenotypic variation, greatly narrowing the scope of the functional genome. PMID:27185945

  13. Revealing effective classifiers through network comparison

    NASA Astrophysics Data System (ADS)

    Gallos, Lazaros K.; Fefferman, Nina H.

    2014-11-01

    The ability to compare complex systems can provide new insight into the fundamental nature of the processes captured, in ways that are otherwise inaccessible to observation. Here, we introduce the n-tangle method to directly compare two networks for structural similarity, based on the distribution of edge density in network subgraphs. We demonstrate that this method can efficiently introduce comparative analysis into network science and opens the road for many new applications. For example, we show how the construction of a “phylogenetic tree” across animal taxa according to their social structure can reveal commonalities in the behavioral ecology of the populations, or how students create similar networks according to the University size. Our method can be expanded to study many additional properties, such as network classification, changes during time evolution, convergence of growth models, and detection of structural changes during damage.

  14. Ceres Revealed in a Grain of Salt

    NASA Technical Reports Server (NTRS)

    Zolensky, M. E.; Bodnar, R. J.; Fries, M.; Chan, Q. H.-S.; Kebukawa, Y.; Mikouchi, T.; Hagiya, K.; Komatsu, M.; Ohsumi, K.; Steele, A.

    2016-01-01

    Introduction: Zag and Monahans (1998) are H chondrite regolith breccias containing 4.5 giga-year-old halite crystals which contain abundant inclusions of aqueous fluids, solids and organics. These all originated on a cryo-volcanically-active C class asteroid, probably 1 Ceres; the halite was transported to the regolith of the H chondrite parent asteroid, potentially 6 Hebe. Detailed analysis of these solids will thus potentially reveal the mineralogy of Ceres. Mineralogy of solids in the Monahans Halite Solid grains are present in the halites, which were entrained within the mother brines during eruption, including material from the interior and surface of the erupting body. The solids include abundant, widely variable organics that could not have been significantly heated (which would have resulted in the loss of fluids from the halite). Our analyses by Raman microprobe, SEM/EDX, synchrotron X-ray diffraction, UPLC-FD/QToF-MS, C-XANES and TEM reveal that these trapped grains include macromolecular carbon (MMC) similar in structure to CV3 chondrite matrix carbon, aliphatic carbon compounds, olivine (Fo99-59), high- and low-Ca pyroxene, feldspars, phyllosilicates, magnetite, sulfides, metal, lepidocrocite, carbonates, diamond, apatite and zeolites. Conclusions: The halite in Monahans and Zag derive from a water and carbon-rich object that was cryo-volcanically active in the early solar system, probably Ceres. The Dawn spacecraft found that Ceres includes C chondrite materials. Our samples include both protolith and aqueously-altered samples of the body, permitting understanding of alteration conditions. Whatever the halite parent body, it was rich in a wide variety of organics and warm, liquid water at the solar system's dawn.

  15. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    NASA Astrophysics Data System (ADS)

    Warren, J.; Bilheux, H.; Kang, M.; Voisin, S.; Cheng, C.; Horita, J.; Perfect, E.

    2011-12-01

    In situ quantification of soil-plant water fluxes have not been fully successful due to a lack of non-destructive techniques capable of revealing roots or water fluxes at relevant spatial scales. Neutron imaging is a unique non-invasive tool that can assess sub-millimeter scale material properties and transport in situ, and which has been successfully applied to characterize soil and plant water status. Here, we have applied neutron radiography and tomography to quantify water transport through individual maize roots in response to internal plant demand. Zea mays seedlings were grown for 10 days in Flint silica sand within 2.6 cm diameter Al chambers. Using a reactor-based neutron source at Oak Ridge National Laboratory (HFIR), water fluxes were tracked through the maize soil-root systems by collecting consecutive neutron radiographs over a 12 h period following irrigation with D2O. D has a much lower neutron attenuation than H, thus D2O displacement of existing H2O within the plant vascular system, or influx of D2O into previously dry tissue or soil is readily tracked by changes in image intensity through time. Plant water release and uptake was regulated by periodically cycling on a high-intensity grow light. From each maize replicate, selected regions of interest (ROI) were delineated around individual roots, root free soil, stem and leaf segments. Changes in ROI were tracked through time to reveal patterns of water flux. The hydration of root and stem tissue cycled in response to illumination; root water content often increased during darkness, then decreased with illumination as water was transported from the root into the stem. Relative root-shoot hydration through time illustrates the balance between demand, storage capacity and uptake, which varies depending on root characteristics and its localized soil environment. The dynamic transport of water between soil, individual roots, stems and leaves was readily visualized and quantified illustrating the value

  16. Revealing the Hot Side of Epsilon Aurigae

    NASA Astrophysics Data System (ADS)

    Hoard, Donald; Stencel, Robert; Howell, Steve

    2012-12-01

    We request a small investment of 24 minutes of Spitzer time, to obtain four IRAC observations of epsilon Aurigae. A naked eye object located near Capella, epsilon Aurigae is the eclipsing binary star with the longest known orbital period, showing a single long duration (~2 yr) eclipse every 27.1 yr. For much of the last 200 years, the nature of the eclipsing object defied explanation. We recently demonstrated that epsilon Aurigae consists of a high luminosity F0 post-AGB star in orbit with a B5 V star surrounded by a solar system sized (~8 AU diameter) disk of cool, dust-dominated material. The eclipse of epsilon Aurigae is a rare event; moreover, it is a unique astrophysical opportunity, since the backlighting of the disk by the high luminosity eclipsed star reveals details that cannot be detected in similar dusty disks around single stars. The current eclipse started in August 2009 and ended in July 2011; we are now in the post-eclipse phase, when the irradiation-heated side of the disk will begin rotating into view. The goals for these observations include: (1) extend our ongoing IRAC monitoring campaign covering the current eclipse to post-eclipse visits; (2) provide a consistent, well-calibrated space-based set of IR photometry for comparison with ongoing ground-based work; and (3) use the composite results to constrain the thermal profile of the disk. A key expectation of these particular observations is to reveal the irradiation-heated portion of the disk, which will be visible on its trailing side following eclipse. Observations of this side of the disk will be crucial to test and constrain new models of disk structure. As part of our overall monitoring campaign with Spitzer, Hubble, Herschel, and numerous ground-based facilities, these proposed observations will make an important contribution to the understanding of stellar evolution in binary stars, including mass transfer and evolution studies, along with new insights into astrophysical disks and post

  17. Dynamic Environmental Photosynthetic Imaging Reveals Emergent Phenotypes.

    PubMed

    Cruz, Jeffrey A; Savage, Linda J; Zegarac, Robert; Hall, Christopher C; Satoh-Cruz, Mio; Davis, Geoffry A; Kovac, William Kent; Chen, Jin; Kramer, David M

    2016-06-22

    Understanding and improving the productivity and robustness of plant photosynthesis requires high-throughput phenotyping under environmental conditions that are relevant to the field. Here we demonstrate the dynamic environmental photosynthesis imager (DEPI), an experimental platform for integrated, continuous, and high-throughput measurements of photosynthetic parameters during plant growth under reproducible yet dynamic environmental conditions. Using parallel imagers obviates the need to move plants or sensors, reducing artifacts and allowing simultaneous measurement on large numbers of plants. As a result, DEPI can reveal phenotypes that are not evident under standard laboratory conditions but emerge under progressively more dynamic illumination. We show examples in mutants of Arabidopsis of such "emergent phenotypes" that are highly transient and heterogeneous, appearing in different leaves under different conditions and depending in complex ways on both environmental conditions and plant developmental age. These emergent phenotypes appear to be caused by a range of phenomena, suggesting that such previously unseen processes are critical for plant responses to dynamic environments. PMID:27336966

  18. Feather corticosterone reveals developmental stress in seabirds.

    PubMed

    Will, Alexis P; Suzuki, Yuya; Elliott, Kyle H; Hatch, Scott A; Watanuki, Yutaka; Kitaysky, Alexander S

    2014-07-01

    In nest-bound avian offspring, food shortages typically trigger a release of the stress hormone corticosterone (CORT). Recent studies indicate that CORT is passively deposited in the tissue of growing feathers and thus may provide an integrated measure of stress incurred during development in the nest. The current hypothesis predicts that, assuming a constant rate of feather growth, elevated CORT circulating in the blood corresponds to higher levels of CORT in feather tissue, but experimental evidence for nutritionally stressed chicks is lacking. Here, we examined how food limitation affects feather CORT content in the rhinoceros auklet (Cerorhinca moncerata). We (i) used captive chicks reared on control versus restricted diets, and (ii) applied this technique to free-living chicks with unknown nutritional histories that fledged at three separate colonies. We found that (i) feather growth was not affected by experimentally induced nutritional stress; (ii) captive chicks raised on a restricted diet had higher levels of CORT in their primary feathers; (iii) feather CORT deposition is a sensitive method of detecting nutritional stress; and (iv) free-living fledglings from the colony with poor reproductive performance had higher CORT in their primary feathers. We conclude that feather CORT is a sensitive integrated measure revealing the temporal dynamics of food limitations experienced by rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine tool in ecological and evolutionary studies of bird species with similar preferential allocation of limited resources to feather development.

  19. Biosignatures as revealed by spectropolarimetry of Earthshine.

    PubMed

    Sterzik, Michael F; Bagnulo, Stefano; Palle, Enric

    2012-02-29

    Low-resolution intensity spectra of Earth's atmosphere obtained from space reveal strong signatures of life ('biosignatures'), such as molecular oxygen and methane with abundances far from chemical equilibrium, as well as the presence of a 'red edge' (a sharp increase of albedo for wavelengths longer than 700 nm) caused by surface vegetation. Light passing through the atmosphere is strongly linearly polarized by scattering (from air molecules, aerosols and cloud particles) and by reflection (from oceans and land). Spectropolarimetric observations of local patches of Earth's sky light from the ground contain signatures of oxygen, ozone and water, and are used to characterize the properties of clouds and aerosols. When applied to exoplanets, ground-based spectropolarimetry can better constrain properties of atmospheres and surfaces than can standard intensity spectroscopy. Here we report disk-integrated linear polarization spectra of Earthshine, which is sunlight that has been first reflected by Earth and then reflected back to Earth by the Moon. The observations allow us to determine the fractional contribution of clouds and ocean surface, and are sensitive to visible areas of vegetation as small as 10 per cent. They represent a benchmark for the diagnostics of the atmospheric composition, mean cloud height and surfaces of exoplanets.

  20. Community structure revealed by phase locking.

    PubMed

    Zhou, Ming-Yang; Zhuo, Zhao; Cai, Shi-min; Fu, Zhongqian

    2014-09-01

    Community structure can naturally emerge in paths to synchronization, and scratching it from the paths is a tough issue that accounts for the diverse dynamics of synchronization. In this paper, with assumption that the synchronization on complex networks is made up of local and collective processes, we proposed a scheme to lock the local synchronization (phase locking) at a stable state, meanwhile, suppress the collective synchronization based on Kuramoto model. Through this scheme, the network dynamics only contains the local synchronization, which suggests that the nodes in the same community synchronize together and these synchronization clusters well reveal the community structure of network. Furthermore, by analyzing the paths to synchronization, the relations or overlaps among different communities are also obtained. Thus, the community detection based on the scheme is performed on five real networks and the observed community structures are much more apparent than modularity-based fast algorithm. Our results not only provide a deep insight to understand the synchronization dynamics on complex network but also enlarge the research scope of community detection.

  1. Revealing Invisible Photonic Inscriptions: Images from Strain.

    PubMed

    Ding, Tao; Cao, Guoshuai; Schäfer, Christian G; Zhao, Qibin; Gallei, Markus; Smoukov, Stoyan K; Baumberg, Jeremy J

    2015-06-24

    Photonic structural materials have received intensive interest and have been strongly developed over the past few years for image displays, sensing, and anticounterfeit materials. Their "smartness" arises from their color responsivity to changes of environment, strain, or external fields. Here, we introduce a novel invisible photonic system that reveals encrypted images or characters by simply stretching, or immersing in solvents. This type of intriguing photonic material is composed of regularly arranged core-shell particles that are selectively cross-linked by UV irradiation, giving different strain response compared to un-cross-linked regions. The images reversibly appear and disappear when cycling the strain and releasing it. The unique advantages of this soft polymer opal system compared with other types of photonic gels are that it can be produced in roll to roll quantities, can be vigorously deformed to achieve strong color changes, and has no solvent evaporation issues because it is a photonic rubber system. We demonstrate potential applications together with a fabrication procedure which is straightforward and scalable, vital for user take-up. Our work deepens understanding of this rubbery photonic system based on core-shell nanospheres. PMID:26039279

  2. Overnight lexical consolidation revealed by speech segmentation.

    PubMed

    Dumay, Nicolas; Gareth Gaskell, M

    2012-04-01

    Two experiments explored the consolidation of spoken words, and assessed whether post-sleep novel competitor effects truly reflect engagement of these novel words in competition for lexical segmentation. Two types of competitor relationships were contrasted: the onset-aligned case (such as "frenzylk"), where the novel word is a close variant of the existing word: they start at the same time point and overlap on most of their segments; and the fully embedding case (such as "lirmucktoze"), where the existing word corresponds to a smaller embedded portion of its novel competitor and is thus less noticeable. Experiment 1 (pause detection) revealed a similar performance for both cases, with no competitor effect immediately after exposure, but significant inhibition after 24 h and seven days. Experiment 2 (word spotting) produced exactly the same pattern; however, as is the case with existing word carriers (cf. McQueen, Norris, & Cutler, 1994), the inhibition was much stronger for fully embedded than for onset-aligned targets (e.g., "lirmuckt" vs. "frenzyl"). Meanwhile, explicit measures of learning, i.e., free recall and recognition, improved over time. These results cannot be explained by either consolidation of episodic traces or acquisition of new phonological/dialectal variants. We argue instead that they reflect a general trait of vocabulary learning and consolidation. PMID:22261419

  3. Revealing Invisible Photonic Inscriptions: Images from Strain

    PubMed Central

    2015-01-01

    Photonic structural materials have received intensive interest and have been strongly developed over the past few years for image displays, sensing, and anticounterfeit materials. Their “smartness” arises from their color responsivity to changes of environment, strain, or external fields. Here, we introduce a novel invisible photonic system that reveals encrypted images or characters by simply stretching, or immersing in solvents. This type of intriguing photonic material is composed of regularly arranged core–shell particles that are selectively cross-linked by UV irradiation, giving different strain response compared to un-cross-linked regions. The images reversibly appear and disappear when cycling the strain and releasing it. The unique advantages of this soft polymer opal system compared with other types of photonic gels are that it can be produced in roll to roll quantities, can be vigorously deformed to achieve strong color changes, and has no solvent evaporation issues because it is a photonic rubber system. We demonstrate potential applications together with a fabrication procedure which is straightforward and scalable, vital for user take-up. Our work deepens understanding of this rubbery photonic system based on core–shell nanospheres. PMID:26039279

  4. VISTA Reveals the Secret of the Unicorn

    NASA Astrophysics Data System (ADS)

    2010-10-01

    A new infrared image from ESO's VISTA survey telescope reveals an extraordinary landscape of glowing tendrils of gas, dark clouds and young stars within the constellation of Monoceros (the Unicorn). This star-forming region, known as Monoceros R2, is embedded within a huge dark cloud. The region is almost completely obscured by interstellar dust when viewed in visible light, but is spectacular in the infrared. An active stellar nursery lies hidden inside a massive dark cloud rich in molecules and dust in the constellation of Monoceros. Although it appears close in the sky to the more familiar Orion Nebula it is actually almost twice as far from Earth, at a distance of about 2700 light-years. In visible light a grouping of massive hot stars creates a beautiful collection of reflection nebulae where the bluish starlight is scattered from parts of the dark, foggy outer layers of the molecular cloud. However, most of the new-born massive stars remain hidden as the thick interstellar dust strongly absorbs their ultraviolet and visible light. In this gorgeous infrared image taken from ESO's Paranal Observatory in northern Chile, the Visible and Infrared Survey Telescope for Astronomy (VISTA [1], eso0949) penetrates the dark curtain of cosmic dust and reveals in astonishing detail the folds, loops and filaments sculpted from the dusty interstellar matter by intense particle winds and the radiation emitted by hot young stars. "When I first saw this image I just said 'Wow!' I was amazed to see all the dust streamers so clearly around the Monoceros R2 cluster, as well as the jets from highly embedded young stellar objects. There is such a great wealth of exciting detail revealed in these VISTA images," says Jim Emerson, of Queen Mary, University of London and leader of the VISTA consortium. With its huge field of view, large mirror and sensitive camera, VISTA is ideal for obtaining deep, high quality infrared images of large areas of the sky, such as the Monoceros R2 region

  5. Biosignatures as revealed by spectropolarimetry of Earthshine.

    PubMed

    Sterzik, Michael F; Bagnulo, Stefano; Palle, Enric

    2012-03-01

    Low-resolution intensity spectra of Earth's atmosphere obtained from space reveal strong signatures of life ('biosignatures'), such as molecular oxygen and methane with abundances far from chemical equilibrium, as well as the presence of a 'red edge' (a sharp increase of albedo for wavelengths longer than 700 nm) caused by surface vegetation. Light passing through the atmosphere is strongly linearly polarized by scattering (from air molecules, aerosols and cloud particles) and by reflection (from oceans and land). Spectropolarimetric observations of local patches of Earth's sky light from the ground contain signatures of oxygen, ozone and water, and are used to characterize the properties of clouds and aerosols. When applied to exoplanets, ground-based spectropolarimetry can better constrain properties of atmospheres and surfaces than can standard intensity spectroscopy. Here we report disk-integrated linear polarization spectra of Earthshine, which is sunlight that has been first reflected by Earth and then reflected back to Earth by the Moon. The observations allow us to determine the fractional contribution of clouds and ocean surface, and are sensitive to visible areas of vegetation as small as 10 per cent. They represent a benchmark for the diagnostics of the atmospheric composition, mean cloud height and surfaces of exoplanets. PMID:22382980

  6. Integrative Analysis Reveals Regulatory Programs in Endometriosis.

    PubMed

    Yang, Huan; Kang, Kai; Cheng, Chao; Mamillapalli, Ramanaiah; Taylor, Hugh S

    2015-09-01

    Endometriosis is a common gynecological disease found in approximately 10% of reproductive-age women. Gene expression analysis has been performed to explore alterations in gene expression associated with endometriosis; however, the underlying transcription factors (TFs) governing such expression changes have not been investigated in a systematic way. In this study, we propose a method to integrate gene expression with TF binding data and protein-protein interactions to construct an integrated regulatory network (IRN) for endometriosis. The IRN has shown that the most regulated gene in endometriosis is RUNX1, which is targeted by 14 of 26 TFs also involved in endometriosis. Using 2 published cohorts, GSE7305 (Hover, n = 20) and GSE7307 (Roth, n = 36) from the Gene Expression Omnibus database, we identified a network of TFs, which bind to target genes that are differentially expressed in endometriosis. Enrichment analysis based on the hypergeometric distribution allowed us to predict the TFs involved in endometriosis (n = 40). This included known TFs such as androgen receptor (AR) and critical factors in the pathology of endometriosis, estrogen receptor α, and estrogen receptor β. We also identified several new ones from which we selected FOXA2 and TFAP2C, and their regulation was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). Further, our analysis revealed that the function of AR and p53 in endometriosis is regulated by posttranscriptional changes and not by differential gene expression. Our integrative analysis provides new insights into the regulatory programs involved in endometriosis.

  7. Revealing the quantum regime in tunnelling plasmonics.

    PubMed

    Savage, Kevin J; Hawkeye, Matthew M; Esteban, Rubén; Borisov, Andrei G; Aizpurua, Javier; Baumberg, Jeremy J

    2012-11-22

    When two metal nanostructures are placed nanometres apart, their optically driven free electrons couple electrically across the gap. The resulting plasmons have enhanced optical fields of a specific colour tightly confined inside the gap. Many emerging nanophotonic technologies depend on the careful control of this plasmonic coupling, including optical nanoantennas for high-sensitivity chemical and biological sensors, nanoscale control of active devices, and improved photovoltaic devices. But for subnanometre gaps, coherent quantum tunnelling becomes possible and the system enters a regime of extreme non-locality in which previous classical treatments fail. Electron correlations across the gap that are driven by quantum tunnelling require a new description of non-local transport, which is crucial in nanoscale optoelectronics and single-molecule electronics. Here, by simultaneously measuring both the electrical and optical properties of two gold nanostructures with controllable subnanometre separation, we reveal the quantum regime of tunnelling plasmonics in unprecedented detail. All observed phenomena are in good agreement with recent quantum-based models of plasmonic systems, which eliminate the singularities predicted by classical theories. These findings imply that tunnelling establishes a quantum limit for plasmonic field confinement of about 10(-8)λ(3) for visible light (of wavelength λ). Our work thus prompts new theoretical and experimental investigations into quantum-domain plasmonic systems, and will affect the future of nanoplasmonic device engineering and nanoscale photochemistry.

  8. Anticipatory looks reveal expectations about discourse relations.

    PubMed

    Rohde, Hannah; Horton, William S

    2014-12-01

    Previous research provides evidence for expectation-driven processing within sentences at phonological, lexical, and syntactic levels of linguistic structure. Less well-established is whether comprehenders also anticipate pragmatic relationships between sentences. To address this, we evaluate a unit of discourse structure that comprehenders must infer to hold between sentences in order for a discourse to make sense-the intersentential coherence relation. In a novel eyetracking paradigm, we trained participants to associate particular spatial locations with particular coherence relations. Experiment 1 shows that the subset of listeners who successfully acquired the location∼relation mappings during training subsequently looked to these locations during testing in response to a coherence-signaling intersentential connective. Experiment 2 finds that listeners' looks during sentences containing coherence-biasing verbs reveal expectations about upcoming sentence types. This work extends existing research on prediction beyond sentence-internal structure and provides a new methodology for examining the cues that comprehenders use to establish relationships at the discourse level.

  9. Revealing the values behind convenience food consumption.

    PubMed

    Botonaki, Anna; Mattas, Konstadinos

    2010-12-01

    The increasing importance of convenience in consumer food choices has attracted researchers' interest. In the effort to understand how convenience affects consumers' food preferences, values are believed to play an important role. The present study attempts to examine the way personal values suggested by Schwartz (1992) are associated with behaviour and attitudes regarding convenience food. A number of constructs describing food related attitudes and behaviours were developed and their relationship with personal values was analyzed following the methodology proposed by Brunsø, Scholderer, and Grunert (2004). Data were collected through a questionnaire survey from a random sample of consumers in Thessaloniki city, Greece. The results reveal that convenience food consumption and convenience orientation in the food domain are mainly connected with values that motivate people to seek new experiences, act independently and enhance their own personal interests, while are in conflict with values of conservation and self-transcendence. The opposite holds for other food related attitudes and behaviours like involvement with cooking and variety in diet. The findings seem to be of particular interest not only for marketers of food products, but also for food policy makers. PMID:20875475

  10. VISTA Reveals the Secret of the Unicorn

    NASA Astrophysics Data System (ADS)

    2010-10-01

    A new infrared image from ESO's VISTA survey telescope reveals an extraordinary landscape of glowing tendrils of gas, dark clouds and young stars within the constellation of Monoceros (the Unicorn). This star-forming region, known as Monoceros R2, is embedded within a huge dark cloud. The region is almost completely obscured by interstellar dust when viewed in visible light, but is spectacular in the infrared. An active stellar nursery lies hidden inside a massive dark cloud rich in molecules and dust in the constellation of Monoceros. Although it appears close in the sky to the more familiar Orion Nebula it is actually almost twice as far from Earth, at a distance of about 2700 light-years. In visible light a grouping of massive hot stars creates a beautiful collection of reflection nebulae where the bluish starlight is scattered from parts of the dark, foggy outer layers of the molecular cloud. However, most of the new-born massive stars remain hidden as the thick interstellar dust strongly absorbs their ultraviolet and visible light. In this gorgeous infrared image taken from ESO's Paranal Observatory in northern Chile, the Visible and Infrared Survey Telescope for Astronomy (VISTA [1], eso0949) penetrates the dark curtain of cosmic dust and reveals in astonishing detail the folds, loops and filaments sculpted from the dusty interstellar matter by intense particle winds and the radiation emitted by hot young stars. "When I first saw this image I just said 'Wow!' I was amazed to see all the dust streamers so clearly around the Monoceros R2 cluster, as well as the jets from highly embedded young stellar objects. There is such a great wealth of exciting detail revealed in these VISTA images," says Jim Emerson, of Queen Mary, University of London and leader of the VISTA consortium. With its huge field of view, large mirror and sensitive camera, VISTA is ideal for obtaining deep, high quality infrared images of large areas of the sky, such as the Monoceros R2 region

  11. Radio Telescopes Reveal Unseen Galactic Cannibalism

    NASA Astrophysics Data System (ADS)

    2008-06-01

    Radio-telescope images have revealed previously-unseen galactic cannibalism -- a triggering event that leads to feeding frenzies by gigantic black holes at the cores of galaxies. Astronomers have long suspected that the extra-bright cores of spiral galaxies called Seyfert galaxies are powered by supermassive black holes consuming material. However, they could not see how the material is started on its journey toward the black hole. Optical/Radio Comparison Visible-light (left) and radio (right) image of galaxy pair: Radio image shows gas streaming between galaxies. CREDIT: Kuo et al., NRAO/AUI/NSF Click on image for more graphics. One leading theory said that Seyfert galaxies have been disturbed by close encounters with neighboring galaxies, thus stirring up their gas and bringing more of it within the gravitational reach of the black hole. However, when astronomers looked at Seyferts with visible-light telescopes, only a small fraction showed any evidence of such an encounter. Now, new images of hydrogen gas in Seyferts made using the National Science Foundation's Very Large Array (VLA) radio telescope show the majority of them are, in fact, disturbed by ongoing encounters with neighbor galaxies. "The VLA lifted the veil on what's really happening with these galaxies," said Cheng-Yu Kuo, a graduate student at the University of Virginia. "Looking at the gas in these galaxies clearly showed that they are snacking on their neighbors. This is a dramatic contrast with their appearance in visible starlight," he added. The effect of the galactic encounters is to send gas and dust toward the black hole and produce energy as the material ultimately is consumed. Black holes, concentrations of matter so dense that not even light can escape their gravitational pull, reside at the cores of many galaxies. Depending on how rapidly the black hole is eating, the galaxy can show a wide range of energetic activity. Seyfert galaxies have the mildest version of this activity, while

  12. Antioxidant peptidomics reveals novel skin antioxidant system.

    PubMed

    Yang, Hailong; Wang, Xu; Liu, Xiuhong; Wu, Jing; Liu, Cunbao; Gong, Weiming; Zhao, Zhiqiang; Hong, Jing; Lin, Donghai; Wang, Yizheng; Lai, Ren

    2009-03-01

    It is generally agreed that reactive oxygen species (ROS) contribute to skin aging, skin disorders, and skin diseases. Skin possesses an extremely efficient antioxidant system. This antioxidant activity is conferred by two systems: antioxidant enzymes and small molecules that can scavenge ROS by donating electrons. No gene-encoded secreted ROS scavengers have been reported. Amphibian skin is a multifunctional organ acting in defense, respiration, and water regulation, although it seems susceptible. Amphibian skins are easily harmed by biological or non-biological attacks such as microorganism infection or radiation injury. Among vertebrates, skins of amphibian are exposed to more dangers of radiation injury than others. Radiation toxicity occurs by directly attacking the genetic material and/or by generating ROS. In addition, amphibian skin respiration and inflammatory response also induce ROS generation. It is rational to hypothesize that amphibian skins should have potent free radical scavenging and radioprotective ability for their survival. Rana pleuraden is distributed in Southwest of China; it lives in the subtropical plateau (altitude around 2300 m) where there is strong ultraviolet radiation and long duration of sunshine. By peptidomics and genomics approaches, a large amount of antioxidant peptides belonging to 11 different groups with variable structures were isolated from the skin secretions of R. pleuraden. Their free radical scavenging and anti-inflammatory abilities were studied. All of these peptide share highly homologous preproregions, although mature antioxidant peptides have very divergent primary structures, suggesting the possibility of a common ancestor. Some peptides were also found to have multifunctional properties, such as combined antioxidant, anti-inflammatory, and antimicrobial activities. According to our knowledge, no gene-encoded specific antioxidant peptides have been reported except metallothionein. Our work possibly reveals a new

  13. Saturn Probe: Revealing Solar System Origins

    NASA Astrophysics Data System (ADS)

    Spilker, T. R.

    2015-12-01

    Comparative studies of the gas giant and ice giant planets are needed to reliably discriminate among competing theories of the origin and evolution of giant planets and the solar system, but we lack critical measurements. A Saturn atmospheric entry probe mission would fill a vital part of that gap, allowing comparative studies of Jupiter and Saturn, providing the basis for later comparisons with the ice giants Uranus and Neptune, and informing studies of extrasolar planetary systems now being characterized. The Galileo Probe mission provided the first in situ studies of Jupiter's atmosphere. Similar measurements at Saturn, Uranus and Neptune would provide an important comparative planetology context for the Galileo results. Cassini's "Proximal Orbits" in 2017 will reveal Saturn's internal structure to complement the Juno mission's similar measurements at Jupiter. A Saturn entry probe, complementing the Galileo Probe investigations at Jupiter, would complete a solid basis for improved understanding of both Jupiter and Saturn, an important stepping stone to understanding Uranus and Neptune and solar system formation and evolution. The 2012 Decadal Survey ("DS") added Saturn Probe science objectives to NASA's New Frontiers Program: highest-priority Tier 1 objectives any New Frontiers implementation must achieve, and Tier 2, high priority but lower than Tier 1. A DS mission concept study using extremely conservative assumptions concluded that a Saturn Probe project could fit within New Frontiers resource constraints, giving a PI confidence that they could pursue some Tier 2 objectives, customizing for the proper balance of science return, science team composition, procured or contributed instruments, etc. Contributed instruments could significantly enhance the payload and the science team for greater science return. They also provide international collaboration opportunities, with science benefits well demonstrated by missions such as Cassini-Huygens and Rosetta.

  14. Distinct cytoskeletal domains revealed in sperm cells

    PubMed Central

    1984-01-01

    Antibodies against different cytoskeletal proteins were used to study the cytoskeletal organization of human spermatozoa. A positive staining with actin antibodies was seen in both the acrosomal cap region and the principal piece region of the tail. However, no staining was obtained with nitrobenzoxadiazol-phallacidin, suggesting that most of the actin was in the nonpolymerized form. Most of the myosin immunoreactivity was confirmed to a narrow band in the neck region of spermatozoa. Tubulin was located to the entire tail, whereas vimentin was only seen in a discrete band-like structure encircling the sperm head, apparently coinciding with the equatorial segment region. Surface staining of the spermatozoa with fluorochrome-coupled Helix pomatia agglutinin revealed a similar band-like structure that co-distributed with the vimentin- specific staining. Instead, other lectin conjugates used labeled either the acrosomal cap region (peanut and soybean agglutinins), both the acrosomal cap and the postacrosomal region of the head (concanavalin A), or the whole sperm cell surface membrane (wheat germ and lens culinaris agglutinins and ricinus communis agglutinin l). In lectin blotting experiments, the Helix pomatia agglutinin-binding was assigned to a 80,000-mol-wt polypeptide which, together with vimentin, also resisted treatment with Triton X-100. Only the acrosomal cap and the principal piece of the tail were decorated with rabbit and hydridoma antibodies against an immunoanalogue of erythrocyte alpha-spectrin (p230). p230 appeared to be the major calmodulin-binding polypeptide in spermatozoa, as shown by a direct overlay assay of electrophoretic blots of spermatozoa with 125I-calmodulin. The results indicate that spermatozoa have a highly specialized cytoskeletal organization and that the distribution of actin, spectrin, and vimentin can be correlated with distinct surface specializations of the sperm cells. This suggest that cytoskeleton may regulate the maintenance

  15. NASA's Hyperwall Revealing the Big Picture

    NASA Technical Reports Server (NTRS)

    Sellers, Piers

    2011-01-01

    NASA:s hyperwall is a sophisticated visualization tool used to display large datasets. The hyperwall, or video wall, is capable of displaying multiple high-definition data visualizations and/or images simultaneously across an arrangement of screens. Functioning as a key component at many NASA exhibits, the hyperwall is used to help explain phenomena, ideas, or examples of world change. The traveling version of the hyperwall is typically comprised of nine 42-50" flat-screen monitors arranged in a 3x3 array (as depicted below). However, it is not limited to monitor size or number; screen sizes can be as large as 52" and the arrangement of screens can include more than nine monitors. Generally, NASA satellite and model data are used to highlight particular themes in atmospheric, land, and ocean science. Many of the existing hyperwall stories reveal change across space and time, while others display large-scale still-images accompanied by descriptive, story-telling captions. Hyperwall content on a variety of Earth Science topics already exists and is made available to the public at: eospso.gsfc.nasa.gov/hyperwall. Keynote and PowerPoint presentations as well as Summary of Story files are available for download on each existing topic. New hyperwall content and accompanying files will continue being developed to promote scientific literacy across a diverse group of audience members. NASA invites the use of content accessible through this website but requests the user to acknowledge any and all data sources referenced in the content being used.

  16. Private haplotypes can reveal local adaptation

    PubMed Central

    2014-01-01

    Background Genome-wide scans for regions that demonstrate deviating patterns of genetic variation have become common approaches for finding genes targeted by selection. Several genomic patterns have been utilized for this purpose, including deviations in haplotype homozygosity, frequency spectra and genetic differentiation between populations. Results We describe a novel approach based on the Maximum Frequency of Private Haplotypes – MFPH – to search for signals of recent population-specific selection. The MFPH statistic is straightforward to compute for phased SNP- and sequence-data. Using both simulated and empirical data, we show that MFPH can be a powerful statistic to detect recent population-specific selection, that it performs at the same level as other commonly used summary statistics (e.g. FST, iHS and XP-EHH), and that MFPH in some cases capture signals of selection that are missed by other statistics. For instance, in the Maasai, MFPH reveals a strong signal of selection in a region where other investigated statistics fail to pick up a clear signal that contains the genes DOCK3, MAPKAPK3 and CISH. This region has been suggested to affect height in many populations based on phenotype-genotype association studies. It has specifically been suggested to be targeted by selection in Pygmy groups, which are on the opposite end of the human height spectrum compared to the Maasai. Conclusions From the analysis of both simulated and publicly available empirical data, we show that MFPH represents a summary statistic that can provide further insight concerning population-specific adaptation. PMID:24885734

  17. Dramatic Outburst Reveals Nearest Black Hole

    NASA Astrophysics Data System (ADS)

    2000-01-01

    Sgr. The radio observations revealed the presence of a jet escaping from the system at mind-boggling speeds. Only three other galactic X-ray stellar systems have been found to eject material at such speeds. They have been dubbed "microquasars" because, on a smaller scale, they resemble quasars, which lie at the hearts of distant galaxies and also spew out high-velocity jets of particles. In galaxy-core quasars, the black holes are millions of times more massive than the Sun; in the more nearby microquasars the black holes are roughly three to twenty times more massive than the Sun. The extremely high velocity of the jets suggests that their origin lies close to the event horizon of a black hole. Microquasar activity is thought to arise when the black hole in the binary system draws material away from its companion star. The material surrounding the black hole forms a rapidly spinning disk called an accretion disk. This disk is heated by friction to millions of degrees, causing it to emit X-rays. As spiralling gas moves into the gravity well of the black hole, it moves faster and faster. Magnetic fields in the disk are believed to expel the charged subatomic particles at speeds close to that of light. As the charged particles interact with the magnetic fields, they emit radio waves. If some of the material escapes by being magnetically expelled into space, the matter may continue moving at the tremendous speed it had attained near the black hole. After their ejection, the jets of particles expand and cool, fading from astronomers' view. V4641 Sgr excites astronomers because it is close and because it acted so differently from other microquasars. In other microquasars, outbursts have dimmed more slowly over weeks or months rather than hours. "There's something fundamentally different about this one; it's more extreme than any other example," Hjellming said. "And because this system happens to be so close to us, `it is very likely that there are more objects like V4641

  18. Passive seismology reveals biannual calving periodicity

    NASA Astrophysics Data System (ADS)

    Bartholomaus, T. C.; Larsen, C. F.; West, M. E.; Oneel, S.

    2013-12-01

    Iceberg calving is a large and variable component of the total mass loss from marine-terminating glaciers worldwide. However, the processes that control the size and variability of calving fluxes are poorly understood. Even more basic descriptions of iceberg calving, such as its seasonality, are uncertain. Here, we present nearly two years of automatically-estimated calving fluxes at Yahtse Glacier, a tidewater glacier whose terminus flows at ~7 km/yr towards the Gulf of Alaska. At the terminus, ice losses to calving and submarine melt total approximately 1.5 km^3/yr. In order to identify temporal variability in this mean rate, we develop a statistical model of calving size based on characteristics of calving-generated icequakes. These characteristics include 4 amplitude-based variables and 5 variables related to the shape of the icequake envelope. We build our model by combining automatically-detected icequakes (O'Neel et al., 2007) located at the terminus of Yahtse Glacier (Jones et al., 2013) with a training set of 1400 icequakes produced by visually-observed calving events (Bartholomaus et al., 2012). In each of the models tested (regression trees, multinomial logistic regression and multiple linear regession), icequake duration emerges as the single best predictor of iceberg size, consistent with past studies (Qamar, 1988; O'Neel et al., 2007). Additional predictors, such as the mean icequake amplitude and the kurtosis of the icequake envelope improve the predictive capability of the model and reduce the mean squared error to well-within the error of the in-person classification. Once validated, we apply our model to ~ 400,000 icequakes produced by calving events at Yahtse Glacier between June 2009 and September 2011. These results reveal fluctuations in calving rate at a range of timescales, including twice per year. We suggest that the roughly 50%, biannual variation in calving rate is the result of the trade-off between two competing processes at the

  19. Microradiometers Reveal Ocean Health, Climate Change

    NASA Technical Reports Server (NTRS)

    2013-01-01

    When NASA researcher Stanford Hooker is in the field, he pays close attention to color. For Hooker, being in the field means being at sea. On one such research trip to the frigid waters of the Arctic, with a Coast Guard icebreaker looming nearby and the snow-crusted ice shelf a few feet away, Hooker leaned over the edge of his small boat and lowered a tethered device into the bright turquoise water, a new product devised by a NASA partner and enabled by a promising technology for oceanographers and atmospheric scientists alike. Color is a function of light. Pure water is clear, but the variation in color observed during a visit to the beach or a flight along a coastline depends on the water s depth and the constituents in it, how far down the light penetrates and how it is absorbed and scattered by dissolved and suspended material. Hooker cares about ocean color because of what it can reveal about the health of the ocean, and in turn, the health of our planet. "The main thing we are interested in is the productivity of the water," Hooker says. The seawater contains phytoplankton, microscopic plants, which are the food base for the ocean s ecosystems. Changes in the water s properties, whether due to natural seasonal effects or human influence, can lead to problems for delicate ecosystems such as coral reefs. Ocean color can inform researchers about the quantities and distribution of phytoplankton and other materials, providing clues as to how the world ocean is changing. NASA s Coastal Zone Color Scanner, launched in 1978, was the first ocean color instrument flown on a spacecraft. Since then, the Agency s ocean color research capabilities have become increasingly sophisticated with the launch of the SeaWiFS instrument in 1997 and the twin MODIS instruments carried into orbit on NASA s Terra (1999) and Aqua (2002) satellites. The technology provides sweeping, global information on ocean color on a scale unattainable by any other means. One issue that arises from

  20. Shocking Detail of Superstar's Activity Revealed

    NASA Astrophysics Data System (ADS)

    1999-10-01

    NASA's Chandra X-ray Observatory has imaged Eta Carinae and revealed a hot inner core around this mysterious superstar. The new X-ray observation shows three distinct structures: an outer, horseshoe shaped ring about two light years in diameter, a hot inner core about 3 light months in diameter, and a hot central source less than a light month in diameter which may contain the superstar. All three structures are thought to represent shock waves produced by matter rushing away from the superstar at supersonic speeds. The temperature of the shock-heated gas ranges from 60 million degrees Celsius in the central regions to 3 million degrees Celsius on the outer structure. An earlier image of Eta Carinae by the Hubble Space Telescope revealed two spectacular bubbles of gas expanding in opposite directions away from a central bright region at speeds in excess of a million miles per hour. The inner region visible in the Chandra image has never been resolved before, and appears to be associated with a central disk of high velocity gas rushing out at much higher speeds perpendicular to the bipolar optical nebula. "It is not what I expected," said Dr. Fred Seward of the Harvard-Smithsonian Center for Astrophysics. "I expected to see a strong point source with a little diffuse emission cloud around it. Instead, we see just the opposite- a bright cloud of diffuse emission, and much less radiation from the center." "The Chandra image contains some puzzles for existing ideas of how a star can produce such hot and intense X-rays," agreed Prof. Kris Davidson of the University of Minnesota. "In the most popular theory, X-rays are made by colliding gas streams from two stars so close together that they'd look like a point source to us. But what happens to gas streams that escape to farther distances? The extended hot stuff in the middle of the new image gives demanding new conditions for any theory to meet." Eta Carinae is one of the most enigmatic and intriguing objects in our

  1. Chandra Data Reveal Rapidly Whirling Black Holes

    NASA Astrophysics Data System (ADS)

    2008-01-01

    A new study using results from NASA's Chandra X-ray Observatory provides one of the best pieces of evidence yet that many supermassive black holes are spinning extremely rapidly. The whirling of these giant black holes drives powerful jets that pump huge amounts of energy into their environment and affects galaxy growth. A team of scientists compared leading theories of jets produced by rotating supermassive black holes with Chandra data. A sampling of nine giant galaxies that exhibit large disturbances in their gaseous atmospheres showed that the central black holes in these galaxies must be spinning at near their maximum rates. People Who Read This Also Read... NASA’s Swift Satellite Catches First Supernova in The Act of Exploding Black Holes Have Simple Feeding Habits Jet Power and Black Hole Assortment Revealed in New Chandra Image Erratic Black Hole Regulates Itself "We think these monster black holes are spinning close to the limit set by Einstein's theory of relativity, which means that they can drag material around them at close to the speed of light," said Rodrigo Nemmen, a visiting graduate student at Penn State University, and lead author of a paper on the new results presented at American Astronomical Society in Austin, Texas. The research reinforces other, less direct methods previously used which have indicated that some stellar and supermassive black holes are spinning rapidly. According to Einstein's theory, a rapidly spinning black hole makes space itself rotate. This effect, coupled with gas spiraling toward the black hole, can produce a rotating, tightly wound vertical tower of magnetic field that flings a large fraction of the inflowing gas away from the vicinity of the black hole in an energetic, high-speed jet. Computer simulations by other authors have suggested that black holes may acquire their rapid spins when galaxies merge, and through the accretion of gas from their surroundings. "Extremely fast spin might be very common for large

  2. The lower atmosphere of Pluto revealed

    NASA Astrophysics Data System (ADS)

    2009-03-01

    ), attached to ESO's Very Large Telescope, have now revealed that the atmosphere as a whole, not just the upper atmosphere, has a mean temperature of minus 180 degrees Celsius, and so it is indeed "much hotter" than the surface. In contrast to the Earth's atmosphere [2], most, if not all, of Pluto's atmosphere is thus undergoing a temperature inversion: the temperature is higher, the higher in the atmosphere you look. The change is about 3 to 15 degrees per kilometre. On Earth, under normal circumstances, the temperature decreases through the atmosphere by about 6 degrees per kilometre. "It is fascinating to think that with CRIRES we are able to precisely measure traces of a gas in an atmosphere 100 000 times more tenuous than the Earth's, on an object five times smaller than our planet and located at the edge of the Solar System," says co-author Hans-Ulrich Käufl. "The combination of CRIRES and the VLT is almost like having an advanced atmospheric research satellite orbiting Pluto." The reason why Pluto's surface is so cold is linked to the existence of Pluto's atmosphere, and is due to the sublimation of the surface ice; much like sweat cools the body as it evaporates from the surface of the skin, this sublimation has a cooling effect on the surface of Pluto. In this respect, Pluto shares some properties with comets, whose coma and tails arise from sublimating ice as they approach the Sun. The CRIRES observations also indicate that methane is the second most common gas in Pluto's atmosphere, representing half a percent of the molecules. "We were able to show that these quantities of methane play a crucial role in the heating processes in the atmosphere and can explain the elevated atmospheric temperature," says Lellouch. Two different models can explain the properties of Pluto's atmosphere. In the first, the astronomers assume that Pluto's surface is covered with a thin layer of methane, which will inhibit the sublimation of the nitrogen frost. The second scenario invokes

  3. What Facial Appearance Reveals Over Time: When Perceived Expressions in Neutral Faces Reveal Stable Emotion Dispositions

    PubMed Central

    Adams, Reginald B.; Garrido, Carlos O.; Albohn, Daniel N.; Hess, Ursula; Kleck, Robert E.

    2016-01-01

    It might seem a reasonable assumption that when we are not actively using our faces to express ourselves (i.e., when we display nonexpressive, or neutral faces), those around us will not be able to read our emotions. Herein, using a variety of expression-related ratings, we examined whether age-related changes in the face can accurately reveal one’s innermost affective dispositions. In each study, we found that expressive ratings of neutral facial displays predicted self-reported positive/negative dispositional affect, but only for elderly women, and only for positive affect. These findings meaningfully replicate and extend earlier work examining age-related emotion cues in the face of elderly women (Malatesta et al., 1987a). We discuss these findings in light of evidence that women are expected to, and do, smile more than men, and that the quality of their smiles predicts their life satisfaction. Although ratings of old male faces did not significantly predict self-reported affective dispositions, the trend was similar to that found for old female faces. A plausible explanation for this gender difference is that in the process of attenuating emotional expressions over their lifetimes, old men reveal less evidence of their total emotional experiences in their faces than do old women. PMID:27445944

  4. What Facial Appearance Reveals Over Time: When Perceived Expressions in Neutral Faces Reveal Stable Emotion Dispositions.

    PubMed

    Adams, Reginald B; Garrido, Carlos O; Albohn, Daniel N; Hess, Ursula; Kleck, Robert E

    2016-01-01

    It might seem a reasonable assumption that when we are not actively using our faces to express ourselves (i.e., when we display nonexpressive, or neutral faces), those around us will not be able to read our emotions. Herein, using a variety of expression-related ratings, we examined whether age-related changes in the face can accurately reveal one's innermost affective dispositions. In each study, we found that expressive ratings of neutral facial displays predicted self-reported positive/negative dispositional affect, but only for elderly women, and only for positive affect. These findings meaningfully replicate and extend earlier work examining age-related emotion cues in the face of elderly women (Malatesta et al., 1987a). We discuss these findings in light of evidence that women are expected to, and do, smile more than men, and that the quality of their smiles predicts their life satisfaction. Although ratings of old male faces did not significantly predict self-reported affective dispositions, the trend was similar to that found for old female faces. A plausible explanation for this gender difference is that in the process of attenuating emotional expressions over their lifetimes, old men reveal less evidence of their total emotional experiences in their faces than do old women. PMID:27445944

  5. Stated and revealed inequality aversion in three subject pools

    PubMed Central

    Beranek, Benjamin; Cubitt, Robin; Gächter, Simon

    2016-01-01

    This paper reports data from three subject pools (n=717 subjects) using techniques based on those of Loewenstein, et al. (1989) and Blanco, et al. (2011) to obtain parameters, respectively, of stated and revealed inequality aversion. We provide a replication opportunity for those papers, with two innovations: (i) a design which allows stated and revealed preferences to be compared at the individual level; (ii) assessment of robustness of findings across subjects from a UK university, a Turkish university and Amazon Mechanical Turk. Our findings on stated aversion to inequality are qualitatively similar to those of Loewenstein, et al. in each of our subject pools, whereas there are notable differences between some of our findings on revealed preference and those of Blanco, et al. We find that revealed advantageous inequality aversion is often stronger than revealed dis-advantageous inequality aversion. In most subject pools, we find some (weak) correlation between corresponding parameters of stated and revealed inequality aversion. PMID:27069847

  6. High anion gap metabolic acidosis secondary to pyroglutamic aciduria (5-oxoprolinuria): association with prescription drugs and malnutrition.

    PubMed

    Brooker, G; Jeffery, J; Nataraj, T; Sair, M; Ayling, R

    2007-07-01

    Two cases of High Anion Gap Metabolic Acidosis (HAGMA) due to pyroglutamic acid (5-oxoproline) are described. In both cases the HAGMA developed during an episode of hospital treatment, in conjunction with paracetamol and antibiotic prescription, and the surviving patient made an uneventful recovery after the drugs were withdrawn. Clinicians need to be aware of this cause for metabolic acidosis because it may be a more common metabolic disturbance in compromised patients than would be expected, and the discontinuation of drugs implicated in the aetiology is therapeutic.

  7. Mutations in ALDH6A1 encoding methylmalonate semialdehyde dehydrogenase are associated with dysmyelination and transient methylmalonic aciduria

    PubMed Central

    2013-01-01

    Background Methylmalonate semialdehyde dehydrogenase (MMSDH) deficiency is a rare autosomal recessive disorder with varied metabolite abnormalities, including accumulation of 3-hydroxyisobutyric, 3-hydroxypropionic, 3-aminoisobutyric and methylmalonic acids, as well as β-alanine. Existing reports describe a highly variable clinical and biochemical phenotype, which can make diagnosis a challenge. To date, only three reported cases have been confirmed at the molecular level, through identification of homozygous mutations in ALDH6A1, the gene encoding MMSDH. Confirmation by enzyme assay has until now not been possible, due to the extreme instability of the enzyme substrate. Methods and results We report a child with severe developmental delays, abnormal myelination on brain MRI, and transient/variable elevations in lactate, methylmalonic acid, 3-hydroxyisobutyric and 3-aminoisobutyric acids. Compound heterozygous mutations were identified by exome sequencing and confirmed by Sanger sequencing within exon 6 (c.514 T > C; p. Tyr172His) and exon 12 (c.1603C > T; p. Arg535Cys) of ALDH6A1. The resulting amino acid changes, both occurring in residues conserved among mammals, are predicted to be damaging at the protein level. Subsequent MMSDH enzyme assay demonstrated reduced activity in patient fibroblasts, measuring 2.5 standard deviations below the mean. Conclusions We present the fourth reported case of MMSDH deficiency with confirmation at the molecular level, and expand on what is already an extremely variable clinical and biochemical phenotype. Furthermore, this is the first report to demonstrate a corresponding reduction in MMSDH enzyme activity. This report illustrates the emerging utilization of whole exome sequencing and variant data filtering using clinical data as an early tool in the diagnosis of rare and variable conditions. PMID:23835272

  8. 21 CFR 1.21 - Failure to reveal material facts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Failure to reveal material facts. 1.21 Section 1.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS General Labeling Requirements § 1.21 Failure to reveal material facts....

  9. 21 CFR 1.21 - Failure to reveal material facts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Failure to reveal material facts. 1.21 Section 1.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS General Labeling Requirements § 1.21 Failure to reveal material facts....

  10. 21 CFR 1.21 - Failure to reveal material facts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Failure to reveal material facts. 1.21 Section 1.21 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS General Labeling Requirements § 1.21 Failure to reveal material facts....

  11. How Costly is Hospital Quality? A Revealed-Preference Approach*

    PubMed Central

    Romley, John A.; Goldman, Dana P.

    2013-01-01

    We analyze the cost of quality improvement in hospitals, dealing with two challenges. Hospital quality is multidimensional and hard to measure, while unobserved productivity may influence quality supply. We infer the quality of hospitals in Los Angeles from patient choices. We then incorporate ‘revealed quality’ into a cost function, instrumenting with hospital demand. We find that revealed quality differentiates hospitals, but is not strongly correlated with clinical quality. Revealed quality is quite costly, and tends to increase with hospital productivity. Thus, non-clinical aspects of the hospital experience (perhaps including patient amenities) play important roles in hospital demand, competition, and costs. PMID:22299199

  12. General view of the archaeological site showing excavation and revealing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    General view of the archaeological site showing excavation and revealing the steps leading down into the eighteenth-century burial vault - Harry Buck House, North of Main Street (14800 Governor Oden Bowie Drive), Upper Marlboro, Prince George's County, MD

  13. [Deep vein thrombosis revealing myeloproliferative syndrome in two adolescents].

    PubMed

    Bertrand, A; Heissat, S; Caron, N; Viremouneix, L; Pracros, J-P; Javouhey, E; Lachaux, A; Mialou, V

    2014-05-01

    Deep vein thrombosis occurs in 30% of patients with essential thrombocythemia, but rarely at initial diagnosis. We report two pediatric patients with essential thrombocythemia revealed by atypical deep vein thrombosis. First, a 16-year-old girl presented Budd-Chiari syndrome revealed by a hemorrhagic shock. Clinical exam revealed isolated splenomegaly. A search for thrombophilia found a factor V Leiden homozygous mutation and a Jak2 mutation. Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder. The second case, a 17-year-old girl, had a routine examination by her physician that revealed splenomegaly. Ultrasonography displayed thrombus in the splenic and portal vein. An isolated Jak2 mutation was found and a myeloproliferative disorder was confirmed by bone marrow biopsy. The diagnosis of myeloproliferative disorder was made in both patients presenting atypical venous thrombosis with a Jak2 mutation and confirmed by bone marrow biopsy. These initial presentations of myeloproliferative disorders are rare in childhood and possibly underdiagnosed. PMID:24709317

  14. 14. DETAIL VIEW, FLUTED PILASTER AND PANELLED REVEAL IN DOORWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. DETAIL VIEW, FLUTED PILASTER AND PANELLED REVEAL IN DOORWAY BETWEEN VESTIBULE AND STAIRHALL (NOTE WOOD GRAINING), WITH SCALE - Bowieville, 522 Church Road South, Leeland, Prince George's County, MD

  15. Everett Weinreb, Photographer, April 1989 FOUNDATION DETAIL REVEALED AS RESULT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Everett Weinreb, Photographer, April 1989 FOUNDATION DETAIL REVEALED AS RESULT OF HOUSE DEMOLITION - Irvine Ranch Agricultural Headquarters, Boyd Tenant House, Southeast of Intersection of San Diego & Santa Ana Freeways, Irvine, Orange County, CA

  16. Genome-Wide Scan Reveals Mutation Associated with Melanoma

    MedlinePlus

    ... 1999 Spotlight on Research 2012 July 2012 (historical) Genome-Wide Scan Reveals Mutation Associated with Melanoma A ... out to see if a technology called whole genome sequencing would help them find other genetic risk ...

  17. Revealing of HII-regions in Galaxies with Panoramic Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hakopian, S. A.; Balayan, S. K.

    2016-06-01

    Observations intended to investigation and revealing of nodes of processes of nuclear and starforming activity in galaxies were performed via panoramic spectroscopy. Data obtained on Mrk 1050 revealed evidence of starforming activity also outside the central engine of high surface brightness. Two small HII-regions, being likely a part of the chain, are located in the part of the spiral branch coming from the nucleus part.

  18. Camelid genomes reveal evolution and adaptation to desert environments.

    PubMed

    Wu, Huiguang; Guang, Xuanmin; Al-Fageeh, Mohamed B; Cao, Junwei; Pan, Shengkai; Zhou, Huanmin; Zhang, Li; Abutarboush, Mohammed H; Xing, Yanping; Xie, Zhiyuan; Alshanqeeti, Ali S; Zhang, Yanru; Yao, Qiulin; Al-Shomrani, Badr M; Zhang, Dong; Li, Jiang; Manee, Manee M; Yang, Zili; Yang, Linfeng; Liu, Yiyi; Zhang, Jilin; Altammami, Musaad A; Wang, Shenyuan; Yu, Lili; Zhang, Wenbin; Liu, Sanyang; Ba, La; Liu, Chunxia; Yang, Xukui; Meng, Fanhua; Wang, Shaowei; Li, Lu; Li, Erli; Li, Xueqiong; Wu, Kaifeng; Zhang, Shu; Wang, Junyi; Yin, Ye; Yang, Huanming; Al-Swailem, Abdulaziz M; Wang, Jun

    2014-10-21

    Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

  19. External ear nodule revealing a disseminated Kaposi disease.

    PubMed

    Rachadi, Hanane; Zemmez, Youssef; Znati, Kaoutar; Ismaili, Nadia; Hassam, Badreddine

    2016-01-01

    Kaposi disease (KD) is an angiogenetic tumor process, characterized by its various clinical aspects. Its pathogenesis is multifactorial and it was attributed to HHV-8 infection. We report an original case of disseminated KD revealed by solitary lesion of external ear in a patient treated by corticosteroids for bullous pemphigoid. PMID:27617947

  20. Chemical milling solution reveals stress corrosion cracks in titanium alloy

    NASA Technical Reports Server (NTRS)

    Braski, D. N.

    1967-01-01

    Solution of hydrogen flouride, hydrogen peroxide, and water reveals hot salt stress corrosion cracks in various titanium alloys. After the surface is rinsed in water, dried, and swabbed with the solution, it can be observed by the naked eye or at low magnification.

  1. Nilaja Sun's "No Child"...: Revealing Teaching and Learning through Theater

    ERIC Educational Resources Information Center

    Hetland, Lois

    2009-01-01

    This article presents an analysis of Nilaja Sun's one-woman play, "No Child" . . ., that applies the Studio Habits of Mind framework to reveal essential features of great teaching artistry and great teaching. The play conveys much about twenty-first century schools and the policies that control them; about respect, equity, justice, and the lack of…

  2. [Two cases of cryptococcal meningitis revealed by an ischemic stroke].

    PubMed

    Kouame-Assouan, A E; Cowppli-Bony, P; Aka-Anghui Diarra, E; Assi, B; Doumbia, M; Diallo, L; Adjien, K C; Akani, E; Sonan, T; Diagana, M; Boa, Y E; Kouassi, B

    2007-02-01

    The usual clinical expression of neuromeningeal cryptococcosis is a meningoencephalitis. We report two cases of neurocryptococcosis which have been revealed by an unusual clinical aspect: an ischemic stroke with a vasculitis mechanism. The two patients had a positive reaction for the HIV and we discussed the responsibility of the HIV or the Cryptococcus in the occurrence of the cerebral infarct.

  3. Integrated genomics of Mucorales reveals novel therapeutic targets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

  4. Perspective view. Fivestory reinforced concrete factory building reveals the structural ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Perspective view. Five-story reinforced concrete factory building reveals the structural frame on the exterior of the facade. Twelve bay facade facing onto Clay Avenue (north facade) has first floor openings bricked up. Mix of typical factory windows and glass block windows fill the majority of the openings on the rest of building - Russell Industrial Center, 1600 Clay Avenue, Detroit, MI

  5. Detail of south granite pier revealing riveted truss ends and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of south granite pier revealing riveted truss ends and iron footing plates on top of granite cap stones. View north - New York, New Haven & Hartford Railroad, Fort Point Channel Rolling Lift Bridge, Spanning Fort Point Channel, Boston, Suffolk County, MA

  6. Thrombotic Microangiopathy Revealing Bone Metastases from an Ethmoid Sinus Carcinoma

    PubMed Central

    Morisse, Mony Chenda; Kontar, Loay; Bihan, Céline; Boone, Mathieu; Lachaier, Emma; Titeca-Beauport, Dimitri; Maizel, Julien; Chauffert, Bruno

    2016-01-01

    Cancer-related thrombotic microangiopathy (TMA) is a rare entity whose clinical and biological characteristics have been described in various tumors. Here we describe the first case of cancer-related TMA revealing diffuse bone metastases from an ethmoid sinus carcinoma. PMID:27721770

  7. Hospital study reveals strategies for improving media relations.

    PubMed

    Fitzgerald, P E; Embrey-Wahl, L

    1987-01-01

    A nationwide study revealed that hospital administrators feel inadequate when dealing with the media, and also think the media does not understand the hospital business. Many strategies are available to counter these problems, including some that emphasize issues related to bed size. PMID:3583722

  8. Experimentally implementable criteria revealing substructures of genuine multipartite entanglement

    SciTech Connect

    Huber, Marcus; Schimpf, Hans; Gabriel, Andreas; Spengler, Christoph; Bruss, Dagmar; Hiesmayr, Beatrix C.

    2011-02-15

    We present a general framework that reveals substructures of genuine multipartite entanglement. Via simple inequalities it is possible to discriminate different sets of multipartite qubit states. These inequalities are beneficial regarding experimental examinations as only local measurements are required. Furthermore, the number of observables scales favorably with system size. In exemplary cases we demonstrate the noise resistance and discuss implementations.

  9. Revealing the Effects of Cognitive Education Programmes through Dynamic Assessment

    ERIC Educational Resources Information Center

    Tzuriel, David

    2011-01-01

    The major objective of this paper is to demonstrate the effectiveness of dynamic assessment (DA) in revealing outcomes of cognitive education programmes. Three programmes based on "mediated learning experience" theory are reviewed: "Feuerstein's Instrumental Enrichment", "Bright Start", and "Peer Mediation with Young Children". In all three…

  10. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways

    PubMed Central

    Das, Anupam; Espinosa-Cantú, Adriana; De Maeyer, Dries; Arslan, Ahmed; Van Pee, Michiel; van der Zande, Elisa; Meert, Wim; Yang, Yudi; Zhu, Bo; Marchal, Kathleen; DeLuna, Alexander; Van Noort, Vera; Jelier, Rob; Verstrepen, Kevin J.

    2015-01-01

    Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID:26545090

  11. The Basics of How to Reveal Epilepsy--Part Two

    ERIC Educational Resources Information Center

    Mittan, Robert J.

    2009-01-01

    In the April 2009 edition of "Exceptional Parent," Part One of this series explored why, for their own emotional well-being, it is so important for parents to tell others about their or their child's epilepsy. This month's installment will discuss the basics of how to reveal epilepsy to others, including some additional advantages one receives in…

  12. Carbohydrate active enzymes revealed in Coptotermes formosanus transcriptome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A normalized cDNA library of Coptotermes formosanus was constructed using mixed RNA isolated from workers, soldiers, nymphs and alates of both sexes. Sequencing of this library generated 131,637 EST and 25,939 unigenes were assembled. Carbohydrate active enzymes (CAZymes) revealed in this library we...

  13. TSV reveal height and dimension metrology by the TSOM method

    NASA Astrophysics Data System (ADS)

    Vartanian, Victor; Attota, Ravikiran; Park, Haesung; Orji, George; Allen, Richard A.

    2013-04-01

    This paper reports on an investigation to determine whether through-focus scanning optical microscopy (TSOM) is applicable to micrometer-scale through-silicon via (TSV) reveal metrology. TSOM has shown promise as an alternative inspection and dimensional metrology technique for FinFETs and defects. In this paper TSOM measurements were simulated using 546 nm light and applied to copper TSV reveal pillars with height in the 3 μm to 5 μm range and diameter of 5 μm. Simulation results, combined with white light interferometric profilometry, are used in an attempt to correlate TSOM image features to variations in TSV height, diameter, and sidewall angle (SWA). Simulations illustrate the sensitivity of Differential TSOM Images (DTI's) using the metric of Optical Intensity Range (OIR), for 5 μm diameter and 5 μm height TSV Cu reveal structures, for variation of SWA (Δ = 2°, OIR = 2.35), height (Δ = 20 nm, OIR = 0.28), and diameter (Δ = 40 nm, OIR = 0.57), compared to an OIR noise floor of 0.01. In addition, white light interferometric profilometry reference data is obtained on multiple TSV reveal structures in adjacent die, and averages calculated for each die's SWA, height, and diameter. TSOM images are obtained on individual TSV's within each set, with DTI's obtained by comparing TSV's from adjacent die. The TSOM DTI's are compared to average profilometry data from identical die to determine whether there are correlations between DTI and profilometry data. However, with several significant TSV reveal features not accounted for in the simulation model, it is difficult to draw conclusions comparing profilometry measurements to TSOM DTI's when such features generate strong optical interactions. Thus, even for similar DTI images there are no discernible correlations to SWA, diameter, or height evident in the profilometry data. The use of a more controlled set of test structures may be advantageous in correlating TSOM to optical images.

  14. Systematic toxicological analysis revealing a rare case of captan ingestion.

    PubMed

    Gottzein, Anne K; Musshoff, Frank; Madea, Burkhard

    2013-07-01

    This article presents a case of suicide by intoxication with various pharmaceuticals, particularly anticonvulsants, combined with the fungicide captan. A cause of death could not be ascertained at autopsy. However, systematic toxicological analysis (STA) including a screening via solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) for (semi) volatile organic compounds revealed results suggesting a possible cause of death. The effects of captan on the human organism, its metabolism, and distribution will be discussed. Macroscopically, the cause of death was unascertained. STA revealed clonazepam, citalopram, and its metabolites, lamotrigine, levetiracetam, lacosamide, clonazepam, captan, and its metabolite tetrahydrophthalimide (THPI). For the first time, it was detected in human viscera. A quantification of THPI was performed to obtain distribution in the organs. The significance of a complete STA must be emphasized. The presence of THPI would have been missed without previous detection of captan. Consequently, this fatality would not have been investigated satisfactorily.

  15. Direct visualization reveals kinetics of meiotic chromosome synapsis

    SciTech Connect

    Rog, Ofer; Dernburg, Abby  F.

    2015-03-17

    The synaptonemal complex (SC) is a conserved protein complex that stabilizes interactions along homologous chromosomes (homologs) during meiosis. The SC regulates genetic exchanges between homologs, thereby enabling reductional division and the production of haploid gametes. Here, we directly observe SC assembly (synapsis) by optimizing methods for long-term fluorescence recording in C. elegans. We report that synapsis initiates independently on each chromosome pair at or near pairing centers—specialized regions required for homolog associations. Once initiated, the SC extends rapidly and mostly irreversibly to chromosome ends. Quantitation of SC initiation frequencies and extension rates reveals that initiation is a rate-limiting step in homolog interactions. Eliminating the dynein-driven chromosome movements that accompany synapsis severely retards SC extension, revealing a new role for these conserved motions. This work provides the first opportunity to directly observe and quantify key aspects of meiotic chromosome interactions and will enable future in vivo analysis of germline processes.

  16. [Deep dorsal penile vein thrombosis revealing Behcet's disease].

    PubMed

    Beddouche, Ali; Ouaziz, Hicham; Zougaghi, Sinane; Alaoui, Abdelilah; Dergamoun, Hamza; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

    2016-01-01

    Deep dorsal penile vein thrombosis (DDPVT)is a rare and little known urologic emergency. It requires an early etiological and symptomatic approach to preserve erectile function and prevent recurrences. This study reports a case of dorsal penile vein thrombosis revealed by spontaneous priapism that didn't resolve adequately and confirmed by penile Doppler ultrasound. After management of priapism and DDPVT, the etiological investigation revealed Behcet's disease whose diagnosis was based on the association of a major criteria, such as oral aphthous ulcers with 3 minor criteria such as: genital aphthous ulcers, ocular involvement, and a positive skin pathergy test within 24h. The patient underwent etiological treatment with good clinical evolution and preservation of erectile function. PMID:27583081

  17. Multisystem Langerhans Cell Histiocytosis in Adults Revealed by Skin Lesions.

    PubMed

    Atarguine, Hanane; Hocar, Ouafa; Oussmane, Samia; Mouafik, Sara Batoul; Hamdaoui, Abderrachid; Hafiane, Hanan; Belbaraka, Rhizlane; Akhdari, Nadia; Amal, Said

    2016-01-01

    A 37-year-old woman with no remarkable medical or family history presented with papules and vesicles on an erythematous background involving the neck, sacrum, and folds (postauricular, axillary, inguinal, and under the breasts) (Figure 1). During the previous year, she was treated with local and systemic antifungals without improvement. Her history included a secondary amenorrhea, polydipsia, and polyuria (6 L/d) that started 2 years prior. Physical examination revealed chronic bilateral purulent otorrhea with thick eardrums. Histologic examination of skin biopsy revealed a highly suggestive appearance of multisystem Langerhans cell histiocytosis (LCH) with immunohistochemistry (anti-PS100 and anti-CD1a), which were positive (Figure 2A and 2B). Pituitary magnetic resonance imaging showed a thickening of the pituitary stalk in relation to a location histiocytic (Figure 3). Bone gaps were objectified on two radiographic tibial diaphyseal. Results from computed tomography (CT) scan showed a magma coelio mesenteric, axillary, and inguinal lymph nodes. PMID:27319965

  18. Stable Chromosome Condensation Revealed by Chromosome Conformation Capture.

    PubMed

    Eagen, Kyle P; Hartl, Tom A; Kornberg, Roger D

    2015-11-01

    Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. PMID:26544940

  19. Ascites and other incidental findings revealing undiagnosed systemic rheumatoid arthritis.

    PubMed

    Szeto, Matthew Chak Hin; Disney, Benjamin; Perkins, Philip; Wood, Gordon

    2015-06-08

    We describe a case of a 43-year-old man presenting to the gastroenterology outpatient department with exudative ascites. Mediastinal lymphadenopathy, pericardial effusion and pleural effusion were detected on further imaging. Further clinical examination revealed subcutaneous nodules on the left arm, which were confirmed to be rheumatoid nodules on histology. Inflammatory markers were elevated with positive serology for rheumatoid factor and anticyclic citrullinated protein antibody. Our investigations excluded tuberculosis, pancreatitis and malignancy in the patient. Following review by a rheumatologist, a diagnosis of systemic rheumatoid arthritis (RA) was made. Pleuritis and pericarditis are well recognised as extra-articular manifestation of RA. Ascites, however, is rarely recognised as a manifestation of RA. Our literature search revealed two other cases of ascites due to RA disease activity, and both patients had long-standing known RA. This case adds to the discussion on whether ascites and peritonitis should be classified as extra-articular manifestations of RA.

  20. Acting without seeing: eye movements reveal visual processing without awareness.

    PubMed

    Spering, Miriam; Carrasco, Marisa

    2015-04-01

    Visual perception and eye movements are considered to be tightly linked. Diverse fields, ranging from developmental psychology to computer science, utilize eye tracking to measure visual perception. However, this prevailing view has been challenged by recent behavioral studies. Here, we review converging evidence revealing dissociations between the contents of perceptual awareness and different types of eye movement. Such dissociations reveal situations in which eye movements are sensitive to particular visual features that fail to modulate perceptual reports. We also discuss neurophysiological, neuroimaging, and clinical studies supporting the role of subcortical pathways for visual processing without awareness. Our review links awareness to perceptual-eye movement dissociations and furthers our understanding of the brain pathways underlying vision and movement with and without awareness.

  1. Mitogenome revealed multiple postdomestication genetic mixtures of West African sheep.

    PubMed

    Brahi, O H D; Xiang, H; Chen, X; Farougou, S; Zhao, X

    2015-10-01

    Notable diversity observed within African ovine breeds makes them of great interests, but limited studies on genetic origins and domestications remain poorly understood. Here, we investigate the evolutionary status of West African native breeds, Djallonke and Sahelian sheep using mitogenome sequencing. Compared with other ovine mitogenome sequences, West African sheep were revealed a Eurasian origin, and the initially tamed sheep breeds in West Africa have been genetically mixed with each other and mixed with European breeds. Worldwide domestic sheep is deemed the Eurasian origin and migrated west to Europe and Africa and east to the Far East, in which dispersed and received selection for acclimation to autochthonic environment independently and ultimately evolved into different native breeds, respectively. Our results contribute to the comprehensive understanding of the domestic sheep origin and reveal multiple postdomestication genetic amelioration processes.

  2. Benign Cystic Peritoneal Mesothelioma Revealed by Small Bowel Obstruction.

    PubMed

    Bray Madoué, Kaimba; Boniface, Moifo; Annick Laure, Edzimbi; Pierre, Herve

    2016-01-01

    Benign cystic peritoneal mesothelioma is a rare tumor which frequently occurs in women of reproductive age. Abdominal pain associated with pelvic or abdominal mass is the common clinical presentation. We report the case of a 22-year-old woman with a pathological proved benign cystic mesothelioma of the peritoneum revealed by a small bowel obstruction and a painful left-sided pelvic mass with signs of psoitis. Contrast enhanced abdominal CT-scan demonstrated a large pelvic cystic mass with mass effect on rectosigmoid and pelvic organs. The patient underwent surgical removal of the tumor. Pathological examination revealed the diagnosis of benign cystic mesothelioma of the peritoneum. The outcome was excellent with a 12-month recoil.

  3. Benign Cystic Peritoneal Mesothelioma Revealed by Small Bowel Obstruction

    PubMed Central

    Bray Madoué, Kaimba; Boniface, Moifo; Annick Laure, Edzimbi; Pierre, Herve

    2016-01-01

    Benign cystic peritoneal mesothelioma is a rare tumor which frequently occurs in women of reproductive age. Abdominal pain associated with pelvic or abdominal mass is the common clinical presentation. We report the case of a 22-year-old woman with a pathological proved benign cystic mesothelioma of the peritoneum revealed by a small bowel obstruction and a painful left-sided pelvic mass with signs of psoitis. Contrast enhanced abdominal CT-scan demonstrated a large pelvic cystic mass with mass effect on rectosigmoid and pelvic organs. The patient underwent surgical removal of the tumor. Pathological examination revealed the diagnosis of benign cystic mesothelioma of the peritoneum. The outcome was excellent with a 12-month recoil. PMID:27066288

  4. Intracranial hemorrhage revealing pseudohypoparathyroidism as a cause of fahr syndrome.

    PubMed

    Swami, Abhijit; Kar, Giridhari

    2011-01-01

    Pseudohypoparathyroidism is an infrequently encountered disease. It is one of the causes of Fahr syndrome which also is a rare clinical entity caused by multiple diseases. A 4-year-old man hospitalized for sudden onset left hemiparesis and hypertension was diagnosed to have right thalamic and midbrain hemorrhage on plain CT scan of the head which also revealed co-existent extensive intracranial calcifications involving the basal ganglia and cerebellum bilaterally. General physical examination revealed features of Albright hereditary osteodystrophy, goitre, hypertension, left hemiparesis, and signs of cerebellar dysfunction. Laboratory findings suggested hypocalcemia, hyperphosphatemia along with high TSH, low FT(4), low FT(3), and high anti-TPO antibody. Though bilateral intracranial calcifications are usually encountered as an incidental radiological finding in the CT scan of brain, in this case, the patient admitted for thalamic and midbrain hemorrhage was on investigation for associated intracranial calcification, and goitre was also found to have coexisting pseudohypoparathyroidism and autoimmune hypothyroidism.

  5. Revealing topological superconductivity in extended quantum spin Hall Josephson junctions.

    PubMed

    Lee, Shu-Ping; Michaeli, Karen; Alicea, Jason; Yacoby, Amir

    2014-11-01

    Quantum spin Hall-superconductor hybrids are promising sources of topological superconductivity and Majorana modes, particularly given recent progress on HgTe and InAs/GaSb. We propose a new method of revealing topological superconductivity in extended quantum spin Hall Josephson junctions supporting "fractional Josephson currents." Specifically, we show that as one threads magnetic flux between the superconductors, the critical current traces an interference pattern featuring sharp fingerprints of topological superconductivity-even when noise spoils parity conservation.

  6. A circadian sleep disorder reveals a complex clock.

    PubMed

    Mignot, Emmanuel; Takahashi, Joseph S

    2007-01-12

    Circadian rhythms are established by transcription of clock genes and autoregulatory transcriptional feedback loops. In this issue, Xu et al. (2007) characterize mice expressing a human Per2 mutation identified in patients with familial advanced sleep phase syndrome. Their results reveal that PER2 phosphorylation, by CK1delta and other kinases, is surprisingly complex and has opposite effects on PER2 levels and period length. PMID:17218251

  7. A shoulder-hand syndrome revealing a lung cancer.

    PubMed

    Akasbi, N; Elidrissi, M; Tahiri, L; Shimi, M; Kadi, N; Elouazzani, F Z; Elmrini, A; Harzy, T

    2013-02-01

    Shoulder-hand syndrome is a reflex sympathetic dystrophy which is usually associated with minor trauma, fracture or surgical procedures on bones, or follows peripheral nerve injury. In the present report, we describe a patient who developed sympathetic dystrophy which revealed a lung cancer. Reflex sympathetic dystrophy, therefore, should be considered an occasional manifestation of a paraneoplastic syndrome warranting a thorough search for underlying malignancy.

  8. Parascapular mass revealing primary tuberculosis of the posterior arch

    PubMed Central

    Arbault, Anais; Ornetti, Paul; Chevallier, Olivier; Avril, Julien; Pottecher, Pierre

    2016-01-01

    We report the case of a parascapular abscess revealing primary tuberculosis of the posterior arch in a 31-year-old man. Sectional imaging is essential in order to detect the different lesions of this atypical spinal tuberculosis as osteolysis of the posterior arch extendible to vertebral body, osteocondensation, epidural extension which is common in this location, and high specificity of a zygapophysial, costo-vertebral or transverse arthritis.

  9. Transient light-induced intracellular oxidation revealed by redox biosensor

    SciTech Connect

    Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

    2013-10-04

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

  10. Active medulloblastoma enhancers reveal subgroup-specific cellular origins.

    PubMed

    Lin, Charles Y; Erkek, Serap; Tong, Yiai; Yin, Linlin; Federation, Alexander J; Zapatka, Marc; Haldipur, Parthiv; Kawauchi, Daisuke; Risch, Thomas; Warnatz, Hans-Jörg; Worst, Barbara C; Ju, Bensheng; Orr, Brent A; Zeid, Rhamy; Polaski, Donald R; Segura-Wang, Maia; Waszak, Sebastian M; Jones, David T W; Kool, Marcel; Hovestadt, Volker; Buchhalter, Ivo; Sieber, Laura; Johann, Pascal; Chavez, Lukas; Gröschel, Stefan; Ryzhova, Marina; Korshunov, Andrey; Chen, Wenbiao; Chizhikov, Victor V; Millen, Kathleen J; Amstislavskiy, Vyacheslav; Lehrach, Hans; Yaspo, Marie-Laure; Eils, Roland; Lichter, Peter; Korbel, Jan O; Pfister, Stefan M; Bradner, James E; Northcott, Paul A

    2016-02-01

    Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is lacking. Here, using H3K27ac and BRD4 chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors, validated by ChIP-seq, that is responsible for subgroup divergence, and implicates candidate cells of origin for Group 4. Our integrated analysis of enhancer elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.

  11. Using metabarcoding to reveal and quantify plant-pollinator interactions

    PubMed Central

    Pornon, André; Escaravage, Nathalie; Burrus, Monique; Holota, Hélène; Khimoun, Aurélie; Mariette, Jérome; Pellizzari, Charlène; Iribar, Amaia; Etienne, Roselyne; Taberlet, Pierre; Vidal, Marie; Winterton, Peter; Zinger, Lucie; Andalo, Christophe

    2016-01-01

    Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole. PMID:27255732

  12. Using metabarcoding to reveal and quantify plant-pollinator interactions.

    PubMed

    Pornon, André; Escaravage, Nathalie; Burrus, Monique; Holota, Hélène; Khimoun, Aurélie; Mariette, Jérome; Pellizzari, Charlène; Iribar, Amaia; Etienne, Roselyne; Taberlet, Pierre; Vidal, Marie; Winterton, Peter; Zinger, Lucie; Andalo, Christophe

    2016-01-01

    Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole. PMID:27255732

  13. Interior Evolution of Ceres and Vesta Revealed by Dawn

    NASA Astrophysics Data System (ADS)

    Raymond, C. A.; Russell, C. T.; Bland, M. T.; Castillo, J. C.; De Sanctis, M. C.; Ermakov, A.; Jaumann, R.; Konopliv, A. S.; Marchi, S.; McCord, T. B.; McSween, H. Y., Jr.; Nathues, A.; Park, R. S.; Prettyman, T. H.; Toplis, M. J.; Zuber, M. T.

    2015-12-01

    Dawn's exploration of Vesta and Ceres has revealed their geophysical characteristics, informing the processes that shaped the bodies. Dawn has determined the average diameter of Ceres to be 940 km, smaller than the previously estimated 975 km [1]. This implies a density of 2160 kg/m3, indicating that Ceres is less differentiated than predicted [2]. Ceres' entire surface is cratered, implying the lack of a thick (10's of km) water ice layer at the surface. Variability in Ceres' crater morphology indicates that the near-surface layer has variable strength and rheology, likely due to heterogeneity in the near-surface mixture of rock, ice and salt. These observations may indicate that Ceres lost a significant amount of an original surface ice layer due to impact erosion. The lack of large impact basins on Ceres can be interpreted to be the result of viscous relaxation. These data provide insights into Ceres' thermal evolution and mechanical properties, which appear to be unique to this warm, icy body. In contrast to Ceres, Vesta formed very early and hot, resulting in a fully differentiated body. Dawn's exploration revealed geophysical and geochemical evidence for an iron-rich core and basaltic crust. However, unlike the pre-Dawn paradigm of Vesta's evolution, Dawn found that the crust and mantle of Vesta are less distinct than predicted by classical differentiation models. [1] Thomas, P. C., et al., Differentiation of the asteroid Ceres as revealed by its shape, Nature, 437, 224-226, 2005; [2] McCord et al., Ceres: Its Origin, Evolution and Structure and Dawn's Potential Contribution, Space Sci Rev
DOI 10.1007/s11214-010-9729-9, 2011.

  14. How the ``Blues'' reveals the intimacy of music and physics

    NASA Astrophysics Data System (ADS)

    Gibson, J. Murray

    2013-03-01

    Little do most people know when they hear blues piano - and you'll hear some live in this talk - that physics permeates the style, as it does all of music. Why should you care? By deconstructing blues piano the intimacy of physics, mathematics and music will be revealed in its glory.[1] The exercise says something about how the brains of the music composer and of the listener must be intimately linked to the physical principles of acoustics. And it provides a great vehicle to explain physical phenomena to non-scientists - everything from quantum mechanics to protein structure.

  15. Nonclassical light revealed by the joint statistics of simultaneous measurements.

    PubMed

    Luis, Alfredo

    2016-04-15

    Nonclassicality cannot be a single-observable property, since the statistics of any quantum observable is compatible with classical physics. We develop a general procedure to reveal nonclassical behavior of light states from the joint statistics arising in the practical measurement of multiple observables. Beside embracing previous approaches, this protocol can disclose nonclassical features for standard examples of classical-like behavior, such as SU(2) and Glauber coherent states. When combined with other criteria, this would imply that every light state is nonclassical.

  16. Indentation Tests Reveal Geometry-Regulated Stiffening of Nanotube Junctions.

    PubMed

    Ozden, Sehmus; Yang, Yang; Tiwary, Chandra Sekhar; Bhowmick, Sanjit; Asif, Syed; Penev, Evgeni S; Yakobson, Boris I; Ajayan, Pulickel M

    2016-01-13

    Here we report a unique method to locally determine the mechanical response of individual covalent junctions between carbon nanotubes (CNTs), in various configurations such as "X", "Y", and "Λ"-like. The setup is based on in situ indentation using a picoindenter integrated within a scanning electron microscope. This allows for precise mapping between junction geometry and mechanical behavior and uncovers geometry-regulated junction stiffening. Molecular dynamics simulations reveal that the dominant contribution to the nanoindentation response is due to the CNT walls stretching at the junction. Targeted synthesis of desired junction geometries can therefore provide a "structural alphabet" for construction of macroscopic CNT networks with tunable mechanical response. PMID:26618517

  17. The molecular architecture of axonemes revealed by cryoelectron tomography.

    PubMed

    Nicastro, Daniela; Schwartz, Cindi; Pierson, Jason; Gaudette, Richard; Porter, Mary E; McIntosh, J Richard

    2006-08-18

    Eukaryotic flagella and cilia are built on a 9 + 2 array of microtubules plus >250 accessory proteins, forming a biological machine called the axoneme. Here we describe the three-dimensional structure of rapidly frozen axonemes from Chlamydomonas and sea urchin sperm, using cryoelectron tomography and image processing to focus on the motor enzyme dynein. Our images suggest a model for the way dynein generates force to slide microtubules. They also reveal two dynein linkers that may provide "hard-wiring" to coordinate motor enzyme action, both circumferentially and along the axoneme. Periodic densities were also observed inside doublet microtubules; these may contribute to doublet stability. PMID:16917055

  18. Electronic properties of nanoentities revealed by electrically driven rotation

    PubMed Central

    Fan, D. L.; Zhu, Frank Q.; Xu, Xiaobin; Cammarata, Robert C.; Chien, C. L.

    2012-01-01

    Direct electric measurement via small contacting pads on individual quasi-one-dimensional nanoentities, such as nanowires and carbon nanotubes, are usually required to access its electronic properties. We show in this work that 1D nanoentities in suspension can be driven to rotation by AC electric fields. The chirality of the resultantrotation unambiguously reveals whether the nanoentities are metal, semiconductor, or insulator due to the dependence of the Clausius–Mossotti factor on the material conductivity and frequency. This contactless method provides rapid and parallel identification of the electrical characteristics of 1D nanoentities. PMID:22645373

  19. A Dilated Cardiomyopathy Revealing a Neuroblastoma: Which Link?

    PubMed

    Duhil de Bénazé, Gwenaelle; Iserin, Franck; Durand, Philippe; Schleiermacher, Gudrun; Orbach, Daniel

    2016-10-01

    Acute cardiac dysfunctions associated to neuroblastoma have rarely been reported. Cases already described are mainly related to high blood pressure, and rarely to an "acute catecholamine cardiomyopathy" more frequently found in adults with pheochromocytoma or secreting paraganglioma. We here report a case of an 8-month-old infant with severe acute cardiac failure with dilated cardiomyopathy and moderate ischemic myocardial signs, revealing a favorable histoprognosis neuroblastoma. After specific treatment, evolution was favorable, and cardiac function completely recovered. The association of reversible ischemic signs with high plasmatic level of catecholamines suggests the existence of a catecholamine-induced acute cardiac dysfunction which imitates a Tako-Tsubo syndrome in neuroblastoma.

  20. Missing piece of first-responder DNA repair machine revealed

    SciTech Connect

    2009-01-01

    Scientists from the U.S. Department of Energy's Lawrence Berkeley National Laboratory and the Scripps Research Institute have revealed the role played by the least-understood part of a first-responder molecule that rushes in to bind and repair breaks in DNA strands, a process that helps people avoid cancer. With this final piece of the puzzle in place, scientists can better understand how the repair mechanism fends off cancer in healthy people, and conversely, how it helps cancer cells resist chemotherapy. This could enable researchers to develop more effective therapies with fewer side effects. http://newscenter.lbl.gov/press-releases/2009/10/01/dna-repair-uncovered/

  1. [Chronic septic granulomatosis in children revealed by invasive pulmonary aspergillosis].

    PubMed

    Zohra, Fitouri; Nadia, Matoussi; Nadia, Aloui; Khedija, Boussetta; Mouna, Chiha; Azza, Hammou; Saida, Ben Becher

    2005-11-01

    Chronic granulomatosis disease (GCD) is a hereditary abnormality of phagocytic cells, frequently revealed by invasive pulmonary Aspergillosis. The authors report the case of 8 year old girl investigates for hypotrophia, reccurent lung disease and hemoptysia. She was treated for pulmonary tuberculosis because of biological inflammatory syndrome, right alveolar opacity and positive tuberculin skin test. The course was marked by the developement of a thoracic wall mass. Anti- aspergillus serology was positive; culture of the thoracic mass puncture and bronchoalveolar lavage isolated fumigatus Aspergillus. GCD was suggested and confirmed by the NBT test.

  2. Mediated amperometry reveals different modes of yeast responses to sugars.

    PubMed

    Garjonyte, Rasa; Melvydas, Vytautas; Malinauskas, Albertas

    2016-02-01

    Menadione-mediated amperometry at carbon paste electrodes modified with various yeasts (Saccharomyces cerevisiae, Candida pulcherrima, Pichia guilliermondii and Debaryomyces hansenii) was employed to monitor redox activity inside the yeast cells induced by glucose, fructose, sucrose, maltose or galactose. Continuous measurements revealed distinct modes (transient or gradually increasing) of the current development during the first 2 to 3 min after subjection to glucose, fructose and sucrose at electrodes containing S. cerevisiae and non-Saccharomyces strains. Different modes (increasing or decreasing) of the current development after yeast subjection to galactose at electrodes with S. cerevisiae or D. hansenii and at electrodes with C. pulcherrima and P. guilliermondii suggested different mechanisms of galactose assimilation.

  3. Survey reveals nature of corrosion in HF alky units

    SciTech Connect

    Dobis, J.D. ); Clarida, D.R. ); Richert, J.P. )

    1995-03-06

    The results of a National Association of Corrosion Engineers survey of 62 HF alkylation units reveal relatively low incidence of service-related cracking of carbon steel. Hydrogen blistering, however, is prevalent, especially in the main acid circuit and overhead condensers. Based on these and other survey results, several recommendations are made to enable refiners to monitor and reduce corrosion in these special units. The paper discusses the survey results, construction materials, post-weld heat treatments, small-diameter piping, construction inspection, bolting, gaskets, block valves, maintenance practices, cracking, blistering, areas of vulnerability, and recommendations.

  4. Cohesin's role as an active chromatin domain anchorage revealed.

    PubMed

    Feig, Christine; Odom, Duncan T

    2013-12-11

    Cohesin is a conserved protein complex indispensible for proper cell division, because it secures sister-chromatid cohesion following DNA replication until segregation is required at the onset of anaphase. Recent studies have revealed functions beyond this, showing that cohesin binds to interphase chromatin regulating gene expression at select loci via long-range chromosomal interactions. In this issue of The EMBO Journal, Sofueva et al (2013) use a combination of chromatin conformation capture methods, classical FISH imaging, and loss-of-function studies to elegantly demonstrate how cohesin controls the 3D architectural organization of the genome.

  5. Revealing and Characterizing Dark Excitons through Coherent Multidimensional Spectroscopy.

    PubMed

    Tollerud, Jonathan O; Cundiff, Steven T; Davis, Jeffrey A

    2016-08-26

    Dark excitons are of fundamental importance in a broad range of contexts but are difficult to study using conventional optical spectroscopy due to their weak interaction with light. We show how coherent multidimensional spectroscopy can reveal and characterize dark states. Using this approach, we identify parity-forbidden and spatially indirect excitons in InGaAs/GaAs quantum wells and determine details regarding lifetimes, homogeneous and inhomogeneous linewidths, broadening mechanisms, and coupling strengths. The observations of coherent coupling between these states and bright excitons hint at a role for a multistep process by which excitons in the barrier can relax into the quantum wells. PMID:27610881

  6. A Dilated Cardiomyopathy Revealing a Neuroblastoma: Which Link?

    PubMed

    Duhil de Bénazé, Gwenaelle; Iserin, Franck; Durand, Philippe; Schleiermacher, Gudrun; Orbach, Daniel

    2016-10-01

    Acute cardiac dysfunctions associated to neuroblastoma have rarely been reported. Cases already described are mainly related to high blood pressure, and rarely to an "acute catecholamine cardiomyopathy" more frequently found in adults with pheochromocytoma or secreting paraganglioma. We here report a case of an 8-month-old infant with severe acute cardiac failure with dilated cardiomyopathy and moderate ischemic myocardial signs, revealing a favorable histoprognosis neuroblastoma. After specific treatment, evolution was favorable, and cardiac function completely recovered. The association of reversible ischemic signs with high plasmatic level of catecholamines suggests the existence of a catecholamine-induced acute cardiac dysfunction which imitates a Tako-Tsubo syndrome in neuroblastoma. PMID:27571126

  7. Revealing and Characterizing Dark Excitons through Coherent Multidimensional Spectroscopy

    NASA Astrophysics Data System (ADS)

    Tollerud, Jonathan O.; Cundiff, Steven T.; Davis, Jeffrey A.

    2016-08-01

    Dark excitons are of fundamental importance in a broad range of contexts but are difficult to study using conventional optical spectroscopy due to their weak interaction with light. We show how coherent multidimensional spectroscopy can reveal and characterize dark states. Using this approach, we identify parity-forbidden and spatially indirect excitons in InGaAs/GaAs quantum wells and determine details regarding lifetimes, homogeneous and inhomogeneous linewidths, broadening mechanisms, and coupling strengths. The observations of coherent coupling between these states and bright excitons hint at a role for a multistep process by which excitons in the barrier can relax into the quantum wells.

  8. Pneumoretroperitoneum and Pneumomediastinum Revealing a Left Colon Perforation

    PubMed Central

    Montori, Giulia; Di Giovanni, Giacomo; Mzoughi, Zeineb; Angot, Cedric; Al Samman, Sophie; Solaini, Leonardo; Cheynel, Nicolas

    2015-01-01

    Left colon perforation usually occurs in complicated diverticulitis or cancer. The most frequent signs are intraperitoneal abscess or peritonitis. In cases of retroperitoneal colonic perforation, diagnosis may be difficult. A 59-year-old woman presented with left thigh pain and with abdominal discomfort associated with mild dyspnea. Computed tomography scan showed air bubbles and purulent collection in the retroperitoneum, with subcutaneous emphysema extending from the left thigh to the neck. Computed tomography scan also revealed portal vein gas and thrombosis with multiple liver abscesses. An emergency laparotomy revealed a perforation of the proximal left colon. No masses were found. A left colectomy was performed. The retroperitoneum was drained and washed extensively. A negative pressure wound therapy was applied. A second-look laparotomy was performed 48 hours later. The retroperitoneum was drained and an end colostomy was performed. Intensive Care Unit postoperative stay was 9 days, and the patient was discharged on the 32nd postoperative day. Pneumoretroperitoneum and pneumomediastinum are rare signs of colonic retroperitoneal perforation. The diagnosis may be delayed, especially in the absence of peritoneal irritation. Clinical, laboratory, and especially radiologic parameters might be useful. Surgical treatment must be prompt to improve prognosis. PMID:26414818

  9. Parallel lipoplex folding pathways revealed using magnetic tweezers

    PubMed Central

    Sun, Zhiqiang; Tikhonova, Elena B.; Zgurskaya, Helen I.; Rybenkov, Valentin V.

    2012-01-01

    Lipid-coated DNA nanoparticles (lipoplexes) are a powerful gene delivery tool with promising therapeutic applications. The mechanism of lipoplex assembly remains poorly understood. We explored DNA packing by a cationic lipid DSTAP (distearoyl trimethylammonium-propane) using magnetic tweezers. DSTAP-induced DNA condensation occurred as a series of bursts with the mean step size of 60 nm to 80 nm. The pause time preceding the steps could be approximated as a bimodal distribution, which reveals at least two distinct condensation pathways. The rapidly condensed DNA was more resilient to force-induced decondensation. The proportion of the stable, fast-formed complexes decreased at high salt concentrations. A similar trend was observed in bulk experiments. Lipoplexes assembled at low salt concentration more efficiently shielded DNA from fluorescent dyes and DNase even after transfer to the high salt conditions. These data reveal that lipoplex folding occurs via two parallel pathways even at the single molecule level. The progress through the two pathways can be monitored in real time using single DNA manipulations. The relative efficiency of the two pathways can be varied by external conditions. PMID:22988939

  10. Direct visualization reveals kinetics of meiotic chromosome synapsis

    DOE PAGES

    Rog, Ofer; Dernburg, Abby  F.

    2015-03-17

    The synaptonemal complex (SC) is a conserved protein complex that stabilizes interactions along homologous chromosomes (homologs) during meiosis. The SC regulates genetic exchanges between homologs, thereby enabling reductional division and the production of haploid gametes. Here, we directly observe SC assembly (synapsis) by optimizing methods for long-term fluorescence recording in C. elegans. We report that synapsis initiates independently on each chromosome pair at or near pairing centers—specialized regions required for homolog associations. Once initiated, the SC extends rapidly and mostly irreversibly to chromosome ends. Quantitation of SC initiation frequencies and extension rates reveals that initiation is a rate-limiting step inmore » homolog interactions. Eliminating the dynein-driven chromosome movements that accompany synapsis severely retards SC extension, revealing a new role for these conserved motions. This work provides the first opportunity to directly observe and quantify key aspects of meiotic chromosome interactions and will enable future in vivo analysis of germline processes.« less

  11. Economic choices reveal probability distortion in macaque monkeys.

    PubMed

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing.

  12. Blue whale earplug reveals lifetime contaminant exposure and hormone profiles.

    PubMed

    Trumble, Stephen J; Robinson, Eleanor M; Berman-Kowalewski, Michelle; Potter, Charles W; Usenko, Sascha

    2013-10-15

    Lifetime contaminant and hormonal profiles have been reconstructed for an individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the earplug as a natural aging matrix that is also capable of archiving and preserving lipophilic compounds. These unprecedented lifetime profiles (i.e., birth to death) were reconstructed with a 6-mo resolution for a wide range of analytes including cortisol (stress hormone), testosterone (developmental hormone), organic contaminants (e.g., pesticides and flame retardants), and mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over baseline. Testosterone profiles suggest this male blue whale reached sexual maturity at approximately 10 y of age, which corresponds well with and improves on previous estimates. Early periods of the reconstructed contaminant profiles for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes), polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate significant maternal transfer occurred at 0-12 mo. The total lifetime organic contaminant burden measured between the earplug (sum of contaminants in laminae layers) and blubber samples from the same organism were similar. Total mercury profiles revealed reduced maternal transfer and two distinct pulse events compared with organic contaminants. The use of a whale earplug to reconstruct lifetime chemical profiles will allow for a more comprehensive examination of stress, development, and contaminant exposure, as well as improve the assessment of contaminant use/emission, environmental noise, ship traffic, and climate change on these important marine sentinels. PMID:24043814

  13. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth.

    PubMed

    Cuomo, Christina A; Desjardins, Christopher A; Bakowski, Malina A; Goldberg, Jonathan; Ma, Amy T; Becnel, James J; Didier, Elizabeth S; Fan, Lin; Heiman, David I; Levin, Joshua Z; Young, Sarah; Zeng, Qiandong; Troemel, Emily R

    2012-12-01

    Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungal-related parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and Nematocida sp1, which are natural pathogens of Caenorhabditis nematodes and provide model systems for studying microsporidian pathogenesis. We performed deep sequencing of transcripts from a time course of N. parisii infection. Examination of pathogen gene expression revealed compact transcripts and a dramatic takeover of host cells by Nematocida. We also performed phylogenomic analyses of Nematocida and other microsporidian genomes to refine microsporidian phylogeny and identify evolutionary events of gene loss, acquisition, and modification. In particular, we found that all microsporidia lost the tumor-suppressor gene retinoblastoma, which we speculate could accelerate the parasite cell cycle and increase the mutation rate. We also found that microsporidia acquired transporters that could import nucleosides to fuel rapid growth. In addition, microsporidian hexokinases gained secretion signal sequences, and in a functional assay these were sufficient to export proteins out of the cell; thus hexokinase may be targeted into the host cell to reprogram it toward biosynthesis. Similar molecular changes appear during formation of cancer cells and may be evolutionary strategies adopted independently by microsporidia to proliferate rapidly within host cells. Finally, analysis of genome polymorphisms revealed evidence for a sexual cycle that may provide genetic diversity to alleviate problems caused by clonal growth. Together these events may explain the emergence and success of these diverse intracellular parasites.

  14. Economic Choices Reveal Probability Distortion in Macaque Monkeys

    PubMed Central

    Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-01-01

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. PMID:25698750

  15. NeuCode Proteomics Reveals Bap1 Regulation of Metabolism.

    PubMed

    Baughman, Joshua M; Rose, Christopher M; Kolumam, Ganesh; Webster, Joshua D; Wilkerson, Emily M; Merrill, Anna E; Rhoads, Timothy W; Noubade, Rajkumar; Katavolos, Paula; Lesch, Justin; Stapleton, Donald S; Rabaglia, Mary E; Schueler, Kathy L; Asuncion, Raymond; Domeyer, Melanie; Zavala-Solorio, Jose; Reich, Michael; DeVoss, Jason; Keller, Mark P; Attie, Alan D; Hebert, Alexander S; Westphall, Michael S; Coon, Joshua J; Kirkpatrick, Donald S; Dey, Anwesha

    2016-07-12

    We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology. PMID:27373151

  16. The Microbiome of Brazilian Mangrove Sediments as Revealed by Metagenomics

    PubMed Central

    Andreote, Fernando Dini; Jiménez, Diego Javier; Chaves, Diego; Dias, Armando Cavalcante Franco; Luvizotto, Danice Mazzer; Dini-Andreote, Francisco; Fasanella, Cristiane Cipola; Lopez, Maryeimy Varon; Baena, Sandra; Taketani, Rodrigo Gouvêa; de Melo, Itamar Soares

    2012-01-01

    Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04) in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments. PMID:22737213

  17. Revealing quantum correlation by negativity of the Wigner function

    NASA Astrophysics Data System (ADS)

    Taghiabadi, Razieh; Akhtarshenas, Seyed Javad; Sarbishaei, Mohsen

    2016-05-01

    We analyze two two-mode continuous variable separable states with the same marginal states. We adopt the definition of classicality in the form of well-defined positive Wigner function describing the state and find that although the states possess positive local Wigner functions, they exhibit negative Wigner functions for the global states. Using the negativity of Wigner function as an indicator of nonclassicality, we show that despite these states possess different negativities of the Wigner function, they do not reveal this difference as phase space nonclassicalities such as negativity of the Mandel Q parameter or quadrature squeezing. We then concentrate on quantum correlation of these states and show that quantum discord and local quantum uncertainty, as two well-defined measures of quantum correlation, manifest the difference between negativity of the Wigner functions. The non-Gaussianity of these states is also examined and show that the difference in behavior of their non-Gaussianity is the same as the difference between negativity of their Wigner functions. We also investigate the influence of correlation rank criterion and find that when the states can be produced locally from classical states, the Wigner functions cannot reveal their quantum correlations.

  18. Blue whale earplug reveals lifetime contaminant exposure and hormone profiles.

    PubMed

    Trumble, Stephen J; Robinson, Eleanor M; Berman-Kowalewski, Michelle; Potter, Charles W; Usenko, Sascha

    2013-10-15

    Lifetime contaminant and hormonal profiles have been reconstructed for an individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the earplug as a natural aging matrix that is also capable of archiving and preserving lipophilic compounds. These unprecedented lifetime profiles (i.e., birth to death) were reconstructed with a 6-mo resolution for a wide range of analytes including cortisol (stress hormone), testosterone (developmental hormone), organic contaminants (e.g., pesticides and flame retardants), and mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over baseline. Testosterone profiles suggest this male blue whale reached sexual maturity at approximately 10 y of age, which corresponds well with and improves on previous estimates. Early periods of the reconstructed contaminant profiles for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes), polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate significant maternal transfer occurred at 0-12 mo. The total lifetime organic contaminant burden measured between the earplug (sum of contaminants in laminae layers) and blubber samples from the same organism were similar. Total mercury profiles revealed reduced maternal transfer and two distinct pulse events compared with organic contaminants. The use of a whale earplug to reconstruct lifetime chemical profiles will allow for a more comprehensive examination of stress, development, and contaminant exposure, as well as improve the assessment of contaminant use/emission, environmental noise, ship traffic, and climate change on these important marine sentinels.

  19. Circadian acetylome reveals regulation of mitochondrial metabolic pathways.

    PubMed

    Masri, Selma; Patel, Vishal R; Eckel-Mahan, Kristin L; Peleg, Shahaf; Forne, Ignasi; Ladurner, Andreas G; Baldi, Pierre; Imhof, Axel; Sassone-Corsi, Paolo

    2013-02-26

    The circadian clock is constituted by a complex molecular network that integrates a number of regulatory cues needed to maintain organismal homeostasis. To this effect, posttranslational modifications of clock proteins modulate circadian rhythms and are thought to convert physiological signals into changes in protein regulatory function. To explore reversible lysine acetylation that is dependent on the clock, we have characterized the circadian acetylome in WT and Clock-deficient (Clock(-/-)) mouse liver by quantitative mass spectrometry. Our analysis revealed that a number of mitochondrial proteins involved in metabolic pathways are heavily influenced by clock-driven acetylation. Pathways such as glycolysis/gluconeogenesis, citric acid cycle, amino acid metabolism, and fatty acid metabolism were found to be highly enriched hits. The significant number of metabolic pathways whose protein acetylation profile is altered in Clock(-/-) mice prompted us to link the acetylome to the circadian metabolome previously characterized in our laboratory. Changes in enzyme acetylation over the circadian cycle and the link to metabolite levels are discussed, revealing biological implications connecting the circadian clock to cellular metabolic state.

  20. Piriform Spider Silk Sequences Reveal Unique Repetitive Elements

    PubMed Central

    Perry, David J.; Bittencourt, Daniela; Siltberg-Liberles, Jessica; Rech, Elibio L.; Lewis, Randolph V.

    2010-01-01

    Orb-weaving spider silk fibers are assembled from very large, highly repetitive proteins. The repeated segments contain, in turn, short, simple repetitive amino acid motifs that account for the physical and mechanical properties of the assembled fiber. Of the six orb-weaver silk fibroins, the piriform silk that makes the attachment discs, which lashes the joints of the web and attaches dragline silk to surfaces has not been previously characterized. Piriform silk protein cDNAs were isolated from phage libraries of three species, A. trifasciata, N. clavipes, and N. cruentata. The deduced amino acid sequences from these genes revealed two new repetitive motifs: an alternating proline motif where every other amino acid is proline, and a glutamine-rich motif of 6 to 8 amino acids. Similar to other spider silk proteins, the repeated segments are large (>200 amino acids) and highly homogenized within a species. There is also substantial sequence similarity across the genes from the three species with particular conservation of the repetitive motifs. Northern blot analysis revealed that the messenger RNA is larger than 11kb and is expressed exclusively in the piriform glands of the spider. Phylogenetic analysis of the C-terminal regions of the new proteins with published spidroins robustly shows that the pirifom sequences form an ortholog group. PMID:20954740

  1. Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

    PubMed Central

    Shankaran, Mahalakshmi; King, Chelsea L.; Angel, Thomas E.; Holmes, William E.; Li, Kelvin W.; Colangelo, Marc; Price, John C.; Turner, Scott M.; Bell, Christopher; Hamilton, Karyn L.; Miller, Benjamin F.; Hellerstein, Marc K.

    2015-01-01

    Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders. PMID:26657858

  2. Pneumoretroperitoneum and Pneumomediastinum Revealing a Left Colon Perforation.

    PubMed

    Montori, Giulia; Di Giovanni, Giacomo; Mzoughi, Zeineb; Angot, Cedric; Al Samman, Sophie; Solaini, Leonardo; Cheynel, Nicolas

    2015-06-01

    Left colon perforation usually occurs in complicated diverticulitis or cancer. The most frequent signs are intraperitoneal abscess or peritonitis. In cases of retroperitoneal colonic perforation, diagnosis may be difficult. A 59-year-old woman presented with left thigh pain and with abdominal discomfort associated with mild dyspnea. Computed tomography scan showed air bubbles and purulent collection in the retroperitoneum, with subcutaneous emphysema extending from the left thigh to the neck. Computed tomography scan also revealed portal vein gas and thrombosis with multiple liver abscesses. An emergency laparotomy revealed a perforation of the proximal left colon. No masses were found. A left colectomy was performed. The retroperitoneum was drained and washed extensively. A negative pressure wound therapy was applied. A second-look laparotomy was performed 48 hours later. The retroperitoneum was drained and an end colostomy was performed. Intensive Care Unit postoperative stay was 9 days, and the patient was discharged on the 32nd postoperative day. Pneumoretroperitoneum and pneumomediastinum are rare signs of colonic retroperitoneal perforation. The diagnosis may be delayed, especially in the absence of peritoneal irritation. Clinical, laboratory, and especially radiologic parameters might be useful. Surgical treatment must be prompt to improve prognosis.

  3. Proteomics Reveals Novel Drosophila Seminal Fluid Proteins Transferred at Mating

    PubMed Central

    Findlay, Geoffrey D; Yi, Xianhua; MacCoss, Michael J; Swanson, Willie J

    2008-01-01

    Across diverse taxa, seminal fluid proteins (Sfps) transferred at mating affect the reproductive success of both sexes. Such reproductive proteins often evolve under positive selection between species; because of this rapid divergence, Sfps are hypothesized to play a role in speciation by contributing to reproductive isolation between populations. In Drosophila, individual Sfps have been characterized and are known to alter male sperm competitive ability and female post-mating behavior, but a proteomic-scale view of the transferred Sfps has been missing. Here we describe a novel proteomic method that uses whole-organism isotopic labeling to detect transferred Sfps in mated female D. melanogaster. We identified 63 proteins, which were previously unknown to function in reproduction, and confirmed the transfer of dozens of predicted Sfps. Relative quantification of protein abundance revealed that several of these novel Sfps are abundant in seminal fluid. Positive selection and tandem gene duplication are the prevailing forces of Sfp evolution, and comparative proteomics with additional species revealed lineage-specific changes in seminal fluid content. We also report a proteomic-based gene discovery method that uncovered 19 previously unannotated genes in D. melanogaster. Our results demonstrate an experimental method to identify transferred proteins in any system that is amenable to isotopic labeling, and they underscore the power of combining proteomic and evolutionary analyses to shed light on the complex process of Drosophila reproduction. PMID:18666829

  4. Invoking Thomas Kuhn: What Citation Analysis Reveals about Science Education

    NASA Astrophysics Data System (ADS)

    Loving, Cathleen C.; Cobern, William W.

    This paper analyzes how Thomas Kuhn's writings are used by others, especially science education researchers. Previous research in citation analysis is used to frame questions related to who cites Kuhn, in what manner and why. Research questions first focus on the variety of disciplines invoking Kuhn and to what extent Structure of Scientific Revolutions (SSR) is cited. The Web of Science database provides material from 1982 for this analysis. The science education literature is analyzed using back issues from 1985 of the Journal of Research in Science Teaching and Science Education. An article analysis reveals trends in terms of what Kuhnian ideas are most frequently invoked. Results indicate a wide array of disciplines from beekeeping to law cite Kuhn - especially generic citations to SSR. The science education journal analysis reveals pervasive use of the term paradigm, although use is quite varied. The two areas of research in science education most impacted by Kuhn appear to be conceptual change theory and constructivist epistemologies. Additional uses of Kuhn are discussed. The degree to which Kuhn is invoked in ways supporting the theoretical framework of citation analysis, whether his work is misappropriated, and the impact of Kuhn are discussed.

  5. Nanoscience of single polymer chains revealed by nanofishing.

    PubMed

    Nakajima, Ken; Nishi, Toshio

    2006-01-01

    The invention of atomic force microscopy (AFM) enabled us to study the statistical properties of single polymer chains by a method called "nanofishing," which stretches a single polymer chain adsorbed on a substrate with its one end by picking it at the other end. A force-extension curve obtained for a single polystyrene chain in a Theta solvent (cyclohexane) shows good agreement with a worm-like chain model and, therefore, gives microscopic information about entropic elasticity. Furthermore, the nanofishing technique can be used for dynamic viscoelastic measurement of single polymer chains. An AFM cantilever is mechanically oscillated at its resonant frequency during the stretching process. This technique enables the estimation of quantitative and simultaneous elongation-dependent changes of stiffness and viscosity of a single chain with the use of a phenomenological model. In this study, the effect of solvent on viscosity in low extension regions reveals that the viscosity is attributed to monomer-solvent friction. Thus, static and dynamic nanofishing techniques are shown to give powerful experimental proofs for several basic questions in polymer physics. The techniques are expected to reveal hidden properties of polymer chains or polymer solutions by any types of macroscopic measurements in the future. PMID:17099889

  6. Previously Unrecognized Large Lunar Impact Basins Revealed by Topographic Data

    NASA Technical Reports Server (NTRS)

    Frey, Herbert V.

    2008-01-01

    The discovery of a large population of apparently buried impact craters on Mars, revealed as Quasi- Circular Depressions (QCDs) in Mars Orbiting Laser Altimeter (MOLA) data [1,2,3] and as Circular Thin Areas (CTAs) [4] in crustal thickness model data [5] leads to the obvious question: are there unrecognized impact features on the Moon and other bodies in the solar system? Early analysis of Clementine topography revealed several large impact basins not previously known [6,7], so the answer certainly is "Yes." How large a population of previously undetected impact basins, their size frequency distribution, and how much these added craters and basins will change ideas about the early cratering history and Late Heavy Bombardment on the Moon remains to be determined. Lunar Orbiter Laser Altimeter (LOLA) data [8] will be able to address these issues. As a prelude, we searched the state-of-the-art global topographic grid for the Moon, the Unified Lunar Control Net (ULCN) [9] for evidence of large impact features not previously recognized by photogeologic mapping, as summarized by Wilhelms [lo].

  7. Layer-Specific Intracortical Connectivity Revealed with Diffusion MRI

    PubMed Central

    Leuze, Christoph W.U.; Anwander, Alfred; Bazin, Pierre-Louis; Dhital, Bibek; Stüber, Carsten; Reimann, Katja; Geyer, Stefan; Turner, Robert

    2014-01-01

    In this work, we show for the first time that the tangential diffusion component is orientationally coherent at the human cortical surface. Using diffusion magnetic resonance imaging (dMRI), we have succeeded in tracking intracortical fiber pathways running tangentially within the cortex. In contrast with histological methods, which reveal little regarding 3-dimensional organization in the human brain, dMRI delivers additional understanding of the layer dependence of the fiber orientation. A postmortem brain block was measured at very high angular and spatial resolution. The dMRI data had adequate resolution to allow analysis of the fiber orientation within 4 notional cortical laminae. We distinguished a lamina at the cortical surface where diffusion was tangential along the surface, a lamina below the surface where diffusion was mainly radial, an internal lamina covering the Stria of Gennari, where both strong radial and tangential diffusion could be observed, and a deep lamina near the white matter, which also showed mainly radial diffusion with a few tangential compartments. The measurement of the organization of the tangential diffusion component revealed a strong orientational coherence at the cortical surface. PMID:23099298

  8. Membrane protein properties revealed through data-rich electrostatics calculations

    PubMed Central

    Guerriero, Christopher J.; Brodsky, Jeffrey L.; Grabe, Michael

    2015-01-01

    SUMMARY The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem including: full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane induced pKa shifts, calculation of non-polar energies, and command-line scripting for large scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane potentially revealing interesting functional information. PMID:26118532

  9. Are Extreme T Dwarf Color Outliers Revealing Their Ages?

    NASA Astrophysics Data System (ADS)

    Mace, Gregory N.

    2014-01-01

    Brown dwarfs emerge as the low-mass products of the star formation process and then continue to cool. Those with temperatures between 500-1000K correspond to late-type T dwarf (≥ T7) spectral types. Using the Wide-field Infrared Survey Explorer (WISE) we have septupled the number of T dwarfs in this temperature regime, thereby creating a sizable sample with which to study overall trends and to identify outliers. I will present my spectrophotometric studies of this expanded population and compare the WISE discoveries to the samples revealed by 2MASS and UKIDSS. Additionally, I will discuss the newly discovered T8 subdwarf companion to Wolf 1130 and its utility as a high-gravity, low-metallicity benchmark. Late-type T dwarfs with redder J-H and bluer Y-J colors, as well as suppressed K-band flux, are likely revealing their old age. A broad survey of the most extreme late-type T dwarf color outliers can provide useful indicators of physical parameters. These indicators can then be applied to the diverse sample of directly imaged exoplanet and Y dwarf discoveries.

  10. Blue whale earplug reveals lifetime contaminant exposure and hormone profiles

    PubMed Central

    Trumble, Stephen J.; Robinson, Eleanor M.; Berman-Kowalewski, Michelle; Potter, Charles W.; Usenko, Sascha

    2013-01-01

    Lifetime contaminant and hormonal profiles have been reconstructed for an individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the earplug as a natural aging matrix that is also capable of archiving and preserving lipophilic compounds. These unprecedented lifetime profiles (i.e., birth to death) were reconstructed with a 6-mo resolution for a wide range of analytes including cortisol (stress hormone), testosterone (developmental hormone), organic contaminants (e.g., pesticides and flame retardants), and mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over baseline. Testosterone profiles suggest this male blue whale reached sexual maturity at approximately 10 y of age, which corresponds well with and improves on previous estimates. Early periods of the reconstructed contaminant profiles for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes), polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate significant maternal transfer occurred at 0–12 mo. The total lifetime organic contaminant burden measured between the earplug (sum of contaminants in laminae layers) and blubber samples from the same organism were similar. Total mercury profiles revealed reduced maternal transfer and two distinct pulse events compared with organic contaminants. The use of a whale earplug to reconstruct lifetime chemical profiles will allow for a more comprehensive examination of stress, development, and contaminant exposure, as well as improve the assessment of contaminant use/emission, environmental noise, ship traffic, and climate change on these important marine sentinels. PMID:24043814

  11. Piriform spider silk sequences reveal unique repetitive elements.

    PubMed

    Perry, David J; Bittencourt, Daniela; Siltberg-Liberles, Jessica; Rech, Elibio L; Lewis, Randolph V

    2010-11-01

    Orb-weaving spider silk fibers are assembled from very large, highly repetitive proteins. The repeated segments contain, in turn, short, simple, and repetitive amino acid motifs that account for the physical and mechanical properties of the assembled fiber. Of the six orb-weaver silk fibroins, the piriform silk that makes the attachment discs, which lashes the joints of the web and attaches dragline silk to surfaces, has not been previously characterized. Piriform silk protein cDNAs were isolated from phage libraries of three species: A. trifasciata , N. clavipes , and N. cruentata . The deduced amino acid sequences from these genes revealed two new repetitive motifs: an alternating proline motif, where every other amino acid is proline, and a glutamine-rich motif of 6-8 amino acids. Similar to other spider silk proteins, the repeated segments are large (>200 amino acids) and highly homogenized within a species. There is also substantial sequence similarity across the genes from the three species, with particular conservation of the repetitive motifs. Northern blot analysis revealed that the mRNA is larger than 11 kb and is expressed exclusively in the piriform glands of the spider. Phylogenetic analysis of the C-terminal regions of the new proteins with published spidroins robustly shows that the piriform sequences form an ortholog group.

  12. Revealing short-period normal modes of the atmosphere

    NASA Astrophysics Data System (ADS)

    Shved, G. M.; Ermolenko, S. I.; Hoffmann, P.

    2015-09-01

    Barometer and seismometer measurements at Collm, Germany (51.3° N, 13.0° E) for all of 2002 are used to search for atmospheric normal modes (ANMs) in the frequency range 50-310 µHz. The measurements are spectrally analyzed using a 5-day window sliding along the 1-year series with a 1-day step. The subsequent analysis follows two procedures: (a) revealing features in the frequency distribution of the number of statistically significant spectral peaks in histograms built on the basis of these spectra and (b) calculating the multiplication spectra for the raw spectra. The two procedures yield the same result for the two instruments, i.e., reveal a periodicity in the clustering of atmospheric modes on the frequency axis with a period of ˜6 µHz. The fact that this period is close to 7 μHz, which is predicted by the crude theory of gravity—inertia ANMs [3] for their frequency distribution, suggests that ANMs are generated down to as small a period as ˜1 h.

  13. Phylogenetic analysis reveals the surprising diversity of an oxygenase class.

    PubMed

    Capyk, Jenna K; Eltis, Lindsay D

    2012-03-01

    As metalloenzymes capable of transforming a broad range of substrates with high stereo- and regio-specificity, the multicomponent Rieske oxygenases (ROs) have been studied in bacterial systems for applications in bioremediation and industrial biocatalysis. These studies include genetic and biochemical investigations, determination of enzyme structure, phylogenetic analysis, and enzyme classification. Although RO terminal oxygenase components (RO-Os) share a conserved domain structure, their sequences are highly divergent and present significant challenges for identification and classification. Herein, we present the first global phylogenetic analysis of a broad range of RO-Os from diverse taxonomic groups. We employed objective, structure-based criteria to significantly reduce the inclusion of erroneously aligned sequences in the analysis. Our findings reveal that RO biochemical studies to date have been largely concentrated in an unexpectedly narrow portion of the RO-O sequence landscape. Additionally, our analysis demonstrates the existence two distinct groups of RO-O sequences. Finally, the sequence diversity recognized in this study necessitates a new RO-O classification scheme. We therefore propose a P450-like naming system. Our results reveal a diversity of sequence and potential catalytic functionality that has been wholly unappreciated in the RO literature. This study also demonstrates that many commonly used bioinformatic tools may not be sufficient to analyze the vast amount of data available in current databases. These findings facilitate the expanded exploration of RO catalytic capabilities in both biological and technological contexts and increase the potential for practical exploitation of their activities.

  14. Deciphering CAPTCHAs: what a Turing test reveals about human cognition.

    PubMed

    Hannagan, Thomas; Ktori, Maria; Chanceaux, Myriam; Grainger, Jonathan

    2012-01-01

    Turning Turing's logic on its head, we used widespread letter-based Turing Tests found on the internet (CAPTCHAs) to shed light on human cognition. We examined the basis of the human ability to solve CAPTCHAs, where machines fail. We asked whether this is due to our use of slow-acting inferential processes that would not be available to machines, or whether fast-acting automatic orthographic processing in humans has superior robustness to shape variations. A masked priming lexical decision experiment revealed efficient processing of CAPTCHA words in conditions that rule out the use of slow inferential processing. This shows that the human superiority in solving CAPTCHAs builds on a high degree of invariance to location and continuous transforms, which is achieved during the very early stages of visual word recognition in skilled readers. PMID:22396750

  15. Mediated amperometry reveals different modes of yeast responses to sugars.

    PubMed

    Garjonyte, Rasa; Melvydas, Vytautas; Malinauskas, Albertas

    2016-02-01

    Menadione-mediated amperometry at carbon paste electrodes modified with various yeasts (Saccharomyces cerevisiae, Candida pulcherrima, Pichia guilliermondii and Debaryomyces hansenii) was employed to monitor redox activity inside the yeast cells induced by glucose, fructose, sucrose, maltose or galactose. Continuous measurements revealed distinct modes (transient or gradually increasing) of the current development during the first 2 to 3 min after subjection to glucose, fructose and sucrose at electrodes containing S. cerevisiae and non-Saccharomyces strains. Different modes (increasing or decreasing) of the current development after yeast subjection to galactose at electrodes with S. cerevisiae or D. hansenii and at electrodes with C. pulcherrima and P. guilliermondii suggested different mechanisms of galactose assimilation. PMID:26523505

  16. Treated-skin temperature regularities revealed by IR thermography

    NASA Astrophysics Data System (ADS)

    Vainer, Boris G.

    2001-03-01

    Experimental results disclosing temperature change of human skin affected by various unnatural factors are presented in detail. Thermograms are obtained with the IR thermograph containing high performance InAs CID FPA-based photosensitive unit. Using logarithmic scale of time, evolution of skin temperature after moistening, spirit sponging, and olive oil lubrication is investigated. A comparative analysis of the resulting effects of treatments including alpha-hydroxy acid, cosmetic regenerating cream, spirit, and water, is made. Quantitative distinctions between skin regions characterized by ordinary, and depleted blood supply, including areas located directly above surface main vessels, are revealed. Strongly logarithmic time- dependence of a skin temperature is discovered when the skin is cooled down after its preliminary heating with a hot wax. Non-monotonic change of a local temperature during electrically active procedure is described. Low level light therapy equipment is also applied. A special role of the temperature of nose is discussed.

  17. Synthetic protein interactions reveal a functional map of the cell

    PubMed Central

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.13053.001 PMID:27098839

  18. Complex kinetics of DNA condensation revealed through DNA twist tracing.

    PubMed

    Li, Wei; Wong, Wei Juan; Lim, Ci Ji; Ju, Hai-Peng; Li, Ming; Yan, Jie; Wang, Peng-Ye

    2015-08-01

    Toroid formation is an important mechanism for DNA condensation in cells. The length change during DNA condensation was investigated in previous single-molecule experiments. However, DNA twist is key to understanding the topological kinetics of DNA condensation. In this study, DNA twist as well as DNA length was traced during the DNA condensation by the freely orbiting magnetic tweezers and the tilted magnetic tweezers combined with Brownian dynamics simulations. The experimental results disclose the complex relationship between DNA extension and backbone rotation. Brownian dynamics simulations show that the toroid formation follows a wiggling pathway which leads to the complex DNA backbone rotation as revealed in our experiments. These findings provide the complete description of multivalent cation-dependent DNA toroid formation under tension.

  19. Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.

    PubMed

    Drake, Justin M; Paull, Evan O; Graham, Nicholas A; Lee, John K; Smith, Bryan A; Titz, Bjoern; Stoyanova, Tanya; Faltermeier, Claire M; Uzunangelov, Vladislav; Carlin, Daniel E; Fleming, Daniel Teo; Wong, Christopher K; Newton, Yulia; Sudha, Sud; Vashisht, Ajay A; Huang, Jiaoti; Wohlschlegel, James A; Graeber, Thomas G; Witte, Owen N; Stuart, Joshua M

    2016-08-11

    We used clinical tissue from lethal metastatic castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed master transcriptional regulators, functionally mutated genes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network consisting of druggable kinase pathways. Using MSigDB hallmark gene sets, six major signaling pathways with phosphorylation of several key residues were significantly enriched in CRPC tumors after incorporation of phosphoproteomic data. Individual autopsy profiles developed using these hallmarks revealed clinically relevant pathway information potentially suitable for patient stratification and targeted therapies in late stage prostate cancer. Here, we describe phosphorylation-based cancer hallmarks using integrated personalized signatures (pCHIPS) that shed light on the diversity of activated signaling pathways in metastatic CRPC while providing an integrative, pathway-based reference for drug prioritization in individual patients. PMID:27499020

  20. Macrophage characteristics of stem cells revealed by transcriptome profiling

    SciTech Connect

    Charriere, Guillaume M.; Cousin, Beatrice; Arnaud, Emmanuelle; Saillan-Barreau, Corinne; Andre, Mireille; Massoudi, Ali; Dani, Christian; Penicaud, Luc; Casteilla, Louis . E-mail: casteil@toulouse.inserm.fr

    2006-10-15

    We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Using functional analyses and microarray technology, we first tested whether this intriguing relationship was specific to adipocyte progenitors or could be shared with other progenitors. Measurements of phagocytic activity and gene profiling analysis of different progenitor cells revealed that the latter hypothesis should be retained. These results encouraged us to pursue and to confirm our analysis with a gold-standard stem cell population, embryonic stem cells or ESC. The transcriptomic profiles of ESC and macrophages were clustered together, unlike differentiated ESC. In addition, undifferentiated ESC displayed higher phagocytic activity than other progenitors, and they could phagocytoze apoptotic bodies. These data suggest that progenitors and stem cells share some characteristics of macrophages. This opens new perspectives on understanding stem cell phenotype and functionalities such as a putative role of stem cells in tissue remodeling by discarding dead cells but also their immunomodulation or fusion properties.

  1. Topological structure dynamics revealing collective evolution in active nematics

    PubMed Central

    Shi, Xia-qing; Ma, Yu-qiang

    2013-01-01

    Topological defects frequently emerge in active matter like bacterial colonies, cytoskeleton extracts on substrates, self-propelled granular or colloidal layers and so on, but their dynamical properties and the relations to large-scale organization and fluctuations in these active systems are seldom touched. Here we reveal, through a simple model for active nematics using self-driven hard elliptic rods, that the excitation, annihilation and transportation of topological defects differ markedly from those in non-active media. These dynamical processes exhibit strong irreversibility in active nematics in the absence of detailed balance. Moreover, topological defects are the key factors in organizing large-scale dynamic structures and collective flows, resulting in multi-spatial temporal effects. These findings allow us to control the self-organization of active matter through topological structures. PMID:24346733

  2. Insights revealed by rodent models of sugar binge eating.

    PubMed

    Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

    2015-12-01

    Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study.

  3. Pupillometry reveals reduced unconscious emotional reactivity in autism.

    PubMed

    Nuske, Heather J; Vivanti, Giacomo; Hudry, Kristelle; Dissanayake, Cheryl

    2014-09-01

    Recent theoretical conceptualisations have suggested that emotion processing impairments in autism stem from disruption to the sub-cortical, rapid emotion-processing system. We argue that a clear way to ascertain whether this system is affected in autism is by measuring unconscious emotional reactivity. Using backwards masking, we presented fearful expressions non-consciously (subliminally) as well as consciously (supraliminally), and measured pupillary responses as an index of emotional reactivity in 19 children with autism and 19 typically developing children, aged 2-5 years. The pupillary responses of the children with autism revealed reduced unconscious emotional reactivity, with no group differences on consciously presented emotion. Together, these results indicate a hyporesponsiveness to non-consciously presented emotion suggesting a fundamental difference in emotion processing in autism, which requires consciousness and more time. PMID:25017502

  4. Geophysical imaging reveals topographic stress control of bedrock weathering.

    PubMed

    St Clair, J; Moon, S; Holbrook, W S; Perron, J T; Riebe, C S; Martel, S J; Carr, B; Harman, C; Singha, K; Richter, D deB

    2015-10-30

    Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur. PMID:26516279

  5. How actions create--not just reveal--preferences.

    PubMed

    Ariely, Dan; Norton, Michael I

    2008-01-01

    The neo-classical economics view that behavior is driven by - and reflective of - hedonic utility is challenged by psychologists' demonstrations of cases in which actions do not merely reveal preferences but rather create them. In this view, preferences are frequently constructed in the moment and are susceptible to fleeting situational factors; problematically, individuals are insensitive to the impact of such factors on their behavior, misattributing utility caused by these irrelevant factors to stable underlying preferences. Consequently, subsequent behavior might reflect not hedonic utility but rather this erroneously imputed utility that lingers in memory. Here we review the roles of these streams of utility in shaping preferences, and discuss how neuroimaging offers unique possibilities for disentangling their independent contributions to behavior.

  6. Structural characterization of human heparanase reveals insights into substrate recognition

    PubMed Central

    Wu, Liang; Viola, Cristina M.; Brzozowski, Andrzej M.; Davies, Gideon J.

    2016-01-01

    Heparan Sulfate (HS) is a glycosaminoglycan (GAG) which forms a key component of the extracellular matrix (ECM). Breakdown of HS is carried out by heparanase (HPSE), an endo-β-glucuronidase of the glycoside hydrolase (GH)79 family. Overexpression of HPSE is strongly linked to cancer metastases - reflecting breakdown of extracellular HS and release of stored growth factors. Here we present crystal structures of human HPSE at 1.6-1.9 Å resolution reveal how an endo-acting binding cleft is exposed by proteolytic activation of latent proHPSE. Oligosaccharide complexes map the substrate-binding and sulfate recognition motifs. These data shed light on the structure and interactions for a key enzyme involved in ECM maintenance, and provide a starting point for design of HPSE inhibitors as biochemical tools and anti-cancer therapeutics. PMID:26575439

  7. Physical Principles of Skeletal Minerals Revealed with Spectromicroscopy

    ScienceCinema

    Gilbert, Pupa [U of Wisconsin-Madison, Wisconsin, United States

    2016-07-12

    Skeletal elements of marine and terrestrial organisms have the most fascinating nano-to-macro-structures, attracting the attention of physicists, biologists, chemists, and materials scientists. Using X-PEEM spectromicroscopy we revealed some of the fundamental mechanisms leading to the formation of these biominerals. Specifically, we addressed the following questions and provided the answers: 1Q) How do teeth, bones, and echinoderm and mollusk shells acquire their unusual, curved and complex morphology, if they are composed of single crystals? 1A) Via amorphous precursor phases; 2Q) How does crystallinity propagate through the amorophous precursor phases in sea urchin spicules and teeth? 2A) By secondary nucleation, following random walk patterns; 3Q) How does iridescent mother-of-pearl become ordered? 3A) Gradually, through a kinetic mechanisms in which fastest growing single-crystals win the competition for space, thus end up being approximately co-oriented.

  8. ID-Check: Online Concealed Information Test Reveals True Identity.

    PubMed

    Verschuere, Bruno; Kleinberg, Bennett

    2016-01-01

    The Internet has already changed people's lives considerably and is likely to drastically change forensic research. We developed a web-based test to reveal concealed autobiographical information. Initial studies identified a number of conditions that affect diagnostic efficiency. By combining these moderators, this study investigated the full potential of the online ID-check. Participants (n = 101) tried to hide their identity and claimed a false identity in a reaction time-based Concealed Information Test. Half of the participants were presented with personal details (e.g., first name, last name, birthday), whereas the others only saw irrelevant details. Results showed that participants' true identity could be detected with high accuracy (AUC = 0.98; overall accuracy: 86-94%). Online memory detection can reliably and validly detect whether someone is hiding their true identity. This suggests that online memory detection might become a valuable tool for forensic applications. PMID:26390033

  9. The genome of Tetranychus urticae reveals herbivorous pest adaptations

    PubMed Central

    Grbić, Miodrag; Van Leeuwen, Thomas; Clark, Richard M.; Rombauts, Stephane; Rouzé, Pierre; Grbić, Vojislava; Osborne, Edward J.; Dermauw, Wannes; Ngoc, Phuong Cao Thi; Ortego, Félix; Hernández-Crespo, Pedro; Diaz, Isabel; Martinez, Manuel; Navajas, Maria; Sucena, Élio; Magalhães, Sara; Nagy, Lisa; Pace, Ryan M.; Djuranović, Sergej; Smagghe, Guy; Iga, Masatoshi; Christiaens, Olivier; Veenstra, Jan A.; Ewer, John; Villalobos, Rodrigo Mancilla; Hutter, Jeffrey L.; Hudson, Stephen D.; Velez, Marisela; Yi, Soojin V.; Zeng, Jia; Pires-daSilva, Andre; Roch, Fernando; Cazaux, Marc; Navarro, Marie; Zhurov, Vladimir; Acevedo, Gustavo; Bjelica, Anica; Fawcett, Jeffrey A.; Bonnet, Eric; Martens, Cindy; Baele, Guy; Wissler, Lothar; Sanchez-Rodriguez, Aminael; Tirry, Luc; Blais, Catherine; Demeestere, Kristof; Henz, Stefan R.; Gregory, T. Ryan; Mathieu, Johannes; Verdon, Lou; Farinelli, Laurent; Schmutz, Jeremy; Lindquist, Erika; Feyereisen, René; Van de Peer, Yves

    2016-01-01

    The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant–herbivore interactions, and provides unique opportunities for developing novel plant protection strategies. PMID:22113690

  10. Central tolerance to self revealed by the autoimmune regulator.

    PubMed

    Chan, Alice Y; Anderson, Mark S

    2015-11-01

    The autoimmune regulator (Aire) was initially identified as the gene causing multiorgan system autoimmunity in humans, and deletion of this gene in mice also resulted in organ-specific autoimmunity. Aire regulates the expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs), which play a critical role in the negative selection of autoreactive T cells and the generation of regulatory T cells. More recently, the role of Aire in the development of mTECs has helped elucidate its ability to present the spectrum of TSAs needed to prevent autoimmunity. Molecular characterization of the functional domains of Aire has revealed multiple binding partners that assist Aire's function in altering gene transcription and chromatin remodeling. These recent advances have further highlighted the importance of Aire in central tolerance. PMID:26579596

  11. The genome of Tetranychus urticae reveals herbivorous pest adaptations.

    PubMed

    Grbić, Miodrag; Van Leeuwen, Thomas; Clark, Richard M; Rombauts, Stephane; Rouzé, Pierre; Grbić, Vojislava; Osborne, Edward J; Dermauw, Wannes; Ngoc, Phuong Cao Thi; Ortego, Félix; Hernández-Crespo, Pedro; Diaz, Isabel; Martinez, Manuel; Navajas, Maria; Sucena, Élio; Magalhães, Sara; Nagy, Lisa; Pace, Ryan M; Djuranović, Sergej; Smagghe, Guy; Iga, Masatoshi; Christiaens, Olivier; Veenstra, Jan A; Ewer, John; Villalobos, Rodrigo Mancilla; Hutter, Jeffrey L; Hudson, Stephen D; Velez, Marisela; Yi, Soojin V; Zeng, Jia; Pires-daSilva, Andre; Roch, Fernando; Cazaux, Marc; Navarro, Marie; Zhurov, Vladimir; Acevedo, Gustavo; Bjelica, Anica; Fawcett, Jeffrey A; Bonnet, Eric; Martens, Cindy; Baele, Guy; Wissler, Lothar; Sanchez-Rodriguez, Aminael; Tirry, Luc; Blais, Catherine; Demeestere, Kristof; Henz, Stefan R; Gregory, T Ryan; Mathieu, Johannes; Verdon, Lou; Farinelli, Laurent; Schmutz, Jeremy; Lindquist, Erika; Feyereisen, René; Van de Peer, Yves

    2011-11-23

    The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies.

  12. Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

    PubMed Central

    Chen, Rui; Mias, George I.; Li-Pook-Than, Jennifer; Jiang, Lihua; Lam, Hugo Y. K.; Chen, Rong; Miriami, Elana; Karczewski, Konrad J.; Hariharan, Manoj; Dewey, Frederick E.; Cheng, Yong; Clark, Michael J.; Im, Hogune; Habegger, Lukas; Balasubramanian, Suganthi; O'Huallachain, Maeve; Dudley, Joel T.; Hillenmeyer, Sara; Haraksingh, Rajini; Sharon, Donald; Euskirchen, Ghia; Lacroute, Phil; Bettinger, Keith; Boyle, Alan P.; Kasowski, Maya; Grubert, Fabian; Seki, Scott; Garcia, Marco; Whirl-Carrillo, Michelle; Gallardo, Mercedes; Blasco, Maria A.; Greenberg, Peter L.; Snyder, Phyllis; Klein, Teri E.; Altman, Russ B.; Butte, Atul; Ashley, Euan A.; Nadeau, Kari C.; Gerstein, Mark; Tang, Hua; Snyder, Michael

    2012-01-01

    SUMMARY Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here we present an integrative Personal Omics Profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14-month period. Our iPOP analysis revealed various medical risks, including Type II diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high coverage genomic and transcriptomic data, which provide the basis of our iPOP, discovered extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and disease states by connecting genomic information with additional dynamic omics activity. PMID:22424236

  13. MNase titration reveals differences between nucleosome occupancy and chromatin accessibility

    PubMed Central

    Mieczkowski, Jakub; Cook, April; Bowman, Sarah K.; Mueller, Britta; Alver, Burak H.; Kundu, Sharmistha; Deaton, Aimee M.; Urban, Jennifer A.; Larschan, Erica; Park, Peter J.; Kingston, Robert E.; Tolstorukov, Michael Y.

    2016-01-01

    Chromatin accessibility plays a fundamental role in gene regulation. Nucleosome placement, usually measured by quantifying protection of DNA from enzymatic digestion, can regulate accessibility. We introduce a metric that uses micrococcal nuclease (MNase) digestion in a novel manner to measure chromatin accessibility by combining information from several digests of increasing depths. This metric, MACC (MNase accessibility), quantifies the inherent heterogeneity of nucleosome accessibility in which some nucleosomes are seen preferentially at high MNase and some at low MNase. MACC interrogates each genomic locus, measuring both nucleosome location and accessibility in the same assay. MACC can be performed either with or without a histone immunoprecipitation step, and thereby compares histone and non-histone protection. We find that changes in accessibility at enhancers, promoters and other regulatory regions do not correlate with changes in nucleosome occupancy. Moreover, high nucleosome occupancy does not necessarily preclude high accessibility, which reveals novel principles of chromatin regulation. PMID:27151365

  14. Towards revealing the functions of all genes in plants.

    PubMed

    Rhee, Seung Yon; Mutwil, Marek

    2014-04-01

    The great recent progress made in identifying the molecular parts lists of organisms revealed the paucity of our understanding of what most of the parts do. In this review, we introduce computational and statistical approaches and omics data used for inferring gene function in plants, with an emphasis on network-based inference. We also discuss caveats associated with network-based function predictions such as performance assessment, annotation propagation, the guilt-by-association concept, and the meaning of hubs. Finally, we note the current limitations and possible future directions such as the need for gold standard data from several species, unified access to data and tools, quantitative comparison of data and tool quality, and high-throughput experimental validation platforms for systematic gene function elucidation in plants.

  15. Silk protein aggregation kinetics revealed by Rheo-IR.

    PubMed

    Boulet-Audet, Maxime; Terry, Ann E; Vollrath, Fritz; Holland, Chris

    2014-02-01

    The remarkable mechanical properties of silk fibres stem from a multi-scale hierarchical structure created when an aqueous protein "melt" is converted to an insoluble solid via flow. To directly relate a silk protein's structure and function in response to flow, we present the first application of a Rheo-IR platform, which couples cone and plate rheology with attenuated total reflectance infrared spectroscopy. This technique provides a new window into silk processing by linking shear thinning to an increase in molecular alignment, with shear thickening affecting changes in the silk protein's secondary structure. Additionally, compared to other static characterization methods for silk, Rheo-IR proved particularly useful at revealing the intrinsic difference between natural (native) and reconstituted silk feedstocks. Hence Rheo-IR offers important novel insights into natural silk processing. This has intrinsic academic merit, but it might also be useful when designing reconstituted silk analogues alongside other polymeric systems, whether natural or synthetic.

  16. An adaptive perspective on revealed and concealed cues to empathy.

    PubMed

    Ward, Robert; Shingler, Polly

    2016-02-01

    Wu, Sheppard, and Mitchell (Br. J. Psychol., 2016; 107, 1-22) found that observers could accurately identify people with extreme but not more average empathy scores. Here, we further consider this U-shaped discrimination function. We first examine a statistical issue regarding the construction of the average groups, which are less homogenous by definition than the extreme groups. We then consider the kinds of questions arising when these results are considered within the adaptive framework of signal theory. Some interesting questions arise relating to the signal sender, including the costs and benefits to the sender in revealing and concealing true empathy levels, and the effects of adopting behavioural norms to conceal true levels of empathy.

  17. Geophysical imaging reveals topographic stress control of bedrock weathering.

    PubMed

    St Clair, J; Moon, S; Holbrook, W S; Perron, J T; Riebe, C S; Martel, S J; Carr, B; Harman, C; Singha, K; Richter, D deB

    2015-10-30

    Bedrock fracture systems facilitate weathering, allowing fresh mineral surfaces to interact with corrosive waters and biota from Earth's surface, while simultaneously promoting drainage of chemically equilibrated fluids. We show that topographic perturbations to regional stress fields explain bedrock fracture distributions, as revealed by seismic velocity and electrical resistivity surveys from three landscapes. The base of the fracture-rich zone mirrors surface topography where the ratio of horizontal compressive tectonic stresses to near-surface gravitational stresses is relatively large, and it parallels the surface topography where the ratio is relatively small. Three-dimensional stress calculations predict these results, suggesting that tectonic stresses interact with topography to influence bedrock disaggregation, groundwater flow, chemical weathering, and the depth of the "critical zone" in which many biogeochemical processes occur.

  18. Ternary structure reveals mechanism of a membrane diacylglycerol kinase

    SciTech Connect

    Li, Dianfan; Stansfeld, Phillip J.; Sansom, Mark S. P.; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A.; Aragao, David; Fromme, Petra; Fromme, Raimund; Basu, Shibom; Grotjohann, Ingo; Kupitz, Christopher; Rendek, Kimberley; Weierstall, Uwe; Zatsepin, Nadia A.; Cherezov, Vadim; Liu, Wei; Bandaru, Sateesh; English, Niall J.; Gati, Cornelius; Barty, Anton; Yefanov, Oleksandr; Chapman, Henry N.; Diederichs, Kay; Messerschmidt, Marc; Boutet, Sébastien; Williams, Garth J.; Marvin Seibert, M.; Caffrey, Martin

    2015-12-17

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. As a result, the active site architecture shows clear evidence of having arisen by convergent evolution.

  19. High Frequency Monitoring Reveals Aftershocks in Subcritical Crack Growth

    NASA Astrophysics Data System (ADS)

    Stojanova, M.; Santucci, S.; Vanel, L.; Ramos, O.

    2014-03-01

    By combining direct imaging and acoustic emission measurements, the subcritical propagation of a crack in a heterogeneous material is analyzed. Both methods show that the fracture proceeds through a succession of discrete events. However, the macroscopic opening of the fracture captured by the images results from the accumulation of more-elementary events detected by the acoustics. When the acoustic energy is cumulated over large time scales corresponding to the image acquisition rate, a similar statistics is recovered. High frequency acoustic monitoring reveals aftershocks responsible for a time scale dependent exponent of the power law energy distributions. On the contrary, direct imaging, which is unable to resolve these aftershocks, delivers a misleading exponent value.

  20. Anisotropic MRI contrast reveals enhanced ionic transport in plastic crystals.

    PubMed

    Romanenko, Konstantin; Jin, Liyu; Madsen, Louis A; Pringle, Jennifer M; O'Dell, Luke A; Forsyth, Maria

    2014-11-01

    Organic ionic plastic crystals (OIPCs) are attractive as solid-state electrolytes for electrochemical devices such as lithium-ion batteries and solar and fuel cells. OIPCs offer high ionic conductivity, nonflammability, and versatility of molecular design. Nevertheless, intrinsic ion transport behavior of OIPCs is not fully understood, and their measured properties depend heavily on thermal history. Solid-state magnetic resonance imaging experiments reveal a striking image contrast anisotropy sensitive to the orientation of grain boundaries in polycrystalline OIPCs. Probing triethyl(methyl)phosphonium bis(fluorosulfonyl)imide (P1222FSI) samples with different thermal history demonstrates vast variations in microcrystallite alignment. Upon slow cooling from the melt, microcrystallites exhibit a preferred orientation throughout the entire sample, leading to an order of magnitude increase in conductivity as probed using impedance spectroscopy. This investigation describes both a new conceptual window and a new characterization method for understanding polycrystalline domain structure and transport in plastic crystals and other solid-state conductors. PMID:25312993

  1. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2012-02-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions.

  2. Comparative genomics reveals insights into avian genome evolution and adaptation.

    PubMed

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M; Lee, Chul; Storz, Jay F; Antunes, Agostinho; Greenwold, Matthew J; Meredith, Robert W; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S; Gatesy, John; Hoffmann, Federico G; Opazo, Juan C; Håstad, Olle; Sawyer, Roger H; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A; Green, Richard E; O'Brien, Stephen J; Griffin, Darren; Johnson, Warren E; Haussler, David; Ryder, Oliver A; Willerslev, Eske; Graves, Gary R; Alström, Per; Fjeldså, Jon; Mindell, David P; Edwards, Scott V; Braun, Edward L; Rahbek, Carsten; Burt, David W; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D; Gilbert, M Thomas P; Wang, Jun

    2014-12-12

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits. PMID:25504712

  3. Stardust is revealed after a protective canister is removed

    NASA Technical Reports Server (NTRS)

    1999-01-01

    At Launch Pad 17-A, Cape Canaveral Air Station, the Stardust spacecraft is revealed after removal of a protective canister. Stardust is targeted for launch on Feb. 6 aboard a Boeing Delta II rocket. The spacecraft is destined for a close encounter with the comet Wild 2 in January 2004. Using a silicon-based substance called aerogel, Stardust will capture comet particles flying off the nucleus of the comet. The spacecraft also will bring back samples of interstellar dust. These materials consist of ancient pre-solar interstellar grains and other remnants left over from the formation of the solar system. Scientists expect their analysis to provide important insights into the evolution of the sun and planets and possibly into the origin of life itself. The collected samples will return to Earth in a sample return capsule to be jettisoned as Stardust swings by Earth in January 2006.

  4. Structure of mega-hemocyanin reveals protein origami in snails.

    PubMed

    Gatsogiannis, Christos; Hofnagel, Oliver; Markl, Jürgen; Raunser, Stefan

    2015-01-01

    Mega-hemocyanin is a 13.5 MDa oxygen transporter found in the hemolymph of some snails. Similar to typical gastropod hemocyanins, it is composed of 400 kDa building blocks but has additional 550 kDa subunits. Together, they form a large, completely filled cylinder. The structural basis for this highly complex protein packing is not known so far. Here, we report the electron cryomicroscopy (cryo-EM) structure of mega-hemocyanin complexes from two different snail species. The structures reveal that mega-hemocyanin is composed of flexible building blocks that differ in their conformation, but not in their primary structure. Like a protein origami, these flexible blocks are optimally packed, implementing different local symmetries and pseudosymmetries. A comparison between the two structures suggests a surprisingly simple evolutionary mechanism leading to these large oxygen transporters. PMID:25482543

  5. What does physical rotation reveal about mental rotation?

    PubMed

    Gardony, Aaron L; Taylor, Holly A; Brunyé, Tad T

    2014-02-01

    In a classic psychological science experiment, Shepard and Metzler (1971) discovered that the time participants took to judge whether two rotated abstract block figures were identical increased monotonically with the figures' relative angular disparity. They posited that participants rotate mental images to achieve a match and that mental rotation recruits motor processes. This interpretation has become central in the literature, but until now, surprisingly few researchers have compared mental and physical rotation. We had participants rotate virtual Shepard and Metzler figures mentally and physically; response time, accuracy, and real-time rotation data were collected. Results suggest that mental and physical rotation processes overlap and also reveal novel conclusions about physical rotation that have implications for mental rotation. Notably, participants did not rotate figures to achieve a match, but rather until they reached an off-axis canonical difference, and rotational strategies markedly differed for judgments of whether the figures were the same or different.

  6. Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

    PubMed Central

    Ma, Li-Jun; van der Does, H. Charlotte; Borkovich, Katherine A.; Coleman, Jeffrey J.; Daboussi, Marie-Josée; Di Pietro, Antonio; Dufresne, Marie; Freitag, Michael; Grabherr, Manfred; Henrissat, Bernard; Houterman, Petra M.; Kang, Seogchan; Shim, Won-Bo; Woloshuk, Charles; Xie, Xiaohui; Xu, Jin-Rong; Antoniw, John; Baker, Scott E.; Bluhm, Burton H.; Breakspear, Andrew; Brown, Daren W.; Butchko, Robert A. E.; Chapman, Sinead; Coulson, Richard; Coutinho, Pedro M.; Danchin, Etienne G. J.; Diener, Andrew; Gale, Liane R.; Gardiner, Donald M.; Goff, Stephen; Hammond-Kosack, Kim E.; Hilburn, Karen; Hua-Van, Aurélie; Jonkers, Wilfried; Kazan, Kemal; Kodira, Chinnappa D.; Koehrsen, Michael; Kumar, Lokesh; Lee, Yong-Hwan; Li, Liande; Manners, John M.; Miranda-Saavedra, Diego; Mukherjee, Mala; Park, Gyungsoon; Park, Jongsun; Park, Sook-Young; Proctor, Robert H.; Regev, Aviv; Ruiz-Roldan, M. Carmen; Sain, Divya; Sakthikumar, Sharadha; Sykes, Sean; Schwartz, David C.; Turgeon, B. Gillian; Wapinski, Ilan; Yoder, Olen; Young, Sarah; Zeng, Qiandong; Zhou, Shiguo; Galagan, James; Cuomo, Christina A.; Kistler, H. Corby; Rep, Martijn

    2011-01-01

    Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective. PMID:20237561

  7. Physical Principles of Skeletal Minerals Revealed with Spectromicroscopy

    SciTech Connect

    Gilbert, Pupa

    2009-08-05

    Skeletal elements of marine and terrestrial organisms have the most fascinating nano-to-macro-structures, attracting the attention of physicists, biologists, chemists, and materials scientists. Using X-PEEM spectromicroscopy we revealed some of the fundamental mechanisms leading to the formation of these biominerals. Specifically, we addressed the following questions and provided the answers: 1Q) How do teeth, bones, and echinoderm and mollusk shells acquire their unusual, curved and complex morphology, if they are composed of single crystals? 1A) Via amorphous precursor phases; 2Q) How does crystallinity propagate through the amorophous precursor phases in sea urchin spicules and teeth? 2A) By secondary nucleation, following random walk patterns; 3Q) How does iridescent mother-of-pearl become ordered? 3A) Gradually, through a kinetic mechanisms in which fastest growing single-crystals win the competition for space, thus end up being approximately co-oriented.

  8. Inheritance Patterns in Citation Networks Reveal Scientific Memes

    NASA Astrophysics Data System (ADS)

    Kuhn, Tobias; Perc, Matjaž; Helbing, Dirk

    2014-10-01

    Memes are the cultural equivalent of genes that spread across human culture by means of imitation. What makes a meme and what distinguishes it from other forms of information, however, is still poorly understood. Our analysis of memes in the scientific literature reveals that they are governed by a surprisingly simple relationship between frequency of occurrence and the degree to which they propagate along the citation graph. We propose a simple formalization of this pattern and validate it with data from close to 50 million publication records from the Web of Science, PubMed Central, and the American Physical Society. Evaluations relying on human annotators, citation network randomizations, and comparisons with several alternative approaches confirm that our formula is accurate and effective, without a dependence on linguistic or ontological knowledge and without the application of arbitrary thresholds or filters.

  9. Graph analysis of cortical networks reveals complex anatomical communication substrate

    NASA Astrophysics Data System (ADS)

    Zamora-López, Gorka; Zhou, Changsong; Kurths, Jürgen

    2009-03-01

    Sensory information entering the nervous system follows independent paths of processing such that specific features are individually detected. However, sensory perception, awareness, and cognition emerge from the combination of information. Here we have analyzed the corticocortical network of the cat, looking for the anatomical substrate which permits the simultaneous segregation and integration of information in the brain. We find that cortical communications are mainly governed by three topological factors of the underlying network: (i) a large density of connections, (ii) segregation of cortical areas into clusters, and (iii) the presence of highly connected hubs aiding the multisensory processing and integration. Statistical analysis of the shortest paths reveals that, while information is highly accessible to all cortical areas, the complexity of cortical information processing may arise from the rich and intricate alternative paths in which areas can influence each other.

  10. Ternary structure reveals mechanism of a membrane diacylglycerol kinase

    PubMed Central

    Li, Dianfan; Stansfeld, Phillip J.; Sansom, Mark S. P.; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A.; Aragao, David; Fromme, Petra; Fromme, Raimund; Basu, Shibom; Grotjohann, Ingo; Kupitz, Christopher; Rendek, Kimberley; Weierstall, Uwe; Zatsepin, Nadia A.; Cherezov, Vadim; Liu, Wei; Bandaru, Sateesh; English, Niall J.; Gati, Cornelius; Barty, Anton; Yefanov, Oleksandr; Chapman, Henry N.; Diederichs, Kay; Messerschmidt, Marc; Boutet, Sébastien; Williams, Garth J.; Marvin Seibert, M.; Caffrey, Martin

    2015-01-01

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution. PMID:26673816

  11. Stochastic heart-rate model can reveal pathologic cardiac dynamics

    NASA Astrophysics Data System (ADS)

    Kuusela, Tom

    2004-03-01

    A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

  12. Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

    PubMed

    Bougher, S; Jakosky, B; Halekas, J; Grebowsky, J; Luhmann, J; Mahaffy, P; Connerney, J; Eparvier, F; Ergun, R; Larson, D; McFadden, J; Mitchell, D; Schneider, N; Zurek, R; Mazelle, C; Andersson, L; Andrews, D; Baird, D; Baker, D N; Bell, J M; Benna, M; Brain, D; Chaffin, M; Chamberlin, P; Chaufray, J-Y; Clarke, J; Collinson, G; Combi, M; Crary, F; Cravens, T; Crismani, M; Curry, S; Curtis, D; Deighan, J; Delory, G; Dewey, R; DiBraccio, G; Dong, C; Dong, Y; Dunn, P; Elrod, M; England, S; Eriksson, A; Espley, J; Evans, S; Fang, X; Fillingim, M; Fortier, K; Fowler, C M; Fox, J; Gröller, H; Guzewich, S; Hara, T; Harada, Y; Holsclaw, G; Jain, S K; Jolitz, R; Leblanc, F; Lee, C O; Lee, Y; Lefevre, F; Lillis, R; Livi, R; Lo, D; Ma, Y; Mayyasi, M; McClintock, W; McEnulty, T; Modolo, R; Montmessin, F; Morooka, M; Nagy, A; Olsen, K; Peterson, W; Rahmati, A; Ruhunusiri, S; Russell, C T; Sakai, S; Sauvaud, J-A; Seki, K; Steckiewicz, M; Stevens, M; Stewart, A I F; Stiepen, A; Stone, S; Tenishev, V; Thiemann, E; Tolson, R; Toublanc, D; Vogt, M; Weber, T; Withers, P; Woods, T; Yelle, R

    2015-11-01

    The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability.

  13. Proteomic profiling reveals insights into Triticeae stigma development and function.

    PubMed

    Nazemof, Nazila; Couroux, Philippe; Rampitsch, Christof; Xing, Tim; Robert, Laurian S

    2014-11-01

    To our knowledge, this study represents the first high-throughput characterization of a stigma proteome in the Triticeae. A total of 2184 triticale mature stigma proteins were identified using three different gel-based approaches combined with mass spectrometry. The great majority of these proteins are described in a Triticeae stigma for the first time. These results revealed many proteins likely to play important roles in stigma development and pollen-stigma interactions, as well as protection against biotic and abiotic stresses. Quantitative comparison of the triticale stigma transcriptome and proteome showed poor correlation, highlighting the importance of having both types of analysis. This work makes a significant contribution towards the elucidation of the Triticeae stigma proteome and provides novel insights into its role in stigma development and function. PMID:25170101

  14. Insights revealed by rodent models of sugar binge eating.

    PubMed

    Murray, Susan M; Tulloch, Alastair J; Chen, Eunice Y; Avena, Nicole M

    2015-12-01

    Binge eating is seen across the spectrum of eating disorder diagnoses as well as among individuals who do not meet diagnostic criteria. Analyses of the specific types of foods that are frequently binged upon reveal that sugar-rich items feature prominently in binge-type meals, making the effects of binge consumption of sugar an important focus of study. One avenue to do this involves the use of animal models. Foundational and recent studies of animal models of sugar bingeing, both outlined here, lend insight into the various neurotransmitters and neuropeptides that may participate in or be altered by this behavior. Further, several preclinical studies incorporating sugar bingeing paradigms have explored the utility of pharmacological agents that target such neural systems for reducing sugar bingeing in an effort to enhance clinical treatment. Indeed, the translational implications of findings generated using animal models of sugar bingeing are considered here, along with potential avenues for further study. PMID:26510689

  15. Deciphering CAPTCHAs: what a Turing test reveals about human cognition.

    PubMed

    Hannagan, Thomas; Ktori, Maria; Chanceaux, Myriam; Grainger, Jonathan

    2012-01-01

    Turning Turing's logic on its head, we used widespread letter-based Turing Tests found on the internet (CAPTCHAs) to shed light on human cognition. We examined the basis of the human ability to solve CAPTCHAs, where machines fail. We asked whether this is due to our use of slow-acting inferential processes that would not be available to machines, or whether fast-acting automatic orthographic processing in humans has superior robustness to shape variations. A masked priming lexical decision experiment revealed efficient processing of CAPTCHA words in conditions that rule out the use of slow inferential processing. This shows that the human superiority in solving CAPTCHAs builds on a high degree of invariance to location and continuous transforms, which is achieved during the very early stages of visual word recognition in skilled readers.

  16. Dramatic changes in electronic structure revealed by fractionally charged nuclei

    SciTech Connect

    Cohen, Aron J.; Mori-Sánchez, Paula

    2014-01-28

    Discontinuous changes in the electronic structure upon infinitesimal changes to the Hamiltonian are demonstrated. These are revealed in one and two electron molecular systems by full configuration interaction (FCI) calculations when the realm of the nuclear charge is extended to be fractional. FCI electron densities in these systems show dramatic changes in real space and illustrate the transfer, hopping, and removal of electrons. This is due to the particle nature of electrons seen in stretched systems and is a manifestation of an energy derivative discontinuity at constant number of electrons. Dramatic errors of density functional theory densities are seen in real space as this physics is missing from currently used approximations. The movements of electrons in these simple systems encapsulate those in real physical processes, from chemical reactions to electron transport and pose a great challenge for the development of new electronic structure methods.

  17. Revealing the superior perceptibility of words in Arabic.

    PubMed

    Jordan, Timothy R; Paterson, Kevin B; Almabruk, Abubaker A A

    2010-01-01

    When alphabetic stimuli are presented very briefly, people perceive real words better than nonwords. It is generally accepted that this word superiority effect reflects the efficiency of visual word perception. However, much of what is known about this effect comes from research conducted in languages using the Latin alphabet (eg English, French, Italian), and little is known about whether alphabetic languages with visual properties fundamentally different from Latinate languages also produce word superiority effects. We report an experiment in which stimuli (words, illegal nonwords, and pseudowords) were presented in Arabic, which is a cursive script, read from right to left. The findings revealed advantages for words over pseudowords and illegal nonwords, and for pseudowords over illegal nonwords, indicating that the superiority effects reported for Latinate languages are also observed in Arabic. Implications of these findings for understanding the processes involved in word recognition are discussed. PMID:20465177

  18. Freshwater foraminiferans revealed by analysis of environmental DNA samples.

    PubMed

    Holzmann, Maria; Habura, Andrea; Giles, Hannah; Bowser, Samuel S; Pawlowski, Jan

    2003-01-01

    Sediment-dwelling protists are among the most abundant meiobenthic organisms, ubiquitous in all types of aquatic ecosystems. Yet, because their isolation and identification are difficult, their diversity remains largely unknown. In the present work, we applied molecular methods to examine the diversity of freshwater Foraminifera, a group of granuloreticulosan protists largely neglected until now. By using specific PCR primers, we detected the presence of Foraminifera in all sediment samples examined. Phylogenetic analysis of amplified SSU rDNA sequences revealed two distinct groups of freshwater foraminiferans. All obtained sequences branched within monothalamous (single-chambered), marine Foraminifera, suggesting a repeated colonization of freshwater environments. The results of our study challenge the traditional view of Foraminifera as essentially marine organisms, and provide a conceptual framework for charting the molecular diversity of freshwater granuloreticulosan protists.

  19. Revealing the Genetic Basis of Natural Bacterial Phenotypic Divergence

    PubMed Central

    Freddolino, Peter L.; Goodarzi, Hani

    2014-01-01

    Divergent phenotypes for distantly related strains of bacteria, such as differing antibiotic resistances or organic solvent tolerances, are of keen interest both from an evolutionary perspective and for the engineering of novel microbial organisms and consortia in synthetic biology applications. A prerequisite for any practical application of this phenotypic diversity is knowledge of the genetic determinants for each trait of interest. Sequence divergence between strains is often so extensive as to make brute-force approaches to identifying the loci contributing to a given trait impractical. Here we describe a global linkage analysis approach, GLINT, for rapid discovery of the causal genetic variants underlying phenotypic divergence between distantly related strains of Escherichia coli. This general strategy will also be usable, with minor modifications, for revealing genotype-phenotype associations between naturally occurring strains of other bacterial species. PMID:24317396

  20. Collagenous gastritis revealed by severe anemia in a child.

    PubMed

    Côté, J F; Hankard, G F; Faure, C; Mougenot, J F; Holvoet, L; Cézard, J P; Navarro, J; Peuchmaur, M

    1998-08-01

    Collagenous gastritis is a rare histopathological disorder of unknown origin, characterized by a subepithelial collagen deposit greater than 10 microm thick, associated with an inflammatory infiltrate of the gastric mucosa. This report describes a second pediatric case of collagenous gastritis, revealed by severe anemia caused by gastric bleeding, as was the first case. Unlike the adult cases of collagenous gastritis, lesions were limited to the stomach, and remained unchanged on six series of biopsies taken during a 30 month follow-up, despite treatment with omeprazole, sucralfate and corticosteroids. An immunohistochemical study showed signs of local immune activation on all biopsy specimens, including overexpression of HLA-DR by epithelial cells, increased numbers of CD3+ intraepithelial lymphocytes, and CD25+ cells in the lamina propria. Although the cause of the disease remains unclear, our findings suggest that the histopathological lesions of collagenous gastritis may result from a local immune process. PMID:9712433

  1. Ternary structure reveals mechanism of a membrane diacylglycerol kinase.

    PubMed

    Li, Dianfan; Stansfeld, Phillip J; Sansom, Mark S P; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A; Aragao, David; Fromme, Petra; Fromme, Raimund; Basu, Shibom; Grotjohann, Ingo; Kupitz, Christopher; Rendek, Kimberley; Weierstall, Uwe; Zatsepin, Nadia A; Cherezov, Vadim; Liu, Wei; Bandaru, Sateesh; English, Niall J; Gati, Cornelius; Barty, Anton; Yefanov, Oleksandr; Chapman, Henry N; Diederichs, Kay; Messerschmidt, Marc; Boutet, Sébastien; Williams, Garth J; Marvin Seibert, M; Caffrey, Martin

    2015-12-17

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.

  2. ID-Check: Online Concealed Information Test Reveals True Identity.

    PubMed

    Verschuere, Bruno; Kleinberg, Bennett

    2016-01-01

    The Internet has already changed people's lives considerably and is likely to drastically change forensic research. We developed a web-based test to reveal concealed autobiographical information. Initial studies identified a number of conditions that affect diagnostic efficiency. By combining these moderators, this study investigated the full potential of the online ID-check. Participants (n = 101) tried to hide their identity and claimed a false identity in a reaction time-based Concealed Information Test. Half of the participants were presented with personal details (e.g., first name, last name, birthday), whereas the others only saw irrelevant details. Results showed that participants' true identity could be detected with high accuracy (AUC = 0.98; overall accuracy: 86-94%). Online memory detection can reliably and validly detect whether someone is hiding their true identity. This suggests that online memory detection might become a valuable tool for forensic applications.

  3. Early MAVEN Deep Dip campaign reveals thermosphere and ionosphere variability.

    PubMed

    Bougher, S; Jakosky, B; Halekas, J; Grebowsky, J; Luhmann, J; Mahaffy, P; Connerney, J; Eparvier, F; Ergun, R; Larson, D; McFadden, J; Mitchell, D; Schneider, N; Zurek, R; Mazelle, C; Andersson, L; Andrews, D; Baird, D; Baker, D N; Bell, J M; Benna, M; Brain, D; Chaffin, M; Chamberlin, P; Chaufray, J-Y; Clarke, J; Collinson, G; Combi, M; Crary, F; Cravens, T; Crismani, M; Curry, S; Curtis, D; Deighan, J; Delory, G; Dewey, R; DiBraccio, G; Dong, C; Dong, Y; Dunn, P; Elrod, M; England, S; Eriksson, A; Espley, J; Evans, S; Fang, X; Fillingim, M; Fortier, K; Fowler, C M; Fox, J; Gröller, H; Guzewich, S; Hara, T; Harada, Y; Holsclaw, G; Jain, S K; Jolitz, R; Leblanc, F; Lee, C O; Lee, Y; Lefevre, F; Lillis, R; Livi, R; Lo, D; Ma, Y; Mayyasi, M; McClintock, W; McEnulty, T; Modolo, R; Montmessin, F; Morooka, M; Nagy, A; Olsen, K; Peterson, W; Rahmati, A; Ruhunusiri, S; Russell, C T; Sakai, S; Sauvaud, J-A; Seki, K; Steckiewicz, M; Stevens, M; Stewart, A I F; Stiepen, A; Stone, S; Tenishev, V; Thiemann, E; Tolson, R; Toublanc, D; Vogt, M; Weber, T; Withers, P; Woods, T; Yelle, R

    2015-11-01

    The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability. PMID:26542579

  4. Ternary structure reveals mechanism of a membrane diacylglycerol kinase

    NASA Astrophysics Data System (ADS)

    Li, Dianfan; Stansfeld, Phillip J.; Sansom, Mark S. P.; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A.; Aragao, David; Fromme, Petra; Fromme, Raimund; Basu, Shibom; Grotjohann, Ingo; Kupitz, Christopher; Rendek, Kimberley; Weierstall, Uwe; Zatsepin, Nadia A.; Cherezov, Vadim; Liu, Wei; Bandaru, Sateesh; English, Niall J.; Gati, Cornelius; Barty, Anton; Yefanov, Oleksandr; Chapman, Henry N.; Diederichs, Kay; Messerschmidt, Marc; Boutet, Sébastien; Williams, Garth J.; Marvin Seibert, M.; Caffrey, Martin

    2015-12-01

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.

  5. Comparative genomics reveals insights into avian genome evolution and adaptation.

    PubMed

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M; Lee, Chul; Storz, Jay F; Antunes, Agostinho; Greenwold, Matthew J; Meredith, Robert W; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S; Gatesy, John; Hoffmann, Federico G; Opazo, Juan C; Håstad, Olle; Sawyer, Roger H; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A; Green, Richard E; O'Brien, Stephen J; Griffin, Darren; Johnson, Warren E; Haussler, David; Ryder, Oliver A; Willerslev, Eske; Graves, Gary R; Alström, Per; Fjeldså, Jon; Mindell, David P; Edwards, Scott V; Braun, Edward L; Rahbek, Carsten; Burt, David W; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D; Gilbert, M Thomas P; Wang, Jun

    2014-12-12

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.

  6. Drought-Responsive Mechanisms in Plant Leaves Revealed by Proteomics

    PubMed Central

    Wang, Xiaoli; Cai, Xiaofeng; Xu, Chenxi; Wang, Quanhua; Dai, Shaojun

    2016-01-01

    Plant drought tolerance is a complex trait that requires a global view to understand its underlying mechanism. The proteomic aspects of plant drought response have been extensively investigated in model plants, crops and wood plants. In this review, we summarize recent proteomic studies on drought response in leaves to reveal the common and specialized drought-responsive mechanisms in different plants. Although drought-responsive proteins exhibit various patterns depending on plant species, genotypes and stress intensity, proteomic analyses show that dominant changes occurred in sensing and signal transduction, reactive oxygen species scavenging, osmotic regulation, gene expression, protein synthesis/turnover, cell structure modulation, as well as carbohydrate and energy metabolism. In combination with physiological and molecular results, proteomic studies in leaves have helped to discover some potential proteins and/or metabolic pathways for drought tolerance. These findings provide new clues for understanding the molecular basis of plant drought tolerance. PMID:27763546

  7. Comparative genomics reveals insights into avian genome evolution and adaptation

    PubMed Central

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M.; Lee, Chul; Storz, Jay F.; Antunes, Agostinho; Greenwold, Matthew J.; Meredith, Robert W.; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R.; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T.; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V.; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S.; Gatesy, John; Hoffmann, Federico G.; Opazo, Juan C.; Håstad, Olle; Sawyer, Roger H.; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W.; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F.; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A.; Green, Richard E.; O’Brien, Stephen J.; Griffin, Darren; Johnson, Warren E.; Haussler, David; Ryder, Oliver A.; Willerslev, Eske; Graves, Gary R.; Alström, Per; Fjeldså, Jon; Mindell, David P.; Edwards, Scott V.; Braun, Edward L.; Rahbek, Carsten; Burt, David W.; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D.; Gilbert, M. Thomas P.; Wang, Jun

    2015-01-01

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits. PMID:25504712

  8. Coupled nucleotide covariations reveal dynamic RNA interaction patterns.

    PubMed Central

    Gultyaev, A P; Franch, T; Gerdes, K

    2000-01-01

    Evolutionarily conserved structures in related RNA molecules contain coordinated variations (covariations) of paired nucleotides. Analysis of covariations is a very powerful approach to deduce phylogenetically conserved (i.e., functional) conformations, including tertiary interactions. Here we discuss conserved RNA folding pathways that are revealed by covariation patterns. In such pathways, structural requirements for alternative pairings cause some nucleotides to covary with two different partners. Such "coupled" covariations between three or more nucleotides were found in various types of RNAs. The analysis of coupled covariations can unravel important features of RNA folding dynamics and improve phylogeny reconstruction in some cases. Importantly, it is necessary to distinguish between multiple covariations determined by mutually exclusive structures and those determined by tertiary contacts. PMID:11105748

  9. Ternary structure reveals mechanism of a membrane diacylglycerol kinase.

    PubMed

    Li, Dianfan; Stansfeld, Phillip J; Sansom, Mark S P; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A; Aragao, David; Fromme, Petra; Fromme, Raimund; Basu, Shibom; Grotjohann, Ingo; Kupitz, Christopher; Rendek, Kimberley; Weierstall, Uwe; Zatsepin, Nadia A; Cherezov, Vadim; Liu, Wei; Bandaru, Sateesh; English, Niall J; Gati, Cornelius; Barty, Anton; Yefanov, Oleksandr; Chapman, Henry N; Diederichs, Kay; Messerschmidt, Marc; Boutet, Sébastien; Williams, Garth J; Marvin Seibert, M; Caffrey, Martin

    2015-01-01

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution. PMID:26673816

  10. An alternative RNA polymerase I structure reveals a dimer hinge.

    PubMed

    Kostrewa, Dirk; Kuhn, Claus-D; Engel, Christoph; Cramer, Patrick

    2015-09-01

    RNA polymerase I (Pol I) is the central, 14-subunit enzyme that synthesizes the ribosomal RNA (rRNA) precursor in eukaryotic cells. The recent crystal structure of Pol I at 2.8 Å resolution revealed two novel elements: the `expander' in the active-centre cleft and the `connector' that mediates Pol I dimerization [Engel et al. (2013), Nature (London), 502, 650-655]. Here, a Pol I structure in an alternative crystal form that was solved by molecular replacement using the original atomic Pol I structure is reported. The resulting alternative structure lacks the expander but still shows an expanded active-centre cleft. The neighbouring Pol I monomers form a homodimer with a relative orientation distinct from that observed previously, establishing the connector as a hinge between Pol I monomers.

  11. Hybridization Reveals the Evolving Genomic Architecture of Speciation

    PubMed Central

    Kronforst, Marcus R.; Hansen, Matthew E.B.; Crawford, Nicholas G.; Gallant, Jason R.; Zhang, Wei; Kulathinal, Rob J.; Kapan, Durrell D.; Mullen, Sean P.

    2014-01-01

    SUMMARY The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, we compare full genome sequences of 32 butterflies, representing five species from a hybridizing Heliconius butterfly community, to examine genome-wide patterns of introgression and infer how divergence evolves during the speciation process. Our analyses reveal that initial divergence is restricted to a small fraction of the genome, largely clustered around known wing-patterning genes. Over time, divergence evolves rapidly, due primarily to the origin of new divergent regions. Furthermore, divergent genomic regions display signatures of both selection and adaptive introgression, demonstrating the link between microevolutionary processes acting within species and the origin of species across macroevolutionary timescales. Our results provide a uniquely comprehensive portrait of the evolving species boundary due to the role that hybridization plays in reducing the background accumulation of divergence at neutral sites. PMID:24183670

  12. Four not six: Revealing culturally common facial expressions of emotion.

    PubMed

    Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

    2016-06-01

    As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record PMID:27077757

  13. Ethiopian population dermatoglyphic study reveals linguistic stratification of diversity.

    PubMed

    Yohannes, Seile; Bekele, Endashaw

    2015-01-01

    The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund's variance, Nei's measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei's standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01), the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144), and the Nilo-Saharan origin of the Berta group (PII= 10.66) are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub-divided populations and

  14. Four not six: Revealing culturally common facial expressions of emotion.

    PubMed

    Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

    2016-06-01

    As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record

  15. Next Generation Sequencing Reveals the Hidden Diversity of Zooplankton Assemblages

    PubMed Central

    Harmer, Rachel A.; Somerfield, Paul J.; Atkinson, Angus

    2013-01-01

    Background Zooplankton play an important role in our oceans, in biogeochemical cycling and providing a food source for commercially important fish larvae. However, difficulties in correctly identifying zooplankton hinder our understanding of their roles in marine ecosystem functioning, and can prevent detection of long term changes in their community structure. The advent of massively parallel next generation sequencing technology allows DNA sequence data to be recovered directly from whole community samples. Here we assess the ability of such sequencing to quantify richness and diversity of a mixed zooplankton assemblage from a productive time series site in the Western English Channel. Methodology/Principle Findings Plankton net hauls (200 µm) were taken at the Western Channel Observatory station L4 in September 2010 and January 2011. These samples were analysed by microscopy and metagenetic analysis of the 18S nuclear small subunit ribosomal RNA gene using the 454 pyrosequencing platform. Following quality control a total of 419,041 sequences were obtained for all samples. The sequences clustered into 205 operational taxonomic units using a 97% similarity cut-off. Allocation of taxonomy by comparison with the National Centre for Biotechnology Information database identified 135 OTUs to species level, 11 to genus level and 1 to order, <2.5% of sequences were classified as unknowns. By comparison a skilled microscopic analyst was able to routinely enumerate only 58 taxonomic groups. Conclusions Metagenetics reveals a previously hidden taxonomic richness, especially for Copepoda and hard-to-identify meroplankton such as Bivalvia, Gastropoda and Polychaeta. It also reveals rare species and parasites. We conclude that Next Generation Sequencing of 18S amplicons is a powerful tool for elucidating the true diversity and species richness of zooplankton communities. While this approach allows for broad diversity assessments of plankton it may become increasingly

  16. Running over rough terrain reveals limb control for intrinsic stability

    PubMed Central

    Daley, Monica A.; Biewener, Andrew A.

    2006-01-01

    Legged animals routinely negotiate rough, unpredictable terrain with agility and stability that outmatches any human-built machine. Yet, we know surprisingly little about how animals accomplish this. Current knowledge is largely limited to studies of steady movement. These studies have revealed fundamental mechanisms used by terrestrial animals for steady locomotion. However, it is unclear whether these models provide an appropriate framework for the neuromuscular and mechanical strategies used to achieve dynamic stability over rough terrain. Perturbation experiments shed light on this issue, revealing the interplay between mechanics and neuromuscular control. We measured limb mechanics of helmeted guinea fowl (Numida meleagris) running over an unexpected drop in terrain, comparing their response to predictions of the mass–spring running model. Adjustment of limb contact angle explains 80% of the variation in stance-phase limb loading following the perturbation. Surprisingly, although limb stiffness varies dramatically, it does not influence the response. This result agrees with a mass–spring model, although it differs from previous findings on humans running over surfaces of varying compliance. However, guinea fowl sometimes deviate from mass–spring dynamics through posture-dependent work performance of the limb, leading to substantial energy absorption following the perturbation. This posture-dependent actuation allows the animal to absorb energy and maintain desired velocity on a sudden substrate drop. Thus, posture-dependent work performance of the limb provides inherent velocity control over rough terrain. These findings highlight how simple mechanical models extend to unsteady conditions, providing fundamental insights into neuromuscular control of movement and the design of dynamically stable legged robots and prosthetic devices. PMID:17032779

  17. Subfield profitability analysis reveals an economic case for cropland diversification

    NASA Astrophysics Data System (ADS)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (<2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  18. Ethiopian Population Dermatoglyphic Study Reveals Linguistic Stratification of Diversity

    PubMed Central

    2015-01-01

    The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund’s variance, Nei’s measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei’s standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01), the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144), and the Nilo-Saharan origin of the Berta group (PII= 10.66) are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub

  19. Ethiopian population dermatoglyphic study reveals linguistic stratification of diversity.

    PubMed

    Yohannes, Seile; Bekele, Endashaw

    2015-01-01

    The manifestation of ethnic, blood type, & gender-wise population variations regarding Dermatoglyphic manifestations are of interest to assess intra-group diversity and differentiation. The present study reports on the analysis of qualitaive and quantitative finger Dermatoglyphic traits of 382 individuals cross-sectionally sampled from an administrative region of Ethiopia, consisting of five ethnic cohorts from the Afro-Asiatic & Nilo-Saharan affiliations. These Dermatoglyphic parameters were then applied in the assessment of diversity & differentiation, including Heterozygosity, Fixation, Panmixia, Wahlund's variance, Nei's measure of genetic diversity, and thumb & finger pattern genotypes, which were inturn used in homology inferences as summarized by a Neighbour-Joining tree constructed from Nei's standard genetic distance. Results revealed significant correlation between Dermatoglyphics & population parameters that were further found to be in concordance with the historical accounts of the ethnic groups. Such inductions as the ancient north-eastern presence and subsequent admixure events of the Oromos (PII= 15.01), the high diversity of the Amharas (H= 0.1978, F= 0.6453, and P= 0.4144), and the Nilo-Saharan origin of the Berta group (PII= 10.66) are evidences to this. The study has further tested the possibility of applying Dermatoglyphics in population genetic & anthropologic research, highlighting on the prospect of developing a method to trace back population origins & ancient movement patterns. Additionally, linguistic clustering was deemed significant for the Ethiopian population, coinciding with recent genome wide studies that have ascertained that linguistic clustering as to being more crucial than the geographical patterning in the Ethiopian context. Finally, Dermatoglyphic markers have been proven to be endowed with a strong potential as non-invasive preliminary tools applicable prior to genetic studies to analyze ethnically sub-divided populations and

  20. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    PubMed Central

    2011-01-01

    Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate). The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose phosphates in cytosol. In contrast

  1. Mineralization of developing mouse calvaria as revealed by Raman microspectroscopy.

    PubMed

    Tarnowski, Catherine P; Ignelzi, Michael A; Morris, Michael D

    2002-06-01

    Raman microspectroscopy is a nondestructive vibrational spectroscopic technique that permits the study of organic and mineral species at micron resolution, offers the ability to work with hydrated and dehydrated specimens in vivo or in vitro, and requires minimal specimen preparation. We used Raman microspectroscopy to determine the composition of the mineral environments present in mouse calvaria, the flat bones that comprise the top of the skull. We have acquired Raman transects (lines of point spectra) from mouse calvaria during a developmental time course ranging from embryonic day 13.5 (E13.5; 6 days before birth) to 6 months of age. Exploratory factor analysis (FA) reveals the presence of a variety of apatitic mineral environments throughout the tissue series. The earliest mineral is observed in the fetal day 15.5 (F15.5) mice and is identified as a carbonated apatite. The presence of a heterogeneous mineralized tissue in the postnatal specimens suggests that ionic incorporation and crystal perfection in the lattice yary as the mouse develops. This variation is indicative of the presence of both recently deposited mineral and more matured remodeled mineral. Band area ratios reveal that the mineral/matrix ratio initially increases, reaches a plateau, and then increases again. The carbonate/phosphate band area ratio remains constant from F18.5 to postnatal day 3 (PN3) and then increases with age. Insights into the chemical species, the degree of mineralization, and the multiple mineral environments that are present in normal calvarial tissue will enable us to better understand both normal and abnormal mineralization processes.

  2. Antibody protection reveals extended epitopes on the human TSH receptor.

    PubMed

    Latif, Rauf; Teixeira, Avelino; Michalek, Krzysztof; Ali, M Rejwan; Schlesinger, Max; Baliram, Ramkumarie; Morshed, Syed A; Davies, Terry F

    2012-01-01

    Stimulating, and some blocking, antibodies to the TSH receptor (TSHR) have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD). However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs) have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity. PMID:22957097

  3. Astronomers Reveal Extinct Extra-Terrestrial Fusion Reactor

    NASA Astrophysics Data System (ADS)

    2004-06-01

    An international team of astronomers, studying the left-over remnants of stars like our own Sun, have found a remarkable object where the nuclear reactor that once powered it has only just shut down. This star, the hottest known white dwarf, H1504+65, seems to have been stripped of its entire outer regions during its death throes leaving behind the core that formed its power plant. Scientists from the United Kingdom, Germany and the USA focused two of NASA's space telescopes, the Chandra X-ray Observatory and the Far Ultraviolet Spectroscopic Explorer (FUSE), onto H1504+65 to probe its composition and measure its temperature. The data revealed that the stellar surface is extremely hot, 200,000 degrees, and is virtually free of hydrogen and helium, something never before observed in any star. Instead, the surface is composed mainly of carbon and oxygen, the 'ashes' of the fusion of helium in a nuclear reactor. An important question we must answer is why has this unique star lost the hydrogen and helium, which usually hide the stellar interior from our view? Professor Martin Barstow (University of Leicester) said. 'Studying the nature of the ashes of dead stars give us important clues as to how stars like the Sun live their lives and eventually die. The nuclear waste of carbon and oxygen produced in the process are essential elements for life and are eventually recycled into interstellar space to form new stars, planets and, possibly, living beings.' Professor Klaus Werner (University of Tübingen) said. 'We realized that this star has, on astronomical time scales, only very recently shut down nuclear fusion (about a hundred years ago). We clearly see the bare, now extinct reactor that once powered a bright giant star.' Dr Jeffrey Kruk (Johns Hopkins University) said: 'Astronomers have long predicted that many stars would have carbon-oxygen cores near the end of their lives, but I never expected we would actually be able to see one. This is a wonderful opportunity to

  4. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans.

    PubMed

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E; Metspalu, Mait; Albrechtsen, Anders; Moltke, Ida; Rasmussen, Simon; Stafford, Thomas W; Orlando, Ludovic; Metspalu, Ene; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Mägi, Reedik; Campos, Paula F; Balanovska, Elena; Balanovsky, Oleg; Khusnutdinova, Elza; Litvinov, Sergey; Osipova, Ludmila P; Fedorova, Sardana A; Voevoda, Mikhail I; DeGiorgio, Michael; Sicheritz-Ponten, Thomas; Brunak, Søren; Demeshchenko, Svetlana; Kivisild, Toomas; Villems, Richard; Nielsen, Rasmus; Jakobsson, Mattias; Willerslev, Eske

    2014-01-01

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native

  5. HUBBLE REVEALS THE HEART OF THE WHIRLPOOL GALAXY

    NASA Technical Reports Server (NTRS)

    2002-01-01

    New images from NASA's Hubble Space Telescope are helping researchers view in unprecedented detail the spiral arms and dust clouds of a nearby galaxy, which are the birth sites of massive and luminous stars. The Whirlpool galaxy, M51, has been one of the most photogenic galaxies in amateur and professional astronomy. Easily photographed and viewed by smaller telescopes, this celestial beauty is studied extensively in a range of wavelengths by large ground- and space-based observatories. This Hubble composite image shows visible starlight as well as light from the emission of glowing hydrogen, which is associated with the most luminous young stars in the spiral arms. M51, also known as NGC 5194, is having a close encounter with a nearby companion galaxy, NGC 5195, just off the upper edge of this image. The companion's gravitational pull is triggering star formation in the main galaxy, as seen in brilliant detail by numerous, luminous clusters of young and energetic stars. The bright clusters are highlighted in red by their associated emission from glowing hydrogen gas. This Wide Field Planetary Camera 2 image enables a research group, led by Nick Scoville (Caltech), to clearly define the structure of both the cold dust clouds and the hot hydrogen and link individual clusters to their parent dust clouds. Team members include M. Polletta (U. Geneva); S. Ewald and S. Stolovy (Caltech); R. Thompson and M. Rieke (U. of Arizona). Intricate structure is also seen for the first time in the dust clouds. Along the spiral arms, dust 'spurs' are seen branching out almost perpendicular to the main spiral arms. The regularity and large number of these features suggests to astronomers that previous models of 'two-arm' spiral galaxies may need to be revisited. The new images also reveal a dust disk in the nucleus, which may provide fuel for a nuclear black hole. The team is also studying this galaxy at near-infrared wavelengths with the NICMOS instrument onboard Hubble. At these

  6. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans.

    PubMed

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E; Metspalu, Mait; Albrechtsen, Anders; Moltke, Ida; Rasmussen, Simon; Stafford, Thomas W; Orlando, Ludovic; Metspalu, Ene; Karmin, Monika; Tambets, Kristiina; Rootsi, Siiri; Mägi, Reedik; Campos, Paula F; Balanovska, Elena; Balanovsky, Oleg; Khusnutdinova, Elza; Litvinov, Sergey; Osipova, Ludmila P; Fedorova, Sardana A; Voevoda, Mikhail I; DeGiorgio, Michael; Sicheritz-Ponten, Thomas; Brunak, Søren; Demeshchenko, Svetlana; Kivisild, Toomas; Villems, Richard; Nielsen, Rasmus; Jakobsson, Mattias; Willerslev, Eske

    2014-01-01

    The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native

  7. Diagnostic phylogenetics reveals a new Porcine circovirus 2 cluster.

    PubMed

    Davies, Brendan; Wang, Xiong; Dvorak, Cheryl M T; Marthaler, Douglas; Murtaugh, Michael P

    2016-06-01

    Porcine circovirus 2 (PCV2) was prevalent in swine in the United States before PCV2-associated disease (PCVAD) appeared in 2006. Limited nucleotide sequencing of open reading frame 2 (ORF2) encoding capsid, the only structural protein, revealed the presence of two genotypes, PCV2a and PCV2b. Later, PCV2c and mutant PCV2b, or PCV2d, were also described. However, extensive PCV2 ORF2 sequence databases in veterinary diagnostic laboratories have not been analyzed systematically to determine the genetic diversity of field isolates. Here, we interrogated >1100 PCV2 ORF2 nucleotide sequences to assess population diversity and genetic variation. We detected a novel PCV2 genotype that is substantially different, primarily in ORF2, from all known PCV2. Notably, ORF2 contains a unique carboxyl terminal amino acid insertion resulting in a 238 amino acid ORF2. All other PCV2 ORF2 proteins are 233 or 234 aa in length. Phylogenetic analysis indicates that it is more ancient than other PCV2 genotypes. The findings demonstrate the value of analyzing routine diagnostic laboratory sequence databases in population genetic analyses of animal pathogens. PMID:26948261

  8. Phenotypic Expression in Wheat Revealed Using FT-IR Microspectroscopy

    SciTech Connect

    Brewer, L.; Wetzel, D

    2009-01-01

    Wheat selected for cultivation through the centuries has a glume that is 'soft' instead of 'tough' as naturally occurring. In production, this is desirable because it enables mechanical threshing with efficient separation of kernel from the head of each stalk without damaging the kernel. FT-IR microspectroscopy provides chemically based, objective assessment of genetic expression by measuring the extent of genetic expression. In the Microbeam Molecular Spectroscopy Laboratory, Manhattan, KS, an imaging FT-IR microspectrometer with a detector array focused on the image plane was used to obtain spectral data from dissected glume specimens of nine tough and eleven soft wheat cultivars in a rectangular mapping pattern. With cellulose as the substrate, the extent of lignification is measurable from the ratio of the lignin (1508 cm{sup -1}) baseline adjusted band area to the representative cellulosic (1370 cm{sup -1}) band area. A distinction between soft and tough glumes is obtained in numerical terms. Using a band ratio minimizes variation due to thickness differences. While analyzing mapped sections of glume, care is taken to avoid tabulation of spectral data from vascular bundles. Inclusion of these data would to avoid tabulation of spectral data from vascular bundles. Inclusion of these data would bias the analysis toward the composition of highly lignified vascular bundles. Spatially resolved focal plane array FT-IR microspectroscopy reveals the extent of glume lignification that is coincident with the toughness trait. This enables breeders to rank the degree of lignin expression and discriminate between soft and tough breeding results.

  9. Family level phylogenies reveal modes of macroevolution in RNA viruses

    PubMed Central

    Kitchen, Andrew; Shackelton, Laura A.; Holmes, Edward C.

    2011-01-01

    Despite advances in understanding the patterns and processes of microevolution in RNA viruses, little is known about the determinants of viral diversification at the macroevolutionary scale. In particular, the processes by which viral lineages assigned as different “species” are generated remain largely uncharacterized. To address this issue, we use a robust phylogenetic approach to analyze patterns of lineage diversification in five representative families of RNA viruses. We ask whether the process of lineage diversification primarily occurs when viruses infect new host species, either through cross-species transmission or codivergence, and which are defined here as analogous to allopatric speciation in animals, or by acquiring new niches within the same host species, analogous to sympatric speciation. By mapping probable primary host species onto family level viral phylogenies, we reveal a strong clustering among viral lineages that infect groups of closely related host species. Although this is consistent with lineage diversification within individual hosts, we argue that this pattern more likely represents strong biases in our knowledge of viral biodiversity, because we also find that better-sampled human viruses rarely cluster together. Hence, although closely related viruses tend to infect related host species, it is unlikely that they often infect the same host species, such that evolutionary constraints hinder lineage diversification within individual host species. We conclude that the colonization of new but related host species may represent the principle mode of macroevolution in RNA viruses. PMID:21173251

  10. Perceptual rivalry: reflexes reveal the gradual nature of visual awareness.

    PubMed

    Naber, Marnix; Frässle, Stefan; Einhäuser, Wolfgang

    2011-01-01

    Rivalry is a common tool to probe visual awareness: a constant physical stimulus evokes multiple, distinct perceptual interpretations ("percepts") that alternate over time. Percepts are typically described as mutually exclusive, suggesting that a discrete (all-or-none) process underlies changes in visual awareness. Here we follow two strategies to address whether rivalry is an all-or-none process: first, we introduce two reflexes as objective measures of rivalry, pupil dilation and optokinetic nystagmus (OKN); second, we use a continuous input device (analog joystick) to allow observers a gradual subjective report. We find that the "reflexes" reflect the percept rather than the physical stimulus. Both reflexes show a gradual dependence on the time relative to perceptual transitions. Similarly, observers' joystick deflections, which are highly correlated with the reflex measures, indicate gradual transitions. Physically simulating wave-like transitions between percepts suggest piece-meal rivalry (i.e., different regions of space belonging to distinct percepts) as one possible explanation for the gradual transitions. Furthermore, the reflexes show that dominance durations depend on whether or not the percept is actively reported. In addition, reflexes respond to transitions with shorter latencies than the subjective report and show an abundance of short dominance durations. This failure to report fast changes in dominance may result from limited access of introspection to rivalry dynamics. In sum, reflexes reveal that rivalry is a gradual process, rivalry's dynamics is modulated by the required action (response mode), and that rapid transitions in perceptual dominance can slip away from awareness. PMID:21677786

  11. Candida milleri species reveals intraspecific genetic and metabolic polymorphisms.

    PubMed

    Vigentini, Ileana; Antoniani, Davide; Roscini, Luca; Comasio, Andrea; Galafassi, Silvia; Picozzi, Claudia; Corte, Laura; Compagno, Concetta; Dal Bello, Fabio; Cardinali, Gianluigi; Foschino, Roberto

    2014-09-01

    Candida milleri, together with Candida humilis, is the most representative yeast species found in type I sourdough ecosystems. In this work, comparison of the ITS region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping, mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5 microsatellite analyses, assimilation test of different carbohydrates, and metabolome assessment by FT-IR analysis, were investigated in seventeen strains isolated from four different companies as well as in type strains CBS6897(T) and CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong relatedness was confirmed with C. humilis as well, particularly for three strains. Genetic characterization showed a high degree of intraspecific polymorphism since 12 different genotypes were discriminated. The number of chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over 2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources assimilation. FT-IR spectra from yeast cells cultivated in different media and collected at different growth phases revealed a diversity of behaviour among strains in accordance with the results of PCR-based fingerprinting. A clear evidence of the polymorphic status of C. milleri species is provided thus representing an important feature for the development of technological applications in bakery industries.

  12. Sparse expression bases in cancer reveal tumor drivers.

    PubMed

    Logsdon, Benjamin A; Gentles, Andrew J; Miller, Chris P; Blau, C Anthony; Becker, Pamela S; Lee, Su-In

    2015-02-18

    We define a new category of candidate tumor drivers in cancer genome evolution: 'selected expression regulators' (SERs)-genes driving dysregulated transcriptional programs in cancer evolution. The SERs are identified from genome-wide tumor expression data with a novel method, namely SPARROW ( SPAR: se selected exp R: essi O: n regulators identified W: ith penalized regression). SPARROW uncovers a previously unknown connection between cancer expression variation and driver events, by using a novel sparse regression technique. Our results indicate that SPARROW is a powerful complementary approach to identify candidate genes containing driver events that are hard to detect from sequence data, due to a large number of passenger mutations and lack of comprehensive sequence information from a sufficiently large number of samples. SERs identified by SPARROW reveal known driver mutations in multiple human cancers, along with known cancer-associated processes and survival-associated genes, better than popular methods for inferring gene expression networks. We demonstrate that when applied to acute myeloid leukemia expression data, SPARROW identifies an apoptotic biomarker (PYCARD) for an investigational drug obatoclax. The PYCARD and obatoclax association is validated in 30 AML patient samples.

  13. Parallel Selection Revealed by Population Sequencing in Chicken

    PubMed Central

    Qanbari, Saber; Seidel, Michael; Strom, Tim-Mathias; Mayer, Klaus F.X.; Preisinger, Ruedi; Simianer, Henner

    2015-01-01

    Human-driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern chicken. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying genes relevant to domestication and improvement that ultimately may help to further genetically improve this economically important animal. We used whole genome sequence data from 50 hens of commercial white (WL) and brown (BL) egg-laying chicken along with pool sequences of three meat-type chicken to perform a systematic screening of past selection in modern chicken. Evidence of positive selection was investigated in two steps. First, we explored evidence of parallel fixation in regions with overlapping elevated allele frequencies in replicated populations of layers and broilers, suggestive of selection during domestication or preimprovement ages. We confirmed parallel fixation in BCDO2 and TSHR genes and found four candidates including AGTR2, a gene heavily involved in “Ascites” in commercial birds. Next, we explored differentiated loci between layers and broilers suggestive of selection during improvement in chicken. This analysis revealed evidence of parallel differentiation in genes relevant to appearance and production traits exemplified with the candidate gene OPG, implicated in Osteoporosis, a disorder related to overconsumption of calcium in egg-laying hens. Our results illustrate the potential for population genetic techniques to identify genomic regions relevant to the phenotypes of importance to breeders. PMID:26568375

  14. Early Neolithic water wells reveal the world's oldest wood architecture.

    PubMed

    Tegel, Willy; Elburg, Rengert; Hakelberg, Dietrich; Stäuble, Harald; Büntgen, Ulf

    2012-01-01

    The European Neolithization ~6000-4000 BC represents a pivotal change in human history when farming spread and the mobile style of life of the hunter-foragers was superseded by the agrarian culture. Permanent settlement structures and agricultural production systems required fundamental innovations in technology, subsistence, and resource utilization. Motivation, course, and timing of this transformation, however, remain debatable. Here we present annually resolved and absolutely dated dendroarchaeological information from four wooden water wells of the early Neolithic period that were excavated in Eastern Germany. A total of 151 oak timbers preserved in a waterlogged environment were dated between 5469 and 5098 BC and reveal unexpectedly refined carpentry skills. The recently discovered water wells enable for the first time a detailed insight into the earliest wood architecture and display the technological capabilities of humans ~7000 years ago. The timbered well constructions made of old oak trees feature an unopened tree-ring archive from which annually resolved and absolutely dated environmental data can be culled. Our results question the principle of continuous evolutionary development in prehistoric technology, and contradict the common belief that metal was necessary for complex timber constructions. Early Neolithic craftsmanship now suggests that the first farmers were also the first carpenters. PMID:23284685

  15. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3(-/-) mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  16. Integrative network analysis reveals molecular mechanisms of blood pressure regulation.

    PubMed

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-04-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension.

  17. Transcriptome profiling reveals mosaic genomic origins of modern cultivated barley.

    PubMed

    Dai, Fei; Chen, Zhong-Hua; Wang, Xiaolei; Li, Zefeng; Jin, Gulei; Wu, Dezhi; Cai, Shengguan; Wang, Ning; Wu, Feibo; Nevo, Eviatar; Zhang, Guoping

    2014-09-16

    The domestication of cultivated barley has been used as a model system for studying the origins and early spread of agrarian culture. Our previous results indicated that the Tibetan Plateau and its vicinity is one of the centers of domestication of cultivated barley. Here we reveal multiple origins of domesticated barley using transcriptome profiling of cultivated and wild-barley genotypes. Approximately 48-Gb of clean transcript sequences in 12 Hordeum spontaneum and 9 Hordeum vulgare accessions were generated. We reported 12,530 de novo assembled transcripts in all of the 21 samples. Population structure analysis showed that Tibetan hulless barley (qingke) might have existed in the early stage of domestication. Based on the large number of unique genomic regions showing the similarity between cultivated and wild-barley groups, we propose that the genomic origin of modern cultivated barley is derived from wild-barley genotypes in the Fertile Crescent (mainly in chromosomes 1H, 2H, and 3H) and Tibet (mainly in chromosomes 4H, 5H, 6H, and 7H). This study indicates that the domestication of barley may have occurred over time in geographically distinct regions. PMID:25197090

  18. Jamming Criticality Revealed by Removing Localized Buckling Excitations

    NASA Astrophysics Data System (ADS)

    Charbonneau, Patrick; Corwin, Eric I.; Parisi, Giorgio; Zamponi, Francesco

    2015-03-01

    Recent theoretical advances offer an exact, first-principles theory of jamming criticality in infinite dimension as well as universal scaling relations between critical exponents in all dimensions. For packings of frictionless spheres near the jamming transition, these advances predict that nontrivial power-law exponents characterize the critical distribution of (i) small interparticle gaps and (ii) weak contact forces, both of which are crucial for mechanical stability. The scaling of the interparticle gaps is known to be constant in all spatial dimensions d —including the physically relevant d =2 and 3, but the value of the weak force exponent remains the object of debate and confusion. Here, we resolve this ambiguity by numerical simulations. We construct isostatic jammed packings with extremely high accuracy, and introduce a simple criterion to separate the contribution of particles that give rise to localized buckling excitations, i.e., bucklers, from the others. This analysis reveals the remarkable dimensional robustness of mean-field marginality and its associated criticality.

  19. Eukaryote Culturomics of the Gut Reveals New Species

    PubMed Central

    Gouba, Nina; Raoult, Didier; Drancourt, Michel

    2014-01-01

    The repertoire of microeukaryotes in the human gut has been poorly explored, mainly in individuals living in northern hemisphere countries. We further explored this repertoire using PCR-sequencing and culture in seven individuals living in four tropical countries. A total of 41 microeukaryotes including 38 different fungal species and three protists were detected. Four fungal species, Davidiella tassiana, Davidiella sp., Corticiaceae sp., and Penicillium sp., were uniquely detected by culture; 27 fungal species were uniquely detected using PCR-sequencing and Candida albicans, Candida glabrata, Trichosporon asahii, Clavispora lusitaniae, Debaryomyces hansenii, Malassezia restricta, and Malassezia sp. were detected using both molecular and culture methods. Fourteen microeukaryotes were shared by the seven individuals, whereas 27 species were found in only one individual, including 11 species in Amazonia, nine species in Polynesia, five species in India, and two species in Senegal. These data support a worldwide distribution of Malassezia sp., Trichosporon sp., and Candida sp. in the gut mycobiome. Here, 13 fungal species and two protists, Stentor roeseli and Vorticella campanula, were observed for first time in the human gut. This study revealed a previously unsuspected diversity in the repertoire of human gut microeukaryotes, suggesting spots for further exploring this repertoire. PMID:25210972

  20. Beyond Contagion: Reality Mining Reveals Complex Patterns of Social Influence

    PubMed Central

    Alshamsi, Aamena; Pianesi, Fabio; Lepri, Bruno; Pentland, Alex; Rahwan, Iyad

    2015-01-01

    Contagion, a concept from epidemiology, has long been used to characterize social influence on people’s behavior and affective (emotional) states. While it has revealed many useful insights, it is not clear whether the contagion metaphor is sufficient to fully characterize the complex dynamics of psychological states in a social context. Using wearable sensors that capture daily face-to-face interaction, combined with three daily experience sampling surveys, we collected the most comprehensive data set of personality and emotion dynamics of an entire community of work. From this high-resolution data about actual (rather than self-reported) face-to-face interaction, a complex picture emerges where contagion (that can be seen as adaptation of behavioral responses to the behavior of other people) cannot fully capture the dynamics of transitory states. We found that social influence has two opposing effects on states: adaptation effects that go beyond mere contagion, and complementarity effects whereby individuals’ behaviors tend to complement the behaviors of others. Surprisingly, these effects can exhibit completely different directions depending on the stable personality or emotional dispositions (stable traits) of target individuals. Our findings provide a foundation for richer models of social dynamics, and have implications on organizational engineering and workplace well-being. PMID:26313449

  1. Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.

    PubMed

    Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; Han, Gye Won; Liu, Wei; Zatsepin, Nadia A; James, Daniel; Wang, Dingjie; Nelson, Garrett; Weierstall, Uwe; Sawaya, Michael R; Xu, Qingping; Messerschmidt, Marc; Williams, Garth J; Boutet, Sébastien; Yefanov, Oleksandr M; White, Thomas A; Wang, Chong; Ishchenko, Andrii; Tirupula, Kalyan C; Desnoyer, Russell; Coe, Jesse; Conrad, Chelsie E; Fromme, Petra; Stevens, Raymond C; Katritch, Vsevolod; Karnik, Sadashiva S; Cherezov, Vadim

    2015-05-01

    Angiotensin II type 1 receptor (AT(1)R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT(1)R blockers (ARBs), the structural basis for AT(1)R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT(1)R in complex with its selective antagonist ZD7155 at 2.9-Å resolution. The AT(1)R-ZD7155 complex structure revealed key structural features of AT(1)R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT(1)R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT(1)R structure-function relationship and structure-based drug design.

  2. Quantification of the stapedial reflex reveals delayed responses in autism.

    PubMed

    Lukose, Richard; Brown, Kevin; Barber, Carol M; Kulesza, Randy Joseph

    2013-10-01

    Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three- or four-neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right-left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses. PMID:23825093

  3. Temperature-cycle microscopy reveals single-molecule conformational heterogeneity.

    PubMed

    Yuan, Haifeng; Gaiduk, Alexander; Siekierzycka, Joanna R; Fujiyoshi, Satoru; Matsushita, Michio; Nettels, Daniel; Schuler, Benjamin; Seidel, Claus A M; Orrit, Michel

    2015-03-01

    Our previous temperature-cycle study reported FRET transitions between different states on FRET-labeled polyprolines [Yuan et al., PCCP, 2011, 13, 1762]. The conformational origin of such transitions, however, was left open. In this work, we apply temperature-cycle microscopy of single FRET-labeled polyproline and dsDNA molecules and compare their responses to resolve the conformational origin of different FRET states. We observe different steady-state FRET distributions and different temperature-cycle responses in the two samples. Our temperature-cycle results on single molecules resemble the results in steady-state measurements but reveal a dark state which could not be observed otherwise. By comparing the timescales and probabilities of different FRET states in temperature-cycle traces, we assign the conformational heterogeneity reflected by different FRET states to linker dynamics, dye-chain and dye-dye interactions. The dark state and low-FRET state are likely due to dye-dye interactions at short separations.

  4. Artemin Crystal Structure Reveals Insights into Heparan Sulfate Binding

    SciTech Connect

    Silvian,L.; Jin, P.; Carmillo, P.; Boriack-Sjodin, P.; Pelletier, C.; Rushe, M.; Gong, B.; Sah, D.; Pepinsky, B.; Rossomando, A.

    2006-01-01

    Artemin (ART) promotes the growth of developing peripheral neurons by signaling through a multicomponent receptor complex comprised of a transmembrane tyrosine kinase receptor (cRET) and a specific glycosylphosphatidylinositol-linked co-receptor (GFR{alpha}3). Glial cell line-derived neurotrophic factor (GDNF) signals through a similar ternary complex but requires heparan sulfate proteoglycans (HSPGs) for full activity. HSPG has not been demonstrated as a requirement for ART signaling. We crystallized ART in the presence of sulfate and solved its structure by isomorphous replacement. The structure reveals ordered sulfate anions bound to arginine residues in the pre-helix and amino-terminal regions that were organized in a triad arrangement characteristic of heparan sulfate. Three residues in the pre-helix were singly or triply substituted with glutamic acid, and the resulting proteins were shown to have reduced heparin-binding affinity that is partly reflected in their ability to activate cRET. This study suggests that ART binds HSPGs and identifies residues that may be involved in HSPG binding.

  5. Statistical universals reveal the structures and functions of human music.

    PubMed

    Savage, Patrick E; Brown, Steven; Sakai, Emi; Currie, Thomas E

    2015-07-21

    Music has been called "the universal language of mankind." Although contemporary theories of music evolution often invoke various musical universals, the existence of such universals has been disputed for decades and has never been empirically demonstrated. Here we combine a music-classification scheme with statistical analyses, including phylogenetic comparative methods, to examine a well-sampled global set of 304 music recordings. Our analyses reveal no absolute universals but strong support for many statistical universals that are consistent across all nine geographic regions sampled. These universals include 18 musical features that are common individually as well as a network of 10 features that are commonly associated with one another. They span not only features related to pitch and rhythm that are often cited as putative universals but also rarely cited domains including performance style and social context. These cross-cultural structural regularities of human music may relate to roles in facilitating group coordination and cohesion, as exemplified by the universal tendency to sing, play percussion instruments, and dance to simple, repetitive music in groups. Our findings highlight the need for scientists studying music evolution to expand the range of musical cultures and musical features under consideration. The statistical universals we identified represent important candidates for future investigation.

  6. Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

    DOE PAGES

    Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.; Poole, Farris L.; Benton, H. Paul; Ivanisevic, Julijana; Tran, Minerva L.; Wall, Judy D.; Elias, Dwayne A.; Adams, Michael W. W.; et al

    2016-04-05

    Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using 15NO3 as a nitrogen source. In contrast to a control (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2 strains conserve nitrogen-containingmore » metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.« less

  7. Identification of disulfide bond isomerase substrates reveals bacterial virulence factors

    PubMed Central

    Ren, Guoping; Champion, Matthew M.; Huntley, Jason F.

    2014-01-01

    Summary Bacterial pathogens are exposed to toxic molecules inside the host and require efficient systems to form and maintain correct disulfide bonds for protein stability and function. The intracellular pathogen Francisella tularensis encodes a disulfide bond formation protein ortholog, DsbA, which previously was reported to be required for infection of macrophages and mice. However, the molecular mechanisms by which F. tularensis DsbA contributes to virulence are unknown. Here, we demonstrate that F. tularensis DsbA is a bifunctional protein that oxidizes and, more importantly, isomerizes complex disulfide connectivity in substrates. A single amino acid in the conserved cis-proline loop of the DsbA thioredoxin domain was shown to modulate both isomerase activity and F. tularensis virulence. Trapping experiments in F. tularensis identified over 50 F. tularensis DsbA substrates, including outer membrane proteins, virulence factors, and many hypothetical proteins. Six of these hypothetical proteins were randomly selected and deleted, revealing two novel proteins, FTL_1548 and FTL_1709, which are required for F. tularensis virulence. We propose that the extreme virulence of F. tularensis is partially due to the bifunctional nature of DsbA, that many of the newly-identified substrates are required for virulence, and that the development of future DsbA inhibitors could have broad anti-bacterial implications. PMID:25257164

  8. Next generation sequencing in synovial sarcoma reveals novel gene mutations

    PubMed Central

    Vlenterie, Myrella; Hillebrandt-Roeffen, Melissa H.S.; Flucke, Uta E.; Groenen, Patricia J.T.A.; Tops, Bastiaan B.J.; Kamping, Eveline J.; Pfundt, Rolph; de Bruijn, Diederik R.H.; van Kessel, Ad H.M. Geurts; van Krieken, Han J.H.J.M.; van der Graaf, Winette T.A.; Versleijen-Jonkers, Yvonne M.H.

    2015-01-01

    Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18), however, they show heterogeneous clinical behavior. We analyzed multiple SS to reveal additional genetic alterations besides the translocation. Twenty-six SS from 22 patients were sequenced for 409 cancer-related genes using the Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform. The detected variants were verified by Sanger sequencing and compared to matched normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan array (Affymetrix, USA). In total, eight somatic mutations were detected in eight samples. These mutations have not been reported previously in SS. Two of these, in KRAS and CCND1, represent known oncogenic mutations in other malignancies. Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4. DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was found in a metastatic lesion progressing under pazopanib, but not in the responding lesion. Our results emphasize t(X;18) as a single initiating event in SS and as the main oncogenic driver. Our results also show the occurrence of additional genetic events, mutations or chromosomal aberrations, occurring more frequently in SS with an onset in adults. PMID:26415226

  9. Voluminous volcanism on early mars revealed in valles marineris

    USGS Publications Warehouse

    McEwen, A.S.; Malin, M.C.; Carr, M.H.; Hartmann, W.K.

    1999-01-01

    The relative rates and importance of impact cratering, volcanism, erosion, and the deposition of sediments to the early geological history of Mars are poorly known. That history is recorded in the upper crust of the planet, which is best exposed along the 4,000km-long canyon system called Valles Marineris. Previous studies of the stratigraphy of this region have assumed that it consists of megabreccia and fractured bedrock resulting from impacts, overlain by or interbedded with relatively thin layers of lava, and with the layering restricted to the uppermost level of the crust. Here we report new high-resolution images that reveal ubiquitous horizontal layering to depths of at least 8 km in the canyons. Megabreccia should be only coarsely layered and fractured bedrock should be unlayered, so these observations indicate that volcanic or sedimentary processes were much more important in early martian history than previously believed. Morphological and compositional data suggest that the layers were formed mainly by volcanic flood lavas. Mars was therefore probably very volcanically active during at least the first billion years and after the period when the heaviest impact bombardment had ended.

  10. Distributed neural system for emotional intelligence revealed by lesion mapping.

    PubMed

    Barbey, Aron K; Colom, Roberto; Grafman, Jordan

    2014-03-01

    Cognitive neuroscience has made considerable progress in understanding the neural architecture of human intelligence, identifying a broadly distributed network of frontal and parietal regions that support goal-directed, intelligent behavior. However, the contributions of this network to social and emotional aspects of intellectual function remain to be well characterized. Here we investigated the neural basis of emotional intelligence in 152 patients with focal brain injuries using voxel-based lesion-symptom mapping. Latent variable modeling was applied to obtain measures of emotional intelligence, general intelligence and personality from the Mayer, Salovey, Caruso Emotional Intelligence Test (MSCEIT), the Wechsler Adult Intelligence Scale and the Neuroticism-Extroversion-Openness Inventory, respectively. Regression analyses revealed that latent scores for measures of general intelligence and personality reliably predicted latent scores for emotional intelligence. Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal and parietal brain regions. The results support an integrative framework for understanding the architecture of executive, social and emotional processes and make specific recommendations for the interpretation and application of the MSCEIT to the study of emotional intelligence in health and disease.

  11. Eukaryote culturomics of the gut reveals new species.

    PubMed

    Gouba, Nina; Raoult, Didier; Drancourt, Michel

    2014-01-01

    The repertoire of microeukaryotes in the human gut has been poorly explored, mainly in individuals living in northern hemisphere countries. We further explored this repertoire using PCR-sequencing and culture in seven individuals living in four tropical countries. A total of 41 microeukaryotes including 38 different fungal species and three protists were detected. Four fungal species, Davidiella tassiana, Davidiella sp., Corticiaceae sp., and Penicillium sp., were uniquely detected by culture; 27 fungal species were uniquely detected using PCR-sequencing and Candida albicans, Candida glabrata, Trichosporon asahii, Clavispora lusitaniae, Debaryomyces hansenii, Malassezia restricta, and Malassezia sp. were detected using both molecular and culture methods. Fourteen microeukaryotes were shared by the seven individuals, whereas 27 species were found in only one individual, including 11 species in Amazonia, nine species in Polynesia, five species in India, and two species in Senegal. These data support a worldwide distribution of Malassezia sp., Trichosporon sp., and Candida sp. in the gut mycobiome. Here, 13 fungal species and two protists, Stentor roeseli and Vorticella campanula, were observed for first time in the human gut. This study revealed a previously unsuspected diversity in the repertoire of human gut microeukaryotes, suggesting spots for further exploring this repertoire. PMID:25210972

  12. Sparse expression bases in cancer reveal tumor drivers

    PubMed Central

    Logsdon, Benjamin A.; Gentles, Andrew J.; Miller, Chris P.; Blau, C. Anthony; Becker, Pamela S.; Lee, Su-In

    2015-01-01

    We define a new category of candidate tumor drivers in cancer genome evolution: ‘selected expression regulators’ (SERs)—genes driving dysregulated transcriptional programs in cancer evolution. The SERs are identified from genome-wide tumor expression data with a novel method, namely SPARROW (SPARse selected expRessiOn regulators identified With penalized regression). SPARROW uncovers a previously unknown connection between cancer expression variation and driver events, by using a novel sparse regression technique. Our results indicate that SPARROW is a powerful complementary approach to identify candidate genes containing driver events that are hard to detect from sequence data, due to a large number of passenger mutations and lack of comprehensive sequence information from a sufficiently large number of samples. SERs identified by SPARROW reveal known driver mutations in multiple human cancers, along with known cancer-associated processes and survival-associated genes, better than popular methods for inferring gene expression networks. We demonstrate that when applied to acute myeloid leukemia expression data, SPARROW identifies an apoptotic biomarker (PYCARD) for an investigational drug obatoclax. The PYCARD and obatoclax association is validated in 30 AML patient samples. PMID:25583238

  13. Pyrosequencing Reveals Fungal Communities in the Rhizosphere of Xinjiang Jujube

    PubMed Central

    Wang, Xiao-Hui; Li, Jian-Gui; Qin, Wei; Xiao, Cheng-Ze; Zhao, Xu; Jiang, Hong-Xia; Sui, Jun-Kang; Sa, Rong-Bo; Wang, Wei-Yan; Liu, Xun-Li

    2015-01-01

    Fungi are important soil components as both decomposers and plant symbionts and play a major role in ecological and biogeochemical processes. However, little is known about the richness and structure of fungal communities. DNA sequencing technologies allow for the direct estimation of microbial community diversity, avoiding culture-based biases. We therefore used 454 pyrosequencing to investigate the fungal communities in the rhizosphere of Xinjiang jujube. We obtained no less than 40,488 internal transcribed spacer (ITS) rDNA reads, the number of each sample was 6943, 6647, 6584, 6550, 6860, and 6904, and we used bioinformatics and multivariate statistics to analyze the results. The index of diversity showed greater richness in the rhizosphere fungal community of a 3-year-old jujube than in that of an 8-year-old jujube. Most operational taxonomic units belonged to Ascomycota, and taxonomic analyses identified Hypocreales as the dominant fungal order. Our results demonstrated that the fungal orders are present in different proportions in different sampling areas. Redundancy analysis (RDA) revealed a significant correlation between soil properties and the abundance of fungal phyla. Our results indicated lower fungal diversity in the rhizosphere of Xinjiang jujube than that reported in other studies, and we hope our findings provide a reference for future research. PMID:25685820

  14. Network deconstruction reveals network structure in responsive microgels.

    PubMed

    Smith, Michael H; Herman, Emily S; Lyon, L Andrew

    2011-04-14

    Detailed characterization of hydrogel particle erosion revealed critical physicochemical differences between spheres, where network decomposition was informative of network structure. Real-time, in situ monitoring of the triggered erosion of colloidal hydrogels (microgels) was performed via multiangle light scattering. The solution-average molar mass and root-mean-square radii of eroding particles were measured as a function of time for microgels prepared from N-isopropylacrylamide (NIPAm) or N-isopropylmethacrylamide (NIPMAm), copolymerized with a chemically labile cross-linker (1,2-dihydroxylethylene)bisacrylamide (DHEA). Precipitation polymerization was employed to yield particles of comparable dimensions but with distinct topological features. Heterogeneous cross-linker incorporation resulted in a heterogeneous network structure for pNIPAm microgels. During the erosion reaction, mass loss proceeded from the exterior toward the interior of the polymer. In contrast, pNIPMAm microgels had a more homogeneous network structure, which resulted in a more uniform mass loss throughout the particle during erosion. Although both particle types degraded into low molar mass products, pNIPAm microgels were incapable of complete dissolution due to the presence of nondegradable cross-links arising from chain transfer and branching during particle synthesis. The observations described herein provide insight into key design parameters associated with the synthesis of degradable hydrogel particles, which may be of use in various biotechnological applications. PMID:21425815

  15. Acoustic telemetry reveals cryptic residency of whale sharks.

    PubMed

    Cagua, E Fernando; Cochran, Jesse E M; Rohner, Christoph A; Prebble, Clare E M; Sinclair-Taylor, Tane H; Pierce, Simon J; Berumen, Michael L

    2015-04-01

    Although whale sharks (Rhincodon typus) have been documented to move thousands of kilometres, they are most frequently observed at a few predictable seasonal aggregation sites. The absence of sharks at the surface during visual surveys has led to the assumption that sharks disperse to places unknown during the long 'off-seasons' at most of these locations. Here we compare 2 years of R. typus visual sighting records from Mafia Island in Tanzania to concurrent acoustic telemetry of tagged individuals. Sightings revealed a clear seasonal pattern with a peak between October and February and no sharks observed at other times. By contrast, acoustic telemetry demonstrated year-round residency of R. typus. The sharks use a different habitat in the off-season, swimming deeper and further away from shore, presumably in response to prey distributions. This behavioural change reduces the sharks' visibility, giving the false impression that they have left the area. We demonstrate, for the first time to our knowledge, year-round residency of unprovisioned, individual R. typus at an aggregation site, and highlight the importance of using multiple techniques to study the movement ecology of marine megafauna.

  16. Small molecules reveal an alternative mechanism of Bax activation

    PubMed Central

    Brahmbhatt, Hetal; Uehling, David; Al-awar, Rima; Leber, Brian; Andrews, David

    2016-01-01

    The pro-apoptotic protein Bax commits a cell to death by permeabilizing the mitochondrial outer membrane (MOM). To obtain small-molecule probes for elucidating the molecular mechanism(s) of Bax activation, we screened for compounds that induced Bax-mediated liposome permeabilization. We identified five structurally different small molecules that promoted both Bax targeting to and oligomerization at membranes. All five compounds initiated Bax oligomerization in the absence of membranes by a mechanism unlike Bax activation by Bcl-2 homology 3 domain (BH3) proteins. Some of the compounds induced Bax/Bak-dependent apoptosis in cells. Activation of Bax by the most active compound was poorly inhibited by the anti-apoptotic protein Bcl-XL and requires a cysteine residue at position 126 of Bax that is not required for activation by BH3 proteins. Our results reveal a novel pathway for Bax activation independent of pro-apoptotic BH3 proteins that may have important implications for the regulation of Bax activity in cells. PMID:26916338

  17. Revealing different aggregation pathways of amyloidogenic proteins by ultrasound velocimetry.

    PubMed

    Smirnovas, Vytautas; Winter, Roland

    2008-04-15

    In this work, we performed a detailed thermodynamic study, including ultrasound velocimetry, densimetry, calorimetry, and FTIR spectroscopy, of an aggregation-prone protein (insulin) under different salt-screening conditions to gain a deeper insight into the scenario of physicochemical events during its temperature-induced unfolding and aggregation reactions. Differences in aggregation and fibrillization pathways are reflected in changes of the partial molar volume, the coefficients of thermal expansion and compressibility, and the infrared spectral properties of the protein. Combining all experimental data allows setting up a scheme for the temperature-dependent insulin aggregation reaction in the presence and absence of NaCl. As revealed by complementary atomic force microscopy studies, under charge-screening conditions, a process involving structural reorganization, ripening, and formation of more compact nuclei from amorphous oligomers is involved in the formation of mature fibrillar morphologies. In this work, our focus was to put forward a comprehensive discussion of the use of ultrasound velocimetry in disentangling different aggregation pathways. In fact, ultrasound velocimetry proved to be very sensitive to changes in aggregation pathway, highlighting the importance of density and compressibility changes in the different aggregation and fibrillization reactions of the protein.

  18. Individual olfactory perception reveals meaningful nonolfactory genetic information.

    PubMed

    Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam

    2015-07-14

    Each person expresses a potentially unique subset of ∼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10(-10)), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

  19. Laser microsurgery reveals conserved viscoelastic behavior of the kinetochore.

    PubMed

    Cojoc, Gheorghe; Roscioli, Emanuele; Zhang, Lijuan; García-Ulloa, Alfonso; Shah, Jagesh V; Berns, Michael W; Pavin, Nenad; Cimini, Daniela; Tolić, Iva M; Gregan, Juraj

    2016-03-28

    Accurate chromosome segregation depends on proper kinetochore-microtubule attachment. Upon microtubule interaction, kinetochores are subjected to forces generated by the microtubules. In this work, we used laser ablation to sever microtubules attached to a merotelic kinetochore, which is laterally stretched by opposing pulling forces exerted by microtubules, and inferred the mechanical response of the kinetochore from its length change. In both mammalian PtK1 cells and in the fission yeast Schizosaccharomyces pombe, kinetochores shortened after microtubule severing. Interestingly, the inner kinetochore-centromere relaxed faster than the outer kinetochore. Whereas in fission yeast all kinetochores relaxed to a similar length, in PtK1 cells the more stretched kinetochores remained more stretched. Simple models suggest that these differences arise because the mechanical structure of the mammalian kinetochore is more complex. Our study establishes merotelic kinetochores as an experimental model for studying the mechanical response of the kinetochore in live cells and reveals a viscoelastic behavior of the kinetochore that is conserved in yeast and mammalian cells. PMID:27002163

  20. Angiosperm genome comparisons reveal early polyploidy in the monocot lineage

    PubMed Central

    Tang, Haibao; Bowers, John E.; Wang, Xiyin; Paterson, Andrew H.

    2009-01-01

    Although the timing and extent of a whole-genome duplication occurring in the common lineage of most modern cereals are clear, the existence or extent of more ancient genome duplications in cereals and perhaps other monocots has been hinted at, but remain unclear. We present evidence of additional duplication blocks of deeper hierarchy than the pancereal rho (ρ) duplication, covering at least 20% of the cereal transcriptome. These more ancient duplicated regions, herein called σ, are evident in both intragenomic and intergenomic analyses of rice and sorghum. Resolution of such ancient duplication events improves the understanding of the early evolutionary history of monocots and the origins and expansions of gene families. Comparisons of syntenic blocks reveal clear structural similarities in putatively homologous regions of monocots (rice) and eudicots (grapevine). Although the exact timing of the σ-duplication(s) is unclear because of uncertainties of the molecular clock assumption, our data suggest that it occurred early in the monocot lineage after its divergence from the eudicot clade. PMID:19966307

  1. A novel assay reveals hygrotactic behavior in Drosophila.

    PubMed

    Ji, Feiteng; Zhu, Yan

    2015-01-01

    Humidity is one of the most important factors that determines the geographical distribution and survival of terrestrial animals. The ability to detect variation in humidity is conserved across many species. Here, we established a novel behavioral assay that revealed the thirsty Drosophila exhibits strong hygrotactic behavior, and it can locate water by detecting humidity gradient. In addition, exposure to high levels of moisture was sufficient to elicit proboscis extension reflex behavior in thirsty flies. Furthermore, we found that the third antennal segment was necessary for hygrotactic behavior in thirsty flies, while arista was required for the avoidance of moist air in hydrated flies. These results indicated that two types of hygroreceptor cells exist in Drosophila: one located in the third antennal segment that mediates hygrotactic behavior in thirst status, and the other located in arista which is responsible for the aversive behavior toward moist air in hydration status. Using a neural silencing screen, we demonstrated that synaptic output from the mushroom body α/β surface and posterior neurons was required for both hygrotactic behavior and moisture-aversive behavior.

  2. Mitochondrial Genome Sequences Effectively Reveal the Phylogeny of Hylobates Gibbons

    PubMed Central

    Chan, Yi-Chiao; Roos, Christian; Inoue-Murayama, Miho; Inoue, Eiji; Shih, Chih-Chin; Pei, Kurtis Jai-Chyi; Vigilant, Linda

    2010-01-01

    Background Uniquely among hominoids, gibbons exist as multiple geographically contiguous taxa exhibiting distinctive behavioral, morphological, and karyotypic characteristics. However, our understanding of the evolutionary relationships of the various gibbons, especially among Hylobates species, is still limited because previous studies used limited taxon sampling or short mitochondrial DNA (mtDNA) sequences. Here we use mtDNA genome sequences to reconstruct gibbon phylogenetic relationships and reveal the pattern and timing of divergence events in gibbon evolutionary history. Methodology/Principal Findings We sequenced the mitochondrial genomes of 51 individuals representing 11 species belonging to three genera (Hylobates, Nomascus and Symphalangus) using the high-throughput 454 sequencing system with the parallel tagged sequencing approach. Three phylogenetic analyses (maximum likelihood, Bayesian analysis and neighbor-joining) depicted the gibbon phylogenetic relationships congruently and with strong support values. Most notably, we recover a well-supported phylogeny of the Hylobates gibbons. The estimation of divergence times using Bayesian analysis with relaxed clock model suggests a much more rapid speciation process in Hylobates than in Nomascus. Conclusions/Significance Use of more than 15 kb sequences of the mitochondrial genome provided more informative and robust data than previous studies of short mitochondrial segments (e.g., control region or cytochrome b) as shown by the reliable reconstruction of divergence patterns among Hylobates gibbons. Moreover, molecular dating of the mitogenomic divergence times implied that biogeographic change during the last five million years may be a factor promoting the speciation of Sundaland animals, including Hylobates species. PMID:21203450

  3. Knock-out models reveal new aquaporin functions.

    PubMed

    Verkman, Alan S

    2009-01-01

    Knockout mice have been informative in the discovery of unexpected biological functions of aquaporins. Knockout mice have confirmed the predicted roles of aquaporins in transepithelial fluid transport, as in the urinary concentrating mechanism and glandular fluid secretion. A less obvious, though predictable role of aquaporins is in tissue swelling under stress, as in the brain in stroke, tumor and infection. Phenotype analysis of aquaporin knockout mice has revealed several unexpected cellular roles of aquaporins whose mechanisms are being elucidated. Aquaporins facilitate cell migration, as seen in aquaporin-dependent tumor angiogenesis and tumor metastasis, by a mechanism that may involve facilitated water transport in lamellipodia of migrating cells. The ' aquaglyceroporins', aquaporins that transport both glycerol and water, regulate glycerol content in epidermis, fat and other tissues, and lead to a multiplicity of interesting consequences of gene disruption including dry skin, resistance to skin carcinogenesis, impaired cell proliferation and altered fat metabolism. An even more surprising role of a mammalian aquaporin is in neural signal transduction in the central nervous system. The many roles of aquaporins might be exploited for clinical benefit by modulation of aquaporin expression/function - as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer. PMID:19096787

  4. Trends in the global tropopause thickness revealed by radiosondes

    NASA Astrophysics Data System (ADS)

    Feng, Sha; Fu, Yunfei; Xiao, Qingnong

    2012-10-01

    The first global trends in the thickness of the tropopause layer (TL) are analyzed based on radiosonde data in the Integrated Global Radiosonde Archive (IGRA) for the period of 1965-2004. It reveals that TL has been thickening for the entire globe with positive trends of 0.16 ± 0.12 km/decade during this period. Statistically significant thickening is observed in the tropics, North Hemisphere (NH) extratropics, and NH poles. Accompanied by overall cooling of -0.58 ± 0.40 K/decade in TL's top, remarkable rising trends of 0.35 ± 0.29 km/decade are observed in the correspoding height. However, the anti-correlation of the trends in the tropopause temperature and the corresponding height is not observed in its lower boundary, namely the first lapse rate tropopause (LRT), for all the latitude bands as suggested by the previous studies. The results imply that the temperature of the TL is primarily couple with the height of its upper boundary as the thickness of the TL is more correlated with the temperature of the lower stratosphere than with the tempeature of the upper troposphere. Long-term changes in TL may in turn carry more information how tropopause change in response to climate change than in the sharp “tropopause surface” only.

  5. Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs

    SciTech Connect

    Curtis, Bruce A.; Tanifuji, Goro; Burki, Fabien; Gruber, Ansgar; Irimia, Manuuel; Maruyama, Shinichiro; Arias, Maria C.; Ball, Steven G.; Gile, Gillian H.; Hirakawa, Yoshihisa; Hopkins, Julia F.; Kuo, Alan; Rensing, Stefan A.; Schmutz, Jeremy; Symeonidi, Aikaterini; Elias, Marek; Eveleigh, Robert J. M.; Herman, Emily K.; Klute, Mary J.; Nakayama, Takuro; Obornik, Miroslav; Reyes-Prieto, Adrian; Armbrust, E. Virginia; Aves, Stephen J.; Beiko, Robert G.; Coutinho, Pedro; Dacks, Joel B.; Durnford, Dion G.; Fast, Naomi M.; Green, Beverley R.; Grisdale, Cameron J.; Hempel, Franziska; Henrissat, Bernard; Hoppner, Marc P.; Ishida, Ken-Ichiro; Kim, Eunsoo; Koreny, Ludek; Kroth, Peter G.; Liu, Yuan; Malik, Shehre-Banoo; Maier, Uwe G.; McRose, Darcy; Mock, Thomas; Neilson, Jonathan A. D.; Onodera, Naoko T.; Poole, Anthony M.; Pritham, Ellen J.; Richards, Thomas A.; Rocap, Gabrielle; Roy, Scott W.; Sarai, Chihiro; Schaack, Sarah; Shirato, Shu; Slamovits, Claudio H.; Spencer, Davie F.; Suzuki, Shigekatsu; Worden, Alexandra Z.; Zauner, Stefan; Barry, Kerrie; Bell, Callum; Bharti, Arvind K.; Crow, John A.; Grimwood, Jane; Kramer, Robin; Lindquist, Erika; Lucas, Susan; Salamov, Asaf; McFadden, Geoffrey I.; Lane, Christopher E.; Keeling, Patrick J.; Gray, Michael W.; Grigoriev, Igor V.; Archibald, John M.

    2012-08-10

    Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have 21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host- and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.

  6. Fine-scaled human genetic structure revealed by SNP microarrays.

    PubMed

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure. PMID:19411602

  7. Revealing the intricate effect of collaboration on innovation.

    PubMed

    Inoue, Hiroyasu; Liu, Yang-Yu

    2015-01-01

    We studied the Japan and U.S. patent records of several decades to demonstrate the effect of collaboration on innovation. We found that statistically inventor teams slightly outperform solo inventors while company teams perform equally well as solo companies. By tracking the performance record of individual teams, we found that inventor teams' performance generally degrades with more repeat collaborations. Though company teams' performance displays strongly bursty behavior, long-term collaboration does not significantly help innovation. To systematically study the effect of repeat collaboration, we defined the repeat collaboration number of a team as the average number of collaborations over all the teammate pairs. We found that mild repeat collaboration improves the performance of Japanese inventor teams and U.S. company teams. Yet, excessive repeat collaboration does not significantly help innovation at both the inventor and company levels in both countries. To control for unobserved heterogeneity, we performed a detailed regression analysis and the results were consistent with our simple observations. The presented results revealed the intricate effect of collaboration on innovation, which may also be observed in other creative projects. PMID:25799138

  8. Enzyme kinetics: the whole picture reveals hidden meanings.

    PubMed

    Pinto, Maria F; Estevinho, Berta N; Crespo, Rosa; Rocha, Fernando A; Damas, Ana M; Martins, Pedro M

    2015-06-01

    The methodology adopted by Michaelis and Menten in 1913 is still routinely used to characterize the catalytic power and selectivity of enzymes. These kinetic measurements must be performed soon after the purified enzyme is mixed with a large excess of substrate. Other time scales and solution compositions are no less physiologically relevant, but fall outside the range of applicability of the classical formalism. Here we show that the complete picture of an enzyme's mode of function is critically obscured by the limited scope of conventional kinetic analysis, even in the simplest case of a single active site without inhibition. This picture is now unveiled in a mathematically closed form that remains valid over the reaction time for all combinations of enzyme/substrate concentrations and rate constants. Algebraic simplicity is maintained in the new formalism when stationary reaction phases are considered. By achieving this century-old objective, the otherwise hidden role of the reversible binding step is revealed and atypical kinetic profiles are explained. Most singular kinetic behaviors are identified in a critical region of conditions that coincide with typical cell conditions. Because it is not covered by the Michaelis-Menten model, the critical region has been missed until now by low- and high-throughput screenings of new drugs. New possibilities are therefore raised for novel and once-promising inhibitors to therapeutically target enzymes.

  9. Tremor patches in Cascadia revealed by seismic array analysis

    NASA Astrophysics Data System (ADS)

    Ghosh, Abhijit; Vidale, John E.; Sweet, Justin R.; Creager, Kenneth C.; Wech, Aaron G.

    2009-09-01

    Episodic tremor and slip (ETS) events in Cascadia have recently been observed, illuminating the general area that radiates seismic energy in the form of non-volcanic tremor (NVT). However, the picture of the ETS zone remains fuzzy because of difficulties in tremor detection and location. To observe the intimate details of tremor, we deployed a dense 84-element small-aperture seismic array on the Olympic Peninsula, Washington, above the tremor migration path. It recorded the main ETS event in May 2008, as well as a weaker tremor episode two months earlier. Using a beamforming technique, we are able to capture and track tremor activity with an unprecedented resolution from southern Puget Sound to the Strait of Juan de Fuca. The array technique reveals up to four times more duration of tremor compared to the conventional envelope cross-correlation method. Our findings suggest that NVT is not uniformly distributed on the subduction interface, and unveils several distinct patches that release much of the tremor moment. The patches appear to be devoid of ordinary earthquakes, and may indicate the heterogeneity in fault strength that affects the modes of stress release within the ETS zone.

  10. Revealing amphiphilic nanodomains of anti-biofouling polymer coatings.

    PubMed

    Amadei, Carlo A; Yang, Rong; Chiesa, Matteo; Gleason, Karen K; Santos, Sergio

    2014-04-01

    Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be ∼1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry. PMID:24617757

  11. Single molecule studies reveal new mechanisms for microtubule severing

    NASA Astrophysics Data System (ADS)

    Ross, Jennifer; Diaz-Valencia, Juan Daniel; Morelli, Margaret; Zhang, Dong; Sharp, David

    2011-03-01

    Microtubule-severing enzymes are hexameric complexes made from monomeric enzyme subunits that remove tubulin dimers from the microtubule lattice. Severing proteins are known to remodel the cytoskeleton during interphase and mitosis, and are required in proper axon morphology and mammalian bone and cartilage development. We have performed the first single molecule imaging to determine where and how severing enzymes act to cut microtubules. We have focused on the original member of the group, katanin, and the newest member, fidgetin to compare their biophysical activities in vitro. We find that, as expected, severing proteins localize to areas of activity. Interestingly, the association is very brief: they do not stay bound nor do they bind cooperatively at active sites. The association duration changes with the nucleotide content, implying that the state in the catalytic cycle dictates binding affinity with the microtubule. We also discovered that, at lower concentrations, both katanin and fidgetin can depolymerize taxol-stabilized microtubules by removing terminal dimers. These studies reveal the physical regulation schemes to control severing activity in cells, and ultimately regulate cytoskeletal architecture. This work is supported by the March of Dimes Grant #5-FY09-46.

  12. Statistical universals reveal the structures and functions of human music

    PubMed Central

    Savage, Patrick E.; Brown, Steven; Sakai, Emi; Currie, Thomas E.

    2015-01-01

    Music has been called “the universal language of mankind.” Although contemporary theories of music evolution often invoke various musical universals, the existence of such universals has been disputed for decades and has never been empirically demonstrated. Here we combine a music-classification scheme with statistical analyses, including phylogenetic comparative methods, to examine a well-sampled global set of 304 music recordings. Our analyses reveal no absolute universals but strong support for many statistical universals that are consistent across all nine geographic regions sampled. These universals include 18 musical features that are common individually as well as a network of 10 features that are commonly associated with one another. They span not only features related to pitch and rhythm that are often cited as putative universals but also rarely cited domains including performance style and social context. These cross-cultural structural regularities of human music may relate to roles in facilitating group coordination and cohesion, as exemplified by the universal tendency to sing, play percussion instruments, and dance to simple, repetitive music in groups. Our findings highlight the need for scientists studying music evolution to expand the range of musical cultures and musical features under consideration. The statistical universals we identified represent important candidates for future investigation. PMID:26124105

  13. Revealing accretion onto black holes through X-ray reflection

    NASA Astrophysics Data System (ADS)

    Plant, D.; Fender, R.; Ponti, G.; Munoz-Darias, T.; Coriat, M.

    2014-07-01

    Understanding the dynamics behind black hole state transitions and the changes they reflect in outbursts has become long-standing problem. The X-ray reflection spectrum describes the interaction between the hard X-ray source (the power-law continuum) and the cool accretion disc it illuminates, and thus permits an indirect view of how the two evolve. We present a systematic analysis of the reflection spectrum throughout three outbursts (500+ RXTE observations) of the black hole binary GX 339-4, representing the largest study applying a self-consistent treatment of reflection to date. Particular attention is payed to the coincident evolution of the power-law and reflection, which can be used to determine the accretion geometry. The hard state is found to be distinctly reflection weak, however the ratio of reflection to power-law gradually increases as the source luminosity rises. In contrast the reflection is found dominate the power-law throughout most of the soft state, with increasing supremacy as the source decays. Using results from archival and AO-12 observations of GX 339-4 with XMM-Newton we reveal the dynamics driving this evolution and the nature of accretion onto black holes in outburst.

  14. [Meningococcal Septicemia Revealing Multiple Myeloma: A Case Report].

    PubMed

    Arakawa, Risturo; Mori, Nobuaki; Kagawa, Narito; Higuchi, Akiko; Tanaka, Masashi; Aoki, Yasuko; Seki, Shiko; Suzuki, Ryo

    2016-05-01

    Meningococcal infection is among the most devastating diseases. It is rarely seen in Japan. However, several environmental and host factors have been associated with increased risks of Neisseria meningitidis infection. We present a case of invasive N. meningitidis infection that revealed the presence of multiple myeloma. A 55-year-old Japanese man was admitted with fever and altered consciousness. He was sent to the intensive care unit for septic shock and disseminated intravascular coagulation. In addition to standard septic shock and multiple organ failure treatment, polymyxin-B immobilized column direct hemoperfusion was performed. His blood culture was positive for N. meningitidis. The patient gradually improved and was discharged on day 35. We evaluated the risk factors for the development of meningococcal infection. A laboratory examination showed that the patient was negative for human immunodeficiency virus antibody and had a normal total complement function. However, his serum immunoglobulin G level was high, and serum and urine protein electrophoresis detected a monoclonal gammopathy. A bone marrow examination led to the diagnosis of multiple myeloma. Because N. meningitidis bacteria spreads between individuals in close contact through the exchange of oral secretions, droplet precautions and antimicrobial chemoprophylaxis (ciprofloxacin, 500 mg) were implemented to prevent the spread of the meningococcal infection. Sporadic meningococcal infection warrants an evaluation for immunodeficiency and the prevention of secondary infection. PMID:27529971

  15. Modeling malaria genomics reveals transmission decline and rebound in Senegal.

    PubMed

    Daniels, Rachel F; Schaffner, Stephen F; Wenger, Edward A; Proctor, Joshua L; Chang, Hsiao-Han; Wong, Wesley; Baro, Nicholas; Ndiaye, Daouda; Fall, Fatou Ba; Ndiop, Medoune; Ba, Mady; Milner, Danny A; Taylor, Terrie E; Neafsey, Daniel E; Volkman, Sarah K; Eckhoff, Philip A; Hartl, Daniel L; Wirth, Dyann F

    2015-06-01

    To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006-2010 with a significant rebound in 2012-2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.

  16. Spatial Congruity Effects Reveal Metaphorical Thinking, not Polarity Correspondence.

    PubMed

    Dolscheid, Sarah; Casasanto, Daniel

    2015-01-01

    Spatial congruity effects have often been interpreted as evidence for metaphorical thinking, but an alternative account based on polarity correspondence (a.k.a. markedness) has challenged this view. Here we compared metaphor- and polarity-correspondence-based explanations for spatial congruity effects, using musical pitch as a testbed. In one experiment, English speakers classified high- and low-frequency pitches as "high" and "low," or as "front" and "back," to determine whether space-pitch congruity effects could be elicited by any marked spatial continuum. Although both pairs of terms describe bipolar spatial continuums, we found congruity effects only for high/low judgments, indicating that markedness is not sufficient to produce space-pitch congruity effects. A second experiment confirmed that there were no space-pitch congruity effects for another pair of terms that have clear markedness (big/small), but which do not denote spatial height. By contrast, this experiment showed congruity effects for words that cued an appropriate vertical spatial schema (tall/short), even though these words are not used conventionally in English to describe pitches, ruling out explanations for the observed pattern of results based on verbal polysemy. Together, results suggest that space-pitch congruity effects reveal metaphorical uses of spatial schemas, not polarity correspondence effects. PMID:26635713

  17. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

    PubMed

    Tempel, Wolfram; Rabeh, Wael M; Bogan, Katrina L; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A; Park, Hee-Won; Brenner, Charles

    2007-10-01

    The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+. PMID:17914902

  18. Single-cell chromatin accessibility reveals principles of regulatory variation

    PubMed Central

    Buenrostro, Jason D.; Wu, Beijing; Litzenburger, Ulrike M.; Ruff, Dave; Gonzales, Michael L.; Snyder, Michael P.; Chang, Howard Y.; Greenleaf, William J.

    2015-01-01

    Cell-to-cell variation is a universal feature of life that impacts a wide range of biological phenomena, from developmental plasticity1,2 to tumor heterogeneity3. While recent advances have improved our ability to document cellular phenotypic variation4–8 the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of cellular DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells via assay for transposase-accessible chromatin using sequencing (ATAC-seq). Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single-cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provides insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type specific accessibility variance across 8 cell types. Targeted perturbations of cell cycle or transcription factor signaling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome topological domains9 de novo, linking single-cell accessibility variation to three-dimensional genome organization. All together, single-cell analysis of DNA accessibility provides new insight into cellular variation of the “regulome.” PMID:26083756

  19. Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action

    DOE PAGES

    Huo, Lu; Davis, Ian; Liu, Fange; Andi, Babak; Esaki, Shingo; Iwaki, Hiroaki; Hasegawa, Yoshie; Orville, Allen M.; Liu, Aimin

    2015-01-07

    Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for ‘disarming’ the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacylmore » intermediate and an NAD+-bound complex from an active site mutant. These covalent intermediates are characterized by single-crystal and solution-state electronic absorption spectroscopy. The crystal structures reveal that the substrate undergoes an E/Z isomerization at the enzyme active site before an sp3-to-sp2 transition during enzyme-mediated oxidation.« less

  20. Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action

    SciTech Connect

    Huo, Lu; Davis, Ian; Liu, Fange; Andi, Babak; Esaki, Shingo; Iwaki, Hiroaki; Hasegawa, Yoshie; Orville, Allen M.; Liu, Aimin

    2015-01-07

    Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for ‘disarming’ the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl intermediate and an NAD+-bound complex from an active site mutant. These covalent intermediates are characterized by single-crystal and solution-state electronic absorption spectroscopy. The crystal structures reveal that the substrate undergoes an E/Z isomerization at the enzyme active site before an sp3-to-sp2 transition during enzyme-mediated oxidation.

  1. Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier

    PubMed Central

    Rinschen, Markus M.; Wu, Xiongwu; König, Tim; Pisitkun, Trairak; Hagmann, Henning; Pahmeyer, Caroline; Lamkemeyer, Tobias; Kohli, Priyanka; Schnell, Nicole; Schermer, Bernhard; Dryer, Stuart; Brooks, Bernard R.; Beltrao, Pedro; Krueger, Marcus

    2014-01-01

    Diseases of the kidney filtration barrier are a leading cause of ESRD. Most disorders affect the podocytes, polarized cells with a limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas of in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified in an unbiased tandem mass spectrometry–based approach. We discovered 2449 phosphorylated proteins corresponding to 4079 identified high-confidence phosphorylated residues and performed a systematic bioinformatics analysis of this dataset. We discovered 146 phosphorylation sites on proteins abundantly expressed in podocytes. The prohibitin homology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), located within a phosphorylation motif that is mutated in human genetic forms of proteinuria. The T234 site resides at the interface of podocin dimers. Free energy calculation through molecular dynamic simulations revealed a role for T234 in regulating podocin dimerization. We show that phosphorylation critically regulates formation of high molecular weight complexes and that this may represent a general principle for the assembly of proteins containing prohibitin homology domains. PMID:24511133

  2. Geometric Mechanics Reveals Optimal Complex Terrestrial Undulation Patterns

    NASA Astrophysics Data System (ADS)

    Gong, Chaohui; Astley, Henry; Schiebel, Perrin; Dai, Jin; Travers, Matthew; Goldman, Daniel; Choset, Howie; CMU Team; GT Team

    Geometric mechanics offers useful tools for intuitively analyzing biological and robotic locomotion. However, utility of these tools were previously restricted to systems that have only two internal degrees of freedom and in uniform media. We show kinematics of complex locomotors that make intermittent contacts with substrates can be approximated as a linear combination of two shape bases, and can be represented using two variables. Therefore, the tools of geometric mechanics can be used to analyze motions of locomotors with many degrees of freedom. To demonstrate the proposed technique, we present studies on two different types of snake gaits which utilize combinations of waves in the horizontal and vertical planes: sidewinding (in the sidewinder rattlesnake C. cerastes) and lateral undulation (in the desert specialist snake C. occipitalis). C. cerastes moves by generating posteriorly traveling body waves in the horizontal and vertical directions, with a relative phase offset equal to +/-π/2 while C. occipitalismaintains a π/2 offset of a frequency doubled vertical wave. Geometric analysis reveals these coordination patterns enable optimal movement in the two different styles of undulatory terrestrial locomotion. More broadly, these examples demonstrate the utility of geometric mechanics in analyzing realistic biological and robotic locomotion.

  3. Modeling malaria genomics reveals transmission decline and rebound in Senegal

    PubMed Central

    Daniels, Rachel F.; Schaffner, Stephen F.; Wenger, Edward A.; Proctor, Joshua L.; Chang, Hsiao-Han; Wong, Wesley; Baro, Nicholas; Ndiaye, Daouda; Fall, Fatou Ba; Ndiop, Medoune; Ba, Mady; Milner, Danny A.; Taylor, Terrie E.; Neafsey, Daniel E.; Volkman, Sarah K.; Eckhoff, Philip A.; Hartl, Daniel L.; Wirth, Dyann F.

    2015-01-01

    To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006–2010 with a significant rebound in 2012–2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination. PMID:25941365

  4. Revealing water’s secrets: deuterium depleted water

    PubMed Central

    2013-01-01

    Background The anomalous properties of water have been of great interest for generations of scientists. However the impact of small amount of deuterium content which is always present in water has never been explored before. For the first time the fundamental properties of deuterium depleted (light) water at 4°C and 20°C are here presented. Results The obtained results show the important role of the deuterium in the properties of bulk water. At 4°C the lowest value of the kinematic viscosity (1.46 mm2/s) has been found for 96.5 ppm D/H ratio. The significant deviation in surface tension values has been observed in deuterium depleted water samples at the both temperature regimes. The experimental data provides direct evidence that density, surface tension and viscosity anomalies of water are caused by the presence of variable concentration of deuterium which leads to the formation of water clusters of different size and quantity. Conclusions The investigated properties of light water reveal the origin of the water anomalies. The new theoretical model of cluster formation with account of isotope effect is proposed. PMID:23773696

  5. Multiple etiologies for Alzheimer disease are revealed by segregation analysis

    SciTech Connect

    Rao, V.S.; Connor-Lacke, L.; Cupplies, L.A.; Growdon, J.H.; Farrer, L.A.; Duijn, C.M. van

    1994-11-01

    We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.

  6. [Information processing in the human brain revealed by eyeblink].

    PubMed

    Nakano, Tamami

    2014-01-01

    People spontaneously generate an eyeblink every few seconds. It is generally accepted that eyeblinks are necessary for ocular lubrication, but spontaneous eyeblinks actually occur several times more frequently than necessary for lubrication. Thus, the functional role of most spontaneous eyeblinks has remained unclear. We found that peoples blinked in synchrony while viewing the same video stories. This blink synchronization specifically occured at the implicit breakpoints of the video stories. Moreover, in face-to-face communication, the listeners blinked with a delay of 0.25-0.5 s after the speaker blinked at the end and during pauses in speech. In contrast, the individuals with autism spectrum disorders, which are characterized by impaired social communication, did not show any eyeblink synchronization with the speaker. These facts demonstrate that spontaneous eyeblink is involved in the contextual segmentation of information, and that eyeblinks have a social function to share the contextual segmentation with others. Futhermore, our neuroimaging study revealed that, while viewing videos, cortical activity momentarily decreases in the dorsal attention network after blink onset but increases in the default-mode network. These results suggest that the spontaneous eyeblink is involved in the disengagement of attention at an implicit contextual breakpoint by controlling the balance between the two competing networks. PMID:24371126

  7. Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

    SciTech Connect

    Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; Han, Gye Won; Liu, Wei; Zatsepin, Nadia A.; James, Daniel; Wang, Dingjie; Nelson, Garrett; Weierstall, Uwe; Sawaya, Michael R.; Xu, Qingping; Messerschmidt, Marc; Williams, Garth J.; Boutet, Sébastien; Yefanov, Oleksandr M.; White, Thomas A.; Wang, Chong; Ishchenko, Andrii; Tirupula, Kalyan C.; Desnoyer, Russell; Coe, Jesse; Conrad, Chelsie E.; Fromme, Petra; Stevens, Raymond C.; Katritch, Vsevolod; Karnik, Sadashiva S.; Cherezov, Vadim

    2015-05-07

    We report that angiotensin II type 1 receptor (AT1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT1R blockers (ARBs), the structural basis for AT1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT1R in complex with its selective antagonist ZD7155 at 2.9 Å resolution. The AT1R-ZD7155 complex structure revealed key structural features ofAT1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design.

  8. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    PubMed Central

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-01-01

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level. PMID:27690004

  9. Tectonic deformation revealed in baldcypress trees at Reelfoot Lake, Tennessee

    SciTech Connect

    VanArsdale, R.; Stahle, D.; Cleaveland, M. )

    1991-07-01

    Tree-ring analyses of baldcypress (Taxodium distichum) from Reelfoot Lake, Tennessee, support historical accounts that the lake formed during the great New Madrid earthquakes of 1811--1812. Due to ground subsidence and permanent flooding all of the bottomland hardwood trees within the impounded area were killed. However, many water tolerant baldcypress survived, and hundreds of 200 to 800 year old baldcypress outline the positions of former stream channels drowned by the subsidence. Dendrochronological analyses of multiple cores from 21 baldcypress in the lake reveal several pronounced growth responses to the 1811--1812 earthquakes. These responses include a great surge in radial growth during the decade following the earthquakes and a permanent reduction in wood density beginning in 1812. These and other growth responses to the 1811--1912 earthquakes may allow us to determine if there have been other large earthquakes in the Reelfoot basin during the late Holocene and may help date the formation of other suspected sunk lands in the New Madrid seismic zone. 14 refs., 6 figs.

  10. Recombination patterns reveal information about centromere location on linkage maps.

    PubMed

    Limborg, Morten T; McKinney, Garrett J; Seeb, Lisa W; Seeb, James E

    2016-05-01

    Linkage mapping is often used to identify genes associated with phenotypic traits and for aiding genome assemblies. Still, many emerging maps do not locate centromeres - an essential component of the genomic landscape. Here, we demonstrate that for genomes with strong chiasma interference, approximate centromere placement is possible by phasing the same data used to generate linkage maps. Assuming one obligate crossover per chromosome arm, information about centromere location can be revealed by tracking the accumulated recombination frequency along linkage groups, similar to half-tetrad analyses. We validate the method on a linkage map for sockeye salmon (Oncorhynchus nerka) with known centromeric regions. Further tests suggest that the method will work well in other salmonids and other eukaryotes. However, the method performed weakly when applied to a male linkage map (rainbow trout; O. mykiss) characterized by low and unevenly distributed recombination - a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations, our method should work well for high-density maps in species with strong recombination interference and will enrich many existing and future mapping resources. PMID:26561199

  11. Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression

    PubMed Central

    Koo, Hyun-Jung; Park, Wook-Ha; Yang, Jae-Seong; Yu, Myeong-Hee; Kim, Sanguk; Pak, Youngmi Kim

    2011-01-01

    The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ0) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ0 cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions. PMID:21738461

  12. Automatic decoding of facial movements reveals deceptive pain expressions

    PubMed Central

    Bartlett, Marian Stewart; Littlewort, Gwen C.; Frank, Mark G.; Lee, Kang

    2014-01-01

    Summary In highly social species such as humans, faces have evolved to convey rich information for social interaction, including expressions of emotions and pain [1–3]. Two motor pathways control facial movement [4–7]. A subcortical extrapyramidal motor system drives spontaneous facial expressions of felt emotions. A cortical pyramidal motor system controls voluntary facial expressions. The pyramidal system enables humans to simulate facial expressions of emotions not actually experienced. Their simulation is so successful that they can deceive most observers [8–11]. Machine vision may, however, be able to distinguish deceptive from genuine facial signals by identifying the subtle differences between pyramidally and extrapyramidally driven movements. Here we show that human observers could not discriminate real from faked expressions of pain better than chance, and after training, improved accuracy to a modest 55%. However a computer vision system that automatically measures facial movements and performs pattern recognition on those movements attained 85% accuracy. The machine system’s superiority is attributable to its ability to differentiate the dynamics of genuine from faked expressions. Thus by revealing the dynamics of facial action through machine vision systems, our approach has the potential to elucidate behavioral fingerprints of neural control systems involved in emotional signaling. PMID:24656830

  13. Revealing Amphiphilic Nanodornains of Anti-Biofouling Polymer Coatings

    SciTech Connect

    Amadei, CA; Yang, R; Chiesa, M; Gleason, KK; Santos, S

    2014-04-09

    Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be similar to 1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

  14. Revealing amphiphilic nanodomains of anti-biofouling polymer coatings.

    PubMed

    Amadei, Carlo A; Yang, Rong; Chiesa, Matteo; Gleason, Karen K; Santos, Sergio

    2014-04-01

    Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be ∼1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

  15. Super-resolution Microscopy Reveals Compartmentalization of Peroxisomal Membrane Proteins*

    PubMed Central

    Galiani, Silvia; Waithe, Dominic; Reglinski, Katharina; Cruz-Zaragoza, Luis Daniel; Garcia, Esther; Clausen, Mathias P.; Schliebs, Wolfgang; Erdmann, Ralf; Eggeling, Christian

    2016-01-01

    Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future. PMID:27311714

  16. An acoustic microscopy technique reveals hidden morphological defenses in Daphnia.

    PubMed

    Laforsch, Christian; Ngwa, Wilfred; Grill, Wolfgang; Tollrian, Ralph

    2004-11-01

    Inducible defenses are common strategies for coping with the selective force of predation in heterogeneous environments. In recent years the conspicuous and often dramatic morphological plasticity of several waterflea species of the genus Daphnia have been found to be inducible defenses activated by chemical cues released by predators. However, the exact defensive mechanisms remained mysterious. Because even some minute morphological alterations proved to be protective against predatory invertebrates, it has been suggested that the visible morphological changes are only the tip of the iceberg of the entire protective mechanisms. Here we applied a method of ultrasonic microscopy with vector contrast at 1.2 GHz to probe hidden morphological defenses. We found that induction with predator kairomones increases the stability of the carapace in two Daphnia species up to 350%. This morphological plasticity provides a major advantage for the induced morphs during predation because predatory invertebrates need to crush or puncture the carapace of their prey to consume them. Our ultrastructural analyses revealed that the internal architecture of the carapace ensures maximal rigidity with minimal material investment. Our results uncover hidden morphological plasticity and suggest a reconsideration of former classification systems in defended and undefended genotypes in Daphnia and possibly in other prey organisms as well.

  17. Comparative genomic analysis reveals bilateral breast cancers are genetically independent.

    PubMed

    Song, Fangfang; Li, Xiangchun; Song, Fengju; Zhao, Yanrui; Li, Haixin; Zheng, Hong; Gao, Zhibo; Wang, Jun; Zhang, Wei; Chen, Kexin

    2015-10-13

    Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately. PMID:26378809

  18. Strategy revealing phenotypic differences among synthetic oscillator designs.

    PubMed

    Lomnitz, Jason G; Savageau, Michael A

    2014-09-19

    Considerable progress has been made in identifying and characterizing the component parts of genetic oscillators, which play central roles in all organisms. Nonlinear interaction among components is sufficiently complex that mathematical models are required to elucidate their elusive integrated behavior. Although natural and synthetic oscillators exhibit common architectures, there are numerous differences that are poorly understood. Utilizing synthetic biology to uncover basic principles of simpler circuits is a way to advance understanding of natural circadian clocks and rhythms. Following this strategy, we address the following questions: What are the implications of different architectures and molecular modes of transcriptional control for the phenotypic repertoire of genetic oscillators? Are there designs that are more realizable or robust? We compare synthetic oscillators involving one of three architectures and various combinations of the two modes of transcriptional control using a methodology that provides three innovations: a rigorous definition of phenotype, a procedure for deconstructing complex systems into qualitatively distinct phenotypes, and a graphical representation for illuminating the relationship between genotype, environment, and the qualitatively distinct phenotypes of a system. These methods provide a global perspective on the behavioral repertoire, facilitate comparisons of alternatives, and assist the rational design of synthetic gene circuitry. In particular, the results of their application here reveal distinctive phenotypes for several designs that have been studied experimentally as well as a best design among the alternatives that has yet to be constructed and tested. PMID:25019938

  19. On galaxy spiral arms' nature as revealed by rotation frequencies

    NASA Astrophysics Data System (ADS)

    Roca-Fàbrega, Santi; Valenzuela, Octavio; Figueras, Francesca; Romero-Gómez, Mercè; Velázquez, Héctor; Antoja, Teresa; Pichardo, Bárbara

    2013-07-01

    High-resolution N-body simulations using different codes and initial condition techniques reveal two different behaviours for the rotation frequency of transient spiral arms like structures. Whereas unbarred discs present spiral arms nearly corotating with disc particles, strong barred models (bulged or bulgeless) quickly develop a bar-spiral structure dominant in density, with a pattern speed almost constant in radius. As the bar strength decreases the arm departs from bar rigid rotation and behaves similar to the unbarred case. In strong barred models, we detect in the frequency space other subdominant and slower modes at large radii, in agreement with previous studies, however, we also detect them in the configuration space. We propose that the distinctive behaviour of the dominant spiral modes can be exploited in order to constraint the nature of Galactic spiral arms by the astrometric survey Gaia and by 2D spectroscopic surveys like Calar Alto Legacy Integral Field Area Survey (CALIFA) and Mapping Nearby Galaxies at APO (MANGA) in external galaxies.

  20. [Diagnosis and treatment of spastic angina revealed by cardiac arrest].

    PubMed

    Halna du Fretay, X; Mohammed Saeed, D; Benamer, H

    2014-12-01

    The prevalence of vasospastic angina is said to be low in Europe, but maybe because of a lack of diagnosis in the daily practice. However, coronary spasm is a common cause of cardiac arrest, especially among patients free of cardiac illness, and it should be systematically investigated after an unexplained cardiac arrest. Intracoronary spasm provocation test exposes patients to a lower risk compared to the risk of spontaneous spastic angina. Accurate modalities and diagnostic criteria have to be clarified for European population. Avoiding external causes of coronary spasm (such as cigarette smoking or more generally consuming coronary spasm inducing drugs) and prescribing antispastic medicine (first of all calcium channel blockers) are the basis of vasospastic angina treatment. However, recurrent coronary spasms have been reported despite an appropriate treatment and implantable automatic defibrillator has been implanted after case discussion when the onset of illness was cardiac arrest. We report the case of a patient recovering from cardiac arrest who had a positive spasm coronary provocation test, and was treated with calcium channel blockers and had been an automatic defibrillator implanted, with a coronary spasm provocation test performed afterward still contentious. While discussing this case, we are making a literature review of the diagnosis and treatment of spastic angina revealed by cardiac arrest.

  1. Key herbivores reveal limited functional redundancy on inshore coral reefs

    NASA Astrophysics Data System (ADS)

    Johansson, C. L.; van de Leemput, I. A.; Depczynski, M.; Hoey, A. S.; Bellwood, D. R.

    2013-12-01

    Marine ecosystems are facing increasing exposure to a range of stressors and declines in critical ecological functions. The likelihood of further loss of functions and resilience is dependent, in part, on the extent of functional redundancy (i.e. the capacity of one species to functionally compensate for the loss of another species) within critical functional groups. We used multiple metrics; species richness, generic richness, abundance and reserve capacity (i.e. the relative number of individuals available to fulfil the function if the numerically dominant species is lost), as indicators to assess the potential functional redundancy of four functional groups of herbivorous fishes (browsers, excavators, grazers and scrapers) in two of the worlds' most intact coral reef ecosystems: the Great Barrier Reef (GBR) and Ningaloo Reef in Western Australia. We found marked variations in potential redundancy among habitats within each reef system and functional groups. Despite negligible fishing of herbivorous fishes, coastal habitats in both reef systems had lower functional redundancy compared to offshore locations for all herbivorous fishes collectively and the four functional groups independently. This pattern was consistent in all four indicators of redundancy. The potential vulnerability of these coastal habitats is highlighted by recent shifts from coral to macroalgal dominance on several coastal reefs of the GBR. Our approach provides a simple yet revealing evaluation of potential functional redundancy. Moreover, it highlights the spatial variation in potential vulnerability and resilience of reef systems.

  2. Immunoprofiling of Rice Root Cortex Reveals Two Cortical Subdomains

    PubMed Central

    Henry, Sophia; Divol, Fanchon; Bettembourg, Mathilde; Bureau, Charlotte; Guiderdoni, Emmanuel; Périn, Christophe; Diévart, Anne

    2016-01-01

    The formation and differentiation of aerenchyma, i.e., air-containing cavities that are critical for flooding tolerance, take place exclusively in the cortex. The understanding of development and differentiation of the cortex is thus an important issue; however, studies on this tissue are limited, partly because of the lack of available molecular tools. We screened a commercially available library of cell wall antibodies to identify markers of cortical tissue in rice roots. Out of the 174 antibodies screened, eight were cortex-specific. Our analysis revealed that two types of cortical tissues are present in rice root seedlings. We named these cell layers “inner” and “outer” based on their location relative to the stele. We then used the antibodies to clarify cell identity in lateral roots. Without these markers, previous studies could not distinguish between the cortex and sclerenchyma in small lateral roots. By immunostaining lateral root sections, we showed that the internal ground tissue in small lateral roots has outer cortical identity. PMID:26779208

  3. Maximal Neighbor Similarity Reveals Real Communities in Networks

    NASA Astrophysics Data System (ADS)

    Žalik, Krista Rizman

    2015-12-01

    An important problem in the analysis of network data is the detection of groups of densely interconnected nodes also called modules or communities. Community structure reveals functions and organizations of networks. Currently used algorithms for community detection in large-scale real-world networks are computationally expensive or require a priori information such as the number or sizes of communities or are not able to give the same resulting partition in multiple runs. In this paper we investigate a simple and fast algorithm that uses the network structure alone and requires neither optimization of pre-defined objective function nor information about number of communities. We propose a bottom up community detection algorithm in which starting from communities consisting of adjacent pairs of nodes and their maximal similar neighbors we find real communities. We show that the overall advantage of the proposed algorithm compared to the other community detection algorithms is its simple nature, low computational cost and its very high accuracy in detection communities of different sizes also in networks with blurred modularity structure consisting of poorly separated communities. All communities identified by the proposed method for facebook network and E-Coli transcriptional regulatory network have strong structural and functional coherence.

  4. Ternary structure reveals mechanism of a membrane diacylglycerol kinase

    DOE PAGES

    Li, Dianfan; Stansfeld, Phillip J.; Sansom, Mark S. P.; Keogh, Aaron; Vogeley, Lutz; Howe, Nicole; Lyons, Joseph A.; Aragao, David; Fromme, Petra; Fromme, Raimund; et al

    2015-12-17

    Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternarymore » structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. As a result, the active site architecture shows clear evidence of having arisen by convergent evolution.« less

  5. Structure of the Angiotensin Receptor Revealed by Serial Femtosecond Crystallography

    DOE PAGES

    Zhang, Haitao; Unal, Hamiyet; Gati, Cornelius; Han, Gye Won; Liu, Wei; Zatsepin, Nadia A.; James, Daniel; Wang, Dingjie; Nelson, Garrett; Weierstall, Uwe; et al

    2015-05-07

    We report that angiotensin II type 1 receptor (AT1R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT1R blockers (ARBs), the structural basis for AT1R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT1R in complex with its selective antagonist ZD7155 at 2.9 Å resolution. Themore » AT1R-ZD7155 complex structure revealed key structural features ofAT1R and critical interactions for ZD7155 binding. Finally, docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design.« less

  6. Global Population Genetic Structure of Caenorhabditis remanei Reveals Incipient Speciation

    PubMed Central

    Dey, Alivia; Jeon, Yong; Wang, Guo-Xiu; Cutter, Asher D.

    2012-01-01

    Mating system transitions dramatically alter the evolutionary trajectories of genomes that can be revealed by contrasts of species with disparate modes of reproduction. For such transitions in Caenorhabditis nematodes, some major causes of genome variation in selfing species have been discerned. And yet, we have only limited understanding of species-wide population genetic processes for their outcrossing relatives, which represent the reproductive state of the progenitors of selfing species. Multilocus–multipopulation sequence polymorphism data provide a powerful means to uncover the historical demography and evolutionary processes that shape genomes. Here we survey nucleotide polymorphism across the X chromosome for three populations of the outcrossing nematode Caenorhabditis remanei and demonstrate its divergence from a fourth population describing a closely related new species from China, C. sp. 23. We find high genetic variation globally and within each local population sample. Despite geographic barriers and moderate genetic differentiation between Europe and North America, considerable gene flow connects C. remanei populations. We discovered C. sp. 23 while investigating C. remanei, observing strong genetic differentiation characteristic of reproductive isolation that was confirmed by substantial F2 hybrid breakdown in interspecific crosses. That C. sp. 23 represents a distinct biological species provides a cautionary example of how standard practice can fail for mating tests of species identity in this group. This species pair permits full application of divergence population genetic methods to obligately outcrossing species of Caenorhabditis and also presents a new focus for interrogation of the genetics and evolution of speciation with the Caenorhabditis model system. PMID:22649079

  7. Substrate Channel in Nitrogenase Revealed by a Molecular Dynamics Approach

    SciTech Connect

    Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C.

    2014-03-22

    Mo-dependent nitrogenase catalyzes the biological reduction of N2 to 2NH3 at the FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized sub-microsecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel not previously reported. The viability of the proposed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, with discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

  8. In vivo behavior of NTBI revealed by automated quantification system.

    PubMed

    Ito, Satoshi; Ikuta, Katsuya; Kato, Daisuke; Lynda, Addo; Shibusa, Kotoe; Niizeki, Noriyasu; Toki, Yasumichi; Hatayama, Mayumi; Yamamoto, Masayo; Shindo, Motohiro; Iizuka, Naomi; Kohgo, Yutaka; Fujiya, Mikihiro

    2016-08-01

    Non-Tf-bound iron (NTBI), which appears in serum in iron overload, is thought to contribute to organ damage; the monitoring of serum NTBI levels may therefore be clinically useful in iron-overloaded patients. However, NTBI quantification methods remain complex, limiting their use in clinical practice. To overcome the technical difficulties often encountered, we recently developed a novel automated NTBI quantification system capable of measuring large numbers of samples. In the present study, we investigated the in vivo behavior of NTBI in human and animal serum using this newly established automated system. Average NTBI in healthy volunteers was 0.44 ± 0.076 μM (median 0.45 μM, range 0.28-0.66 μM), with no significant difference between sexes. Additionally, serum NTBI rapidly increased after iron loading, followed by a sudden disappearance. NTBI levels also decreased in inflammation. The results indicate that NTBI is a unique marker of iron metabolism, unlike other markers of iron metabolism, such as serum ferritin. Our new automated NTBI quantification method may help to reveal the clinical significance of NTBI and contribute to our understanding of iron overload. PMID:27086349

  9. Enzyme kinetics: the whole picture reveals hidden meanings.

    PubMed

    Pinto, Maria F; Estevinho, Berta N; Crespo, Rosa; Rocha, Fernando A; Damas, Ana M; Martins, Pedro M

    2015-06-01

    The methodology adopted by Michaelis and Menten in 1913 is still routinely used to characterize the catalytic power and selectivity of enzymes. These kinetic measurements must be performed soon after the purified enzyme is mixed with a large excess of substrate. Other time scales and solution compositions are no less physiologically relevant, but fall outside the range of applicability of the classical formalism. Here we show that the complete picture of an enzyme's mode of function is critically obscured by the limited scope of conventional kinetic analysis, even in the simplest case of a single active site without inhibition. This picture is now unveiled in a mathematically closed form that remains valid over the reaction time for all combinations of enzyme/substrate concentrations and rate constants. Algebraic simplicity is maintained in the new formalism when stationary reaction phases are considered. By achieving this century-old objective, the otherwise hidden role of the reversible binding step is revealed and atypical kinetic profiles are explained. Most singular kinetic behaviors are identified in a critical region of conditions that coincide with typical cell conditions. Because it is not covered by the Michaelis-Menten model, the critical region has been missed until now by low- and high-throughput screenings of new drugs. New possibilities are therefore raised for novel and once-promising inhibitors to therapeutically target enzymes. PMID:25808291

  10. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength

    PubMed Central

    Paskin, Taylor R.; Jellies, John; Bacher, Jessica; Beane, Wendy S.

    2014-01-01

    Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green), as well as ultraviolet (UV) and infrared (IR) which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV) causing the most intense photophobic responses while longer wavelengths produce no effect (red) or an apparent attraction (IR). In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength) and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment. PMID:25493551

  11. Single-cell chromatin accessibility reveals principles of regulatory variation.

    PubMed

    Buenrostro, Jason D; Wu, Beijing; Litzenburger, Ulrike M; Ruff, Dave; Gonzales, Michael L; Snyder, Michael P; Chang, Howard Y; Greenleaf, William J

    2015-07-23

    Cell-to-cell variation is a universal feature of life that affects a wide range of biological phenomena, from developmental plasticity to tumour heterogeneity. Although recent advances have improved our ability to document cellular phenotypic variation, the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of mammalian DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) integrated into a programmable microfluidics platform. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type-specific accessibility variance across eight cell types. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome compartments de novo, linking single-cell accessibility variation to three-dimensional genome organization. Single-cell analysis of DNA accessibility provides new insight into cellular variation of the 'regulome'.

  12. Tracking of Arctic terns Sterna paradisaea reveals longest animal migration.

    PubMed

    Egevang, Carsten; Stenhouse, Iain J; Phillips, Richard A; Petersen, Aevar; Fox, James W; Silk, Janet R D

    2010-02-01

    The study of long-distance migration provides insights into the habits and performance of organisms at the limit of their physical abilities. The Arctic tern Sterna paradisaea is the epitome of such behavior; despite its small size (<125 g), banding recoveries and at-sea surveys suggest that its annual migration from boreal and high Arctic breeding grounds to the Southern Ocean may be the longest seasonal movement of any animal. Our tracking of 11 Arctic terns fitted with miniature (1.4-g) geolocators revealed that these birds do indeed travel huge distances (more than 80,000 km annually for some individuals). As well as confirming the location of the main wintering region, we also identified a previously unknown oceanic stopover area in the North Atlantic used by birds from at least two breeding populations (from Greenland and Iceland). Although birds from the same colony took one of two alternative southbound migration routes following the African or South American coast, all returned on a broadly similar, sigmoidal trajectory, crossing from east to west in the Atlantic in the region of the equatorial Intertropical Convergence Zone. Arctic terns clearly target regions of high marine productivity both as stopover and wintering areas, and exploit prevailing global wind systems to reduce flight costs on long-distance commutes.

  13. Historical Reconstruction Reveals Recovery in Hawaiian Coral Reefs

    PubMed Central

    Kittinger, John N.; Pandolfi, John M.; Blodgett, Jonathan H.; Hunt, Terry L.; Jiang, Hong; Maly, Kepā; McClenachan, Loren E.; Schultz, Jennifer K.; Wilcox, Bruce A.

    2011-01-01

    Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (∼AD 1400–1820) and an ongoing recovery in the NWHI (∼AD 1950–2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>103 km2). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts. PMID:21991311

  14. Integrative modelling reveals mechanisms linking productivity and plant species richness.

    PubMed

    Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

    2016-01-21

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems. PMID:26760203

  15. Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

    SciTech Connect

    Ma, Li Jun; van der Does, H. C.; Borkovich, Katherine A.; Coleman, Jeffrey J.; Daboussi, Marie-Jose; Di Pietro, Antonio; Dufresne, Marie; Freitag, Michael; Grabherr, Manfred; Henrissat, Bernard; Houterman, Petra M.; Kang, Seogchan; Shim, Won-Bo; Wolochuk, Charles; Xie, Xiaohui; Xu, Jin Rong; Antoniw, John; Baker, Scott E.; Bluhm, Burton H.; Breakspear, Andrew; Brown, Daren W.; Butchko, Robert A.; Chapman, Sinead; Coulson, Richard; Coutinho, Pedro M.; Danchin, Etienne G.; Diener, Andrew; Gale, Liane R.; Gardiner, Donald; Goff, Steven; Hammond-Kossack, Kim; Hilburn, Karen; Hua-Van, Aurelie; Jonkers, Wilfried; Kazan, Kemal; Kodira, Chinnappa D.; Koehrsen, Michael; Kumar, Lokesh; Lee, Yong Hwan; Li, Liande; Manners, John M.; Miranda-Saavedra, Diego; Mukherjee, Mala; Park, Gyungsoon; Park, Jongsun; Park, Sook Young; Proctor, Robert H.; Regev, Aviv; Ruiz-Roldan, M. C.; Sain, Divya; Sakthikumar, Sharadha; Sykes, Sean; Schwartz, David C.; Turgeon, Barbara G.; Wapinski, Ilan; Yoder, Olen; Young, Sarah; Zeng, Qiandong; Zhou, Shiguo; Galagan, James; Cuomo, Christina A.; Kistler, H. Corby; Rep, Martijn

    2010-03-18

    Fusarium species are among the most important phytopathogenic and toxigenic fungi, having significant impact on crop production and animal health. Distinctively, members of the F. oxysporum species complex exhibit wide host range but discontinuously distributed host specificity, reflecting remarkable genetic adaptability. To understand the molecular underpinnings of diverse phenotypic traits and their evolution in Fusarium, we compared the genomes of three economically important and phylogenetically related, yet phenotypically diverse plant-pathogenic species, F. graminearum, F. verticillioides and F. oxysporum f. sp. lycopersici. Our analysis revealed greatly expanded lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes, accounting for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity. Experimentally, we demonstrate for the first time the transfer of two LS chromosomes between strains of F. oxysporum, resulting in the conversion of a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in the F. oxysporum species complex, putting the evolution of fungal pathogenicity into a new perspective.

  16. Candida milleri species reveals intraspecific genetic and metabolic polymorphisms.

    PubMed

    Vigentini, Ileana; Antoniani, Davide; Roscini, Luca; Comasio, Andrea; Galafassi, Silvia; Picozzi, Claudia; Corte, Laura; Compagno, Concetta; Dal Bello, Fabio; Cardinali, Gianluigi; Foschino, Roberto

    2014-09-01

    Candida milleri, together with Candida humilis, is the most representative yeast species found in type I sourdough ecosystems. In this work, comparison of the ITS region and the D1/D2 domain of 26S rDNA gene partial sequences, karyotyping, mtDNA-RFLP analysis, Intron Splice Site dispersion (ISS-PCR) and (GTG)5 microsatellite analyses, assimilation test of different carbohydrates, and metabolome assessment by FT-IR analysis, were investigated in seventeen strains isolated from four different companies as well as in type strains CBS6897(T) and CBS5658(T). Most isolates were ascribed to C. milleri, even if a strong relatedness was confirmed with C. humilis as well, particularly for three strains. Genetic characterization showed a high degree of intraspecific polymorphism since 12 different genotypes were discriminated. The number of chromosomes varied from 9 to 13 and their size ranged from less than 0.3 to over 2 Mbp. Phenotypic traits let to recognize 9 different profiles of carbon sources assimilation. FT-IR spectra from yeast cells cultivated in different media and collected at different growth phases revealed a diversity of behaviour among strains in accordance with the results of PCR-based fingerprinting. A clear evidence of the polymorphic status of C. milleri species is provided thus representing an important feature for the development of technological applications in bakery industries. PMID:24929720

  17. Can strong correlations be experimentally revealed for Ҡ -mesons?

    NASA Astrophysics Data System (ADS)

    Hiesmayr, Beatrix C.

    2014-11-01

    In 1964 the physicists John St. Bell working at CERN took the 1935-idea of Einstein-Podolsky-Rosen seriously and found that all theories based on local realism have to satisfy a certain inequality, nowadays dubbed Bell's inequality. Experiments with ordinary matter systems or light show violations of Bell's inequality favouring the quantum theory though a loophole free experiment has not yet been performed. This contribution presents an experimentally feasible Bell inequality for systems at higher energy scales, i.e. entangled neutral Ҡ -meson pairs that are typically produced in Φ -mesons decays or proton-antiproton annihilation processes. Strong requirements have to be overcome in order to achieve a conclusive tests, such a proposal was recently published. Surprisingly, this new Bell inequality reveals new features for weakly decaying particles, in particular, a strong sensitivity to the combined charge-conjugation-parity (CP) symmetry. Here-with, a puzzling relation between a symmetry breaking for mesons and Bell's inequality—which is a necessary and sufficient condition for the security of quantum cryptography protocols— is established. This becomes the more important since CP symmetry is related to the cosmological question why the antimatter disappeared after the Big Bang.

  18. Individual Differences Reveal Correlates of Hidden Hearing Deficits

    PubMed Central

    Masud, Salwa; Mehraei, Golbarg; Verhulst, Sarah; Shinn-Cunningham, Barbara G.

    2015-01-01

    Clinical audiometry has long focused on determining the detection thresholds for pure tones, which depend on intact cochlear mechanics and hair cell function. Yet many listeners with normal hearing thresholds complain of communication difficulties, and the causes for such problems are not well understood. Here, we explore whether normal-hearing listeners exhibit such suprathreshold deficits, affecting the fidelity with which subcortical areas encode the temporal structure of clearly audible sound. Using an array of measures, we evaluated a cohort of young adults with thresholds in the normal range to assess both cochlear mechanical function and temporal coding of suprathreshold sounds. Listeners differed widely in both electrophysiological and behavioral measures of temporal coding fidelity. These measures correlated significantly with each other. Conversely, these differences were unrelated to the modest variation in otoacoustic emissions, cochlear tuning, or the residual differences in hearing threshold present in our cohort. Electroencephalography revealed that listeners with poor subcortical encoding had poor cortical sensitivity to changes in interaural time differences, which are critical for localizing sound sources and analyzing complex scenes. These listeners also performed poorly when asked to direct selective attention to one of two competing speech streams, a task that mimics the challenges of many everyday listening environments. Together with previous animal and computational models, our results suggest that hidden hearing deficits, likely originating at the level of the cochlear nerve, are part of “normal hearing.” PMID:25653371

  19. Cassava root membrane proteome reveals activities during storage root maturation.

    PubMed

    Naconsie, Maliwan; Lertpanyasampatha, Manassawe; Viboonjun, Unchera; Netrphan, Supatcharee; Kuwano, Masayoshi; Ogasawara, Naotake; Narangajavana, Jarunya

    2016-01-01

    Cassava (Manihot esculenta Crantz) is one of the most important crops of Thailand. Its storage roots are used as food, feed, starch production, and be the important source for biofuel and biodegradable plastic production. Despite the importance of cassava storage roots, little is known about the mechanisms involved in their formation. This present study has focused on comparison of the expression profiles of cassava root proteome at various developmental stages using two-dimensional gel electrophoresis and LC-MS/MS. Based on an anatomical study using Toluidine Blue, the secondary growth was confirmed to be essential during the development of cassava storage root. To investigate biochemical processes occurring during storage root maturation, soluble and membrane proteins were isolated from storage roots harvested from 3-, 6-, 9-, and 12-month-old cassava plants. The proteins with differential expression pattern were analysed and identified to be associated with 8 functional groups: protein folding and degradation, energy, metabolism, secondary metabolism, stress response, transport facilitation, cytoskeleton, and unclassified function. The expression profiling of membrane proteins revealed the proteins involved in protein folding and degradation, energy, and cell structure were highly expressed during early stages of development. Integration of these data along with the information available in genome and transcriptome databases is critical to expand knowledge obtained solely from the field of proteomics. Possible role of identified proteins were discussed in relation with the activities during storage root maturation in cassava.

  20. Ecosystem-specific selection pressures revealed through comparative population genomics.

    PubMed

    Coleman, Maureen L; Chisholm, Sallie W

    2010-10-26

    Bacterial populations harbor vast genetic diversity that is continually shaped by abiotic and biotic selective pressures, as well as by neutral processes. Individuals coexisting in the same geographically defined population often have significantly different gene content, but whether this variation is largely adaptive or neutral remains poorly understood. Here we quantify heterogeneity in gene content for two model marine microbes, Prochlorococcus and Pelagibacter, within and between populations in the Atlantic and Pacific Oceans, to begin to understand the selective pressures that are shaping these "population genomes." We discovered a large fraction of genes that are rare in each population, reflecting continual gene transfer and loss. Despite this high variation within each population, only a few genes significantly differ in abundance between the two biogeochemically distinct environments; nearly all of these are related to phosphorus acquisition and are enriched in the Atlantic relative to the Pacific. Moreover, P-related genes from the two sites form phylogenetically distinct clusters, whereas housekeeping genes do not, consistent with a recent spread of adaptive P-related genes in the Atlantic populations. These findings implicate phosphorus availability as the dominant selective force driving divergence between these populations, and demonstrate the promise of this approach for revealing selective agents in more complex microbial systems.

  1. Acoustic telemetry reveals cryptic residency of whale sharks

    PubMed Central

    Cagua, E. Fernando; Cochran, Jesse E. M.; Rohner, Christoph A.; Prebble, Clare E. M.; Sinclair-Taylor, Tane H.; Pierce, Simon J.; Berumen, Michael L.

    2015-01-01

    Although whale sharks (Rhincodon typus) have been documented to move thousands of kilometres, they are most frequently observed at a few predictable seasonal aggregation sites. The absence of sharks at the surface during visual surveys has led to the assumption that sharks disperse to places unknown during the long ‘off-seasons’ at most of these locations. Here we compare 2 years of R. typus visual sighting records from Mafia Island in Tanzania to concurrent acoustic telemetry of tagged individuals. Sightings revealed a clear seasonal pattern with a peak between October and February and no sharks observed at other times. By contrast, acoustic telemetry demonstrated year-round residency of R. typus. The sharks use a different habitat in the off-season, swimming deeper and further away from shore, presumably in response to prey distributions. This behavioural change reduces the sharks' visibility, giving the false impression that they have left the area. We demonstrate, for the first time to our knowledge, year-round residency of unprovisioned, individual R. typus at an aggregation site, and highlight the importance of using multiple techniques to study the movement ecology of marine megafauna. PMID:25832816

  2. Spatial Congruity Effects Reveal Metaphorical Thinking, not Polarity Correspondence

    PubMed Central

    Dolscheid, Sarah; Casasanto, Daniel

    2015-01-01

    Spatial congruity effects have often been interpreted as evidence for metaphorical thinking, but an alternative account based on polarity correspondence (a.k.a. markedness) has challenged this view. Here we compared metaphor- and polarity-correspondence-based explanations for spatial congruity effects, using musical pitch as a testbed. In one experiment, English speakers classified high- and low-frequency pitches as “high” and “low,” or as “front” and “back,” to determine whether space-pitch congruity effects could be elicited by any marked spatial continuum. Although both pairs of terms describe bipolar spatial continuums, we found congruity effects only for high/low judgments, indicating that markedness is not sufficient to produce space-pitch congruity effects. A second experiment confirmed that there were no space-pitch congruity effects for another pair of terms that have clear markedness (big/small), but which do not denote spatial height. By contrast, this experiment showed congruity effects for words that cued an appropriate vertical spatial schema (tall/short), even though these words are not used conventionally in English to describe pitches, ruling out explanations for the observed pattern of results based on verbal polysemy. Together, results suggest that space-pitch congruity effects reveal metaphorical uses of spatial schemas, not polarity correspondence effects. PMID:26635713

  3. Cold exposure reveals two populations of microtubules in pulmonary endothelia

    PubMed Central

    Ochoa, Cristhiaan D.; Stevens, Troy

    2011-01-01

    Microtubules are composed of α-tubulin and β-tubulin dimers. Microtubules yield tubulin dimers when exposed to cold, which reassemble spontaneously to form microtubule fibers at 37°C. However, mammalian neurons, glial cells, and fibroblasts have cold-stable microtubules. While studying the microtubule toxicity mechanisms of the exotoxin Y from Pseudomonas aeruginosa in pulmonary microvascular endothelial cells, we observed that some endothelial microtubules were very difficult to disassemble in the cold. As a consequence, we designed studies to test the hypothesis that microvascular endothelium has a population of cold-stable microtubules. Pulmonary microvascular endothelial cells and HeLa cells (control) were grown under regular cell culture conditions, followed by exposure to an ice-cold water bath and a microtubule extraction protocol. Polymerized microtubules were detected by immunofluorescence confocal microscopy and Western blot analyses. After cold exposure, immunofluorescence revealed that the majority of HeLa cell microtubules disassembled, whereas a smaller population of endothelial cell microtubules disassembled. Immunoblot analyses showed that microvascular endothelial cells express the microtubule cold-stabilizing protein N-STOP (neuronal stable tubule-only polypeptides), and that N-STOP binds to endothelial microtubules after cold exposure, but not if microtubules are disassembled with nocodazole before cold exposure. Hence, pulmonary endothelia have a population of cold-stable microtubules. PMID:20971804

  4. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners

    PubMed Central

    Barnoud, Thibaut; Wilkey, Daniel W.; Merchant, Michael L.; Clark, Jennifer A.; Donninger, Howard

    2016-01-01

    RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K-Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID:26999212

  5. Effective Connectivity Reveals Strategy Differences in an Expert Calculator

    PubMed Central

    Minati, Ludovico; Sigala, Natasha

    2013-01-01

    Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material. PMID:24086291

  6. Soils reveal widespread manganese enrichment from industrial inputs.

    PubMed

    Herndon, Elizabeth M; Jin, Lixin; Brantley, Susan L

    2011-01-01

    It is well-known that metals are emitted to the air by human activities and subsequently deposited to the land surface; however, we have not adequately evaluated the geographic extent and ecosystem impacts of industrial metal loading to soils. Here, we demonstrate that atmospheric inputs have widely contaminated soils with Mn in industrialized regions. Soils record elemental fluxes impacting the Earth's surface and can be analyzed to quantify inputs and outputs during pedogenesis. We use a mass balance model to interpret details of Mn enrichment by examining soil, bedrock, precipitation, and porefluid chemistry in a first-order watershed in central Pennsylvania, USA. This reveals that ∼ 53% of Mn in ridge soils can be attributed to atmospheric deposition from anthropogenic sources. An analysis of published data sets indicates that over half of the soils surveyed in Pennsylvania (70%), North America (60%), and Europe (51%) are similarly enriched in Mn. We conclude that soil Mn enrichment due to industrial inputs is extensive, yet patchy in distribution due to source location, heterogeneity of lithology, vegetation, and other attributes of the land surface. These results indicate that atmospheric transport must be considered a potentially critical component of the global Mn cycle during the Anthropocene.

  7. Revealing and reducing uncertainties in climate impact assessments

    NASA Astrophysics Data System (ADS)

    Clark, M. P.

    2015-12-01

    Water resources planning and management involves understanding the vulnerability of water resource systems to a wide range of different stresses. A key responsibility is to identify defensible options for the design and management of systems under an uncertain and changing climate. In the water resources sector this requires defining a range of different climate change narratives in order to evaluate the vulnerability of infrastructure and the effectiveness of different management strategies to climate-related stresses. Recent research is just now beginning to reveal how different methodological choices can impact portrayals of climate risk. We present research showing that the common approaches to climate change assessments in the water sector are affected by substantial uncertainties in methods used for climate downscaling and hydrologic modeling, and suggest that many of these uncertainties are reducible. For example, improving continental scale hydrologic model parameters can reduce one source of uncertainty. We also present research to improve characterization of uncertainty, in order to reduce the extent to which the portrayal of climate change impacts depends on ad hoc methodological choices and provide a holistic estimate of the degree to which the climate change signal emerges from the envelope of uncertainty. We hope that this presentation stimulates discussion on the best practices for climate impact assessments, and ways to improve the robustness of water resources planning under a changing climate.

  8. Eukaryote culturomics of the gut reveals new species.

    PubMed

    Gouba, Nina; Raoult, Didier; Drancourt, Michel

    2014-01-01

    The repertoire of microeukaryotes in the human gut has been poorly explored, mainly in individuals living in northern hemisphere countries. We further explored this repertoire using PCR-sequencing and culture in seven individuals living in four tropical countries. A total of 41 microeukaryotes including 38 different fungal species and three protists were detected. Four fungal species, Davidiella tassiana, Davidiella sp., Corticiaceae sp., and Penicillium sp., were uniquely detected by culture; 27 fungal species were uniquely detected using PCR-sequencing and Candida albicans, Candida glabrata, Trichosporon asahii, Clavispora lusitaniae, Debaryomyces hansenii, Malassezia restricta, and Malassezia sp. were detected using both molecular and culture methods. Fourteen microeukaryotes were shared by the seven individuals, whereas 27 species were found in only one individual, including 11 species in Amazonia, nine species in Polynesia, five species in India, and two species in Senegal. These data support a worldwide distribution of Malassezia sp., Trichosporon sp., and Candida sp. in the gut mycobiome. Here, 13 fungal species and two protists, Stentor roeseli and Vorticella campanula, were observed for first time in the human gut. This study revealed a previously unsuspected diversity in the repertoire of human gut microeukaryotes, suggesting spots for further exploring this repertoire.

  9. Sequential analysis of the numerical Stroop effect reveals response suppression.

    PubMed

    Cohen Kadosh, Roi; Gevers, Wim; Notebaert, Wim

    2011-09-01

    Automatic processing of irrelevant stimulus dimensions has been demonstrated in a variety of tasks. Previous studies have shown that conflict between relevant and irrelevant dimensions can be reduced when a feature of the irrelevant dimension is repeated. The specific level at which the automatic process is suppressed (e.g., perceptual repetition, response repetition), however, is less understood. In the current experiment we used the numerical Stroop paradigm, in which the processing of irrelevant numerical values of 2 digits interferes with the processing of their physical size, to pinpoint the precise level of the suppression. Using a sequential analysis, we dissociated perceptual repetition from response repetition of the relevant and irrelevant dimension. Our analyses of reaction times, error rates, and diffusion modeling revealed that the congruity effect is significantly reduced or even absent when the response sequence of the irrelevant dimension, rather than the numerical value or the physical size, is repeated. These results suggest that automatic activation of the irrelevant dimension is suppressed at the response level. The current results shed light on the level of interaction between numerical magnitude and physical size as well as the effect of variability of responses and stimuli on automatic processing.

  10. Polymyalgia Rheumatica Revealing a Lymphoma: A Two-Case Report

    PubMed Central

    Chouk, Mickaël

    2016-01-01

    Introduction. Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatism types in elderly population. The link between cancer and PMR is a matter of debate. Methods. We report two cases of PMR leading to the diagnosis of lymphoma and the growing interest of PET-TDM in this indication. Results. A 84-year-old man known for idiopathic neutropenia presented an inflammatory arthromyalgia of the limb girdle since one month. Blood exams highlighted the presence of a monoclonal B cell clone. Bone marrow concluded to a B cell lymphoma of the marginal zone. He was successfully treated with 0.3 mg/kg/d of prednisone, and response was sustained after 6 months. A 73-year-old man known for prostatic neoplasia in remission for 5 years presented arthromyalgia of the limb girdle since one month. PET-CT revealed bursitis of the hips and the shoulders, no prostatic cancer recurrence, and a metabolically active iliac lymphadenopathy whose pathologic exam concluded to a low grade follicular lymphoma. He was successfully treated with 0.3 mg/kg/d of prednisone. Conclusion. These observations may imply that lymphoma is sometimes already present when PMR is diagnosed and PET-CT is a useful tool in the initial assessment of PMR to avoid missing neoplasia. PMID:27597921

  11. Revealing structural effects: electrochemical reactions of butanols on platinum.

    PubMed

    Rodríguez, José L; Souto, Ricardo M; Fernández-Mérida, Luis; Pastor, Elena

    2002-05-01

    Spectroelectrochemical studies on the reactivity of butanol isomers on Pt electrodes in perchloric acid medium led to the observation of structural effects that result from the different arrangements of atoms in the organic molecules. The use of differential electrochemical mass spectrometry (DEMS) to detect volatile products showed that all four isomers react on the electrode, though different product yields were observed for each compound. In spite of the differences in the electrochemical behaviour of the butanol isomers, a series of general processes accounts for the results obtained. The formation of strongly adsorbed residues by a dehydration process leading to the formation of a C=C bond was proposed for all isomers. Electroreduction of the adsorbates produces C(4) and C(3) alkanes, and the latter reveal the existence of a fragmentation process. The C(4) hydrocarbons can be formed by hydrogenation of these residues and by hydrogenolysis of alcohol molecules in the bulk solution which react at the electrode with adsorbed hydrogen. On the other hand, CO(2) is formed during electrooxidation of the adsorbed species. Partial-oxidation products containing a carbonyl group were detected from 0.2 M solutions of 1-butanol, isobutyl alcohol and sec-butyl alcohol. The tertiary alcohol tert-butyl alcohol only reacts in its adsorbed state.

  12. Fine-scaled human genetic structure revealed by SNP microarrays.

    PubMed

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.

  13. Microscopic study reveals the singular origins of growth

    NASA Astrophysics Data System (ADS)

    Yaari, G.; Nowak, A.; Rakocy, K.; Solomon, S.

    2008-04-01

    Anderson [Science 177, 293 (1972)] proposed the concept of complexity in order to describe the emergence and growth of macroscopic collective patterns out of the simple interactions of many microscopic agents. In the physical sciences this paradigm was implemented systematically and confirmed repeatedly by successful confrontation with reality. In the social sciences however, the possibilities to stage experiments to validate it are limited. During the 90's a series of dramatic political and economic events have provided the opportunity to do so. We exploit the resulting empirical evidence to validate a simple agent based alternative to the classical logistic dynamics. The post-liberalization empirical data from Poland confirm the theoretical prediction that the dynamics is dominated by singular rare events which insure the resilience and adaptability of the system. We have shown that growth is led by few singular “growth centers" (Fig. 1), that initially developed at a tremendous rate (Fig. 3), followed by a diffusion process to the rest of the country and leading to a positive growth rate uniform across the counties. In addition to the interdisciplinary unifying potential of our generic formal approach, the present work reveals the strong causal ties between the “softer" social conditions and their “hard" economic consequences.

  14. A parasite reveals cryptic phylogeographic history of its host.

    PubMed Central

    Nieberding, C.; Morand, S.; Libois, R.; Michaux, J. R.

    2004-01-01

    This study compares the continental phylogeographic patterns of two wild European species linked by a host-parasite relationship: the field mouse Apodemus sylvaticus and one of its specific parasites, the nematode Heligmosomoides polygyrus. A total of 740 base pairs (bp) of the mitochondrial cytochrome b (cyt b) gene were sequenced in 122 specimens of H. polygyrus and compared with 94 cyt b gene sequences (974 bp) previously acquired for A. sylvaticus. The results reveal partial spatial and temporal congruences in the differentiation of both species' lineages: the parasite and its host present three similar genetic and geographical lineages, i.e. Western European, Italian and Sicilian, and both species recolonized northwestern Europe from the Iberian refuge at the end of the Pleistocene. However, H. polygyrus presents three particular differentiation events. The relative rate of molecular evolution of the cyt b gene was estimated to be 1.5-fold higher in the parasite than in its host. Therefore, the use of H. polygyrus as a biological magnifying glass is discussed as this parasite may highlight previously undetected historical events of its host. The results show how incorporating phylogeographic information of an obligate associate can help to better understand the phylogeographic pattern of its host. PMID:15615681

  15. Scurvy revealed by difficulty walking: three cases in young children.

    PubMed

    Kitcharoensakkul, Maleewan; Schulz, Christa G; Kassel, Rachel; Khanna, Geetika; Liang, Shannon; Ngwube, Alexander; Baszis, Kevin W; Hunstad, David A; White, Andrew J

    2014-06-01

    Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. Dietary histories eventually revealed that all 3 patients had sharply limited intake of fruits and vegetables secondary to oral aversion, and 1 patient had autism. Radiographic changes of long bones were observed in all patients. Interestingly, all patients had concomitant vitamin D deficiency. After replacement with vitamin C, all patients recovered and started to walk again with improved leg pain. These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children. PMID:24847751

  16. Bioluminescence to reveal structure and interaction of coastal planktonic communities

    NASA Astrophysics Data System (ADS)

    Moline, Mark A.; Blackwell, Shelley M.; Case, James F.; Haddock, Steven H. D.; Herren, Christen M.; Orrico, Cristina M.; Terrill, Eric

    2009-02-01

    Ecosystem function will in large part be determined by functional groups present in biological communities. The simplest distinction with respect to functional groups of an ecosystem is the differentiation between primary and secondary producers. A challenge thus far has been to examine these groups simultaneously with sufficient temporal and spatial resolution for observations to be relevant to the scales of change in coastal oceans. This study takes advantage of general differences in the bioluminescence flash kinetics between planktonic dinoflagellates and zooplankton to measure relative abundances of the two groups within the same-time space volume. This novel approach for distinguishing these general classifications using a single sensor is validated using fluorescence data and exclusion experiments. The approach is then applied to data collected from an autonomous underwater vehicle surveying >500 km in Monterey Bay and San Luis Obispo Bay, CA during the summers of 2002-2004. The approach also reveals that identifying trophic interaction between the two planktonic communities may also be possible.

  17. Historical reconstruction reveals recovery in Hawaiian coral reefs.

    PubMed

    Kittinger, John N; Pandolfi, John M; Blodgett, Jonathan H; Hunt, Terry L; Jiang, Hong; Maly, Kepā; McClenachan, Loren E; Schultz, Jennifer K; Wilcox, Bruce A

    2011-01-01

    Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (~AD 1400-1820) and an ongoing recovery in the NWHI (~AD 1950-2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>10(3) km(2)). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts. PMID:21991311

  18. Archaeopteryx feathers and bone chemistry fully revealed via synchrotron imaging

    PubMed Central

    Bergmann, U.; Morton, R. W.; Manning, P. L.; Sellers, W. I.; Farrar, S.; Huntley, K. G.; Wogelius, R. A.; Larson, P.

    2010-01-01

    Evolution of flight in maniraptoran dinosaurs is marked by the acquisition of distinct avian characters, such as feathers, as seen in Archaeopteryx from the Solnhofen limestone. These rare fossils were pivotal in confirming the dinosauria-avian lineage. One of the key derived avian characters is the possession of feathers, details of which were remarkably preserved in the Lagerstätte environment. These structures were previously simply assumed to be impressions; however, a detailed chemical analysis has, until now, never been completed on any Archaeopteryx specimen. Here we present chemical imaging via synchrotron rapid scanning X-ray fluorescence (SRS-XRF) of the Thermopolis Archaeopteryx, which shows that portions of the feathers are not impressions but are in fact remnant body fossil structures, maintaining elemental compositions that are completely different from the embedding geological matrix. Our results indicate phosphorous and sulfur retention in soft tissue as well as trace metal (Zn and Cu) retention in bone. Other previously unknown chemical details of Archaeopteryx are also revealed in this study including: bone chemistry, taphonomy (fossilization process), and curation artifacts. SRS-XRF represents a major advancement in the study of the life chemistry and fossilization processes of Archaeopteryx and other extinct organisms because it is now practical to image the chemistry of large specimens rapidly at concentration levels of parts per million. This technique has wider application to the archaeological, forensic, and biological sciences, enabling the mapping of “unseen” compounds critical to understanding biological structures, modes of preservation, and environmental context. PMID:20457935

  19. Laser microsurgery reveals conserved viscoelastic behavior of the kinetochore

    PubMed Central

    Cojoc, Gheorghe; Roscioli, Emanuele; Zhang, Lijuan; García-Ulloa, Alfonso; Shah, Jagesh V.; Berns, Michael W.; Pavin, Nenad

    2016-01-01

    Accurate chromosome segregation depends on proper kinetochore–microtubule attachment. Upon microtubule interaction, kinetochores are subjected to forces generated by the microtubules. In this work, we used laser ablation to sever microtubules attached to a merotelic kinetochore, which is laterally stretched by opposing pulling forces exerted by microtubules, and inferred the mechanical response of the kinetochore from its length change. In both mammalian PtK1 cells and in the fission yeast Schizosaccharomyces pombe, kinetochores shortened after microtubule severing. Interestingly, the inner kinetochore–centromere relaxed faster than the outer kinetochore. Whereas in fission yeast all kinetochores relaxed to a similar length, in PtK1 cells the more stretched kinetochores remained more stretched. Simple models suggest that these differences arise because the mechanical structure of the mammalian kinetochore is more complex. Our study establishes merotelic kinetochores as an experimental model for studying the mechanical response of the kinetochore in live cells and reveals a viscoelastic behavior of the kinetochore that is conserved in yeast and mammalian cells. PMID:27002163

  20. An acoustic microscopy technique reveals hidden morphological defenses in Daphnia

    PubMed Central

    Laforsch, Christian; Ngwa, Wilfred; Grill, Wolfgang; Tollrian, Ralph

    2004-01-01

    Inducible defenses are common strategies for coping with the selective force of predation in heterogeneous environments. In recent years the conspicuous and often dramatic morphological plasticity of several waterflea species of the genus Daphnia have been found to be inducible defenses activated by chemical cues released by predators. However, the exact defensive mechanisms remained mysterious. Because even some minute morphological alterations proved to be protective against predatory invertebrates, it has been suggested that the visible morphological changes are only the tip of the iceberg of the entire protective mechanisms. Here we applied a method of ultrasonic microscopy with vector contrast at 1.2 GHz to probe hidden morphological defenses. We found that induction with predator kairomones increases the stability of the carapace in two Daphnia species up to 350%. This morphological plasticity provides a major advantage for the induced morphs during predation because predatory invertebrates need to crush or puncture the carapace of their prey to consume them. Our ultrastructural analyses revealed that the internal architecture of the carapace ensures maximal rigidity with minimal material investment. Our results uncover hidden morphological plasticity and suggest a reconsideration of former classification systems in defended and undefended genotypes in Daphnia and possibly in other prey organisms as well. PMID:15520396

  1. Scurvy revealed by difficulty walking: three cases in young children.

    PubMed

    Kitcharoensakkul, Maleewan; Schulz, Christa G; Kassel, Rachel; Khanna, Geetika; Liang, Shannon; Ngwube, Alexander; Baszis, Kevin W; Hunstad, David A; White, Andrew J

    2014-06-01

    Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. Dietary histories eventually revealed that all 3 patients had sharply limited intake of fruits and vegetables secondary to oral aversion, and 1 patient had autism. Radiographic changes of long bones were observed in all patients. Interestingly, all patients had concomitant vitamin D deficiency. After replacement with vitamin C, all patients recovered and started to walk again with improved leg pain. These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children.

  2. Revealing the intricate effect of collaboration on innovation.

    PubMed

    Inoue, Hiroyasu; Liu, Yang-Yu

    2015-01-01

    We studied the Japan and U.S. patent records of several decades to demonstrate the effect of collaboration on innovation. We found that statistically inventor teams slightly outperform solo inventors while company teams perform equally well as solo companies. By tracking the performance record of individual teams, we found that inventor teams' performance generally degrades with more repeat collaborations. Though company teams' performance displays strongly bursty behavior, long-term collaboration does not significantly help innovation. To systematically study the effect of repeat collaboration, we defined the repeat collaboration number of a team as the average number of collaborations over all the teammate pairs. We found that mild repeat collaboration improves the performance of Japanese inventor teams and U.S. company teams. Yet, excessive repeat collaboration does not significantly help innovation at both the inventor and company levels in both countries. To control for unobserved heterogeneity, we performed a detailed regression analysis and the results were consistent with our simple observations. The presented results revealed the intricate effect of collaboration on innovation, which may also be observed in other creative projects.

  3. Proteomics reveals potential biomarkers of seed vigor in sugarbeet.

    PubMed

    Catusse, Julie; Meinhard, Juliane; Job, Claudette; Strub, Jean-Marc; Fischer, Uwe; Pestsova, Elena; Westhoff, Peter; Van Dorsselaer, Alain; Job, Dominique

    2011-05-01

    To unravel biomarkers of seed vigor, an important trait conditioning crop yield, a comparative proteomic study was conducted with sugarbeet seed samples of varying vigor as generated by an invigoration treatment called hydropriming and an aging treatment called controlled deterioration. Comparative proteomics revealed proteins exhibiting contrasting behavior between seed samples. Thus, 18 proteins were up-regulated during priming and down-regulated during aging and further displayed an up-regulation upon priming of the aged seeds, meaning that down-regulation of these spot volumes during aging was reversible upon subsequent priming. Also, 11 proteins exhibited the converse behavior characterized by a decrease and an increase of the spot volumes during priming and aging of the control seeds, respectively, and a decrease in the spot volumes upon priming of the aged seeds. The results underpinned the role in seed vigor of several metabolic pathways involved in lipid and starch mobilization, protein synthesis or the methyl cycle. They also corroborate previous studies suggesting that the glyoxylate enzyme isocitrate lyase, the capacity of protein synthesis and components of abscisic acid signaling pathways are likely contributors of seed vigor.

  4. Maximal Neighbor Similarity Reveals Real Communities in Networks

    PubMed Central

    Žalik, Krista Rizman

    2015-01-01

    An important problem in the analysis of network data is the detection of groups of densely interconnected nodes also called modules or communities. Community structure reveals functions and organizations of networks. Currently used algorithms for community detection in large-scale real-world networks are computationally expensive or require a priori information such as the number or sizes of communities or are not able to give the same resulting partition in multiple runs. In this paper we investigate a simple and fast algorithm that uses the network structure alone and requires neither optimization of pre-defined objective function nor information about number of communities. We propose a bottom up community detection algorithm in which starting from communities consisting of adjacent pairs of nodes and their maximal similar neighbors we find real communities. We show that the overall advantage of the proposed algorithm compared to the other community detection algorithms is its simple nature, low computational cost and its very high accuracy in detection communities of different sizes also in networks with blurred modularity structure consisting of poorly separated communities. All communities identified by the proposed method for facebook network and E-Coli transcriptional regulatory network have strong structural and functional coherence. PMID:26680448

  5. Revealing the structure of the world airline network.

    PubMed

    Verma, T; Araújo, N A M; Herrmann, H J

    2014-07-09

    Resilience of most critical infrastructures against failure of elements that appear insignificant is usually taken for granted. The World Airline Network (WAN) is an infrastructure that reduces the geographical gap between societies, both small and large, and brings forth economic gains. With the extensive use of a publicly maintained data set that contains information about airports and alternative connections between these airports, we empirically reveal that the WAN is a redundant and resilient network for long distance air travel, but otherwise breaks down completely due to removal of short and apparently insignificant connections. These short range connections with moderate number of passengers and alternate flights are the connections that keep remote parts of the world accessible. It is surprising, insofar as there exists a highly resilient and strongly connected core consisting of a small fraction of airports (around 2.3%) together with an extremely fragile star-like periphery. Yet, in spite of their relevance, more than 90% of the world airports are still interconnected upon removal of this core. With standard and unconventional removal measures we compare both empirical and topological perceptions for the fragmentation of the world. We identify how the WAN is organized into different classes of clusters based on the physical proximity of airports and analyze the consequence of this fragmentation.

  6. Integrative modelling reveals mechanisms linking productivity and plant species richness

    NASA Astrophysics Data System (ADS)

    Grace, James B.; Anderson, T. Michael; Seabloom, Eric W.; Borer, Elizabeth T.; Adler, Peter B.; Harpole, W. Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M.; Pärtel, Meelis; Bakker, Jonathan D.; Buckley, Yvonne M.; Crawley, Michael J.; Damschen, Ellen I.; Davies, Kendi F.; Fay, Philip A.; Firn, Jennifer; Gruner, Daniel S.; Hector, Andy; Knops, Johannes M. H.; MacDougall, Andrew S.; Melbourne, Brett A.; Morgan, John W.; Orrock, John L.; Prober, Suzanne M.; Smith, Melinda D.

    2016-01-01

    How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

  7. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    PubMed

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

  8. Color-shape associations revealed with implicit association tests.

    PubMed

    Chen, Na; Tanaka, Kanji; Watanabe, Katsumi

    2015-01-01

    Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow). Makin and Wuerger tested the theory using the Implicit Association Test (IAT) and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow) in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow) can be observed by both direct and indirect experimental methods.

  9. Color-Shape Associations Revealed with Implicit Association Tests

    PubMed Central

    Chen, Na; Tanaka, Kanji; Watanabe, Katsumi

    2015-01-01

    Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow). Makin and Wuerger tested the theory using the Implicit Association Test (IAT) and did not find clear evidence for Kandinsky’s color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky’s theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow) in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people’s color-shape associations (circle-red, square-blue, triangle-yellow) can be observed by both direct and indirect experimental methods. PMID:25625717

  10. Noninvasive genetic sampling reveals intrasex territoriality in wolverines.

    PubMed

    Bischof, Richard; Gregersen, Espen R; Brøseth, Henrik; Ellegren, Hans; Flagstad, Øystein

    2016-03-01

    Due to its conspicuous manifestations and its capacity to shape the configuration and dynamics of wild populations, territorial behavior has long intrigued ecologists. Territoriality and other animal interactions in situ have traditionally been studied via direct observations and telemetry. Here, we explore whether noninvasive genetic sampling, which is increasingly supplementing traditional field methods in ecological research, can reveal territorial behavior in an elusive carnivore, the wolverine (Gulo gulo). Using the locations of genotyped wolverine scat samples collected annually over a period of 12 years in central Norway, we test three predictions: (1) male home ranges constructed from noninvasive genetic sampling data are larger than those of females, (2) individuals avoid areas used by other conspecifics of the same sex (intrasexual territoriality), and (3) avoidance of same-sex territories diminishes or disappears after the territory owner's death. Each of these predictions is substantiated by our results: sex-specific differences in home range size and intrasexual territoriality in wolverine are patently reflected in the spatial and temporal configuration of noninvasively collected genetic samples. Our study confirms that wildlife monitoring programs can utilize the spatial information in noninvasive genetic sampling data to detect and quantify home ranges and social organization. PMID:27087927

  11. Circular RNA profile in gliomas revealed by identification tool UROBORUS

    PubMed Central

    Song, Xiaofeng; Zhang, Naibo; Han, Ping; Moon, Byoung-San; Lai, Rose K.; Wang, Kai; Lu, Wange

    2016-01-01

    Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/. PMID:26873924

  12. How choice reveals, and shapes, expected hedonic outcome

    PubMed Central

    Sharot, Tali; De Martino, Benedetto; Dolan, Raymond J

    2009-01-01

    Humans tend to modify their attitudes to align with past action. For example, after choosing between similarly valued alternatives, people rate the selected option as better than they originally did, and the rejected option as worse. However, it is unknown whether these modifications in evaluation reflect an underlying change in the physiological representation of a stimulus’ expected hedonic value and our emotional response to it. Here, we addressed this question by combining participants’ estimations of the pleasure they will derive from future events, with brain imaging data recorded while they imagined those events, both before, and after, choosing between them. Participants rated the selected alternatives as better after the decision stage relative to before, while discarded alternatives were valued less. Our fMRI findings reveal that post-choice changes in preference are tracked in caudate nucleus activity. Specifically, the difference in BOLD signal associated with the selected and rejected stimuli was enhanced after a decision was taken, reflecting the choice that had just been made. This finding suggests that the physiological representation of a stimulus’ expected hedonic value is altered by a commitment to it. Furthermore, prior to any revaluation induced by the decision process, our data show that BOLD signal in this same region reflects the choices we are likely to make at a later time. PMID:19321772

  13. First cranial remains of a gondwanatherian mammal reveal remarkable mosaicism

    NASA Astrophysics Data System (ADS)

    Krause, David W.; Hoffmann, Simone; Wible, John R.; Kirk, E. Christopher; Schultz, Julia A.; von Koenigswald, Wighart; Groenke, Joseph R.; Rossie, James B.; O'Connor, Patrick M.; Seiffert, Erik R.; Dumont, Elizabeth R.; Holloway, Waymon L.; Rogers, Raymond R.; Rahantarisoa, Lydia J.; Kemp, Addison D.; Andriamialison, Haingoson

    2014-11-01

    Previously known only from isolated teeth and lower jaw fragments recovered from the Cretaceous and Palaeogene of the Southern Hemisphere, the Gondwanatheria constitute the most poorly known of all major mammaliaform radiations. Here we report the discovery of the first skull material of a gondwanatherian, a complete and well-preserved cranium from Upper Cretaceous strata in Madagascar that we assign to a new genus and species. Phylogenetic analysis strongly supports its placement within Gondwanatheria, which are recognized as monophyletic and closely related to multituberculates, an evolutionarily successful clade of Mesozoic mammals known almost exclusively from the Northern Hemisphere. The new taxon is the largest known mammaliaform from the Mesozoic of Gondwana. Its craniofacial anatomy reveals that it was herbivorous, large-eyed and agile, with well-developed high-frequency hearing and a keen sense of smell. The cranium exhibits a mosaic of primitive and derived features, the disparity of which is extreme and probably reflective of a long evolutionary history in geographic isolation.

  14. The eyes of Tullimonstrum reveal a vertebrate affinity.

    PubMed

    Clements, Thomas; Dolocan, Andrei; Martin, Peter; Purnell, Mark A; Vinther, Jakob; Gabbott, Sarah E

    2016-04-28

    Tullimonstrum gregarium is an iconic soft-bodied fossil from the Carboniferous Mazon Creek Lagerstätte (Illinois, USA). Despite a large number of specimens and distinct anatomy, various analyses over the past five decades have failed to determine the phylogenetic affinities of the 'Tully monster', and although it has been allied to such disparate phyla as the Mollusca, Annelida or Chordata, it remains enigmatic. The nature and phylogenetic affinities of Tullimonstrum have defied confident systematic placement because none of its preserved anatomy provides unequivocal evidence of homology, without which comparative analysis fails. Here we show that the eyes of Tullimonstrum possess ultrastructural details indicating homology with vertebrate eyes. Anatomical analysis using scanning electron microscopy reveals that the eyes of Tullimonstrum preserve a retina defined by a thick sheet comprising distinct layers of spheroidal and cylindrical melanosomes. Time-of-flight secondary ion mass spectrometry and multivariate statistics provide further evidence that these microbodies are melanosomes. A range of animals have melanin in their eyes, but the possession of melanosomes of two distinct morphologies arranged in layers, forming retinal pigment epithelium, is a synapomorphy of vertebrates. Our analysis indicates that in addition to evidence of colour patterning, ecology and thermoregulation, fossil melanosomes can also carry a phylogenetic signal. Identification in Tullimonstrum of spheroidal and cylindrical melanosomes forming the remains of retinal pigment epithelium indicates that it is a vertebrate; considering its body parts in this new light suggests it was an anatomically unusual member of total group Vertebrata. PMID:27074512

  15. Marine viruses, a genetic reservoir revealed by targeted viromics

    PubMed Central

    Martínez, Joaquín Martínez; Swan, Brandon K; Wilson, William H

    2014-01-01

    Metagenomics has opened new windows on investigating viral diversity and functions. Viromic studies typically require large sample volumes and filtration through 0.2 μm pore-size filters, consequently excluding or under-sampling tailed and very large viruses. We have optimized a targeted viromic approach that employs fluorescence-activated sorting and whole genome amplification to produce dsDNA-enriched libraries from discrete viral populations from a 1-ml water sample. Using this approach on an environmental sample from the Patagonian Shelf, we produced three distinct libraries. One of the virus libraries was dominated (79.65% of sequences with known viral homology) by giant viruses from the Mimiviridae and Phycodnaviridae families, while the two other viromes were dominated by smaller phycodnaviruses, cyanophages and other bacteriophages. The estimated genotypic richness and diversity in our sorted viromes, with 52–163 estimated genotypes, was much lower than in previous virome reports. Fragment recruitment of metagenome reads to selected reference viral genomes yields high genome coverage, suggesting little amplification and sequencing bias against some genomic regions. These results underscore the value of our approach as an effective way to target and investigate specific virus groups. In particular, it will help reveal the diversity and abundance of giant viruses in marine ecosystems. PMID:24304671

  16. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism

    PubMed Central

    Amitrano, Sara; Marozza, Annabella; Somma, Serena; Imperatore, Valentina; Hadjistilianou, Theodora; De Francesco, Sonia; Toti, Paolo; Galimberti, Daniela; Meloni, Ilaria; Cetta, Francesco; Piu, Pietro; Di Marco, Chiara; Dosa, Laura; Lo Rizzo, Caterina; Carignani, Giulia; Mencarelli, Maria Antonietta; Mari, Francesca; Renieri, Alessandra; Ariani, Francesca

    2015-01-01

    In about 50% of sporadic cases of retinoblastoma, no constitutive RB1 mutations are detected by conventional methods. However, recent research suggests that, at least in some of these cases, there is somatic mosaicism with respect to RB1 normal and mutant alleles. The increased availability of next generation sequencing improves our ability to detect the exact percentage of patients with mosaicism. Using this technology, we re-tested a series of 40 patients with sporadic retinoblastoma: 10 of them had been previously classified as constitutional heterozygotes, whereas in 30 no RB1 mutations had been found in lymphocytes. In 3 of these 30 patients, we have now identified low-level mosaic variants, varying in frequency between 8 and 24%. In 7 out of the 10 cases previously classified as heterozygous from testing blood cells, we were able to test additional tissues (ocular tissues, urine and/or oral mucosa): in three of them, next generation sequencing has revealed mosaicism. Present results thus confirm that a significant fraction (6/40; 15%) of sporadic retinoblastoma cases are due to postzygotic events and that deep sequencing is an efficient method to unambiguously distinguish mosaics. Re-testing of retinoblastoma patients through next generation sequencing can thus provide new information that may have important implications with respect to genetic counseling and family care. PMID:25712084

  17. Statistical universals reveal the structures and functions of human music.

    PubMed

    Savage, Patrick E; Brown, Steven; Sakai, Emi; Currie, Thomas E

    2015-07-21

    Music has been called "the universal language of mankind." Although contemporary theories of music evolution often invoke various musical universals, the existence of such universals has been disputed for decades and has never been empirically demonstrated. Here we combine a music-classification scheme with statistical analyses, including phylogenetic comparative methods, to examine a well-sampled global set of 304 music recordings. Our analyses reveal no absolute universals but strong support for many statistical universals that are consistent across all nine geographic regions sampled. These universals include 18 musical features that are common individually as well as a network of 10 features that are commonly associated with one another. They span not only features related to pitch and rhythm that are often cited as putative universals but also rarely cited domains including performance style and social context. These cross-cultural structural regularities of human music may relate to roles in facilitating group coordination and cohesion, as exemplified by the universal tendency to sing, play percussion instruments, and dance to simple, repetitive music in groups. Our findings highlight the need for scientists studying music evolution to expand the range of musical cultures and musical features under consideration. The statistical universals we identified represent important candidates for future investigation. PMID:26124105

  18. Ecoinformatics reveals effects of crop rotational histories on cotton yield.

    PubMed

    Meisner, Matthew H; Rosenheim, Jay A

    2014-01-01

    Crop rotation has been practiced for centuries in an effort to improve agricultural yield. However, the directions, magnitudes, and mechanisms of the yield effects of various crop rotations remain poorly understood in many systems. In order to better understand how crop rotation influences cotton yield, we used hierarchical Bayesian models to analyze a large ecoinformatics database consisting of records of commercial cotton crops grown in California's San Joaquin Valley. We identified several crops that, when grown in a field the year before a cotton crop, were associated with increased or decreased cotton yield. Furthermore, there was a negative association between the effect of the prior year's crop on June densities of the pest Lygus hesperus and the effect of the prior year's crop on cotton yield. This suggested that some crops may enhance L. hesperus densities in the surrounding agricultural landscape, because residual L. hesperus populations from the previous year cannot continuously inhabit a focal field and attack a subsequent cotton crop. In addition, we found that cotton yield declined approximately 2.4% for each additional year in which cotton was grown consecutively in a field prior to the focal cotton crop. Because L. hesperus is quite mobile, the effects of crop rotation on L. hesperus would likely not be revealed by small plot experimentation. These results provide an example of how ecoinformatics datasets, which capture the true spatial scale of commercial agriculture, can be used to enhance agricultural productivity.

  19. On the revealing of nonequilibrium phase transitions in water

    NASA Astrophysics Data System (ADS)

    Pershin, S. M.; Krutyansky, L. M.; Luk'yanchenko, V. A.

    2011-09-01

    It has been found that the jump and stabilization of the temperature observed in [L.N. Baturov et al., JETP Lett. 93, 91 (2011)] upon the heating/cooling of water near 4°C at a rate of ˜10-3 K/s are observed in water of any purification degree. However, we have not found the process of the formation/melting of supermolecular structures assumed by Baturov et al., which is sought in the shift of the center of the OH band of Raman scattering, e.g., at ˜150 cm-1, as at the melting of hexagonal 1h ice [S.M. Pershin and A.F. Bunkin, Opt. Spectrosc. 85, 190 (1998); Patent RF No. 98, 103249 (1998)]. It has been shown that the revealed temperature features are absent in the presence of the mixing of water and artificial limitation of convection, as well as in a thin layer; this indicates that the regularity of the phenomenon is doubtful and that convection plays an important role. The visualization of convection flows by potassium permanganate made it possible to detect the reversion of their circulation over the trajectory of surface-wall-bottom-volume symmetry axis at the transition through a point of 4°C. The observed features have been interpreted as a manifestation of Archimedes' principle.

  20. From C to Parton Sea: How Supercomputing Reveals Nucleon Structure

    NASA Astrophysics Data System (ADS)

    Lin, Huey-Wen

    2016-03-01

    Studying the structure of nucleons is not only important to understanding the strong interactions of quarks and gluons, but also to improving the precision of new-physics searches. Since a broad class of experiments, including the LHC and dark-matter detection, require interactions with nucleons, the mission to probe femtoscale physics is also essential for disentangling Standard-Model contributions from potential new physics. These SM backgrounds require parton distribution functions (PDFs) as inputs. However, after decades of experiments and theoretical efforts, there still remain many unknowns, especially in the sea flavor structure and transversely polarized structure. In a discrete spacetime, we can make a direct numerical calculation of the implications of QCD using sufficiently large supercomputing resources. A nonperturbative approach from first principles, lattice QCD, provides hope to expand our understanding of nucleon structure, especially in regions that are difficult to observe in experiments. In this work, we present a first direct calculation of the Bjorken-x dependence of the PDFs using Large-Momentum Effective Theory (LaMET) and comment on the surprising result revealed for the nucleon sea-flavor asymmetry. The work of HWL is supported in part by the M. Hildred Blewett Fellowship of the American Physical Society, www.aps.org.

  1. Initiation process of a thrust fault revealed by analog experiments

    NASA Astrophysics Data System (ADS)

    Yamada, Yasuhiro; Dotare, Tatsuya; Adam, Juergen; Hori, Takane; Sakaguchi, Hide

    2016-04-01

    We conducted 2D (cross-sectional) analog experiments with dry sand using a high resolution digital image correlation (DIC) technique to reveal initiation process of a thrust fault in detail, and identified a number of "weak shear bands" and minor uplift prior to the thrust initiation. The observations suggest that the process can be divided into three stages. Stage 1: characterized by a series of abrupt and short-lived weak shear bands at the location where the thrust will be generated later. Before initiation of the fault, the area to be the hanging wall starts to uplift. Stage 2: defined by the generation of the new thrust and its active displacement. The location of the new thrust seems to be constrained by its associated back-thrust, produced at the foot of the surface slope (by the previous thrust). The activity of the previous thrust turns to zero once the new thrust is generated, but the timing of these two events is not the same. Stage 3: characterized by a constant displacement along the (new) thrust. Similar minor shear bands can be seen in the toe area of the Nankai accretionary prism, SW Japan and we can correlate the along-strike variations in seismic profiles to the model results that show the characteristic features in each thrust development stage.

  2. UAS and Distributed Temperature Sensing Reveal Previously Unseen Atmospheric Processes

    NASA Astrophysics Data System (ADS)

    Higgins, C. W.; Liu, Z.; Holmes, H.; Wing, M.; Predosa, R. A.; Blunck, D.

    2015-12-01

    The frontier of atmospheric boundary layer research lies in times and places of complexity. Transitions between atmospheric states, buoyant flows over complex terrain, and times with only weak forcing mechanisms all have rich physical expressions of atmospheric flow that are not fully understood. These motions often span a large range of scales and are nonstationary. Traditional atmospheric measurement approaches are inadequate in these situations as they do not have the data density or the physical extent to capture the full range of motions. An unmanned aerial system (UAS) is used to lift distributed temperature sensing (DTS) technologies to observe the early morning transition from stable to unstably stratified conditions. The UAS/DTS combination yielded observations of temperature and humidity in the lower atmosphere with never-seen-before resolution and extent. The data reveal a complex interplay of motions that occur during the morning transition that ultimately results in the propagation and growth of unstable wave modes. The observations have given new insight into the appropriate scaling variables for the morning transition time.

  3. Computational models reveal genotype-phenotype associations in Saccharomyces cerevisiae.

    PubMed

    Franco-Duarte, Ricardo; Mendes, Inês; Umek, Lan; Drumonde-Neves, João; Zupan, Blaz; Schuller, Dorit

    2014-07-01

    Genome sequencing is essential to understand individual variation and to study the mechanisms that explain relations between genotype and phenotype. The accumulated knowledge from large-scale genome sequencing projects of Saccharomyces cerevisiae isolates is being used to study the mechanisms that explain such relations. Our objective was to undertake genetic characterization of 172 S. cerevisiae strains from different geographical origins and technological groups, using 11 polymorphic microsatellites, and computationally relate these data with the results of 30 phenotypic tests. Genetic characterization revealed 280 alleles, with the microsatellite ScAAT1 contributing most to intrastrain variability, together with alleles 20, 9 and 16 from the microsatellites ScAAT4, ScAAT5 and ScAAT6. These microsatellite allelic profiles are characteristic for both the phenotype and origin of yeast strains. We confirm the strength of these associations by construction and cross-validation of computational models that can predict the technological application and origin of a strain from the microsatellite allelic profile. Associations between microsatellites and specific phenotypes were scored using information gain ratios, and significant findings were confirmed by permutation tests and estimation of false discovery rates. The phenotypes associated with higher number of alleles were the capacity to resist to sulphur dioxide (tested by the capacity to grow in the presence of potassium bisulphite) and the presence of galactosidase activity. Our study demonstrates the utility of computational modelling to estimate a strain technological group and phenotype from microsatellite allelic combinations as tools for preliminary yeast strain selection.

  4. Polymyalgia Rheumatica Revealing a Lymphoma: A Two-Case Report.

    PubMed

    Verhoeven, Frank; Guillot, Xavier; Chouk, Mickaël; Prati, Clément; Wendling, Daniel

    2016-01-01

    Introduction. Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatism types in elderly population. The link between cancer and PMR is a matter of debate. Methods. We report two cases of PMR leading to the diagnosis of lymphoma and the growing interest of PET-TDM in this indication. Results. A 84-year-old man known for idiopathic neutropenia presented an inflammatory arthromyalgia of the limb girdle since one month. Blood exams highlighted the presence of a monoclonal B cell clone. Bone marrow concluded to a B cell lymphoma of the marginal zone. He was successfully treated with 0.3 mg/kg/d of prednisone, and response was sustained after 6 months. A 73-year-old man known for prostatic neoplasia in remission for 5 years presented arthromyalgia of the limb girdle since one month. PET-CT revealed bursitis of the hips and the shoulders, no prostatic cancer recurrence, and a metabolically active iliac lymphadenopathy whose pathologic exam concluded to a low grade follicular lymphoma. He was successfully treated with 0.3 mg/kg/d of prednisone. Conclusion. These observations may imply that lymphoma is sometimes already present when PMR is diagnosed and PET-CT is a useful tool in the initial assessment of PMR to avoid missing neoplasia. PMID:27597921

  5. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    PubMed Central

    Ray, Ann; Kinch, Lisa N.; de Souza Santos, Marcela; Grishin, Nick V.

    2016-01-01

    ABSTRACT Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. PMID:27460800

  6. New View of Distant Galaxy Reveals Furious Star Formation

    NASA Astrophysics Data System (ADS)

    2007-12-01

    A furious rate of star formation discovered in a distant galaxy shows that galaxies in the early Universe developed either much faster or in a different way from what astronomers have thought. "This galaxy is forming stars at an incredible rate," said Wei-Hao Wang, an astronomer at the National Radio Astronomy Observatory (NRAO) in Socorro, New Mexico. The galaxy, Wang said, is forming the equivalent of 4,000 Suns a year. This is a thousand times more violent than our own Milky Way Galaxy. Location of Distant Galaxy Visible-light, left (from HST) and Infrared, right, (from Spitzer) Images: Circles indicate location of GOODS 850-5. CREDIT: Wang et al., STScI, Spitzer, NASA, NRAO/AUI/NSF Click on image for high-resolution file (1 MB) The galaxy, called GOODS 850-5, is 12 billion light-years from Earth, and thus is seen as it was only about 1.5 billion years after the Big Bang. Wang and his colleagues observed it using the Smithsonian Astrophysical Observatory's Submillimeter Array (SMA) on Mauna Kea in Hawaii. Young stars in the galaxy were enshrouded in dust that was heated by the stars and radiated infrared light strongly. Because of the galaxy's great distance from Earth, the infrared light waves have been stretched out to submillimeter-length radio waves, which are seen by the SMA. The waves were stretched or "redshifted," as astronomers say, by the ongoing expansion of the Universe. "This evidence for prolific star formation is hidden by the dust from visible-light telescopes," Wang explained. The dust, in turn, was formed from heavy elements that had to be built up in the cores of earlier stars. This indicates, Wang said, that significant numbers of stars already had formed, then spewed those heavy elements into interstellar space through supernova explosions and stellar winds. "Seeing the radiation from this heated dust revealed star formation we could have found in no other way," Wang said. Similar dusty galaxies in the early Universe may contain most of the

  7. NICMOS PEERS THROUGH DUST TO REVEAL YOUNG STELLAR DISKS

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The following images were taken by NASA Hubble Space Telescope's Near-Infrared Camera and Multi-Object Spectrometer (NICMOS). All of the objects are extremely young stars, 450 light-years away in the constellation Taurus. Most of the nebulae represent small dust particles around the stars, which are seen because they are reflecting starlight. In the color-coding, regions of greatest dust concentration appear red. All photo credits: D. Padgett (IPAC/Caltech), W. Brandner (IPAC), K. Stapelfeldt (JPL) and NASA [Top left]: CoKu Tau/1. This image shows a newborn binary star system, CoKu Tau/1, lying at the center of four 'wings' of light extending as much as 75 billion miles from the pair. The 'wings' outline the edges of a region in the stars' dusty surroundings, which have been cleared by outflowing gas. A thin, dark lane extends to the left and to right of the binary, suggesting that a disk or ring of dusty material encircles the two young stars. [Top center]: DG Tau B - An excellent example of the complementary nature of Hubble's instruments may be found by comparing the infrared NICMOS image of DG Tau B to the visible-light Wide Field and Planetary Camera 2 (WFPC2) image of the same object. WFPC2 highlights the jet emerging from the system, while NICMOS penetrates some of the dust near the star to more clearly outline the 50 billion-mile-long dust lane (the horizontal dark band, which indicates the presence of a large disk forming around the infant star). The young star itself appears as the bright red spot at the corner of the V-shaped nebula. [Top right]: Haro 6-5B - This image of the young star Haro 6-5B shows two bright regions separated by a dark lane. As seen in the WFPC2 image of the same object, the bright regions represent starlight reflecting from the upper and lower surfaces of the disk, which is thicker at its edges than its center. However, the infrared view reveals the young star just above the dust lane. [Bottom left]: I04016 - A very young star

  8. Revealing the crust of western Romania using CCP tehniques

    NASA Astrophysics Data System (ADS)

    Tataru, D.; Stuart, G.; Grecu, B.

    2012-04-01

    weight is determined from a 2-D Gaussian function whose one standard deviation width is chosen appropriately by the array aperture and/or Fresnel zone at the imaging target (Eagar et al., 2011). Our results reveal an average crustal thickness of 28-30 km beneath the Romanian sector of the Panonian Basin and a thicker crust for stations within the Southern Carpathian Orogen (~35km). For two stations located in the Apuseni Mountains the Moho discontinuity is replaced by a transition zone extended between 36 and 40 km depth. The H-k stacking solutions reveal significant variations in crustal thickness across the study region. Both H-k and GCCP stacking show general agreement in the pattern of Moho topography. Discrepancies between the two results are mostly linear shifts and both exhibit the same broad-scale patterns. Poisson's ratios across the region vary strongly and regional patterns do not directly correlate with variations in Moho depth.

  9. Nucleotide substitutions revealing specific functions of Polycomb group genes.

    PubMed

    Bajusz, Izabella; Sipos, László; Pirity, Melinda K

    2015-04-01

    POLYCOMB group (PCG) proteins belong to the family of epigenetic regulators of genes playing important roles in differentiation and development. Mutants of PcG genes were isolated first in the fruit fly, Drosophila melanogaster, resulting in spectacular segmental transformations due to the ectopic expression of homeotic genes. Homologs of Drosophila PcG genes were also identified in plants and in vertebrates and subsequent experiments revealed the general role of PCG proteins in the maintenance of the repressed state of chromatin through cell divisions. The past decades of gene targeting experiments have allowed us to make significant strides towards understanding how the network of PCG proteins influences multiple aspects of cellular fate determination during development. Being involved in the transmission of specific expression profiles of different cell lineages, PCG proteins were found to control wide spectra of unrelated epigenetic processes in vertebrates, such as stem cell plasticity and renewal, genomic imprinting and inactivation of X-chromosome. PCG proteins also affect regulation of metabolic genes being important for switching programs between pluripotency and differentiation. Insight into the precise roles of PCG proteins in normal physiological processes has emerged from studies employing cell culture-based systems and genetically modified animals. Here we summarize the findings obtained from PcG mutant fruit flies and mice generated to date with a focus on PRC1 and PRC2 members altered by nucleotide substitutions resulting in specific alleles. We also include a compilation of lessons learned from these models about the in vivo functions of this complex protein family. With multiple knockout lines, sophisticated approaches to study the consequences of peculiar missense point mutations, and insights from complementary gain-of-function systems in hand, we are now in a unique position to significantly advance our understanding of the molecular basis of

  10. Internetwork magnetic field as revealed by two-dimensional inversions

    NASA Astrophysics Data System (ADS)

    Danilovic, S.; van Noort, M.; Rempel, M.

    2016-09-01

    Context. Properties of magnetic field in the internetwork regions are still fairly unknown because of rather weak spectropolarimetric signals. Aims: We address the matter by using the two-dimensional (2D) inversion code, which is able to retrieve the information on smallest spatial scales up to the diffraction limit, while being less susceptible to noise than most of the previous methods used. Methods: Performance of the code and the impact of various effects on the retrieved field distribution is tested first on the realistic magneto-hydrodynamic (MHD) simulations. The best inversion scenario is then applied to the real data obtained by Spectropolarimeter (SP) on board Hinode. Results: Tests on simulations show that: (1) the best choice of node position ensures a decent retrieval of all parameters; (2) the code performs well for different configurations of magnetic field; (3) slightly different noise levels or slightly different defocus included in the spatial point spread function (PSF) produces no significant effect on the results; and (4) temporal integration shifts the field distribution to a stronger, more horizontally inclined field. Conclusions: Although the contribution of the weak field is slightly overestimated owing to noise, 2D inversions are able to recover well the overall distribution of the magnetic field strength. Application of the 2D inversion code on the Hinode SP internetwork observations reveals a monotonic field strength distribution. The mean field strength at optical depth unity is ~ 130 G. At higher layers, field strength drops as the field becomes more horizontal. Regarding the distribution of the field inclination, tests show that we cannot directly retrieve it with the observations and tools at hand, however, the obtained distributions are consistent with those expected from simulations with a quasi-isotropic field inclination after accounting for observational effects.

  11. Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

    PubMed Central

    Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

    2013-01-01

    Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

  12. Brij detergents reveal new aspects of membrane microdomain in erythrocytes.

    PubMed

    Casadei, Bruna Renata; De Oliveira Carvalho, Patrícia; Riske, Karin A; Barbosa, Raquel De Melo; De Paula, Eneida; Domingues, Cleyton Crepaldi

    2014-09-01

    Membrane microdomains enriched in cholesterol, sphingolipids (rafts), and specific proteins are involved in important physiological functions. However their structure, size and stability are still controversial. Given that detergent-resistant membranes (DRMs) are in the liquid-ordered state and are rich in raft-like components, they might correspond to rafts at least to some extent. Here we monitor the lateral order of biological membranes by characterizing DRMs from erythrocytes obtained with Brij-98, Brij-58, and TX-100 at 4 °C and 37 °C. All DRMs were enriched in cholesterol and contained the raft markers flotillin-2 and stomatin. However, sphingomyelin (SM) was only found to be enriched in TX-100-DRMs - a detergent that preferentially solubilizes the membrane inner leaflet - while Band 3 was present solely in Brij-DRMs. Electron paramagnetic resonance spectra showed that the acyl chain packing of Brij-DRMs was lower than TX-100-DRMs, providing evidence of their diverse lipid composition. Fatty acid analysis revealed that the SM fraction of the DRMs was enriched in lignoceric acid, which should specifically contribute to the resistance of SM to detergents. These results indicate that lipids from the outer leaflet, particularly SM, are essential for the formation of the liquid-ordered phase of DRMs. At last, the differential solubilization process induced by Brij-98 and TX-100 was monitored using giant unilamellar vesicles. This study suggests that Brij and TX-100-DRMs reflect different degrees of lateral order of the membrane microdomains. Additionally, Brij DRMs are composed by both inner and outer leaflet components, making them more physiologically relevant than TX-100-DRMs to the studies of membrane rafts.

  13. Population Structure in Naegleria fowleri as Revealed by Microsatellite Markers.

    PubMed

    Coupat-Goutaland, Bénédicte; Régoudis, Estelle; Besseyrias, Matthieu; Mularoni, Angélique; Binet, Marie; Herbelin, Pascaline; Pélandakis, Michel

    2016-01-01

    Naegleria sp. is a free living amoeba belonging to the Heterolobosea class. Over 40 species of Naegleria were identified and recovered worldwide in different habitats such as swimming pools, freshwater lakes, soil or dust. Among them, N. fowleri, is a human pathogen responsible for primary amoeboic meningoencephalitis (PAM). Around 300 cases were reported in 40 years worldwide but PAM is a fatal disease of the central nervous system with only 5% survival of infected patients. Since both pathogenic and non pathogenic species were encountered in the environment, detection and dispersal mode are crucial points in the fight against this pathogenic agent. Previous studies on identification and genotyping of N. fowleri strains were focused on RAPD analysis and on ITS sequencing and identified 5 variants: euro-american, south pacific, widespread, cattenom and chooz. Microsatellites are powerful markers in population genetics with broad spectrum of applications (such as paternity test, fingerprinting, genetic mapping or genetic structure analysis). They are characterized by a high degree of length polymorphism. The aim of this study was to genotype N. fowleri strains using microsatellites markers in order to track this population and to better understand its evolution. Six microsatellite loci and 47 strains from different geographical origins were used for this analysis. The microsatellite markers revealed a level of discrimination higher than any other marker used until now, enabling the identification of seven genetic groups, included in the five main genetic groups based on the previous RAPD and ITS analyses. This analysis also allowed us to go further in identifying private alleles highlighting intra-group variability. A better identification of the N. fowleri isolates could be done with this type of analysis and could allow a better tracking of the clinical and environmental N. fowleri strains. PMID:27035434

  14. Genetic Substructure of Kuwaiti Population Reveals Migration History

    PubMed Central

    Alsmadi, Osama; Thareja, Gaurav; Alkayal, Fadi; Rajagopalan, Ramakrishnan; John, Sumi Elsa; Hebbar, Prashantha; Behbehani, Kazem; Thanaraj, Thangavel Alphonse

    2013-01-01

    The State of Kuwait is characterized by settlers from Saudi Arabia, Iran, and other regions of the Arabian Peninsula. The settlements and subsequent admixtures have shaped the genetics of Kuwait. High prevalence of recessive disorders and metabolic syndromes (that increase risk of diabetes) is seen in the peninsula. Understanding the genetic structure of its population will aid studies designed to decipher the underlying causes of these disorders. In this study, we analyzed 572,366 SNP markers from 273 Kuwaiti natives genotyped using the illumina HumanOmniExpress BeadChip. Model-based clustering identified three genetic subgroups with different levels of admixture. A high level of concordance (Mantel test, p=0.0001 for 9999 repeats) was observed between the derived genetic clusters and the surname-based ancestries. Use of Human Genome Diversity Project (HGDP) data to understand admixtures in each group reveals the following: the first group (Kuwait P) is largely of West Asian ancestry, representing Persians with European admixture; the second group (Kuwait S) is predominantly of city-dwelling Saudi Arabian tribe ancestry, and the third group (Kuwait B) includes most of the tent-dwelling Bedouin surnames and is characterized by the presence of 17% African ancestry. Identity by Descent and Homozygosity analyses find Kuwait’s population to be heterogeneous (placed between populations that have large amount of ROH and the ones with low ROH) with Kuwait S as highly endogamous, and Kuwait B as diverse. Population differentiation FST estimates place Kuwait P near Asian populations, Kuwait S near Negev Bedouin tribes, and Kuwait B near the Mozabite population. FST distances between the groups are in the range of 0.005 to 0.008; distances of this magnitude are known to cause false positives in disease association studies. Results of analysis for genetic features such as linkage disequilibrium decay patterns conform to Kuwait’s geographical location at the nexus of

  15. Genetic substructure of Kuwaiti population reveals migration history.

    PubMed

    Alsmadi, Osama; Thareja, Gaurav; Alkayal, Fadi; Rajagopalan, Ramakrishnan; John, Sumi Elsa; Hebbar, Prashantha; Behbehani, Kazem; Thanaraj, Thangavel Alphonse

    2013-01-01

    The State of Kuwait is characterized by settlers from Saudi Arabia, Iran, and other regions of the Arabian Peninsula. The settlements and subsequent admixtures have shaped the genetics of Kuwait. High prevalence of recessive disorders and metabolic syndromes (that increase risk of diabetes) is seen in the peninsula. Understanding the genetic structure of its population will aid studies designed to decipher the underlying causes of these disorders. In this study, we analyzed 572,366 SNP markers from 273 Kuwaiti natives genotyped using the illumina HumanOmniExpress BeadChip. Model-based clustering identified three genetic subgroups with different levels of admixture. A high level of concordance (Mantel test, p=0.0001 for 9999 repeats) was observed between the derived genetic clusters and the surname-based ancestries. Use of Human Genome Diversity Project (HGDP) data to understand admixtures in each group reveals the following: the first group (Kuwait P) is largely of West Asian ancestry, representing Persians with European admixture; the second group (Kuwait S) is predominantly of city-dwelling Saudi Arabian tribe ancestry, and the third group (Kuwait B) includes most of the tent-dwelling Bedouin surnames and is characterized by the presence of 17% African ancestry. Identity by Descent and Homozygosity analyses find Kuwait's population to be heterogeneous (placed between populations that have large amount of ROH and the ones with low ROH) with Kuwait S as highly endogamous, and Kuwait B as diverse. Population differentiation FST estimates place Kuwait P near Asian populations, Kuwait S near Negev Bedouin tribes, and Kuwait B near the Mozabite population. FST distances between the groups are in the range of 0.005 to 0.008; distances of this magnitude are known to cause false positives in disease association studies. Results of analysis for genetic features such as linkage disequilibrium decay patterns conform to Kuwait's geographical location at the nexus of Africa

  16. Shaping Outflows from Evolved Stars: Secrets Revealed by Chandra

    NASA Astrophysics Data System (ADS)

    Kastner, Joel H.

    2011-05-01

    Planetary nebulae (PNe), the near-endpoints of stellar evolution for intermediate-mass stars, exhibit a dizzying variety of optical/near-infrared morphologies: round; elliptical; bipolar; highly point-symmetric; chaotic and clumpy. The physical mechanisms responsible for this morphological menagerie are hotly debated. It is thought that the shape of a PN results from the sculpting of previously ejected, slow-moving (red giant) stellar envelope material by a fast wind from a (newly unveiled) white dwarf at the PN's core. But to explain the large fraction of nonspherical PNe -- which are presumably shaped by aspherical fast winds -- some models now further propose that many (perhaps most) PNe are the products of interacting binary systems. Chandra is yielding valuable insight into these stellar outflow shaping processes. Chandra imaging spectroscopy of PNe provides a unique means to determine the X-ray surface brightness distributions, temperatures, emission measures, and elemental abundances within the "hot bubbles" generated by fast wind shocks. Chandra observations of PNe have also revealed intriguing examples of unresolved X-ray sources that are too hard to be modeled as photospheric emission from hot white dwarfs. Such hard X-ray point sources are likely indicative of the presence of binary companions and/or accretion processes at PN central stars. I summarize the progress in these areas resulting from Chandra's first dozen years, and present early results from the first systematic Chandra survey of PNe in the solar neighborhood -- a survey designed to understand the formation and evolution of hot bubbles, and to establish the frequency and characteristics of point-like X-ray sources, within PNe with names like the Ring, the Dumbbell, the Owl, and Saturn. This work is supported by NASA Astrophysics Data Analysis Program and Chandra X-ray Center (CXC) grants to RIT. The CXC is operated by SAO for and on behalf of NASA under contract NAS8-03060.

  17. The X-ray crystal structure of glutathionylcobalamin revealed.

    PubMed

    Hannibal, Luciana; Smith, Clyde A; Jacobsen, Donald W

    2010-11-01

    The first evidence of a complex between glutathione and cobalamin, glutathionylcobalamin (GSCbl), was presented by Wagner and Bernhauer more than 40 years ago (Ann. N.Y. Acad. Sci. 1964, 112, 580). More recently, NMR and EXAFS solution studies by Brown et al. (Biochemistry 1993, 32, 8421) and Scheuring et al. (Biochemistry 1994, 33, 6310), respectively, provided evidence that the glutathionyl moiety in GSCbl is bound to the cobalt center via a Co-S bond. Despite continued efforts, the structural analysis of glutathionylcobalamin in the solid state has remained elusive. Here, we report the first atomic resolution crystal structure of GSCbl, refined to a crystallographic R factor of 0.0683. The glutathione moiety is bound to the cobalt center through the sulfur atom as expected, with a Co-S bond distance of 2.295(1) Å. This distance agrees with the distance obtained from the EXAFS analysis of GSCbl (2.280(5) Å). However, the bond to the axial α-5,6-dimethylbenzimidazole base (DMB), 2.074(3) Å, is significantly shorter than that determined from the EXAFS measurements (Co-N3B = 2.15(3) Å). The corrin fold angle is 24.7°, the highest ever reported for a cobalamin structure, and points in the direction of the β face of the corrin, toward the glutathione (GS(-)). The GS(-) ligand has been modeled in two conformations, each featuring distinct hydrogen bonding interactions. In both conformations, the α-carboxylate group of the GS(-) ligand interacts with the generally rigid side chain a of the cobalamin molecule, resulting in two distinct conformations. A comparison with the structure of other thiolatocobalamins revealed high similarity in the positions of the atoms in the cysteinyl moiety, the fold of the corrin rings, and the Co-S bond distances.

  18. Behavioral idiosyncrasy reveals genetic control of phenotypic variability

    PubMed Central

    Ayroles, Julien F.; Buchanan, Sean M.; O’Leary, Chelsea; Skutt-Kakaria, Kyobi; Grenier, Jennifer K.; Clark, Andrew G.; Hartl, Daniel L.; de Bivort, Benjamin L.

    2015-01-01

    Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype. PMID:25953335

  19. Persistent predator–prey dynamics revealed by mass extinction

    PubMed Central

    Sallan, Lauren Cole; Kammer, Thomas W.; Ausich, William I.; Cook, Lewis A.

    2011-01-01

    Predator–prey interactions are thought by many researchers to define both modern ecosystems and past macroevolutionary events. In modern ecosystems, experimental removal or addition of taxa is often used to determine trophic relationships and predator identity. Both characteristics are notoriously difficult to infer in the fossil record, where evidence of predation is usually limited to damage from failed attacks, individual stomach contents, one-sided escalation, or modern analogs. As a result, the role of predation in macroevolution is often dismissed in favor of competition and abiotic factors. Here we show that the end-Devonian Hangenberg event (359 Mya) was a natural experiment in which vertebrate predators were both removed and added to an otherwise stable prey fauna, revealing specific and persistent trophic interactions. Despite apparently favorable environmental conditions, crinoids diversified only after removal of their vertebrate consumers, exhibiting predatory release on a geological time scale. In contrast, later Mississippian (359–318 Mya) camerate crinoids declined precipitously in the face of increasing predation pressure from new durophagous fishes. Camerate failure is linked to the retention of obsolete defenses or “legacy adaptations” that prevented coevolutionary escalation. Our results suggest that major crinoid evolutionary phenomena, including rapid diversification, faunal turnover, and species selection, might be linked to vertebrate predation. Thus, interactions observed in small ecosystems, such as Lotka-Volterra cycles and trophic cascades, could operate at geologic time scales and higher taxonomic ranks. Both trophic knock-on effects and retention of obsolete traits might be common in the aftermath of predator extinction. PMID:21536875

  20. Polynesian mitochondrial DNAs reveal three deep maternal lineage clusters.

    PubMed

    Lum, J K; Rickards, O; Ching, C; Cann, R L

    1994-08-01

    The 4000-year-old human population expansion into Remote Oceania has been studied from a variety of genetic perspectives. Here, we report the discovery that Polynesians, traditionally considered to be a single cohesive linguistic and cultural unit, exhibit at least three distinct mitochondrial DNA (mtDNA) groups that probably shared a common maternal ancestor more than 85,000 years ago. The major lineage groups were first identified by PCR amplification of the mitochondrial region V deletion marker, known to be present at high frequency in Polynesian populations. Sequence analysis of mtDNA hypervariable control regions reveals a surprising number of lineages in Polynesia. We also note high sequence divergence between lineage groups deleted and not deleted in region V. Major group I lineages are common in Remote Oceania and include about 95% of the Native Hawaiian, 90% of the Samoan, and 100% of the Tongan donors in our sample. They contain the region V deletion and generally share three control region transition substitutions. This group also contains non-Polynesian individuals, such as Indonesians, Native Americans, Micronesians, Malaysians, Japanese, and Chinese. The group I Polynesians differ by 4.4% in sequence identity from major lineage group II Polynesians, who do not have the region V deletion and who share among themselves four distinct single-base substitutions. Group II individuals are seen at low frequency (< 10%) in Hawaii, Samoa, and the Cook Islands and may represent the predominant maternal lineage group of Papuan Melanesia. Major lineage group III, not found in Hawaii, tentatively links Samoa to Indonesia. Our observation of deep maternal genetic branches in Polynesia today confirms the notion that during the colonization of the Pacific, mainland Asian immigrants mixed with Melanesian peoples already inhabiting Near Oceania and carried a complex assortment of maternal genotypes derived from two distinct geographic sources to isolated island