Successful application of preimplantation genetic diagnosis for Leigh syndrome.

PubMed

Unsal, Evrim; Aktaş, Yasemin; Uner, Ozge; BaltacI, Aysun; Ozcan, Sarp; Turhan, Feriba; Baltaci, Volkan

2008-11-01

To perform preimplantation genetic diagnosis (PGD) for a SURF1 gene mutation of the Leigh syndrome to transfer unaffected or carrier embryo/embryos. Case report. Clinical IVF laboratory. A couple carrying an nt769 G/A mutation that is associated with Leigh syndrome. Oocytes were fertilized by means of intracytoplasmic sperm injection. The resulting embryos were biopsied 3 days after fertilization. One blastomere was taken and whole-genome amplification was performed. Amplification of the mutation site was achieved by polymerase chain reaction (PCR) and restriction digestion was completed. Gel Imager was used to measure the digests of normal and mutant load. Embryo testing by means of PGD-PCR and pregnancy. Successful preimplantation genetic diagnosis for a SURF1 gene mutation and transfer of healthy or carrier embryos. Successful singleton pregnancy resulting in the delivery of healthy baby girl. We report the first case of successful PGD for Leigh syndrome resulting in delivery of a healthy newborn.

Astronauts Ochoa and Tanner during egress training

NASA Image and Video Library

1994-06-23

S94-40073 (23 June 1994) --- Wearing training versions of the launch and entry suits (LES), astronauts Ellen Ochoa, payload commander, and Joseph P. Tanner, mission specialist, await the beginning of a training session on emergency egress procedures. The STS-66 crew participated in the training, held in the Johnson Space Center's (JSC) Shuttle Mockup and Integration Laboratory. Ochoa and Tanner will join three other NASA astronauts and one international mission specialist aboard the Space Shuttle Atlantis in support of the Atmospheric Laboratory for Applications and Science (ATLAS-3) flight scheduled for November of this year.

Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome.

PubMed

Bénit, P; Slama, A; Cartault, F; Giurgea, I; Chretien, D; Lebon, S; Marsac, C; Munnich, A; Rötig, A; Rustin, P

2004-01-01

Respiratory chain complex I deficiency represents a genetically heterogeneous group of diseases resulting from mutations in mitochondrial or nuclear genes. Mutations have been reported in 13 of the 14 subunits encoding the core of complex I (seven mitochondrial and six nuclear genes) and these result in Leigh or Leigh-like syndromes or cardiomyopathy. In this study, a combination of denaturing high performance liquid chromatography and sequence analysis was used to study the NDUFS3 gene in a series of complex I deficient patients. Mutations found in this gene (NADH dehydrogenase iron-sulphur protein 3), coding for the seventh and last subunit of complex I core, were shown to cause late onset Leigh syndrome, optic atrophy, and complex I deficiency. A biochemical diagnosis of complex I deficiency on cultured amniocytes from a later pregnancy was confirmed through the identification of disease causing NDUFS3 mutations in these cells. While mutations in the NDUFS3 gene thus result in Leigh syndrome, a dissimilar clinical phenotype is observed in mutations in the NDUFV2 and NDUFS2 genes, resulting in encephalomyopathy and cardiomyopathy. The reasons for these differences are uncertain.

EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome.

PubMed

Martinelli, Diego; Catteruccia, Michela; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Dionisi-Vici, Carlo; Pontrelli, Giuseppe; Corsetti, Tiziana; Livadiotti, Susanna; Kheifets, Viktoria; Hinman, Andrew; Shrader, William D; Thoolen, Martin; Klein, Matthew B; Bertini, Enrico; Miller, Guy

2012-11-01

Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

Leigh syndrome: Resolving the clinical and genetic heterogeneity paves the way for treatment options.

PubMed

Gerards, Mike; Sallevelt, Suzanne C E H; Smeets, Hubert J M

2016-03-01

Leigh syndrome is a progressive neurodegenerative disorder, affecting 1 in 40,000 live births. Most patients present with symptoms between the ages of three and twelve months, but adult onset Leigh syndrome has also been described. The disease course is characterized by a rapid deterioration of cognitive and motor functions, in most cases resulting in death due to respiratory failure. Despite the high genetic heterogeneity of Leigh syndrome, patients present with identical, symmetrical lesions in the basal ganglia or brainstem on MRI, while additional clinical manifestations and age of onset varies from case to case. To date, mutations in over 60 genes, both nuclear and mitochondrial DNA encoded, have been shown to cause Leigh syndrome, still explaining only half of all cases. In most patients, these mutations directly or indirectly affect the activity of the mitochondrial respiratory chain or pyruvate dehydrogenase complex. Exome sequencing has accelerated the discovery of new genes and pathways involved in Leigh syndrome, providing novel insights into the pathophysiological mechanisms. This is particularly important as no general curative treatment is available for this devastating disorder, although several recent studies imply that early treatment might be beneficial for some patients depending on the gene or process affected. Timely, gene-based personalized treatment may become an important strategy in rare, genetically heterogeneous disorders like Leigh syndrome, stressing the importance of early genetic diagnosis and identification of new genes/pathways. In this review, we provide a comprehensive overview of the most important clinical manifestations and genes/pathways involved in Leigh syndrome, and discuss the current state of therapeutic interventions in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

[Leigh syndrome caused by the mitochondrial DNA G14459A mutation in a Mexican family].

PubMed

Gutiérrez, A; Saldaña-Martínez, A; García-Ramírez, R; Rayo-Mares, D; Carreras, M; López-Pérez, M J; Ruiz-Pesini, E; Montoya, J; Montiel-Sosa, J F

Leigh syndrome is a neurodegenerative and progressive disease that appears usually in childhood due to defects in nuclear or mitochondrial genome. The mutation G14459A in mitochondrial DNA has been associated previously to Leber hereditary optic neuropathy and recently to Leigh syndrome. A 10 months-old Mexican girl diagnosed of Leigh syndrome. Molecular-genetic studies detected the mutation G14459A in a percentage close to homoplasmy and in low heteroplasmy in her mother. The rest of the maternally related family members analyzed were negative. The G14459A mutation, although not very frequently associated to Leigh syndrome, should be analyzed in patients that do not present the most common point mutations.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome.

PubMed

Yang, Yan-ling; Sun, Fang; Zhang, Yao; Qian, Ning; Yuan, Yun; Wang, Zhao-xia; Qi, Yu; Xiao, Jiang-xi; Wang, Xiao-ying; Qi, Zhao-yue; Zhang, Yue-hua; Jiang, Yu-wu; Bao, Xin-hua; Qin, Jiong; Wu, Xi-ru

2006-03-05

Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Sixty-five unrelated cases (35 men and 30 women) who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography (CT) scan or magnetic resonance imaging (MRI). The differential diagnosis of organic acidurias and fatty acid beta-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA (T8993G, T8993C, T9176C, A8344G, A3243G) were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 (26.2%) of the patients. The diagnosis was confirmed by autopsy in 6 (9.2%) patients. The patients had various forms of metabolic encephalomyopathy. Fifty-nine (90.8%) of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty (30.8%) patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases (7.7%). Of these, the A8344G mutation was detected in 2 patients. The T8993G, T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. A G604C mutation was

The "double panda" sign in Leigh disease.

PubMed

Sonam, Kothari; Bindu, P S; Gayathri, Narayanappa; Khan, Nahid Akhtar; Govindaraju, C; Arvinda, Hanumanthapura R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, K; Taly, Arun B

2014-07-01

Although the "face of the giant panda" sign on magnetic resonance imaging (MRI) is traditionally considered to be characteristic of Wilson disease, it has also been reported in other metabolic disorders. This study describes the characteristic "giant panda" sign on MRI in a child with Leigh disease. The diagnosis was based on the history of neurological regression; examination findings of oculomotor abnormalities, hypotonia, and dystonia; raised serum lactate levels; and characteristic brain stem and basal ganglia signal changes on MRI. The midbrain and pontine tegmental signal changes were consistent with the "face of the giant panda and her cub" sign. In addition to Wilson disease, metabolic disorders such as Leigh disease should also be considered in the differential diagnosis of this rare imaging finding. © The Author(s) 2013.

The neuroimaging of Leigh syndrome: case series and review of the literature.

PubMed

Bonfante, Eliana; Koenig, Mary Kay; Adejumo, Rahmat B; Perinjelil, Vinu; Riascos, Roy F

2016-04-01

Leigh syndrome by definition is (1) a neurodegenerative disease with variable symptoms, (2) caused by mitochondrial dysfunction from a hereditary genetic defect and (3) accompanied by bilateral central nervous system lesions. A genetic etiology is confirmed in approximately 50% of patients, with more than 60 identified mutations in the nuclear and mitochondrial genomes. Here we review the clinical features and imaging studies of Leigh syndrome and describe the neuroimaging findings in a cohort of 17 children with genetically confirmed Leigh syndrome. MR findings include lesions in the brainstem in 9 children (53%), basal ganglia in 13 (76%), thalami in 4 (24%) and dentate nuclei in 2 (12%), and global atrophy in 2 (12%). The brainstem lesions were most frequent in the midbrain and medulla oblongata. With follow-up an increased number of lesions from baseline was observed in 7 of 13 children, evolution of the initial lesion was seen in 6, and complete regression of the lesions was seen in 3. No cerebral white matter lesions were found in any of the 17 children. In concordance with the literature, we found that Leigh syndrome follows a similar pattern of bilateral, symmetrical basal ganglia or brainstem changes. Lesions in Leigh syndrome evolve over time and a lack of visible lesions does not exclude the diagnosis. Reversibility of lesions is seen in some patients, making the continued search for treatment and prevention a priority for clinicians and researchers.

NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement.

PubMed

Leshinsky-Silver, E; Lebre, Anne-Sophie; Minai, Limor; Saada, Ann; Steffann, Julie; Cohen, Sarit; Rötig, Agnes; Munnich, Arnold; Lev, Dorit; Lerman-Sagie, Tally

2009-07-01

Complex I deficiency is a frequent cause of Leigh syndrome. We describe a non-consanguineous Ashkenazi-Sephardic Jewish patient with Leigh syndrome due to complex I deficiency. The clinical and neuroradiological presentation showed predominant brainstem involvement. Blue native polyacrylamide gel electrophoresis analysis revealed an impaired assembly of complex I. The patient was found to be compound heterozygous of two mutations in the NDUFS4 gene: p.Asp119His (a novel mutation) and p.Lys154fs (recently described in an Ashkenazi Jewish family). These findings support the suggestion that the p.Lys154fs mutation in NDUFS4 should be evaluated in Ashkenazi Jewish patients presenting with early onset Leigh syndrome even before enzymatic studies. Our results further demonstrated that NDUFS4 presents a hotspot of mutations in the genetic apparatus of oxidative phosphorylation and the correct assembly of the subunit it encodes is essential for completion of the assembly of complex I.

A novel mitochondrial DNA 8597T>C mutation of Leigh syndrome: report of one case.

PubMed

Tsai, Jeng-Dau; Liu, Chin-San; Tsao, Teng-Fu; Sheu, Ji-Nan

2012-02-01

Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system. The brain images of Leigh syndrome are characterized by markedly symmetrical involvement, most frequently of the putamen. We report a 2-year-old girl with Leigh syndrome manifested as acute onset of altered level of consciousness. Brain magnetic resonance images showed abnormal signal intensity over the bilateral basal ganglia and cerebellar dentate nuclei. Despite normal biochemical studies, in particular serum lactate levels, magnetic resonance spectroscopy demonstrated a downward doublet lactate peak. The diagnosis of Leigh syndrome was subsequently confirmed by genetic study which showed a novel mutation at 8597T>C of the mitochondrial ATPase6 gene. Copyright © 2012. Published by Elsevier B.V.

Dichloroacetate treatment in Leigh syndrome caused by mitochondrial DNA mutation.

PubMed

Takanashi, J; Sugita, K; Tanabe, Y; Maemoto, T; Niimi, H

1997-01-01

Sodium dichloroacetate (DCA) was administered to a 1-year-old female case of Leigh syndrome, who had a T > G point mutation at nt 8993 of mitochondrial DNA. Her biochemical and clinical symptoms improved gradually, but proton magnetic resonance spectroscopy revealed reduction of the N-acetylaspartate/creatine ratio, and magnetic resonance imaging showed progressive cerebral atrophy despite the DCA therapy. These results suggest that DCA therapy may not retard the progress of the primary disease in Leigh syndrome, but produced clinical improvement most likely by reducing toxic accumulation of lactate.

Anesthetic considerations in Leigh disease: Case report and literature review.

PubMed

Terkawi, Abdullah Sulieman; Wani, Tariq M; Al-Shuaibi, Khalid M; Tobias, Joseph D

2012-04-01

Leigh disease is an extremely rare disorder, characterized by a progressive neurodegenerative course, with subacute necrotizing encephalomyelopathy. It usually presents in infancy with developmental delay, seizures, dysarthria, and ataxia. These patients may also develop episodes of lactic acidosis that usually lead to respiratory failure and death. Due to the rarity of the condition, the most appropriate anesthetic plan remains unclear. We present a patient with Leigh disease, who required general anesthesia. The pathogenesis of the disease is discussed and previous reports of perioperative care from the literature are reviewed.

A multicenter study on Leigh syndrome: disease course and predictors of survival

PubMed Central

2014-01-01

Background Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. Methods This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. Results A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. Conclusions This is a multicenter study performed in a

A multicenter study on Leigh syndrome: disease course and predictors of survival.

PubMed

Sofou, Kalliopi; De Coo, Irenaeus F M; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B; Lönnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence A; Tulinius, Már; Darin, Niklas

2014-04-15

Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. This is a multicenter study performed in a large cohort of patients with Leigh syndrome

Leigh syndrome: One disorder, more than 75 monogenic causes.

PubMed

Lake, Nicole J; Compton, Alison G; Rahman, Shamima; Thorburn, David R

2016-02-01

Leigh syndrome is the most common pediatric presentation of mitochondrial disease. This neurodegenerative disorder is genetically heterogeneous, and to date pathogenic mutations in >75 genes have been identified, encoded by 2 genomes (mitochondrial and nuclear). More than one-third of these disease genes have been characterized in the past 5 years alone, reflecting the significant advances made in understanding its etiological basis. We review the diverse biochemical and genetic etiology of Leigh syndrome and associated clinical, neuroradiological, and metabolic features that can provide clues for diagnosis. We discuss the emergence of genotype-phenotype correlations, insights gleaned into the molecular basis of disease, and available therapeutic options. © 2015 American Neurological Association.

LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.

PubMed

Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A

2011-03-01

The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (p<0.005) were hyperglycaemia, hepatic cytolysis, and altered consciousness at admission. Compared to a group of SURF1-deficient Leigh syndrome patients assembled from the literature, SLSJ-COX is distinct by the occurrence of metabolic crises, leading to earlier and higher mortality (p=0.001). SLSJ-COX is clinically distinct, with acute fatal acidotic crises on a backdrop of chronic moderate developmental delay and hyperlactataemia. Leigh syndrome is common. Stroke-like episodes can occur. The Leigh syndrome of SLSJ-COX differs from that of SURF1-related COX deficiency. SLSJ-COX has a different spectrum of associated abnormalities, acidotic crises being particularly suggestive of LRPPRC related Leigh syndrome. Even among A354V homozygotes, pronounced differences in survival and severity occur, showing that other genetic and/or environmental factors can influence outcome.

Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations.

PubMed

Sonam, Kothari; Khan, Nahid Akthar; Bindu, Parayil Sankaran; Taly, Arun B; Gayathri, N; Bharath, M M Srinivas; Govindaraju, C; Arvinda, H R; Nagappa, Madhu; Sinha, Sanjib; Thangaraj, K

2014-10-01

Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Davison AAF, Ft. Belvoir Virginia. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

DTIC Science & Technology

1980-12-08

PERCENTAGE FREQUENCY OF WIND DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) 9 T7,28 DAVISON AAF/FT BELVOIR VA 69-70,73-8O JAJ STATION STATION NAME YEARS...I1AC PERCENTAGE FREQUENCY OF WINU * DIRECTION AND SPEED (FROM HOURLY OBSERVATIONS) ?~..... JAj -j&0 AAF/FT AELVOIR VA M_______________ SA Y STATION...7 ~ 66~i~ sV C 4i .3 ,’ :.r.’ _ON .AIIF_[ TD LVOl’ VP , 7.-’-7",7._-_ v.AY SO#TAT ON STATION NAMC iSCARS MONTH NOONS uL. S. T,) retup. WET BULB

Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients.

PubMed

Danis, Daniel; Brennerova, Katarina; Skopkova, Martina; Kurdiova, Timea; Ukropec, Jozef; Stanik, Juraj; Kolnikova, Miriam; Gasperikova, Daniela

2018-04-01

Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or basal ganglia disease, lactic acidosis, and characteristic magnetic resonance imaging findings. At molecular level, deficiency of respiratory complexes and/or pyruvate dehydrogenase complex is usually observed. Nuclear gene SURF1 encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in SURF1 are one of the most frequent causes of cytochrome c-oxidase-related Leigh syndrome cases. Here, we aimed to elucidate the genetic basis of Leigh syndrome in three Slovak families. Three probands presenting with Leigh syndrome were selected for DNA analysis. The first proband, presenting with atypical LS onset without abnormal basal ganglia magnetic resonance imaging findings, was analyzed with whole exome sequencing. In the two remaining probands, SURF1 was screened by Sanger sequencing. Four different heterozygous mutations were identified in SURF1: c.312_321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823_833+7del:p. (?) and c.845_846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect. We identified disease-causing mutations in all three probands, which points to the important role of SURF1 gene in etiology of Leigh syndrome in Slovakia. Our data showed that patients with atypical Leigh syndrome phenotype without lesions in basal ganglia may benefit from the whole exome sequencing method. In the case of probands presenting the typical phenotype, Sanger sequencing of the SURF1 gene seems to be an effective method of DNA analysis.

Efficacy of idebenone for respiratory failure in a patient with Leigh syndrome: a long-term follow-up study.

PubMed

Haginoya, Kazuhiro; Miyabayashi, Shigeaki; Kikuchi, Masahiro; Kojima, Akira; Yamamoto, Katsuya; Omura, Kiyoshi; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Tanaka, Soichiro; Tsuchiya, Shigeru

2009-03-15

Respiratory failure can be the direct cause of death in patients with Leigh syndrome. Unfortunately, no effective treatment strategy is available. Here, we report successful treatment of a patient with Leigh syndrome using idebenone, a derivative of coenzyme Q-10. The patient's brainstem function, especially respiratory function, improved after idebenone treatment. Idebenone may be worth trying in patients with Leigh syndrome.

[A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode/Leigh overlap syndrome].

PubMed

Matsui, Jun; Takano, Tomoyuki; Ryujin, Fukiko; Anzai, Yuko; Yoshioka, Seiichiro; Takeuchi, Yoshihiro; Goto, Yuichi

2014-09-01

We experienced a case in which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was identified as complications following the onset of Leigh syndrome along with a 10191 T>C mutation of the mitochondrial gene. The case pertains to a 26-year-old woman. The disease appeared when she was 11 years old due to divergent strabismus, at which point a diagnosis of juvenile Leigh syndrome was made. Many infraction images not conforming to the vessel region were observed upon a brain MRI which was performed at 26 years of age, thus leading to her being diagnosed with MELAS as a complication. Upoon bibliographical consideration, it was speculated that the clinical features of MELAS/Leigh overlap syndrome clearly differ from Leigh syndrome in terms of age of onset, symptoms, and prognosis. Pleiotropic genetic factors including heteroplasmy were presumed to be involved in the diverse phenotype of overlap syndrome.

STS-115 MS Tanner on Atlantis Middeck

NASA Image and Video Library

2006-09-10

S115-E-05337 (10 Sept. 2006) --- Astronaut Joseph R. Tanner, STS-115 mission specialist, works on the middeck of the Space Shuttle Atlantis on the eve of docking day with the International Space Station.

[Cytochrome c oxydase-deficient Leigh syndrome with homozygous mutation in SURF1 gene].

PubMed

Monnot, S; Chabrol, B; Cano, A; Pellissier, J F; Collignon, P; Montfort, M F; Paquis-Flucklinger, V

2005-05-01

Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis.

Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA).

PubMed

Horváth, R; Abicht, A; Holinski-Feder, E; Laner, A; Gempel, K; Prokisch, H; Lochmüller, H; Klopstock, T; Jaksch, M

2006-01-01

Detailed clinical, neuroradiological, histological, biochemical, and genetic investigations were undertaken in a child suffering from Leigh syndrome. The clinical symptoms started at age five months and led to a severe progressive neurodegenerative disorder causing epilepsy, psychomotor retardation, and tetraspasticity. Biochemical measurement of skeletal muscle showed a severe decrease in mitochondrial complex II. Sequencing of SDHA revealed compound heterozygosity for a nonsense mutation in exon 4 (W119X) and a missense mutation in exon 3 (A83V), both absent in normal controls. In six additional patients--five with Leigh or Leigh-like syndrome and one with neuropathy and ataxia associated with isolated deficiency of complex II--mutations in SDHA were not detected, indicating genetic heterogeneity.

Identification of HIBCH gene mutations causing autosomal recessive Leigh syndrome: a gene involved in valine metabolism.

PubMed

Soler-Alfonso, Claudia; Enns, Gregory M; Koenig, Mary Kay; Saavedra, Heather; Bonfante-Mejia, Eliana; Northrup, Hope

2015-03-01

Leigh syndrome is a progressive neurodegenerative disorder with usual onset of symptoms during the first year of life. The disorder has been associated with mutations in over 30 genes. This difficulty with genetic heterogeneity makes whole exome sequencing a more cost-effective approach for investigation of etiology. We describe an individual with typical Leigh syndrome who was found to have compound heterozygous mutations in the gene HIBCH (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism of valine. She exhibited significant clinical improvement after a valine-restricted diet. A subset of patients with uncharacterized Leigh syndrome present with specific biochemical abnormalities. This report highpoints the challenges and restrictions of routine metabolic testing and features the recognition of inborn errors of metabolism as potential treatable causes of Leigh syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Respiratory chain inhibition: one more feature to propose MPTP intoxication as a Leigh syndrome model.

PubMed

Da Costa, Barbara; Dumon, Elodie; Le Moigno, Laurence; Bodard, Sylvie; Castelnau, Pierre; Letellier, Thierry; Rocher, Christophe

2016-10-01

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice have been widely used to model the loss of dopaminergic neurons. As this treatment leads to basal ganglia degeneration, it was proposed that MPTP mice could be used as a model of Leigh syndrome. However, this mitochondrial pathology is biochemically characterized by a respiratory chain dysfunction. To determine if MPTP can affect in vivo mitochondria function, we measured the activities of mitochondrial respiratory chain complexes in several tissues. Our results show that MPTP affects mainly mitochondrial respiratory chain complex IV, as found in Leigh Syndrome, confirming that acute MPTP intoxicated mice are a good model of Leigh Syndrome.

Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients.

PubMed

Sofou, Kalliopi; de Coo, Irenaeus F M; Ostergaard, Elsebet; Isohanni, Pirjo; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; Lönnqvist, Tuula; Bindoff, Laurence Albert; Tulinius, Már; Darin, Niklas

2018-01-01

Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m.8993T>G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m.8993T>C mutation. Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A novel NDUFS4 frameshift mutation causes Leigh disease in the Hutterite population.

PubMed

Lamont, Ryan E; Beaulieu, Chandree L; Bernier, Francois P; Sparkes, Rebecca; Innes, A Micheil; Jackel-Cram, Candice; Ober, Carole; Parboosingh, Jillian S; Lemire, Edmond G

2017-03-01

Leigh disease is a progressive, infantile-onset, neurodegenerative disorder characterized by feeding difficulties, failure to thrive, hypotonia, seizures, and central respiratory compromise. Metabolic and neuroimaging investigations typically identify abnormalities consistent with a disorder of mitochondrial energy metabolism. Mutations in more than 35 genes affecting the mitochondrial respiratory chain encoded from both the nuclear and mitochondrial genomes have been associated with Leigh disease. The clinical presentations of five individuals of Hutterite descent with Leigh disease are described herein. An identity-by-descent mapping and candidate gene approach was used to identify a novel homozygous c.393dupA frameshift mutation in the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (NDUFS4) gene. The carrier frequency of this mutation was estimated in >1,300 Hutterite individuals to be 1 in 27. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families.

PubMed

Tuppen, Helen A L; Hogan, Vanessa E; He, Langping; Blakely, Emma L; Worgan, Lisa; Al-Dosary, Mazhor; Saretzki, Gabriele; Alston, Charlotte L; Morris, Andrew A; Clarke, Michael; Jones, Simon; Devlin, Anita M; Mansour, Sahar; Chrzanowska-Lightowlers, Zofia M A; Thorburn, David R; McFarland, Robert; Taylor, Robert W

2010-10-01

Isolated complex I deficiency is the most frequently observed oxidative phosphorylation defect in children with mitochondrial disease, leading to a diverse range of clinical presentations, including Leigh syndrome. For most patients the genetic cause of the biochemical defect remains unknown due to incomplete understanding of the complex I assembly process. Nonetheless, a plethora of pathogenic mutations have been described to date in the seven mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear-encoded subunits and in six assembly factors. Whilst several mitochondrial DNA mutations are recurrent, the majority of these mutations are reported in single families. We have sequenced core structural and functional nuclear-encoded subunits of complex I in a cohort of 34 paediatric patients with isolated complex I deficiency, identifying pathogenic mutations in 6 patients. These included a novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was also identified in conjunction with a novel NDUFS2 splice site mutation (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic centre, with microsatellite and single nucleotide polymorphism analyses indicating that this was due to an ancient common founder event. Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes.

[Mitochondrial leukoencephalopathy of infancy: is it an early expression of Leigh syndrome?].

PubMed

Rouco Axpe, I; Garaizar Axpe, C; Labairu Echevarría, M; Sanjurjo Crespo, P; Aldamiz Echevarría, L; Prats Viñas, J M

2003-06-01

Leigh syndrome is probably the most frequent metabolic disorder in infancy and childhood. The classic form of the disease is characterized by bilateral lesions of basal ganglia and brainstem. The extensive involvement of white matter, without radiological basal ganglia abnormalities, is an unusual manifestation of the disease. Four patients who presented the disease during the first year of life are described. The four patients presented a stereotyped clinical picture, consisting of regression of already acquired psychomotor abilities and very prominent pyramidal signs. These clinical manifestations and results of neuroimaging studies suggested a primary leukodystrophy. Increased values of lactic and piruvic acids suggested a mitochondrial disorder. Enzymatic studies confirmed a mitochondrial respiratory chain deficiency in two patients, and a pyruvate dehydrogenase complex defect in the remaining two patients. The pathological findings in the latter two sisters were consistent with the characteristic microscopic lesions of Leigh syndrome, but with atypical distribution. Diagnosis of Leigh syndrome must be taken into consideration in infants presenting with a leukodystrophic clinical and radiological pattern, despite the lack of basal ganglia involvement.

Astronaut Joseph Tanner checks gloves during during launch/entry training

NASA Image and Video Library

1994-06-23

S94-40082 (23 June 1994) --- Astronaut Joseph R. Tanner, mission specialist, checks his glove during a rehearsal for launch and entry phases of the scheduled November flight of STS-66. This rehearsal, held in the Crew Compartment Trainer (CCT) of the Johnson Space Center's (JSC) Shuttle Mockup and Integration Laboratory, was followed by a training session on emergency egress procedures. In November, Tanner will join four other NASA astronauts and a European mission specialist for a week and a half aboard the Space Shuttle Atlantis in Earth-orbit in support of the Atmospheric Laboratory for Applications and Science (ATLAS-3).

The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle.

PubMed

Brautbar, Ariel; Wang, Jing; Abdenur, Jose E; Chang, Richard C; Thomas, Janet A; Grebe, Theresa A; Lim, Cynthia; Weng, Shao-Wen; Graham, Brett H; Wong, Lee-Jun

2008-08-01

The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.

Schizophrenia and Leigh syndrome, a simple comorbidity or the same etiopathogeny: about a case.

PubMed

Mnif, Leila; Sellami, Rim; Masmoudi, Jawaher

2015-01-01

Leigh syndrome is a mitochondrial encephalomyopathy that occurs due to "cytochrome c oxidase deficiency". Few psychiatric disorders have been defined that are associated with Leigh syndrome. The objective of this work is to study relations between mitochondrial dysfunction and psychiatric disorders. It was a 20 year old male patient, who received Modopar, for severe extra pyramidal symptoms caused by Leigh syndrome. He developed, four months ago, acute psychotic symptoms such as audio-visual hallucinations, persecution and mystic delirium. The cerebral MRI has shown signal abnormalities in central grey nucleus. The EEG recording and blood test were normal. The hypothesis of drug induced psychiatric disorders (Modopar) was possible. The evolution under atypical antipsychotic was only partial. In this case, the cerebrospinal fluid and lactate levels mean that mitochondria were not an overall explanation for these psychiatric disorders but may at least play a partial role. Psychiatric disorders may just be acomorbidity.

Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine.

PubMed

Cox, Rachel; Platt, Julia; Chen, Li Chieh; Tang, Sha; Wong, Lee-Jun; Enns, Gregory M

2012-03-01

Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Early spinal cord and brainstem involvement in infantile Leigh syndrome possibly caused by a novel variant.

PubMed

Tenney, Jeffrey R; Prada, Carlos E; Hopkin, Robert J; Hallinan, Barbara E

2013-12-01

Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.

Astronauts Greg Harbaugh and Joe Tanner suit up for training in WETF

NASA Image and Video Library

1996-06-11

S96-12829 (10 June 1996) --- Awaiting his helmet, astronaut Joseph R. Tanner, STS-82 mission specialist assigned to extravehicular activity (EVA) involved with the servicing of the Hubble Space Telescope (HST), is about to be submerged in a 25-ft. deep pool at the Johnson Space Center's weightless environment training facility (WET-F). Obscured in this frame, astronaut Gregory J. Harbaugh was on the other side of the platform, waiting to join Tanner in the spacewalk rehearsal.

Juvenile parkinsonism, hypogonadism and Leigh-like MRI changes in a patient with m.4296G>A mutation in mitochondrial DNA.

PubMed

Martikainen, Mika H; Kytövuori, Laura; Majamaa, Kari

2013-03-01

Leigh syndrome is a mitochondrial disease with considerable clinical and genetic variation. We present a 16-year-old boy with Leigh-like syndrome and broad developmental retardation, parkinsonism and hypogonadism. Sequencing of the entire mitochondrial DNA from blood revealed the m.4296G>A mutation in the MT-TI gene. The mutation was heteroplasmic with a 95% proportion of the mutant genome, while the proportion was 58% in the blood of the patient's clinically healthy mother. Our results suggest that m.4296G>A is pathogenic in humans, and that the phenotype related to this change includes Leigh-like syndrome in adolescence with parkinsonism and hypogonadism, in addition to the previously reported early infantile Leigh syndrome. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Premature Ovarian Failure in French Canadian Leigh Syndrome.

PubMed

Ghaddhab, Chiraz; Morin, Charles; Brunel-Guitton, Catherine; Mitchell, Grant A; Van Vliet, Guy; Huot, Céline

2017-05-01

In all surviving girls with Leigh syndrome, French Canadian variety, a mitochondrial disease, we detected premature ovarian failure, manifested as absent or arrested breast development, lack of menarche, high follicle-stimulating hormone, a prepubertal uterus, and small ovaries. Pubertal onset and progression should be evaluated in girls with mitochondrial diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Astronaut Joseph Tanner is assisted into his EMU during training

NASA Image and Video Library

1994-08-01

S94-40048 (1 August 1994) --- Astronaut Joseph R. Tanner, mission specialist, is assisted by Boeing suit expert Steve Voyles as he prepares to be submerged in a 25-feet deep pool at the Johnson Space Center's (JSC) Weightless Environment Training Facility (WET-F). Though no extravehicular activity (EVA) is planned for the mission, at least two astronauts are trained to perform tasks that would require a space walk in the event of failure of remote systems. In November, Tanner will join four other NASA astronauts and a European mission specialist for a week and a half in space aboard the Space Shuttle Atlantis. The flight will support the Atmospheric Laboratory for Applications and Science (ATLAS-3) mission.

Biochemical and genetic analysis of Leigh syndrome patients in Korea.

PubMed

Chae, Jong-Hee; Lee, Jin Sook; Kim, Ki Joong; Hwang, Yong Seung; Hirano, Michio

2008-06-01

Sixteen Korean patients with Leigh syndrome were identified at the Seoul National University Children's Hospital in 2001-2006. Biochemical or molecular defects were identified in 14 patients (87.5%). Thirteen patients had respiratory chain enzyme defects; 9 had complex I deficiency, and 4 had combined defects of complex I+III+IV. Based on the biochemical defects, targeted genetic studies in 4 patients with complex I deficiency revealed two heteroplasmic mitochondrial DNA mutations in ND genes. One patient had the mitochondrial DNA T8993G point mutation. No mitochondrial DNA defects were identified in 11 (68.7%) of our LS patients, who probably have mutations in nuclear DNA. Although a limited study based in a single tertiary medical center, our findings suggest that isolated complex I deficiency may be the most common cause of Leigh syndrome in Korea.

Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3.

PubMed

Leshinsky-Silver, Esther; Lev, Dorit; Malinger, Gustavo; Shapira, Daniel; Cohen, Sarit; Lerman-Sagie, Tally; Saada, Ann

2010-05-01

Leigh syndrome can be caused by defects in both nuclear and mitochondrial genes involved in energy metabolism. Recently, an increasing number of mutations in mitochondrial DNA encoding regions, especially in NADH dehydrogenase (respiratory chain complex I) subunits, have been reported as causative of early onset Leigh syndrome. We describe a patient whose fetal brain ultrasound demonstrated periventricular pseudocyst suggestive of a possible mitochondrial disorder who presented postnatally with Leigh syndrome. A muscle biopsy demonstrated a partial decrease in complex I and pyruvate dehydrogenase (PDH-E1 alpha) activity. Sequencing of the PDH-E1 alpha gene did not reveal any mutation. Sequencing of the mtDNA revealed a novel heteroplasmic G10254A (D66N) mutation in the ND3 gene. This change results in a substitution of aspartic acid to asparagine in a highly conserved domain of the ND3 subunit. The mutation could not be detected in the mother's blood or urine sediment. Blue native gel electrophoresis of muscle mitochondria revealed a normal size, albeit a decreased level of complex I. The G10254A substitution in the mtDNA-ND3 gene is another cause of maternally inherited Leigh syndrome. This case demonstrates that periventricular pseudocysts may be the initial in utero presentation in patients with mitochondrial disorders. We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome. (c) 2010 Elsevier Inc. All rights reserved.

Dorothy Davison (1890-1984): Manchester medical artist and her work for neurosurgeon Sir Geoffrey Jefferson (1886-1961).

PubMed

Mohr, Peter D

2017-05-01

Miss Davison was a medical artist at the Manchester Royal Infirmary and the University of Manchester from around 1918 until her retirement in 1957. She illustrated books and scientific papers on anthropology, anatomy and surgery, and became well known for her striking pictures produced by the 'Ross board technique'- a difficult process that she helped pioneer from the 1930s and which forms the bulk of the work she undertook for neurosurgeon Geoffrey Jefferson during the 1930s-1950s. His Neurosurgical Department became the main base for her work until his retirement in 1953. She was an active member of the Medical Artist Association (MAA) which she helped found in 1949.

50 CFR Figure 13 to Part 679 - BSAI C. Opilio Tanner Crab Bycatch Limitations Zone

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false BSAI C. Opilio Tanner Crab Bycatch Limitations Zone 13 Figure 13 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL... ECONOMIC ZONE OFF ALASKA Pt. 679, Fig. 13 Figure 13 to Part 679—BSAI C. Opilio Tanner Crab Bycatch...

Japanese Leigh syndrome case treated with EPI-743.

PubMed

Kouga, Takeshi; Takagi, Mariko; Miyauchi, Akihiko; Shimbo, Hiroko; Iai, Mizue; Yamashita, Sumimasa; Murayama, Kei; Klein, Matthew B; Miller, Guy; Goto, Tomohide; Osaka, Hitoshi

2018-02-01

Leigh syndrome is a mitochondrial disease caused by respiratory chain deficiency, and there are no proven effective therapies. EPI-743 is a potent cellular oxidative stress protectant and results of clinical trials for mitochondrial diseases are accumulating. At 5months, a girl presented with the scarce eye movement and diminished muscle tone. She was diagnosed with Leigh encephalopathy from blood and cerebrospinal fluid lactate elevation and MRI findings. Sequence analysis for mitochondrial DNA revealed a T10158C mutation in the mitochondrial encoded ND3 gene in complex I. At 8months, succinate was prescribed expected to restore the electron transport chain system. After that her condition got worse and succinate was discontinued. Subsequent administration of EPI-743 improved her eye movement, fine motor movements of the extremities, and bowel movement. She is now 5years old. Although brain atrophy has progressed, she has still respiratory free time. Our patient showed visible improvement with EPI-743 treatment and the only patient surviving after 4years. There is a possibility that EPI-743 is modifying the natural course of the syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Stefanyshyn-Piper and Tanner perform first EVA during STS-115 / Expedition 13 joint operations

NASA Image and Video Library

2006-09-12

S115-E-05663 (12 Sept. 2006) --- Astronauts Joseph R. Tanner (left) and Heidemarie M. Stefanyshyn-Piper, both STS-115 mission specialists, work in tandem during the mission's first session of extravehicular activity (EVA) while the Space Shuttle Atlantis was docked with the International Space Station. During today's spacewalk, Tanner and Stefanyshyn-Piper worked to connect power cables on the P3/P4 truss, release restraints for the Solar Array Blanket Boxes that hold the solar arrays and the Beta Gimbal Assemblies that serve as the structural link between the truss' integrated electronics and the Solar Array Wings. Stefanyshyn-Piper and Tanner also installed the Solar Alpha Rotary Joint and completed the connection of electrical cables between the new P3 truss and the P1 truss.

Photocopy from Evan Leigh's Modern Cotton Spinning (Vol 1), Manchester, ...

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

Photocopy from Evan Leigh's Modern Cotton Spinning (Vol 1), Manchester, 1873 (PL XX); illustration used by eminent British textile engineer to exemplify the ultimate development in American cotton mill technology. - Harmony Manufacturing Company, Mill Number 3, 100 North Mohawk Street, Cohoes, Albany County, NY

Spatial patterns and movements of red king and Tanner crabs: Implications for the design of marine protected areas

USGS Publications Warehouse

Taggart, S. James; Mondragon, Jennifer; Andrews, A.G.; Nielsen, J.K.

2008-01-01

Most examples of positive population responses to marine protected areas (MPAs) have been documented for tropical reef species with very small home ranges; the utility of MPAs for commercially harvested temperate species that have large movement patterns remains poorly tested. We measured the distribution and abundance of red king Paralithodes camtschaticus and Tanner Chionoecetes bairdi crabs inside and outside of MPAs in Glacier Bay National Park, Alaska, USA. By tagging a sub-sample of crabs with sonic tags, we estimated the movement of adult crabs from one of the MPAs (Muir Inlet) into the central portion of Glacier Bay where fishing still occurs. Tanner crabs and red king crabs moved similar average distances per day, although Tanner crabs had a higher transfer out of the Muir Inlet MPA into the central bay. Tanner crab movements were characterized by large variation among individual crabs, both in distance and direction traveled, while red king crabs migrated seasonally between 2 specific areas. Although Tanner crabs exhibited relatively large movements, distribution and abundance data suggest that they may be restricted at large spatial scales by habitat barriers. MPAs that are effective at protecting king and especially Tanner crab brood stock from fishing mortality will likely need to be larger than is typical of MPAs worldwide. However, by incorporating information on the seasonal movements of red king crabs and the location of habitat barriers for Tanner crabs, MPAs could likely be designed that would effectively protect adults from fishing mortality. ?? Inter-Research 2008.

Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome: a Case Report.

PubMed

Ashrafi, Farzad; Pakdaman, Hossein; Arabahmadi, Mehran; Behnam, Behdad

2017-01-01

Leigh syndrome is a severe progressive neurodegenerative disorder with different clinical presentationsthat usually becomes apparent in the first year of life and rarely in late childhood and elderly years. It is causedby failure of mitochondrial respiratory chain and often results in regression of both mental and motor skills and might even lead to death. In some of the inherited neurodegenerative diseases like Alexander disease, head trauma is reported as a trigger for onset of the disease. We present a late onset Leigh syndrome in a 14-year-old girl whose symptoms were initiating following head trauma.

Astronauts Greg Harbaugh and Joe Tanner suit up for training in WETF

NASA Image and Video Library

1996-06-11

S96-12830 (10 June 1996) --- Astronaut Joseph R. Tanner, STS-82 mission specialist assigned to extravehicular activity (EVA) involved with the servicing of the Hubble Space Telescope (HST), dons the gloves for his extravehicular mobility unit (EMU) space suit. He is about to be submerged in a 25-ft. deep pool at the Johnson Space Center's weightless environment training facility (WET-F) to participate in simulations for some of the EVA work. Out of frame, astronaut Gregory J. Harbaugh was on the other side of the platform, waiting to join Tanner in the spacewalk rehearsal.

Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency.

PubMed

Yüksel, Adnan; Seven, Mehmet; Cetincelik, Umran; Yeşil, Gözde; Köksal, Vedat

2006-06-01

Leigh syndrome is an inherited, progressive neurodegenerative disorder of infancy and childhood. Mutations in the nuclear SURF-1 gene are specifically associated with cytochrome C oxidase-deficient Leigh syndrome. This report describes two patients with similar facial features. One of them was a 2(1/2)-year-old male, and the other was a 3-year-old male with a mutation in SURF-1 gene and facial dysmorphism including frontal bossing, brachycephaly, hypertrichosis, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, hypertrophic gums, irregularly placed teeth, upturned nostril, low-set big ears, and retrognathi. The first patient's magnetic resonance imaging at 15 months of age indicated mild symmetric T2 prolongation involving the subthalamic nuclei. His second magnetic resonance imaging at 2 years old revealed a symmetric T2 prolongation involving the subthalamic nuclei, substantia nigra, and medulla lesions. In the second child, at the age of 2 the first magnetic resonance imaging documented heavy brainstem and subthalamic nuclei involvement. A second magnetic resonance imaging, performed when he was 3 years old, revealed diffuse involvement of the substantia nigra and hyperintense lesions of the central tegmental tract in addition to previous lesions. Facial dysmorphism and magnetic resonance imaging findings, observed in these cases, can be specific findings in Leigh syndrome patients with cytochrome C oxidase deficiency. SURF-1 gene mutations must be particularly reviewed in such patients.

Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.

PubMed

Simon, Mariella; Richard, Elodie M; Wang, Xinjian; Shahzad, Mohsin; Huang, Vincent H; Qaiser, Tanveer A; Potluri, Prasanth; Mahl, Sarah E; Davila, Antonio; Nazli, Sabiha; Hancock, Saege; Yu, Margret; Gargus, Jay; Chang, Richard; Al-Sheqaih, Nada; Newman, William G; Abdenur, Jose; Starr, Arnold; Hegde, Rashmi; Dorn, Thomas; Busch, Anke; Park, Eddie; Wu, Jie; Schwenzer, Hagen; Flierl, Adrian; Florentz, Catherine; Sissler, Marie; Khan, Shaheen N; Li, Ronghua; Guan, Min-Xin; Friedman, Thomas B; Wu, Doris K; Procaccio, Vincent; Riazuddin, Sheikh; Wallace, Douglas C; Ahmed, Zubair M; Huang, Taosheng; Riazuddin, Saima

2015-03-01

Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.Val213Phe]) is the underlying cause of nonsyndromic hearing loss (DFNB94) and compound heterozygous mutations ([c.969T>A; p.Tyr323*] + [c.1142A>G; p.Asn381Ser]) result in mitochondrial respiratory chain deficiency and Leigh syndrome, which is a neurodegenerative disease characterized by symmetric, bilateral lesions in the basal ganglia, thalamus, and brain stem. The severity of the genetic lesions and their effects on NARS2 protein structure cosegregate with the phenotype. A hypothetical truncated NARS2 protein, secondary to the Leigh syndrome mutation p.Tyr323* is not detectable and p.Asn381Ser further decreases NARS2 protein levels in patient fibroblasts. p.Asn381Ser also disrupts dimerization of NARS2, while the hearing loss p.Val213Phe variant has no effect on NARS2 oligomerization. Additionally we demonstrate decreased steady-state levels of mt-tRNAAsn in fibroblasts from the Leigh syndrome patients. In these cells we show that a decrease in oxygen consumption rates (OCR) and electron transport chain (ETC) activity can be rescued by overexpression of wild type NARS2. However, overexpression of the hearing loss associated p.Val213Phe mutant protein in these fibroblasts cannot complement the OCR and ETC defects. Our findings establish lesions in NARS2 as a new cause for nonsyndromic hearing loss and Leigh syndrome.

Late-onset Leigh syndrome with myoclonic epilepsy with ragged-red fibers.

PubMed

Monden, Yukifumi; Mori, Masato; Kuwajima, Mari; Goto, Tamako; Yamagata, Takanori; Momoi, Mariko Y

2013-06-01

We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2 years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Professor James M. Tanner and the sport sciences.

PubMed

Malina, Robert M

2012-09-01

Although Tanner was not directly involved in physical education or the sport sciences, several of his papers addressed issues related to research in the area. To consider the implications of selected papers and research projects for the sport sciences. PAPERS AND IMPLICATIONS: Several early papers addressed ratio standards, somatotype and total cholesterol, and anthropometric and somatotype changes associated weight training and cessation of training in young adult men. The papers have, respectively, implications for current studies of allometric scaling, physique and risk factors for cardiovascular and metabolic complications, and responses to training. The survey of athletes at the 1960 Rome Olympic Games not only added to the literature but to some extent also set the stage for subsequent surveys of Olympic athletes in 1968, 1972 and 1976. Although not directly involved in the mixed-longitudinal study of Training of Youth Athletes (TOYA) in several sports, it was conducted in his department. Results from TOYA indicated no influence of systematic training for sport on growth in height, young adult height and sexual maturation. Growth at Adolescence was also a fixture in many graduate programs. Though not a sport scientist, Tanner contributed directly and indirectly to the field.

[A case of Leigh syndrome associated with respiratory chain complex I deficiency due to mitochondrial gene 13513G>A mutation].

PubMed

Wei, Xiao-Qiong; Kong, Qing-Peng; Zhang, Yao; Yang, Yan-Ling; Chang, Xing-Zhi; Qi, Yu; Qi, Zhao-Yue; Xiao, Jiang-Xi; Qin, Jiong; Wu, Xi-Ru

2009-05-01

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.

Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.

PubMed

Minoia, Francesca; Bertamino, Marta; Picco, Paolo; Severino, Mariasavina; Rossi, Andrea; Fiorillo, Chiara; Minetti, Carlo; Nesti, Claudia; Santorelli, Filippo Maria; Di Rocco, Maja

2017-01-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.

Tanner poses by the Floating Potential Probe during the third EVA of STS-97

NASA Image and Video Library

2000-12-07

STS097-377-006 (7 December 2000) --- --- Space walking Endeavour astronauts topped off their scheduled space walk activities with an image of an evergreen tree (left) placed atop the P6 solar array structure, the highest point in their construction project. Astronaut Joseph R. Tanner, mission specialist, then posed for this photo with the "tree" before returning to the shirt-sleeve environment of the Space Shuttle Endeavour. Astronaut Carlos I. Noriega, mission specialist who shared three STS-97 space walks with Tanner, took the photo with a 35mm camera.

[Leigh syndrome: case report].

PubMed

Roma, Adriano de Carvalho; Pereira, Paula Resende Aquino de Assis; Dantas, Adalmir Morterá

2008-01-01

The authors describe for the first time in the Country a case of a 10-year-old female child, assisted at the Ophthalmology Clinic of the Hospital Universitário Clementino Fraga Filho UFRJ, with Leigh's syndrome that is part of a metabolic disease group known as mitochondrial encephalomyopathies. It is an hereditary disease transmitted by a different mode of inheritance: mitochondrial, X-linked recessive and autosomal recessive. The beginning of clinical manifestations is varied and occurs usually in the first two years of life, with progressive and insidious evolution and exacerbation periods. Diagnosis is difficult because pleomorphic presentation, based on clinical findings and complementary study related to mitochondrial production of ATP and cytochrome c oxidase deficiencies. Considering that there is no specific treatment, this is based on a palliative procedure. So, the identification of this syndrome is very important to keep it under control, since its evolution is progressive.

Spatial distribution of juvenile and adult female Tanner crabs (Chionoecetes bairdi) in a glacial fjord ecosystem: Implications for recruitment processes

USGS Publications Warehouse

Nielsen, J.K.; Taggart, S. James; Shirley, Thomas C.; Mondragon, Jennifer

2007-01-01

A systematic pot survey in Glacier Bay, Alaska, was conducted to characterize the spatial distribution of juvenile and adult female Tanner crabs, and their association with depth and temperature. The information was used to infer important recruitment processes for Tanner crabs in glaciated ecosystems. High-catch areas for juvenile and adult female Tanner crabs were identified using local autocorrelation statistics. Spatial segregation by size class corresponded to features in the glacial landscape: high-catch areas for juveniles were located at the distal ends of two narrow glacial fjords, and high-catch areas for adults were located in the open waters of the central Bay. Juvenile female Tanner crabs were found at nearly all sampled depths (15–439 m) and temperatures (4–8°C), but the biggest catches were at depths <150 m where adults were scarce. Because adults may prey on or compete with juveniles, the distribution of juveniles could be influenced by the distribution of adults. Areas where adults or predators are scarce, such as glacially influenced fjords, could serve as refuges for juvenile Tanner crabs.

Cancer incidence and mortality among Swedish leather tanners.

PubMed Central

Mikoczy, Z; Schütz, A; Hagmar, L

1994-01-01

OBJECTIVES--The aim was to study the incidence of cancer among Swedish leather tanners. METHODS--A cohort of 2026 subjects who had been employed for at least one year between 1900 and 1989 in three Swedish leather tanneries, was established. The cancer incidence and mortality patterns were assessed for the periods 1958-89 and 1952-89 respectively, and cause-specific standardised incidence and mortality ratios (SIRs and SMRs) were calculated. RESULTS--A significantly increased incidence of soft tissue sarcomas (SIR 4.27, 95% confidence interval (95% CI) 1.39-9.97) was found, based on five cases. Excesses, (not statistically significant) was also found for multiple myelomas (SIR 2.54, 95% CI 0.93-5.53), and sinonasal cancer (SIR 3.77, 95% CI 0.46-13.6). CONCLUSIONS--The increased incidence of soft tissue sarcomas adds support to previous findings of an excess mortality in this diagnosis among leather tanners. A plausible cause is exposure to chlorophenols, which had occurred in all three plants. The excess of multiple myelomas may also be associated with exposure to chlorophenol. The association between incidence of cancer and specific chemical exposure will be elucidated in a cohort-based case-referent study. PMID:7951777

Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.

PubMed

Gerards, Mike; Kamps, Rick; van Oevelen, Jo; Boesten, Iris; Jongen, Eveline; de Koning, Bart; Scholte, Hans R; de Angst, Isabel; Schoonderwoerd, Kees; Sefiani, Abdelaziz; Ratbi, Ilham; Coppieters, Wouter; Karim, Latifa; de Coo, René; van den Bosch, Bianca; Smeets, Hubert

2013-03-01

Leigh syndrome is an early onset, often fatal progressive neurodegenerative disorder caused by mutations in the mitochondrial or nuclear DNA. Until now, mutations in more than 35 genes have been reported to cause Leigh syndrome, indicating an extreme genetic heterogeneity for this disorder, but still only explaining part of the cases. The possibility of whole exome sequencing enables not only mutation detection in known candidate genes, but also the identification of new genes associated with Leigh syndrome in small families and isolated cases. Exome sequencing was combined with homozygosity mapping to identify the genetic defect in a Moroccan family with fatal Leigh syndrome in early childhood and specific magnetic resonance imaging abnormalities in the brain. We detected a homozygous nonsense mutation (c.20C>A; p.Ser7Ter) in the thiamine transporter SLC19A3. In vivo overexpression of wild-type SLC19A3 showed an increased thiamine uptake, whereas overexpression of mutant SLC19A3 did not, confirming that the mutation results in an absent or non-functional protein. Seventeen additional patients with Leigh syndrome were screened for mutations in SLC19A3 using conventional Sanger sequencing. Two unrelated patients, both from Moroccan origin and one from consanguineous parents, were homozygous for the same p.Ser7Ter mutation. One of these patients showed the same MRI abnormalities as the patients from the first family. Strikingly, patients receiving thiamine had an improved life-expectancy. One patient in the third family deteriorated upon interruption of the thiamine treatment and recovered after reinitiating. Although unrelated, all patients came from the province Al Hoceima in Northern Morocco. Based on the recombination events the mutation was estimated to have occurred 1250-1750 years ago. Our data shows that SLC19A3 is a new candidate for mutation screening in patients with Leigh syndrome, who might benefit from high doses of thiamine and/or biotin. Especially

Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation.

PubMed

Chuquilin, Miguel; Govindarajan, Raghav; Peck, Dawn; Font-Montgomery, Esperanza

2016-09-01

Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy.

Astronaut Joseph Tanner checks gloves during during launch/entry training

NASA Technical Reports Server (NTRS)

1994-01-01

Astronaut Joseph R. Tanner, mission specialist, checks his gloves during a rehearsal for the launch and entry phases of the scheduled November 1994 flight of STS-66. This rehearsal, held in the crew compartment trainer (CCT) of JSC's Shuttle mockup and integration laboratory, was followed by a training session on emergency egress procedures.

Fulminant neurological deterioration in a neonate with Leigh syndrome due to a maternally transmitted missense mutation in the mitochondrial ND3 gene.

PubMed

Leshinsky-Silver, E; Lev, D; Tzofi-Berman, Z; Cohen, S; Saada, A; Yanoov-Sharav, M; Gilad, E; Lerman-Sagie, T

2005-08-26

Leigh syndrome can result from both nuclear and mitochondrial DNA defects. Mutations in complex V genes of the respiratory chain were considered until recently as the most frequent cause for mitochondrial inherited Leigh syndrome, while gene defects in complex I were related to recessive Leigh syndrome. Recently few reports of mutations in the mitochondrial-encoded complex I subunit genes causing Leigh syndrome have been reported. We describe a 1-month-old baby who acutely deteriorated, with abrupt onset of brainstem dysfunction, due to basal ganglia lesions extending to the brainstem. A muscle biopsy demonstrated complex I deficiency. Subsequent analysis of the mitochondrial genome revealed a homoplastic T10191C mutation in the ND3 gene (in blood and muscle), resulting in a substitution of serine to proline. Hair root analysis revealed a 50% mutant load, reflecting heteroplasmy in early embryonic stages. The mutation was also detected in his mother (5%). Western blot analysis revealed a decrease of the 20 kDa subunit (likely ND6) and of the 30 kDa subunit (NDUFA9), which is probably due to instability attributed to the inability to form subcomplexes with ND3. This is the first description of infantile Leigh syndrome due to a maternally transmitted T10191C substitution in ND3 and not due to a de novo mutation. This mutation is age and tissue dependent and therefore may not be amenable to prenatal testing.

Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome.

PubMed

Matilainen, Sanna; Carroll, Christopher J; Richter, Uwe; Euro, Liliya; Pohjanpelto, Max; Paetau, Anders; Isohanni, Pirjo; Suomalainen, Anu

2017-09-01

Leigh syndrome is a severe infantile encephalopathy with an exceptionally variable genetic background. We studied the exome of a child manifesting with Leigh syndrome at one month of age and progressing to death by the age of 2.4 years, and identified novel compound heterozygous variants in PNPT1, encoding the polynucleotide phosphorylase (PNPase). Expression of the wild type PNPT1 in the subject's myoblasts functionally complemented the defects, and the pathogenicity was further supported by structural predictions and protein and RNA analyses. PNPase is a key enzyme in mitochondrial RNA metabolism, with suggested roles in mitochondrial RNA import and degradation. The variants were predicted to locate in the PNPase active site and disturb the RNA processing activity of the enzyme. The PNPase trimer formation was not affected, but specific RNA processing intermediates derived from mitochondrial transcripts of the ND6 subunit of Complex I, as well as small mRNA fragments, accumulated in the subject's myoblasts. Mitochondrial RNA processing mediated by the degradosome consisting of hSUV3 and PNPase is poorly characterized, and controversy on the role and location of PNPase within human mitochondria exists. Our evidence indicates that PNPase activity is essential for the correct maturation of the ND6 transcripts, and likely for the efficient removal of degradation intermediates. Loss of its activity will result in combined respiratory chain deficiency, and a classic respiratory chain-deficiency-associated disease, Leigh syndrome, indicating an essential role for the enzyme for normal function of the mitochondrial respiratory chain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome.

PubMed

Johnson, Simon C; Yanos, Melana E; Kayser, Ernst-Bernhard; Quintana, Albert; Sangesland, Maya; Castanza, Anthony; Uhde, Lauren; Hui, Jessica; Wall, Valerie Z; Gagnidze, Arni; Oh, Kelly; Wasko, Brian M; Ramos, Fresnida J; Palmiter, Richard D; Rabinovitch, Peter S; Morgan, Philip G; Sedensky, Margaret M; Kaeberlein, Matt

2013-12-20

Mitochondrial dysfunction contributes to numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies. We found that rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of Québec.

PubMed

Han, Velda Xinying; Tan, Teresa S; Wang, Furene S; Tay, Stacey Kiat-Hong

2017-01-01

Leigh syndrome, French-Canadian type is unique to patients from a genetic isolate in the Saguenay-Lac-Saint-Jean region of Québec. It has also been recently described in 10 patients with LRPPRC mutation outside of Québec. It is an autosomal recessive genetic disorder with fatal metabolic crisis and severe neurological morbidity in infancy caused by LRPPRC mutation. The authors report a boy with a novel LRPPRC compound heterozygous missense mutations c.3130C>T, c.3430C>T, and c.4078G>A found on whole-exome sequencing which correlated with isolated cytochrome c-oxidase deficiency found in skeletal muscle. LRPPRC mutation is a rare cause of cytochrome c-oxidase-deficient form of Leigh syndrome outside of Québec. Our patient broadens the spectrum of phenotypes of Leigh syndrome, French-Canadian type. LRPPRC mutation should be considered in children with early childhood neurodegenerative disorder, even in the absence of metabolic crisis. Early evaluation with whole-exome sequencing is useful for early diagnosis and for genetic counseling.

Jett, Tanner and Garneau during re-entry preparations for STS-97

NASA Image and Video Library

2000-12-11

STS097-310-032 (11 December 2000) --- Astronauts (left to right) Marc Garneau, Joseph R. Tanner, both mission specialists, and Brent W. Jett, mission commander, are photographed on the flight deck of the Space Shuttle Endeavour as they prepare for re-entry. Garneau represents the Canadian Space Agency (CSA).

A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.

PubMed

Anderson, S L; Chung, W K; Frezzo, J; Papp, J C; Ekstein, J; DiMauro, S; Rubin, B Y

2008-12-01

Leigh syndrome is a neurodegenerative disorder of infancy or childhood generally due to mutations in nuclear or mitochondrial genes involved in mitochondrial energy metabolism. We performed linkage analysis in an Ashkenazi Jewish (AJ) family without consanguinity with three affected children. Linkage to microsatellite markers D5S1969 and D5S407 led to evaluation of the complex I gene NDUFS4, in which we identified a novel homozygous c.462delA mutation that disrupts the reading frame. The resulting protein lacks a cAMP-dependent protein kinase phosphorylation site required for activation of mitochondrial respiratory chain complex I. In a random sample of 5000 healthy AJ individuals, the carrier frequency of the NDUFS4 mutation c.462delA was 1 in 1000, suggesting that it should be considered in all AJ patients with Leigh syndrome.

[Leigh syndrome resulting from a de novo mitochondrial DNA mutation (T8993G)].

PubMed

Playán, A; Solano-Palacios, A; González de la Rosa, J B; Merino-Arribas, J M; Andreu, A L; López-Pérez, M; Montoya, J

Several degenerative neurological diseases are caused by mutations in the mitochondrial gene coding for subunit 6 of the ATPase. Thus, NARP (neurogenic weakness, ataxia, and retinitis pigmentosa) and Leigh syndromes are associated to a T8993G mutation when the percentage of mutant mitochondrial DNA is low (60 90%) or high (>90%), respectively. Leigh syndrome is also caused by a second mutation in the same position T8993C. The patient, a boy that died at 6 months, had generalized hypotonia, psychomotor delay, hepatomegaly, choreic movements and hyporreflexia. MRI showed hypodensities in the basal ganglia and brain stem as well as hyperlactacidemia. Molecular genetic analysis of the mitochondrial DNA showed that the patient had the T8993G mutation in a percentage higher than 95%. No mutated DNA was detected in blood of the proband s mother, maternal aunt and grandmother. The point mutation T8993G may occur de novo, at high levels, causing neurodegenerative diseases.

Ndufs4 related Leigh syndrome: A case report and review of the literature.

PubMed

Ortigoza-Escobar, Juan Darío; Oyarzabal, Alfonso; Montero, Raquel; Artuch, Rafael; Jou, Cristina; Jiménez, Cecilia; Gort, Laura; Briones, Paz; Muchart, Jordi; López-Gallardo, Ester; Emperador, Sonia; Pesini, Eduardo Ruiz; Montoya, Julio; Pérez, Belén; Rodríguez-Pombo, Pilar; Pérez-Dueñas, Belén

2016-05-01

The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

A patient with congenital hyperlactataemia and Leigh syndrome: an uncommon mitochondrial variant.

PubMed

Ching, C K; Mak, Chloe M; Au, K M; Chan, K Y; Yuen, Y P; Yau, Eric K C; Ma, Louis C K; Chow, H L; Chan, Albert Y W

2013-08-01

We report an uncommon mitochondrial variant in a baby girl with congenital hyperlactataemia and Leigh syndrome. The patient presented with a single episode of generalised clonic convulsion at day 19, and was found to have isolated and persistent hyperlactataemia ranging from 3.34 to 9.26 mmol/L. She had elevated serum lactate-to-pyruvate ratios of up to 35 and high plasma alanine concentration, indicative of a respiratory chain defect. At the age of 8 months, she developed evolving neurological and imaging features compatible with Leigh syndrome. Genetic testing for common mitochondrial DNA mutations, large mitochondrial DNA deletions, and selected nuclear genes was negative. Further analysis of lymphocyte mitochondrial DNA by sequencing revealed an uncommon heteroplasmic variant, NC_012920.1(MT-ND5):m.13094T>C (p.Val253Ala), which was previously shown to reduce complex I activity. In patients in whom there was a high suspicion of mitochondrial disorder, entire mitochondrial DNA analysis may be warranted if initial screening of common mitochondrial DNA mutations is negative.

Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations.

PubMed

Tanigawa, Junpei; Kaneko, Kaori; Honda, Masakazu; Harashima, Hiroko; Murayama, Kei; Wada, Takahito; Takano, Kyoko; Iai, Mizue; Yamashita, Sumimasa; Shimbo, Hiroko; Aida, Noriko; Ohtake, Akira; Osaka, Hitoshi

2012-11-01

We report two patients with Leigh syndrome that showed a combination of facial dysmorphism and MRI imaging indicating an SURF1 deficiency, which was confirmed by sequence analysis. Case 1 is a 3-year-old girl with failure to thrive and developmental delay. She presented with tachypnea at rest and displayed facial dysmorphism including frontal bossing, lateral displacement of inner canthi, esotropia, maxillary hypoplasia, slightly upturned nostril, and hypertrichosis dominant on the forehead and extremities. Case 2 is an 8-year-old boy with respiratory failure. He had been diagnosed as selective complex IV deficiency. Case 2 displayed facial dysmorphism and hypertrichosis. Since both patients displayed characteristic facial dysmorphism and MRI findings, we sequenced the SURF1 gene and identified two heterozygous mutations; c.49+1 G>T and c.752_753del in Case 1, and homozygous c.743 C>A in Case 2. For patients with Leigh syndrome showing these facial dysmorphism and hypertrichosis, sequence analysis of the SURF1 gene may be useful. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Pathogenicity of missense mutations in SURF1 deficiency inducing the Leigh syndrome. Importance in diagnosis.

PubMed

Dubot, A; Hervouet, E; Mandon, G; Zabot, M T; Godinot, C

2004-06-01

Leigh syndrome with cytochrome oxidase (COX) deficiency has been associated with SURF1 mutations. For patient diagnosis, distinction between neutral polymorphisms and pathogenic missense SURF1 mutations in Leigh syndrome is essential. We show that several missense SURF1 mutations did not allow a stable protein to be expressed. Absence of immunologically reactive SURF1 is, therefore, helpful to demonstrate their pathogenicity. In addition, we show that out of two previously described missense mutations housed by the same allele, only one, the T737 C was pathogenic. Indeed, transfection of T737 C mutated SURF1 in SURF1-deficient cells did not restore normal SURF1 stability and COX activity. On the contrary, the G604 C-mutated SURF1 did it and, hence, is a neutral variant.

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

PubMed

Naito, E; Ito, M; Yokota, I; Saijo, T; Matsuda, J; Osaka, H; Kimura, S; Kuroda, Y

1997-08-01

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

Ocean Acidification Affects Hemocyte Physiology in the Tanner Crab (Chionoecetes bairdi)

PubMed Central

Meseck, Shannon L.; Alix, Jennifer H.; Swiney, Katherine M.; Long, W. Christopher; Wikfors, Gary H.; Foy, Robert J.

2016-01-01

We used flow cytometry to determine if there would be a difference in hematology, selected immune functions, and hemocyte pH (pHi), under two different, future ocean acidification scenarios (pH = 7.50, 7.80) compared to current conditions (pH = 8.09) for Chionoecetes bairdi, Tanner crab. Hemocytes were analyzed after adult Tanner crabs were held for two years under continuous exposure to acidified ocean water. Total counts of hemocytes did not vary among control and experimental treatments; however, there were significantly greater number of dead, circulating hemocytes in crabs held at the lowest pH treatment. Phagocytosis of fluorescent microbeads by hemocytes was greatest at the lowest pH treatment. These results suggest that hemocytes were dying, likely by apoptosis, at a rate faster than upregulated phagocytosis was able to remove moribund cells from circulation at the lowest pH. Crab hemolymph pH (pHe) averaged 8.09 and did not vary among pH treatments. There was no significant difference in internal pH (pHi) within hyalinocytes among pH treatments and the mean pHi (7.26) was lower than the mean pHe. In contrast, there were significant differences among treatments in pHi of the semi-granular+granular cells. Control crabs had the highest mean semi-granular+granular pHi compared to the lowest pH treatment. As physiological hemocyte functions changed from ambient conditions, interactions with the number of eggs in the second clutch, percentage of viable eggs, and calcium concentration in the adult crab shell was observed. This suggested that the energetic costs of responding to ocean acidification and maintaining defense mechanisms in Tanner crab may divert energy from other physiological processes, such as reproduction. PMID:26859148

Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family.

PubMed

Weerasinghe, Chamara Arachchighe Lahiru; Bui, Bich-Hong Thi; Vu, Thu Thi; Nguyen, Hong-Loan Thi; Phung, Bao-Khanh; Nguyen, Van-Minh; Pham, Van-Anh; Cao, Vu-Hung; Phan, Tuan-Nghia

2018-05-01

Leigh syndrome is a rare inherited, heterogeneous and progressive neurometabolic disorder that is mainly caused by specific mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). The present study reported a case of childhood Leigh syndrome with a point mutation at bp 8,993 in the mitochondrial ATPase6 gene. A 21‑month‑old male child had developed epilepsy, muscular weakness and vomiting, which was accompanied by high fever. Magnetic resonance imaging indicated typical characteristics of Leigh syndrome, including a symmetric abnormal signal in the dorsal medulla oblongata and Sylvian fissure enlargement in association with an abnormal signal in the periventricular white matter and in the putamina and caudate heads. The diagnosis was further supported with genetic tests including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), sequencing, and quantitative PCR. The patient was found to carry a mitochondrial T8993C (m.T8993C) mutation in peripheral blood with 94.00±1.34% heteroplasmy. Eight of his relatives were also subjected to quantification of the m.T8993C mutation. The percentages of heteroplasmy in samples taken from the grandmother, mother, aunt, cousin 1, and cousin 2 were 16.33±1.67, 66.81±0.85, 71.66±3.22, 87.00±1.79, and 91.24±2.50%, respectively. The mutation was not found in samples taken from the father, the husband of the aunt, or the grandfather of the patient. The obtained data showed that the mutation was maternally inherited and accumulated through generations. Even though the heteroplasmy levels of his mother, aunt, cousin 1, and cousin 2 were relatively high (66.81‑91.24%), they remained asymptomatic, indicating that the threshold at which this mutation shows effects is high. To the best of our knowledge, this is the first report of a case of Leigh syndrome in a Vietnamese individual harboring a mtDNA mutation at the 8,993 bp site, and showing a correlation between the heteroplasmy and clinical

In silico investigation of potential mTOR inhibitors from traditional Chinese medicine for treatment of Leigh syndrome.

PubMed

Chen, Kuan-Chung; Lee, Wen-Yuan; Chen, Hsin-Yi; Chen, Calvin Yu-Chian

2014-01-01

A recent research demonstrates that the inhibition of mammalian target of rapamycin (mTOR) improves survival and health for patients with Leigh syndrome. mTOR proteins can be treated as drug target proteins against Leigh syndrome and other mitochondrial disorders. In this study, we aim to identify potent TCM compounds from the TCM Database@Taiwan as lead compounds of mTOR inhibitors. PONDR-Fit protocol was employed to predict the disordered disposition in mTOR protein before virtual screening. After virtual screening, the MD simulation was employed to validate the stability of interactions between each ligand and mTOR protein in the docking poses from docking simulation. The top TCM compounds, picrasidine M and acerosin, have higher binding affinities with target protein in docking simulation than control. There have H-bonds with residues Val2240 and π interactions with common residue Trp2239. After MD simulation, the top TCM compounds maintain similar docking poses under dynamic conditions. The top two TCM compounds, picrasidine M and acerosin, were extracted from Picrasma quassioides (D. Don) Benn. and Vitex negundo L. Hence, we propose the TCM compounds, picrasidine M and acerosin, as potential candidates as lead compounds for further study in drug development process with the mTOR protein against Leigh syndrome and other mitochondrial disorders.

The clinical spectrum of the m.10191T>C mutation in complex I-deficient Leigh syndrome.

PubMed

Nesbitt, Victoria; Morrison, Patrick J; Crushell, Ellen; Donnelly, Deirdre E; Alston, Charlotte L; He, Langping; McFarland, Robert; Taylor, Robert W

2012-06-01

Mitochondrial respiratory chain diseases represent one of the most common inherited neurometabolic disorders of childhood, affecting a minimum of 1 in 7500 live births. The marked clinical, biochemical, and genetic heterogeneity means that accurate genetic counselling relies heavily upon the identification of the underlying causative mutation in the individual and determination of carrier status in the parents. Isolated complex I deficiency is the most common respiratory chain defect observed in children, resulting in organ-specific or multisystem disease, but most often presenting as Leigh syndrome, for which mitochondrial DNA mutations are important causes. Several recurrent, pathogenic point mutations in the MTND3 gene - including m.10191T>C (p.Ser45Pro) - have been previously identified. In this short clinical review we evaluate the case reports of the m.10191T>C mutation causing complex I-deficient Leigh syndrome described in the literature, in addition to two new ones diagnosed in our laboratory. Both of these appear to have arisen de novo without transmission of the mutation from mother to offspring, illustrating the importance not only of fully characterizing the mitochondrial genome as part of the investigation of children with complex I-deficient Leigh syndrome but also of assessing maternal samples to provide crucial genetic advice for families. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

PubMed

Leshinsky-Silver, E; Levine, A; Nissenkorn, A; Barash, V; Perach, M; Buzhaker, E; Shahmurov, M; Polak-Charcon, S; Lev, D; Lerman-Sagie, T

2003-08-01

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Leigh Syndrome and the Mitochondrial m.13513G>A Mutation: Expanding the Clinical Spectrum.

PubMed

Monlleo-Neila, Laura; Toro, Mireia Del; Bornstein, Belen; Garcia-Arumi, Elena; Sarrias, Axel; Roig-Quilis, Manuel; Munell, Francina

2013-11-01

The mitochondrial DNA m.13513G>A mutation in the ND5 subunit gene is a frequent cause of Leigh syndrome. Patients harboring this mutation typically present with ptosis and cardiac conduction abnormalities, particularly Wolff-Parkinson-White syndrome, and have a late clinical onset, which contrasts with the typical infantile form. The authors describe a patient presenting with intrauterine growth retardation and visual impairment at 3 months of age, followed by infantile spasms, severe gastrointestinal dysmotility, and neurological regression. The patient had hyperlactacidemia and bilateral basal ganglia and brainstem lesions on MRI. Although he did not present cardiac conduction abnormalities, his mother had been diagnosed with Wolff-Parkinson-White syndrome. The m.13513G>A mutation was found in the patient's muscle and in several tissues of his mother. The present results expand the phenotype of Leigh syndrome associated with the m.13513G>A mutation, which should be suspected in patients with early-onset mitochondrial encephalopathy with infantile spasms or prominent gastrointestinal smooth muscle involvement.

Timing of maturation and predictors of Tanner stage transitions in boys enrolled in a contemporary British cohort.

PubMed

Monteilh, Carolyn; Kieszak, Stephanie; Flanders, W Dana; Maisonet, Mildred; Rubin, Carol; Holmes, Adrianne K; Heron, Jon; Golding, Jean; McGeehin, Michael A; Marcus, Michele

2011-01-01

This study describes the timing of puberty in 8- to 14-year-old boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of advanced pubic hair stages. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported pubic hair Tanner staging collected annually. We used survival models to estimate median age of attainment of pubic hair stage >1, stage >2 and stage >3 of pubic hair development. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of pubic hair stages. Approximately 5% of the boys reported Tanner pubic hair stage >1 at age 8; 99% of boys were at stage >1 by age 14. The estimated median ages of entry into stages of pubic hair development were 11.4 years [95% confidence interval (CI) 11.3, 11.4] for stage >1, 12.7 years [95% CI 12.7, 12.8] for stage >2 and 13.5 years [95% CI 13.5, 13.6] for stage >3. Predictors of younger age at Tanner stage >1 included low birthweight, younger maternal age at delivery and being taller at age 8. Associations were found between younger age at attainment of stage >2 and gestational diabetes and taller or heavier body size at age 8. Being taller or heavier at age 8 also predicted younger age at Tanner stage >3. The results give added support to the strong influence of pre-adolescent body size on male pubertal development; the tallest and heaviest boys at 8 years achieved each stage earlier and the shortest boys later. Age at attainment of pubic hair Tanner stages in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. This cohort will continue to be followed for maturational information until age 17. © 2010 Blackwell Publishing Ltd.

Growth as a mirror: Is endocrine disruption challenging Tanner's concept?

PubMed Central

Schell, Lawrence M.; Burnitz, Kristopher K.; Gallo, Mia V.

2012-01-01

Background James Tanner coined the expression `Growth as a Mirror' and summarized in four words the results of more than a century of research on growth. Nineteenth century social reformers saw poor child growth as a reflection of terrible environmental conditions of the working class. Later investigators in anthropology and other fields clarified the connections between poor nutrition, disease, psychosocial stress and poor growth. Aim To evaluate the growth as a mirror concept in light of recent studies of endocrine disruption. Papers and Implications Pollution is recognized as a prominent component of the modern environment. From studies of many pollutants it is clear that some pollutants depress growth while others speed sexual maturation and increase growth, primarily in weight and fatness. While such unwelcome environmental features do not always suppress growth, growth still mirrors the environment in all its complexity and this relationship is key to understanding growth patterns today. For example, Akwesasne Mohawk adolescents are characterized by high rates of obesity and overweight. Their growth reflects the multiple intersecting influences of psychosocial stress, several pollutant exposures and limited dietary chokes. Conclusion Although Tanner did not anticipate the myriad influences of pollutants, the growth as a mirror concept continues to have great validity and utility. PMID:22780455

Vulvovaginitis in a pediatric population: relationship among etiologic agents, age and Tanner staging of breast development.

PubMed

Giugno, Silvina; Risso, Paula; Ocampo, Dolores; Rahman, Gisel; Rubinstein, Dra Anahí V

2014-02-01

Vulvovaginitis accounts for 25% of all pediatric gynecology consultations. To assess the etiology of vulvovaginitis based on age and Tanner staging of breast development. Descriptive, cross-sectional study conducted between January 1st and December 31st, 2011. Patients with vulvovaginitis were assessed based on two outcome measures: age group (GI: 0 to 8.9 years old, GII: 9 to 15.9 years old, and GIII: 16 to 18 years old), and the Tanner staging of breast development (I, II-III, IV-V). Results. Two hundred and twenty-nine patients were included, 78 girls in the GI group, 134 in the GII group, and 17 in the GIII group; 81 girls were classified as TI, 36 as TII-III, and 112 as TIV-V based on Tanner staging. Shigella and Oxyuris were the most commonly found etiologic agents in younger girls. Candida albicans, other Candida species, Gardnerella and Ureaplasma urealyticum were the germs most commonly observed in older patients. Oxyuris was predominant in prepubertal girls, while Candida albicans, in postpubertal girls. Hormonal influence was more relevant than the patient's age in terms of vulvovaginitis etiology.

ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.

PubMed

Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

2014-11-01

Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial enzyme is active in several metabolic pathways involving fatty acids and amino acids, including valine, and is immediately upstream of HIBCH in the valine pathway. Both children were compound heterozygous for a c.473C > A (p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1 activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1 protein was undetectable by immunoblot analysis and transfection of patient cells with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and HIBCH and are probably responsible for the brain pathology in both disorders. Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease. Urine metabolite testing can detect and distinguish between these two disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome.

PubMed

Maalej, Marwa; Kammoun, Thouraya; Alila-Fersi, Olfa; Kharrat, Marwa; Ammar, Marwa; Felhi, Rahma; Mkaouar-Rebai, Emna; Keskes, Leila; Hachicha, Mongia; Fakhfakh, Faiza

2018-03-18

Leigh syndrome (LS) is a rare progressive neurodegenerative disorder occurring in infancy. The most common clinical signs reported in LS are growth retardation, optic atrophy, ataxia, psychomotor retardation, dystonia, hypotonia, seizures and respiratory disorders. The paper reported a manifestation of 3 Tunisian patients presented with LS syndrome. The aim of this study is the MT[HYPHEN]ATP6 and SURF1 gene screening in Tunisian patients affected with classical Leigh syndrome and the computational investigation of the effect of detected mutations on its structure and functions by clinical and bioinformatics analyses. After clinical investigations, three Tunisian patients were tested for mutations in both MT-ATP6 and SURF1 genes by direct sequencing followed by in silico analyses to predict the effects of sequence variation. The result of mutational analysis revealed the absence of mitochondrial mutations in MT-ATP6 gene and the presence of a known homozygous splice site mutation c.516-517delAG in sibling patients added to the presence of a novel double het mutations in LS patient (c.752-18 A > C/c. c.751 + 16G > A). In silico analyses of theses intronic variations showed that it could alters splicing processes as well as SURF1 protein translation. Leigh syndrome (LS) is a rare progressive neurodegenerative disorder occurring in infancy. The most common clinical signs reported in LS are growth retardation, optic atrophy, ataxia, psychomotor retardation, dystonia, hypotonia, seizures and respiratory disorders. The paper reported a manifestation of 3 Tunisian patients presented with LS syndrome. The aim of this study is MT-ATP6 and SURF1 genes screening in Tunisian patients affected with classical Leigh syndrome and the computational investigation of the effect of detected mutations on its structure and functions. After clinical investigations, three Tunisian patients were tested for mutations in both MT-ATP6 and SURF1 genes by direct sequencing followed by in

Astronaut Joseph Tanner is assisted into his EMU during training

NASA Technical Reports Server (NTRS)

1994-01-01

Astronaut Joseph R. Tanner, STS-66 mission specialist, is assisted by Boeing suit expert Steve Voyles in donning the gloves for his extravehicular mobility unit (EMU) as he prepares to be submerged in a 25-feet deep pool at JSC's Weightless Environment Training Facility (WETF). Though no extravehicular activity (EVA) is planned for the mission, at least two astronauts are trained to perform tasks that would require a space walk in the event of failure of remote systems.

Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis.

PubMed

Carrozzo, Rosalba; Rizza, Teresa; Stringaro, Annarita; Pierini, Roberta; Mormone, Elisabetta; Santorelli, Filippo M; Malorni, Walter; Matarrese, Paola

2004-07-01

The key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally-inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK(-) osteosarcoma cell line deprived from its own mtDNA in order to insert mutated mtDNAs. Analysis of mitochondrial features in these cybrids indicated that both mitochondrial DNA mutations produced evidence of biochemical, functional and ultrastructural modifications of mitochondria, and that these modifications were associated with an increased apoptotic proneness. Cybrids were highly susceptible to two different apoptotic stimuli, tumour necrosis factor-alpha and Staurosporin. The mechanism involved was the mitochondrial 'intrinsic' pathway, i.e. the caspase 9-driven cascade. More importantly, our results also indicated that the polarization state of the mitochondrial membrane, i.e. a constitutive hyperpolarization detected in cybrid clones, played a specific role. Interestingly, the different effects of the two mutations in terms of susceptibility to apoptosis probably reflect the deeper bioenergetic defect associated with the L217R mutation. This work provides the first evidence that hyperpolarization of mitochondria may be a 'risk factor' for cells with a deep ATPase dysfunction, such as cells from patients with maternally-inherited Leigh syndrome.

Generation of a human iPSC line from a patient with Leigh syndrome.

PubMed

Galera, Teresa; Zurita, Francisco; González-Páramos, Cristina; Moreno-Izquierdo, Ana; Fraga, Mario F; Fernández, Agustin F; Garesse, Rafael; Gallardo, M Esther

2016-01-01

Human iPSC line LND554SV.3 was generated from heteroplasmic fibroblasts of a patient with Leigh syndrome carrying a mutation in the MT-ND5 gene (m.13513GNA; p.D393N). Reprogramming factors Oct3/4, Sox2, Klf4,and cMyc were delivered using a non-integrative methodology that involves the use of Sendai virus.

Clinical, pathological, and neuroimaging analyses of two cases of Leigh syndrome in a Chinese family.

PubMed

Jin, Taoran; Shen, Hongrui; Zhao, Zhe; Hu, Jing

2014-11-01

In this study, the authors examined the clinical manifestations, skeletal muscle pathological characteristics, and neuroimaging results of 2 cases of Leigh syndrome in a Chinese family. The 2 patients presented with general weakness, and 1 of them presented with an impairment of vision. Skeletal muscle biopsies showed a deficiency in cytochrome c oxidase levels. Brain magnetic resonance imaging showed increased T1 and T2 signal intensities in the centrum ovale and dentate nucleus. Diffusion-weighted imaging showed a high-intensity signal. Magnetic resonance spectroscopy showed elevated levels of lactic acid in lesions. The examination of 1 patient at disease onset and during disease remission showed that the lesions detected by magnetic resonance imaging and diffusion-weighted imaging, and the peak for lactic acid detected by magnetic resonance spectroscopy, decreased during remission. These data suggest that changes in the imaging results of patients with Leigh syndrome correlate with disease course and pathogenetic condition. © The Author(s) 2014.

PDH E1β deficiency with novel mutations in two patients with Leigh syndrome.

PubMed

Quintana, E; Mayr, J A; García Silva, M T; Font, A; Tortoledo, M A; Moliner, S; Ozaez, L; Lluch, M; Cabello, A; Ricoy, J R; Koch, J; Ribes, A; Sperl, W; Briones, P

2009-12-01

Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the PDHA1 gene which encodes the E(1)α subunit, with few cases of mutations in the genes for E(3), E3BP (E(3) binding protein), E(2) and E(1)-phosphatase being reported. Only seven patients with deficiency of the E(1)β subunit have been described, with mutations in the PDHB gene in six of them. Clinically they presented with a non-specific encephalomyopathy. We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E(1) activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. Sequencing of PDHB revealed a homozygous point mutation (c.302T>C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). All three mutations appear to destabilize the E(1) enzyme with a decrease of both E(1)α and E(1)β subunits in immunoblot analysis. To our knowledge, these patients with novel PDHB mutations are the first reported with Leigh syndrome.

Adult onset Leigh syndrome with mitochondrial DNA 8344 A>G mutation.

PubMed

Han, Jee-Young; Sung, Jung-Joon; Park, Hong-Kyun; Yoon, Byung-Nam; Lee, Kwang-Woo

2014-11-01

We report a pedigree of adult-onset Leigh syndrome (LS) with mitochondrial mutation 8344 A>G. A 38-year-old woman presented with optic neuropathy, weakness and cognitive impairment. Family history of optic neuropathy and systemic involvement was suggestive of mitochondrial encephalopathy. Genetic and radiologic studies showed m.8344 A>G mutation with characteristics of LS. To our knowledge this is the first case of adult-onset LS demonstrating the m.8344 A>G mutation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mild clinical manifestation and unusual recovery upon coenzyme Q₁₀ treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.

PubMed

Chen, Zhiting; Zhao, Zhenhua; Ye, Qinyong; Chen, Ying; Pan, Xiaodong; Sun, Bin; Huang, Huapin; Zheng, An

2015-03-01

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one‑year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

STS-115 MS Tanner prepares to remove LES seat on Atlantis Middeck

NASA Image and Video Library

2006-09-09

S115-E-05295 (9 Sept. 2006) --- Astronaut Joseph R. Tanner, STS-115 mission specialist, prepares to remove one of the launch and entry seats on mid deck of Atlantis soon after the crew reached Earth orbit. Atlantis and its crew will see a busy number of days before the mid deck seats get re-deployed for entry and landing.

Management of Leigh syndrome: Current status and new insights.

PubMed

Chen, L; Cui, Y; Jiang, D; Ma, C Y; Tse, H-F; Hwu, W-L; Lian, Q

2018-06-01

Leigh syndrome (LS) is an inherited mitochondrial encephalopathy associated with gene mutations of oxidative phosphorylation pathway that result in early disability and death in affected young children. Currently, LS is incurable and unresponsive to many treatments, although some case reports indicate that supplements can improve the condition. Many novel therapies are being continuously tested in pre-clinical studies. In this review, we summarize the genetic basis of LS, current treatment, pre-clinical studies in animal models and the management of other mitochondrial diseases. Future therapeutical strategies and challenges are also discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Self-assessment of pubertal Tanner stage by realistic colour images in representative Chinese obese and non-obese children and adolescents.

PubMed

Sun, Ying; Tao, Fang-Biao; Su, Pu-Yu

2012-04-01

This investigation aims to evaluate the validity of self-assessment of pubertal Tanner stage in representative Chinese children and adolescents. The study is a nationally representative cross-sectional survey in eight research sites in the large project entitled 'China Puberty Research Collaboration'. Weight, height, self-assessed pubertal Tanner stage and physical examination of pubic hair in each gender, breast development in girls and genital development in boys from were analysed. Realistic colour images of pubertal rating were used as self-assessment of pubertal stage. A large proportion of subjects aged 7.9-18.9 years old were capable of identifying their own pubertal Tanner stage accurately or close to the rater's assessments. Obese group tends to overestimate their pubertal development compared to non-obese peers, except for genital assessment in boys. The k values for non-obese and obese girls were 0.619 (p < 0.0001) and 0.527 (p < 0.0001), respectively, while the k values for non-obese and obese boys were 0.503 (p < 0.0001) and 0.352 (p < 0.0001). Self-assessment of the pubertal stage by using realistic colour images could be a better alternative assessment tool for large epidemiological puberty research compared with Tanner's original black and white pictures. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

Astronaut Joseph R. Tanner works with PCG experiment on middeck

NASA Image and Video Library

1994-11-14

On the Space Shuttle Atlantis' mid-deck, astronaut Joseph R. Tanner, mission specialist, works at area amidst several lockers onboard the Shuttle which support the Protein Crystal Growth (PCG) experiment. This particular section is called the Crystal Observation System, housed in the Thermal Enclosure System (COS/TES). Together with the Vapor Diffusion Apparatus (VDA), housed in a Single Locker Thermal Enclosure (SLTES) which is out of frame, the Cos/TES represents the continuing research into the structures of proteins and other macromolecules such as viruses.

Leigh syndrome: neuropathology and pathogenesis.

PubMed

Lake, Nicole J; Bird, Matthew J; Isohanni, Pirjo; Paetau, Anders

2015-06-01

Leigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.

The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency.

PubMed

Chol, M; Lebon, S; Bénit, P; Chretien, D; de Lonlay, P; Goldenberg, A; Odent, S; Hertz-Pannier, L; Vincent-Delorme, C; Cormier-Daire, V; Rustin, P; Rötig, A; Munnich, A

2003-03-01

Leigh syndrome is a subacute necrotising encephalomyopathy frequently ascribed to mitochondrial respiratory chain deficiency. This condition is genetically heterogeneous, as mutations in both mitochondrial (mt) and nuclear genes have been reported. Here, we report the G13513A transition in the ND5 mtDNA gene in three unrelated children with complex I deficiency and a peculiar MRI aspect distinct from typical Leigh syndrome. Brain MRI consistently showed a specific involvement of the substantia nigra and medulla oblongata sparing the basal ganglia. Variable degrees of heteroplasmy were found in all tissues tested and a high percentage of mutant mtDNA was observed in muscle. The asymptomatic mothers presented low levels of mutant mtDNA in blood leucocytes. This mutation, which affects an evolutionary conserved amino acid (D393N), has been previously reported in adult patients with MELAS or LHON/MELAS syndromes, emphasising the clinical heterogeneity of mitochondrial DNA mutations. Since the G13513A mutation was found in 21% of our patients with Leigh syndrome and complex I deficiency (3/14), it appears that this mutation represents a frequent cause of Leigh-like syndrome, which should be systematically tested for molecular diagnosis in affected children and for genetic counselling in their maternal relatives.

New splicing-site mutations in the SURF1 gene in Leigh syndrome patients.

PubMed

Pequignot, M O; Desguerre, I; Dey, R; Tartari, M; Zeviani, M; Agostino, A; Benelli, C; Fouque, F; Prip-Buus, C; Marchant, D; Abitbol, M; Marsac, C

2001-05-04

The gene SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase, the last complex in the respiratory chain. Mutations of the SURF1 gene result in Leigh syndrome and severe cytochrome c oxidase deficiency. Analysis of seven unrelated patients with cytochrome c oxidase deficiency and typical Leigh syndrome revealed different SURF1 mutations in four of them. Only these four cases had associated demyelinating neuropathy. Three mutations were novel splicing-site mutations that lead to the excision of exon 6. Two different novel heterozygous mutations were found at the same guanine residue at the donor splice site of intron 6; one was a deletion, whereas the other was a transition [588+1G>A]. The third novel splicing-site mutation was a homozygous [516-2_516-1delAG] in intron 5. One patient only had a homozygous polymorphism in the middle of the intron 8 [835+25C>T]. Western blot analysis showed that Surf1 protein was absent in all four patients harboring mutations. Our studies confirm that the SURF1 gene is an important nuclear gene involved in the cytochrome c oxidase deficiency. We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex.

A new mutation in MT-ND1 m.3928G>C p.V208L causes Leigh disease with infantile spasms.

PubMed

Wray, Carter D; Friederich, Marisa W; du Sart, Desiree; Pantaleo, Sarah; Smet, Joél; Kucera, Cathlin; Fenton, Laura; Scharer, Gunter; Van Coster, Rudy; Van Hove, Johan L K

2013-11-01

New mutations in mitochondrial DNA encoded genes of complex I are rarely reported. An infant developed Leigh disease with infantile spasms. Complex I enzyme activity was deficient and response to increasing coenzyme Q concentrations was reduced. Complex I assembly was intact. A new mutation in MT-ND1 m.3928G>C p.V208L, affecting a conserved amino acid in a critical domain, part of the coenzyme Q binding pocket, was present at high heteroplasmy. The unaffected mother did not carry measurable mutant mitochondrial DNA, but concern remained for gonadal mosaicism. Prenatal testing was possible for a subsequent sibling. The ND1 p.V208L mutation causes Leigh disease. © 2013.

Genetic and biochemical findings in Chinese children with Leigh syndrome.

PubMed

Ma, Yan-Yan; Wu, Tong-Fei; Liu, Yu-Peng; Wang, Qiao; Song, Jin-Qing; Li, Xi-Yuan; Shi, Xiu-Yu; Zhang, Wei-Na; Zhao, Meng; Hu, Lin-Yan; Yang, Yan-Ling; Zou, Li-Ping

2013-11-01

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

The human biology of Jim Tanner.

PubMed

Cameron, Noël

2012-09-01

In 1940, during his second year of medical training, Jim Tanner expressed the desire to work, 'where physiology, psychology and sociology meet'. His subsequent exposure to the breadth of an American medical education and to the social and economic environment of post-war Europe distilled his belief in the importance of viewing the human in a broad context. Following his visits to the American longitudinal growth studies in 1948. Jim's dreams of a broad scientific discipline that incorporated both the biology and ecology of the human were strengthened by an inspirational group of embryonic human biologists with whom he developed '… the new Human Biology …' from the '… Physical Anthropology of old…'. With Jo Weiner, Derek Roberts, Geoffrey Harrison, Arthur Mourant, Nigel Barnicot and Kenneth Oakley, Jim was to form the Society for the Study of Human Biology in 1958. The development of human biology over the next 50 years was shaped by the expertise and diversity of that group of visionary scientists who conceived the scientific discipline of 'human biology' in which biology, behaviour and social context define the human species.

The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

PubMed

Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

2015-04-01

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

Leigh syndrome with Fukuyama congenital muscular dystrophy: a case report.

PubMed

Kondo, Hidehito; Tanda, Koichi; Tabata, Chihiro; Hayashi, Kohei; Kihara, Minako; Kizaki, Zenro; Taniguchi-Ikeda, Mariko; Mori, Masato; Murayama, Kei; Ohtake, Akira

2014-09-01

We report the first case of Leigh syndrome (LS) with Fukuyama congenital muscular dystrophy (FCMD). A neonate suffered from lactic acidosis and subsequently presented with poor feeding, muscle weakness, hypotonia, cardiopulmonary dysfunction, and hydrocephalus. He died at 17 months. The findings of brain magnetic resonance imaging indicated some specific features of both LS and FCMD, and FCMD gene mutation was detected. Decreased mitochondrial respiratory complex I and II activity was noted. Mitochondrial DNA sequencing showed no pathogenic mutation. A case with complex I+II deficiency has rarely been reported, suggesting a nuclear gene mutation. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

STS-97 Mission Specialist Tanner during pre-pack and fit check

NASA Technical Reports Server (NTRS)

2000-01-01

STS-97 Mission Specialist Joseph Tanner gets help with his boots from suit technician Erin Canlon during check pre-pack and fit check. Mission STS-97 is the sixth construction flight to the International Space Station. Its payload includes the P6 Integrated Truss Structure and a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission includes two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST.

Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect.

PubMed

Herzer, M; Koch, J; Prokisch, H; Rodenburg, R; Rauscher, C; Radauer, W; Forstner, R; Pilz, P; Rolinski, B; Freisinger, P; Mayr, J A; Sperl, W

2010-02-01

Mitochondrial NADH: ubiquinone oxidoreductase (complex I) deficiency accounts for most defects in mitochondrial oxidative phosphorylation. Pathogenic mutations have been described in all 7 mitochondrial and 12 of the 38 nuclear encoded subunits as well as in assembly factors by interfering with the building of the mature enzyme complex within the inner mitochondrial membrane. We now describe a male patient with a novel homozygous stop mutation in the NDUFAF2 gene. The boy presented with severe apnoea and nystagmus. MRI showed brainstem lesions without involvement of basal ganglia and thalamus, plasma lactate was normal or close to normal. He died after a fulminate course within 2 months after the first crisis. Neuropathology verified Leigh disease. We give a synopsis with other reported patients. Within the clinical spectrum of Leigh disease, patients with mutations in NDUFAF2 present with a distinct clinical pattern with predominantly brainstem involvement on MRI. The diagnosis should not be missed in spite of the normal lactate and lack of thalamus and basal ganglia changes on brain MRI.

Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome

PubMed Central

Gerards, M; Sluiter, W; van den Bosch, B J C; de Wit, L E A; Calis, C M H; Frentzen, M; Akbari, H; Schoonderwoerd, K; Scholte, H R; Jongbloed, R J; Hendrickx, A T M; de Coo, I F M

2009-01-01

Background Leigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or the brainstem. The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene. Methods and results A consanguineous Moroccan family with Leigh syndrome comprise 11 children, three of which are affected. Marker analysis revealed a homozygous region of 11.5 Mb on chromosome 20, containing 111 genes. Eight possible mitochondrial candidate genes were sequenced. Patients were homozygous for an unclassified variant (p.P193L) in the cardiolipin synthase gene (CRLS1). As this variant was present in 20% of a Moroccan control population and enzyme activity was only reduced to 50%, this could not explain the rare clinical phenotype in our family. Patients were also homozygous for an amino acid substitution (p.L159F) in C20orf7, a new complex I assembly factor. Parents were heterozygous and unaffected sibs heterozygous or homozygous wild type. The mutation affects the predicted S-adenosylmethionine (SAM) dependent methyltransferase domain of C20orf7, possibly involved in methylation of NDUFB3 during the assembly process. Blue native gel electrophoresis showed an altered complex I assembly with only 30–40% of mature complex I present in patients and 70–90% in carriers. Conclusions A new cause of Leigh syndrome can be a defect in early complex I assembly due to C20orf7 mutations. PMID:19542079

Hypocapnic hypothesis of Leigh disease.

PubMed

Pronicka, Ewa

2017-04-01

Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes. Hypocapnic hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is hypocapnia (decrease in pCO 2 ) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress. Inside mitochondria, the pH signal of high pH/low bicarbonate ion (HCO - 3 ) is transmitted by soluble adenyl cyclase (sAC) through cAMP dependent manner. The process can initiate brain lesions (necrosis, apoptosis, hypervascularity) in OXPHOS deficient cells residing at the LS area of the brain. The major message of the article is that it is not the ATP depletion but intracellular alkalization (and/or hyperoxia?) which seem to be the cause of LS. The paper includes suggestions concerning the methodology for further research on the LS mechanism and for therapeutic strategy. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Tanner and Burbank store lithium hydroxide canisters beneath the MDDK during Expedition 13 / STS-115 Joint Operations

NASA Image and Video Library

2006-09-16

S115-E-06528 (9-21 Sept. 2006) --- Astronauts Joseph R. Tanner (left) and Daniel C. Burbank, both STS-115 mission specialists, work with the lithium hydroxide (LiOH) canisters beneath Space Shuttle Atlantis' middeck.

Perioperative risk assessment for successful kidney transplant in leigh syndrome: a case report.

PubMed

Ducharlet, Kathryn; Thyagarajan, Dominic; Ierino, Francesco; McMahon, Lawrence P; Lee, Darren

2018-02-01

Leigh syndrome (LS) is a rare neurodegenerative mitochondrial disorder which typically presents in childhood but has a varied clinical course. Renal involvement such as proximal tubulopathy in patients with mitochondrial disorders has been described. However, end stage renal disease (ESRD) is uncommon and literature regarding patients undergoing kidney transplantation is limited. Successful deceased donor renal transplant has not been previously described in a patient with Leigh Syndrome. We report a 21-year-old Han Chinese man who presented with limb weakness and unsteady gait, which progressed rapidly over a period of months until he was wheelchair-bound. He subsequently developed ESRD and was commenced on hemodialysis. Investigations revealed a m.13513G > A mutation with clinical and radiological features consistent with LS. His mitochondrial disease stabilised and he underwent a multidisciplinary assessment for deceased donor kidney transplantation to identify and minimise the LS-associated perioperative risks and potential negative effects of immunosuppressants on his LS. Successful kidney transplantation followed with excellent graft function three and a half years post-transplant and improvement in the patient's physical function. This case highlights the importance of careful pre-transplant perioperative risk assessment and post-transplant care in a rare and heterogeneous neurological disease to achieve an ultimately excellent clinical outcome. To our knowledge, this is the first report of successful deceased donor kidney transplant in a patient with known LS.

Long survival in patients with leigh syndrome and the m.10191T>C mutation in MT-ND3 : a case report and review of the literature.

PubMed

Levy, Rebecca J; Ríos, Purificación Gutierrez; Akman, Hasan O; Sciacco, Monica; Vivo, Darryl C De; DiMauro, Salvatore

2014-10-01

We report an unusual case of Leigh syndrome due to the m.10191T>C mutation in the complex I gene MT-ND3. This mutation has been associated with a spectrum of clinical phenotypes ranging from infant lethality to adult onset. Despite infantile onset and severe symptoms, our patient has survived to early adulthood because of a strict dietary regimen and parental care. This patient is an extreme example of the frequently prolonged course of Leigh syndrome due to this particular mutation. © The Author(s) 2013.

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD).

PubMed

Balasubramaniam, Shanti; Lewis, B; Mock, D M; Said, H M; Tarailo-Graovac, M; Mattman, A; van Karnebeek, C D; Thorburn, D R; Rodenburg, R J; Christodoulou, J

2017-01-01

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS). Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness, and attainment of new developmental milestones, despite lack of biochemical improvements. Whole exome sequencing (WES) analysis failed to identify any other variants which could likely contribute to the observed phenotype, apart from the homoplasmic (100%) m.8993T>G variant initially detected by mitochondrial DNA (mtDNA) sequencing.Hypocitrullinemia has been reported in patients with the m.8993T>G variant and other mitochondrial disorders. However, persistent plasma elevations of C3 and C5-OH have previously only been reported in one other patient with this homoplasmic mutation. We suggest considering the m.8993T>G variant early in the diagnostic evaluation of MCD-like biochemical disturbances, particularly when associated with

Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease.

PubMed

de Haas, Ria; Das, Devashish; Garanto, Alejandro; Renkema, Herma G; Greupink, Rick; van den Broek, Petra; Pertijs, Jeanne; Collin, Rob W J; Willems, Peter; Beyrath, Julien; Heerschap, Arend; Russel, Frans G; Smeitink, Jan A

2017-09-15

Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 -/- mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 -/- mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 -/- mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 -/- mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing.

Usefulness and Reliability of Tanner Pubertal Self-Rating to Urban Black Adolescents in South Africa

ERIC Educational Resources Information Center

Norris, Shane A.; Richter, Linda M.

2005-01-01

Self-rating of pubertal development is the recommended method to assess puberty in large community-based surveys of adolescent development and behavior. The aim of this study was to validate for the first time pubertal self-assessment using the sexual maturation scale developed by Tanner among Black South African adolescents (n=182) aged between…

Spasticity secondary to Leigh syndrome managed with selective dorsal rhizotomy: a case report.

PubMed

Mazarakis, N K; Vloeberghs, M H

2016-09-01

Selective dorsal rhizotomy (SDR) is a surgical technique used to treat spasticity in children secondary to cerebral palsy (CP). We report, to the best of our knowledge for the first time, the case of a child who underwent SDR for the management of spasticity secondary to Leigh syndrome. SDR resulted in excellent functional outcome with significant improvement in spasticity. This result contributes to the mounting evidence that SDR could be used to alleviate spasticity secondary not only to CP but also to other pathologies as well.

Outpatient anesthesia for oral surgery in a juvenile with Leigh disease.

PubMed

Ellis, Zachary; Bloomer, Charles

2005-01-01

We report a case of anesthesia for elective outpatient third molar extraction in a juvenile with Leigh disease, a progressive neurodegenerative disorder related to respiratory chain deficiency. This syndrome usually presents in infancy and is characterized by nervous system dysfunction and respiratory abnormalities. Anesthesia has been reported to aggravate respiratory symptoms and frequently precipitate respiratory failure. Preoperative swallowing difficulty or respiratory symptoms should be carefully diagnosed, because they can be a warning sign of postoperative complications or mortality. Adverse effects of anesthesia may quickly lead into metabolic acidosis. Anesthetics should be carefully chosen that do not interfere with mitochondrial respiration, which can lead to lactic acidosis.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome.

PubMed

Ferrari, Michele; Jain, Isha H; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E; Scherrer-Crosbie, Marielle; Mootha, Vamsi K; Zapol, Warren M

2017-05-23

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.

[The Durkheim Test. Remarks on Susan Leigh Star's Boundary Objects].

PubMed

Gießmann, Sebastian

2015-09-01

The article reconstructs Susan Leigh Star's conceptual work on the notion of 'boundary objects'. It traces the emergence of the concept, beginning with her PhD thesis and its publication as Regions of the Mind in 1989. 'Boundary objects' attempt to represent the distributed, multifold nature of scientific work and its mediations between different 'social worlds'. Being addressed to several 'communities of practice', the term responded to questions from Distributed Artificial Intelligence in Computer Science, Workplace Studies and Computer Supported Cooperative Work (CSCW), and microhistorical approaches inside the growing Science and Technology Studies. Yet the interdisciplinary character and interpretive flexibility of Star’s invention has rarely been noticed as a conceptual tool for media theory. I therefore propose to reconsider Star's 'Durkheim test' for sociotechnical media practices.

Juvenile Leigh syndrome, optic atrophy, ataxia, dystonia, and epilepsy due to T14487C mutation in the mtDNA-ND6 gene: a mitochondrial syndrome presenting from birth to adolescence.

PubMed

Leshinsky-Silver, Esther; Shuvalov, Ruslan; Inbar, Shani; Cohen, Sarit; Lev, Dorit; Lerman-Sagie, Tally

2011-04-01

An increasing number of reports describe mutations in mitochondrial DNA coding regions, especially in mitochondrial DNA- encoded nicotinamide adenine dinucleotide dehydrogenase subunit genes of the respiratory chain complex I, as causing early-onset Leigh syndrome. The authors report the molecular findings in a 24-year-old patient with juvenile-onset Leigh syndrome presenting with optic atrophy, ataxia dystonia, and epilepsy. A brain magnetic resonance imaging revealed bilateral basal ganglia and thalamic hypointensities, and a magnetic resonance spectroscopy revealed an increased lactate peak. The authors identified a T14487C change causing M63V substitution in the mitochondrial ND6 gene. The mutation was heteroplasmic in muscle and blood samples, with different mutation loads, and was absent in the patient's mother's urine and blood samples. They suggest that the T14487C mtDNA mutation should be analyzed in Leigh syndrome, presenting with optic atrophy, ataxia, dystonia, and epilepsy, regardless of age.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

PubMed Central

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; Rezoagli, Emanuele; Thoonen, Robrecht; Cheng, Kai-Hung; Sosnovik, David E.; Scherrer-Crosbie, Marielle; Mootha, Vamsi K.; Zapol, Warren M.

2017-01-01

The most common pediatric mitochondrial disease is Leigh syndrome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that continuously breathing normobaric 11% O2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated survival curves and organ pathology in Ndufs4 KO mice exposed to hypoxia or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as continuous normobaric 17% O2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O2 in mice with late-stage encephalopathy reverses their established neurological disease, evidenced by improved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hypoxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials. PMID:28483998

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

DOE PAGES

Ferrari, Michele; Jain, Isha H.; Goldberger, Olga; ...

2017-05-08

The most common pediatric mitochondrial disease is Leigh syn-drome, an episodic, subacute neurodegeneration that can lead to death within the first few years of life, for which there are no proven general therapies. Mice lacking the complex I subunit, Ndufs4, develop a fatal progressive encephalopathy resembling Leigh syndrome and die at ≈60 d of age. We previously reported that contin-uously breathing normobaric 11% O 2 from an early age prevents neurological disease and dramatically improves survival in these mice. Here, we report three advances. First, we report updated sur-vival curves and organ pathology in Ndufs4 KO mice exposed to hypoxiamore » or hyperoxia. Whereas normoxia-treated KO mice die from neurodegeneration at about 60 d, hypoxia-treated mice eventually die at about 270 d, likely from cardiac disease, and hyperoxia-treated mice die within days from acute pulmonary edema. Second, we report that more conservative hypoxia regimens, such as contin-uous normobaric 17% O 2 or intermittent hypoxia, are ineffective in preventing neuropathology. Finally, we show that breathing normobaric 11% O 2 in mice with late-stage encephalopathy re-verses their established neurological disease, evidenced by im-proved behavior, circulating disease biomarkers, and survival rates. Importantly, the pathognomonic MRI brain lesions and neurohistopathologic findings are reversed after 4 wk of hyp-oxia. Upon return to normoxia, Ndufs4 KO mice die within days. Future work is required to determine if hypoxia can be used to prevent and reverse neurodegeneration in other animal models, and to determine if it can be provided in a safe and practical manner to allow in-hospital human therapeutic trials.« less

Comparison of observed rheological properties of hard wheat flour dough with predictions of the Giesekus-Leonov, White-Metzner and Phan-Thien Tanner models

NASA Technical Reports Server (NTRS)

Dhanasekharan, M.; Huang, H.; Kokini, J. L.; Janes, H. W. (Principal Investigator)

1999-01-01

The measured rheological behavior of hard wheat flour dough was predicted using three nonlinear differential viscoelastic models. The Phan-Thien Tanner model gave good zero shear viscosity prediction, but overpredicted the shear viscosity at higher shear rates and the transient and extensional properties. The Giesekus-Leonov model gave similar predictions to the Phan-Thien Tanner model, but the extensional viscosity prediction showed extension thickening. Using high values of the mobility factor, extension thinning behavior was observed but the predictions were not satisfactory. The White-Metzner model gave good predictions of the steady shear viscosity and the first normal stress coefficient but it was unable to predict the uniaxial extensional viscosity as it exhibited asymptotic behavior in the tested extensional rates. It also predicted the transient shear properties with moderate accuracy in the transient phase, but very well at higher times, compared to the Phan-Thien Tanner model and the Giesekus-Leonov model. None of the models predicted all observed data consistently well. Overall the White-Metzner model appeared to make the best predictions of all the observed data.

[Clinical characteristics and genetic analysis of two cases with Leigh syndrome with acute pulmonary hemorrhage as predominant manifestation].

PubMed

Danqun, Jin; Jie, Ding; Wenjia, Tong; Kefei, Hu

2015-04-01

To analyze clinical and imaging features and genetic characteristics of Leigh syndrome with emergent pulmonary edema. The clinical features and imaging data of 2 cases (1 male, 1 female) seen in Anhui Provincial Children's Hospital from 2012 to 2014 were analyzed and summarized. Venous blood samples were sent to Guangzhou Jinyu Medical Examination Center for genetic analysis. Peripheral blood DNA was extracted and amplified, then sent to a sequencing facility for presence of genetic mutation by comparing with the reference sequence (NC_012920.1). (1) The first patient was a 7 months old boy. The second patient was a 7 months and 21 days old girl. They were presented with abnormal respiration and pulmonary hemorrhage required mechanical ventilation. The first patient had a similar attack after 4 months of his birth, whose psychomotor development was normal, and no abnormal neurological findings. The value of blood lactate was 1.58 mmol/L. The value of pyruvic acid was 0.25 mmol/L. The value of cerebrospinal fluid lactate was 6. 4 mmol/L, which was an abnormal increase. The second patient had abnormal nervous system development, which included motor development retardation and hypotonia. The value of blood lactate was 6. 8 mmol/L, pyruvic acid was 0.31 mmol/L. Cerebrospinal fluid lactate was 8.2 mmol/L. (2) Imaging data: chest X-ray revealed double lung effusion. Bilateral caudate nucleus and lentiform nucleus had high signal, and bilateral internal capsule forelimbs were affected in DWI sequence of head MRI. Hemispheres, basal ganglia, cerebral peduncle, cerebellum, pons, and splenium of corpus callosum had multiple abnormal signals in head MRI of the second patient. NAA peak showed significantly reduced lesion area in magnetic resonance blood-flow scanning, and Cho peak increased significantly, which were double lactate-peak. (3) Genetic testing: ATPase6 m.9185 t > C mutation was found in case 1 that was consistent with Leigh syndrome pathogenesis. Hybrid mutations

Severe infantile leigh syndrome associated with a rare mitochondrial ND6 mutation, m.14487T>C.

PubMed

Tarnopolsky, Mark; Meaney, Brandon; Robinson, Brian; Sheldon, Katherine; Boles, Richard G

2013-08-01

We describe a case of severe infantile-onset complex I deficiency in association with an apparent de novo near-homoplasmic mutation (m.14487T>C) in the mitochondrial ND6 gene, which was previously associated with Leigh syndrome and other neurological disorders. The mutation was near-homoplasmic in muscle by NextGen sequencing (99.4% mutant), homoplasmic in muscle by Sanger sequencing, and it was associated with a severe complex I deficiency in both muscle and fibroblasts. This supports previous data regarding Leigh syndrome being on the severe end of a phenotypic spectrum including progressive myoclonic epilepsy, childhood-onset dystonia, bilateral striatal necrosis, and optic atrophy, depending on the proportion of mutant heteroplasmy. While the mother in all previously reported cases was heteroplasmic, the mother and brother of this case were homoplasmic for the wild-type, m.14487T. Importantly, the current data demonstrate the potential for cases of mutations that were previously reported to be homoplasmic by Sanger sequencing to be less homoplasmic by NextGen sequencing. This case underscores the importance of considering mitochondrial DNA mutations in families with a negative family history, even in offspring of those who have tested negative for a specific mtDNA mutation. Copyright © 2013 Wiley Periodicals, Inc.

Thermal alteration of organic matter in recent marine sediments. 2: Isoprenoids. [Tanner Basin off Southern California

NASA Technical Reports Server (NTRS)

Ikan, R.; Baedecker, M. J.; Kaplan, I. R.

1974-01-01

A series of isoprenoid compounds were isolated from a heat treated marine sediment (from Tanner Basin) which were not present in the original sediment. Among the compounds identified were: phytol, dihydrophytol, c-18-isoprenoid ketone, phytanic and pristanic acids, c-19 and c-20-monoolefines, and the alkanes pristane and phytane. The significance and possible routes leading to these compounds is discussed.

Two new mutations in the MT-TW gene leading to the disruption of the secondary structure of the tRNA(Trp) in patients with Leigh syndrome.

PubMed

Mkaouar-Rebai, Emna; Chamkha, Imen; Kammoun, Fatma; Kammoun, Thouraya; Aloulou, Hajer; Hachicha, Mongia; Triki, Chahnez; Fakhfakh, Faiza

2009-07-01

Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes associated with LS in Tunisian patients. We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome. We revealed the presence of 34 reported polymorphisms, nine novel nucleotide variants and two new mutations (T5523G and A5559G) in the tested patients. These two mutations were localized in two conserved regions of the tRNA(Trp) and affect, respectively, the D-stem and the T-stem of the mitochondrial tRNA leading to a disruption of the secondary structure of this tRNA. SSP-PCR analysis showed that the T5523G and A5559G mutations were present with respective heteroplasmic rates of 66% and 43 %. We report here the first mutational screening of mitochondrial mutations in Tunisian patients with Leigh syndrome which described two novel mutations associated with this disorder.

Complete mtDNA sequencing reveals mutations m.9185T>C and m.13513G>A in three patients with Leigh syndrome.

PubMed

Pelnena, Dita; Burnyte, Birute; Jankevics, Eriks; Lace, Baiba; Dagyte, Evelina; Grigalioniene, Kristina; Utkus, Algirdas; Krumina, Zita; Rozentale, Jolanta; Adomaitiene, Irina; Stavusis, Janis; Pliss, Liana; Inashkina, Inna

2017-12-12

The most common mitochondrial disorder in children is Leigh syndrome, which is a progressive and genetically heterogeneous neurodegenerative disorder caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the present study, a novel and robust method of complete mtDNA sequencing, which allows amplification of the whole mitochondrial genome, was tested. Complete mtDNA sequencing was performed in a cohort of patients with suspected mitochondrial mutations. Patients from Latvia and Lithuania (n = 92 and n = 57, respectively) referred by clinical geneticists were included. The de novo point mutations m.9185T>C and m.13513G>A, respectively, were detected in two patients with lactic acidosis and neurodegenerative lesions. In one patient with neurodegenerative lesions, the mutation m.9185T>C was identified. These mutations are associated with Leigh syndrome. The present data suggest that full-length mtDNA sequencing is recommended as a supplement to nuclear gene testing and enzymatic assays to enhance mitochondrial disease diagnostics.

Catalytic Upgrading of Biomass Pyrolysis Oxygenates with Vacuum Gas Oil Using a Davison Circulating Riser Reactor

DOE PAGES

Jarvis, Mark W.; Olstad, Jessica; Parent, Yves; ...

2018-01-02

We investigate and quantitate the changes in hydrocarbon product composition while evaluating the performance and operability of the National Renewable Energy Laboratory's Davison Circulating Riser (DCR) reactor system when biomass model compounds are cofed with traditional fluid catalyst cracking (FCC) feeds and catalyst: vacuum gas oil (VGO) and equilibrium zeolite catalyst (E-Cat). Three compounds (acetic acid, guaiacol, and sorbitan monooleate) were selected to represent the major classes of oxygenates present in biomass pyrolysis vapors. These vapors can contain 30-50% oxygen as oxygenates, which create conversion complications (increased reactivity and coking) when integrating biomass vapors and liquids into fuel and chemicalmore » processes long dominated by petroleum feedstocks. We used these model compounds to determine the appropriate conditions for coprocessing with petroleum and ultimately pure pyrolysis vapors only as compared with standard baseline conditions obtained with VGO and E-Cat only in the DCR. Model compound addition decreased the DCR catalyst circulation rate, which controls reactor temperature and measures reaction heat demand, while increasing catalyst coking rates. Liquid product analyses included 2-dimensional gas chromatography time-of-flight mass spectroscopy (2D GCxGC TOFS), simulated distillation (SIM DIST), 13C NMR, and carbonyl content. Aggregated results indicated that the model compounds were converted during reaction, and despite functional group differences, product distributions for each model compound were very similar. In addition, we determined that adding model compounds to the VGO feed did not significantly affect the DCR's operability or performance. Future work will assess catalytic upgrading of biomass pyrolysis vapor to fungible hydrocarbon products using upgrading catalysts currently being developed at NREL and at Johnson Matthey.« less

Catalytic Upgrading of Biomass Pyrolysis Oxygenates with Vacuum Gas Oil Using a Davison Circulating Riser Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Mark W.; Olstad, Jessica; Parent, Yves

We investigate and quantitate the changes in hydrocarbon product composition while evaluating the performance and operability of the National Renewable Energy Laboratory's Davison Circulating Riser (DCR) reactor system when biomass model compounds are cofed with traditional fluid catalyst cracking (FCC) feeds and catalyst: vacuum gas oil (VGO) and equilibrium zeolite catalyst (E-Cat). Three compounds (acetic acid, guaiacol, and sorbitan monooleate) were selected to represent the major classes of oxygenates present in biomass pyrolysis vapors. These vapors can contain 30-50% oxygen as oxygenates, which create conversion complications (increased reactivity and coking) when integrating biomass vapors and liquids into fuel and chemicalmore » processes long dominated by petroleum feedstocks. We used these model compounds to determine the appropriate conditions for coprocessing with petroleum and ultimately pure pyrolysis vapors only as compared with standard baseline conditions obtained with VGO and E-Cat only in the DCR. Model compound addition decreased the DCR catalyst circulation rate, which controls reactor temperature and measures reaction heat demand, while increasing catalyst coking rates. Liquid product analyses included 2-dimensional gas chromatography time-of-flight mass spectroscopy (2D GCxGC TOFS), simulated distillation (SIM DIST), 13C NMR, and carbonyl content. Aggregated results indicated that the model compounds were converted during reaction, and despite functional group differences, product distributions for each model compound were very similar. In addition, we determined that adding model compounds to the VGO feed did not significantly affect the DCR's operability or performance. Future work will assess catalytic upgrading of biomass pyrolysis vapor to fungible hydrocarbon products using upgrading catalysts currently being developed at NREL and at Johnson Matthey.« less

Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy

PubMed Central

Ahola, Sofia; Isohanni, Pirjo; Euro, Liliya; Brilhante, Virginia; Palotie, Aarno; Pihko, Helena; Lönnqvist, Tuula; Lehtonen, Tanita; Laine, Jukka; Tyynismaa, Henna

2014-01-01

Objective: We report novel defects of mitochondrial translation elongation factor Ts (EFTs), with high carrier frequency in Finland and expand the manifestations of this disease group from infantile cardiomyopathy to juvenile neuropathy/encephalopathy disorders. Methods: DNA analysis, whole-exome analysis, protein biochemistry, and protein modeling. Results: We used whole-exome sequencing to find the genetic cause of infantile-onset mitochondrial cardiomyopathy, progressing to juvenile-onset Leigh syndrome, neuropathy, and optic atrophy in 2 siblings. We found novel compound heterozygous mutations, c.944G>A [p.C315Y] and c.856C>T [p.Q286X], in the TSFM gene encoding mitochondrial EFTs. The same p.Q286X variant was found as compound heterozygous with a splice site change in a patient from a second family, with juvenile-onset optic atrophy, peripheral neuropathy, and ataxia. Our molecular modeling predicted the coding-region mutations to cause protein instability, which was experimentally confirmed in cultured patient cells, with mitochondrial translation defect and lacking EFTs. Only a single TSFM mutation has been previously described in different populations, leading to an infantile fatal multisystem disorder with cardiomyopathy. Sequence data from 35,000 Finnish population controls indicated that the heterozygous carrier frequency of p.Q286X change was exceptionally high in Finland, 1:80, but no homozygotes were found in the population, in our mitochondrial disease patient collection, or in an intrauterine fetal death material, suggesting early developmental lethality of the homozygotes. Conclusions: We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease. PMID:25037205

Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy.

PubMed

Ahola, Sofia; Isohanni, Pirjo; Euro, Liliya; Brilhante, Virginia; Palotie, Aarno; Pihko, Helena; Lönnqvist, Tuula; Lehtonen, Tanita; Laine, Jukka; Tyynismaa, Henna; Suomalainen, Anu

2014-08-19

We report novel defects of mitochondrial translation elongation factor Ts (EFTs), with high carrier frequency in Finland and expand the manifestations of this disease group from infantile cardiomyopathy to juvenile neuropathy/encephalopathy disorders. DNA analysis, whole-exome analysis, protein biochemistry, and protein modeling. We used whole-exome sequencing to find the genetic cause of infantile-onset mitochondrial cardiomyopathy, progressing to juvenile-onset Leigh syndrome, neuropathy, and optic atrophy in 2 siblings. We found novel compound heterozygous mutations, c.944G>A [p.C315Y] and c.856C>T [p.Q286X], in the TSFM gene encoding mitochondrial EFTs. The same p.Q286X variant was found as compound heterozygous with a splice site change in a patient from a second family, with juvenile-onset optic atrophy, peripheral neuropathy, and ataxia. Our molecular modeling predicted the coding-region mutations to cause protein instability, which was experimentally confirmed in cultured patient cells, with mitochondrial translation defect and lacking EFTs. Only a single TSFM mutation has been previously described in different populations, leading to an infantile fatal multisystem disorder with cardiomyopathy. Sequence data from 35,000 Finnish population controls indicated that the heterozygous carrier frequency of p.Q286X change was exceptionally high in Finland, 1:80, but no homozygotes were found in the population, in our mitochondrial disease patient collection, or in an intrauterine fetal death material, suggesting early developmental lethality of the homozygotes. We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease. © 2014 American Academy of Neurology.

Late-adult onset Leigh syndrome.

PubMed

McKelvie, Penelope; Infeld, Bernard; Marotta, Rosetta; Chin, Judy; Thorburn, David; Collins, Steven

2012-02-01

We report an illustrative case of a 74-year-old man who, in the absence of intercurrent illness, presented with rapid cognitive decline. MRI showed bilateral, symmetrical, high T2-weighted signal in the anterior basal ganglia and medial thalami, extending to the periaqueductal grey matter, basal ganglia and basal frontal lobes. A (18)F-fluorodeoxyglucose-positron emission tomography scan showed widespread reduction of metabolism in the cortex of the frontal, temporal and parietal lobes, posterior cingulate gyrus, precuneus and caudate nuclei, with sparing of the sensorimotor cortex, thalami and lentiform nuclei. A mild vitamin B12 deficiency was found and despite normal thiamine levels, intravenous (IV) thiamine and vitamin B therapy was commenced, with a short course of IV methylprednisolone and tetracycline. Repeat neuropsychological assessment four weeks following treatment revealed increased alertness and interactiveness but significant cognitive decline persisted. Unexpectedly, the patient suffered a transmural anterior myocardial infarction six weeks after presentation and died within 24hours. An a autopsy showed: global reduction in cytochrome oxidase (COX) activity in all skeletal muscles examined; bilateral, symmetrical, hypervascular, focally necrotizing lesions in the substantia nigra, periaqueductal grey matter, superior colliculi, medial thalami anteriorly and posteriorly, as well as in the putamena but the mammillary bodies were not affected. Biochemical analysis of fresh muscle confirmed selective deficiency of complex IV of the oxidative phosphorylation chain. A diagnosis of late-adult onset Leigh syndrome was made. Multiple genetic studies failed to identify the specific underlying mutation. The relevant literature is reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.

A comparison of three infant skinfold reference standards: Tanner-Whitehouse, Cambridge Infant Growth Study, and WHO Child Growth Standards.

PubMed

Miller, Elizabeth M

2015-10-01

As researchers increasingly focus on early infancy as a critical period of development, there is a greater need for methodological tools that can address all aspects of infant growth. Infant skinfold measures, in particular, are measurements in need of reliable reference standards that encompass all ages of infants and provide an accurate assessment of the relative fatness of a population. This report evaluates three published reference standards for infant skinfold measurements: Tanner-Whitehouse, Cambridge Infant Growth Study, and the World Health Organization (WHO) Child Growth Standards. To assess these standards, triceps skinfolds from a population of rural Kenyan infants (n = 250) and triceps skinfolds and subscapular skinfolds from infants in the National Health and Nutrition Examination Survey 1999-2002 (NHANES; n = 1197) were calculated as z-scores from the lambda-mu-sigma curves provided by each reference population. The Tanner-Whitehouse standards represented both the Kenyan and US populations as lean, while the Cambridge standards represented both populations as overfat. The distribution of z-scores based on the WHO standards fell in the middle, but excluded infants from both populations who were below the age of 3 months. Based on these results, the WHO reference standard is the best skinfold reference standard for infants over the age of 3 months. For populations with infants of all ages, the Tanner-Whitehouse standards are recommended, despite representing both study populations as underfat. Ideally, the WHO will extend their reference standard to include infants between the ages of 0 and 3 months. © 2014 John Wiley & Sons Ltd.

Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature.

PubMed

Heidary, Gena; Calderwood, Laurel; Cox, Gerald F; Robson, Caroline D; Teot, Lisa A; Mullon, Jennifer; Anselm, Irina

2014-03-01

Combined oxidative phosphorylation deficiency type 7 (COXPD7) is a rare disorder of mitochondrial metabolism that results in optic atrophy and Leigh syndrome-like disease. We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome. Repeat neuroimaging demonstrated reversibility of the findings in 1 sibling and persistent metabolic stroke in the other. This article highlights the phenotypic manifestations from a novel mutation in the C12orf65 gene and reviews the clinical presentation of the 5 other individuals reported to date who carry mutations in this gene.

MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome.

PubMed

Naess, Karin; Freyer, Christoph; Bruhn, Helene; Wibom, Rolf; Malm, Gunilla; Nennesmo, Inger; von Döbeln, Ulrika; Larsson, Nils-Göran

2009-05-01

Leigh syndrome is a common clinical manifestation in children with mitochondrial disease and other types of inborn errors of metabolism. We characterised clinical symptoms, prognosis, respiratory chain function and performed extensive genetic analysis of 25 Swedish children suffering from Leigh syndrome with the aim to obtain insights into the molecular pathophysiology and to provide a rationale for genetic counselling. We reviewed the clinical history of all patients and used muscle biopsies in order to perform molecular, biochemical and genetic investigations, including sequencing the entire mitochondrial DNA (mtDNA), the mitochondrial DNA polymerase (POLGA) gene and the surfeit locus protein 1 (SURF1) gene. Respiratory chain enzyme activity measurements identified five patients with isolated complex I deficiency and five with combined enzyme deficiencies. No patient presented with isolated complex IV deficiency. Seven patients had a decreased ATP production rate. Extensive sequence analysis identified eight patients with pathogenic mtDNA mutations and one patient with mutations in POLGA. Mutations of mtDNA are a common cause of LS and mtDNA analysis should always be included in the diagnosis of LS patients, whereas SURF1 mutations are not a common cause of LS in Sweden. Unexpectedly, age of onset, clinical symptoms and prognosis did not reveal any clear differences in LS patients with mtDNA or nuclear DNA mutations.

Atypical amyoplasia congenita in an infant with Leigh syndrome: a mitochondrial cause of severe contractures?

PubMed

Wilnai, Yael; Seaver, Laurie H; Enns, Gregory M

2012-09-01

Amyoplasia congenita is a distinct form of arthrogryposis with characteristic features including internally rotated and adducted shoulders, extended elbows, flexion, and ulnar deviation of the wrists, and adducted thumbs. Fetal hypokinesia, secondary to a variety of genetic conditions, neuromuscular disorders, and environmental agents, is associated with contractures. In order to increase our understanding of the phenotypic spectrum associated with SURF 1 deficiency, a common cause of mitochondrial respiratory chain complex IV deficiency and Leigh syndrome, we describe a now 6-year-old boy who presented in the neonatal period with amyoplasia congenita. His development was normal until age 10.5 months, at which time he developed severe hypotonia and choreoathetosis following an episode of viral gastroenteritis. Following the onset of neurological symptoms, he gradually developed severe kyphosis and lower limb contractures. Blood and cerebrospinal fluid lactate levels were elevated and head imaging showed characteristic features of Leigh syndrome. He was found to harbor two pathogenic heterozygous mutations in the SURF 1 gene. In this case, mitochondrial dysfunction and the resultant energy deficiency may have played a role in causing abnormal neuronal development during embryogenesis, causing arthrogryposis. A variety of mitochondrial respiratory chain complex deficiencies have been associated with contractures of varying severity. Therefore, mitochondrial disorders should be considered in the differential diagnosis of neonatal arthrogryposis, especially if other characteristic findings such as lactic acidemia or basal ganglia abnormalities are present. Copyright © 2012 Wiley Periodicals, Inc.

The Driver Whose Heart Was Full of Sand: Leigh's Story--A Play Therapy Case Study of a Bereaved Child

ERIC Educational Resources Information Center

Robson, Maggie

2008-01-01

This paper describes the therapeutic journey of Leigh (not his real name), a nine-year-old boy who was referred for play therapy due to the death of his 15-year-old brother. The play therapy was offered through a joint project called "Playing through Loss" and run jointly between a UK university and the local branch of a national…

Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome.

PubMed

Baertling, Fabian; Sánchez-Caballero, Laura; Timal, Sharita; van den Brand, Mariël Am; Ngu, Lock Hock; Distelmaier, Felix; Rodenburg, Richard Jt; Nijtmans, Leo Gj

2017-03-01

NDUFAF3 is an assembly factor of mitochondrial respiratory chain complex I. Variants in NDUFAF3 have been identified as a cause of severe multisystem mitochondrial disease. In a patient presenting with Leigh syndrome, which has hitherto not been described as a clinical feature of NDUFAF3 deficiency, we identified a novel homozygous variant and confirmed its pathogenicity in patient fibroblasts studies. Furthermore, we present an analysis of complex I assembly routes representative of each functional module and, thereby, link NDUFAF3 to a specific step in complex I assembly. Therefore, our report expands the phenotype of NDUFAF3 deficiency and further characterizes the role of NDUFAF3 in complex I biogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Patterns in connectivity and retention of simulated Tanner crab (Chionoecetes bairdi) larvae in the eastern Bering Sea

NASA Astrophysics Data System (ADS)

Richar, Jonathan I.; Kruse, Gordon H.; Curchitser, Enrique; Hermann, Albert J.

2015-11-01

The eastern Bering Sea (EBS) population of Tanner crab (Chionoecetes bairdi) has exhibited high variability in recruitment to the commercially exploited stock since the late 1970s. Concurrently, apparent shifts in crab distribution have also been observed. Larval advection patterns and associated local retention offer a potential mechanism for these observations. The Regional Ocean Modeling System (ROMS) was used to simulate larval Tanner crab advection patterns over 1978-2004 based on larval hatching sites inferred from the distributions of reproductive females sampled during annual National Marine Fisheries Service trawl surveys. Connectivity among EBS subregions was examined by comparing start and end float locations after 60 days of simulated drift. High levels of retention (>50% of floats) were observed in the majority of source subregions, and contributed significantly to the total number of endpoints in each region. Patterns in advection and resultant interregional connectivity were variable, with strongest sustained connectivity occurring along shelf, within individual domains. Increased settlement potential in the outer domain and southern middle domain after 1990 is consistent with an observed geographic shift in fishery productivity. Apparent reliance of Bristol Bay on local larval retention validates recent spatial fishery management to conserve this area as a subpopulation.

Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder.

PubMed

Nafisinia, Michael; Guo, Yiran; Dang, Xiao; Li, Jiankang; Chen, Yulan; Zhang, Jianguo; Lake, Nicole J; Gold, Wendy A; Riley, Lisa G; Thorburn, David R; Keating, Brendan; Xu, Xun; Hakonarson, Hakon; Christodoulou, John

2017-01-01

Leigh syndrome is a subacute necrotising encephalomyopathy proven by post-mortem analysis of brain tissue showing spongiform lesions with vacuolation of the neuropil followed by demyelination, gliosis and capillary proliferation caused by mutations in one of over 75 different genes, including nuclear- and mitochondrial-encoded genes, most of which are associated with mitochondrial respiratory chain function. In this study, we report a patient with suspected Leigh syndrome presenting with seizures, ptosis, scoliosis, dystonia, symmetrical putaminal abnormalities and a lactate peak on brain MRS, but showing normal MRC enzymology in muscle and liver, thereby complicating the diagnosis. Whole exome sequencing uncovered compound heterozygous mutations in NADH dehydrogenase (ubiquinone) flavoprotein 1 gene (NDUFV1), c.1162+4A>C (NM_007103.3), resulting in skipping of exon 8, and c.640G>A, causing the amino acid substitution p.Glu214Lys, both of which have previously been reported in a patient with complex I deficiency. Patient fibroblasts showed a significant reduction in NDUFV1 protein expression, decreased complex CI and complex IV assembly and consequential reductions in the enzymatic activities of both complexes by 38% and 67%, respectively. The pathogenic effect of these variations was further confirmed by immunoblot analysis of subunits for MRC enzyme complexes in patient muscle, liver and fibroblast where we observed 90%, 60% and 95% reduction in complex CI, respectively. Together these studies highlight the importance of a comprehensive, multipronged approach to the laboratory evaluation of patients with suspected Leigh syndrome.

STS-97 Mission Specialist Tanner talks to media after arrival for launch

NASA Technical Reports Server (NTRS)

2000-01-01

After their arrival at the Shuttle Landing Facility, the STS-97 crew gather to address the media. At the microphone is Mission Specialist Joseph Tanner. Behind him stand Commander Brent Jett, Pilot Michael Bloomfield and Mission Specialists Marc Garneau, who is with the Canadian Space Agency, and Carlos Noriega. Mission STS-97is the sixth construction flight to the International Space Station. Its payload includes the P6 Integrated Truss Structure and a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission includes two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST.

[Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

PubMed

Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

1999-04-01

Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

Respiratory chain complex I deficiency due to NDUFA12 mutations as a new cause of Leigh syndrome.

PubMed

Ostergaard, Elsebet; Rodenburg, Richard J; van den Brand, Mariël; Thomsen, Lise Lykke; Duno, Morten; Batbayli, Mustafa; Wibrand, Flemming; Nijtmans, Leo

2011-11-01

This study investigated a girl with Leigh syndrome born to first-cousin parents of Pakistani descent with an isolated respiratory chain complex I deficiency in muscle and fibroblasts. Her early development was delayed, and from age 2 years she started losing motor abilities. Cerebral MRI showed basal ganglia lesions typical of Leigh syndrome. A genome-wide search for homozygosity was performed with the Affymetrix GeneChip 50K Xba array. The analysis revealed several homozygous regions. Three candidate genes were identified, and in one of the genes, NDUFA12, a homozygous c.178C→T mutation leading to a premature stop codon (p.Arg60X) was found. Western blot analysis showed absence of NDUFA12 protein in patient fibroblasts and functional complementation by a baculovirus system showed restoration of complex I activity. NDUFA12 mutations are apparently not a frequent cause of complex I deficiency, since mutations were not found by screening altogether 122 complex I deficient patients in two different studies. NDUFA12 encodes an accessory subunit of complex I and is a paralogue of NDUFAF2. Despite the complete absence of NDUFA12 protein, a fully assembled and enzymatically active complex I could be found, albeit in reduced amounts. This suggests that NDUFA12 is required either at a late step in the assembly of complex I, or in the stability of complex I.

Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a Drosophila Model of Leigh Syndrome.

PubMed

Loewen, Carin A; Ganetzky, Barry

2018-04-01

Proper mitochondrial activity depends upon proteins encoded by genes in the nuclear and mitochondrial genomes that must interact functionally and physically in a precisely coordinated manner. Consequently, mito-nuclear allelic interactions are thought to be of crucial importance on an evolutionary scale, as well as for manifestation of essential biological phenotypes, including those directly relevant to human disease. Nonetheless, detailed molecular understanding of mito-nuclear interactions is still lacking, and definitive examples of such interactions in vivo are sparse. Here we describe the characterization of a mutation in Drosophila ND23 , a nuclear gene encoding a highly conserved subunit of mitochondrial complex 1. This characterization led to the discovery of a mito-nuclear interaction that affects the ND23 mutant phenotype. ND23 mutants exhibit reduced lifespan, neurodegeneration, abnormal mitochondrial morphology, and decreased ATP levels. These phenotypes are similar to those observed in patients with Leigh syndrome, which is caused by mutations in a number of nuclear genes that encode mitochondrial proteins, including the human ortholog of ND23 A key feature of Leigh syndrome, and other mitochondrial disorders, is unexpected and unexplained phenotypic variability. We discovered that the phenotypic severity of ND23 mutations varies depending on the maternally inherited mitochondrial background. Sequence analysis of the relevant mitochondrial genomes identified several variants that are likely candidates for the phenotypic interaction with mutant ND23 , including a variant affecting a mitochondrially encoded component of complex I. Thus, our work provides an in vivo demonstration of the phenotypic importance of mito-nuclear interactions in the context of mitochondrial disease. Copyright © 2018 by the Genetics Society of America.

[Mitochondrial diseases in children including Leigh syndrome--biochemical and molecular background].

PubMed

Pronicka, Ewa; Piekutowska-Abramczuk, Dorota; Pronicki, Maciej

2008-01-01

Mitochondrial diseases in children are more frequently caused by mutations in nuclear DNA then in mtDNA. Special clinical phenotypes are associated with the mutations in SURF1 gene, in SCO2 gene and with mtDNA depletion syndromes. Leigh syndrome is the most common clinical presentation of various mitochondrial disorders during childhood. Elevation of lactate in blood, cerebrospinal fluid and urine is a simple biochemical marker of mitochondrial disorders but its specificity and sensitivity are low. Biochemical investigation of muscle biopsy and search for mitochondrial mutations remain a gold standard in the diagnosis. The standarized diagnostic criteria to establish level of diagnostic certainty (possible, probable, definite) are proposed to be used in practice; these include clinical features, neuroimaging and muscle biopsy investigations. Further research directions to improve our understanding of mitochondrial pathologies in children are suggested.

Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of Leigh syndrome.

PubMed

Cameron, Jessie M; MacKay, Nevena; Feigenbaum, Annette; Tarnopolsky, Mark; Blaser, Susan; Robinson, Brian H; Schulze, Andreas

2015-09-01

Two siblings with hypertrophic cardiomyopathy and brain atrophy were diagnosed with Complex I deficiency based on low enzyme activity in muscle and high lactate/pyruvate ratio in fibroblasts. Whole exome sequencing results of fibroblast gDNA from one sibling was narrowed down to 190 SNPs or In/Dels in 185 candidate genes by selecting non-synonymous coding sequence base pair changes that were not present in the SNP database. Two compound heterozygous mutations were identified in both siblings in NDUFV2, encoding the 24 kDa subunit of Complex I. The intronic mutation (c.IVS2 + 1delGTAA) is disease causing and has been reported before. The other mutation is novel (c.669_670insG, p.Ser224Valfs*3) and predicted to cause a pathogenic frameshift in the protein. Subsequent investigation of 10 probands with complex I deficiency from different families revealed homozygosity for the intronic c.IVS2 + 1delGTAA mutation in a second, consanguineous family. In this family three of five siblings were affected. Interestingly, they presented with Leigh syndrome but no cardiac involvement. The same genotype had been reported previously in a two families but presenting with hypertrophic cardiomyopathy, trunk hypotonia and encephalopathy. We have identified NDUFV2 mutations in two families with Complex I deficiency, including a novel mutation. The diagnosis of Leigh syndrome expands the clinical phenotypes associated with the c.IVS2 + 1delGTAA mutation in this gene. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

[3-Hydroxy-isobutyryl-CoA hydrolase deficiency in a child with Leigh-like syndrome and literature review].

PubMed

Zhu, Hongmin; Bao, Xinhua; Zhang, Yao

2015-08-01

cases with HIBCH gene mutations had been reported, 6 foreign cases with HIBCH gene mutations were reported. Among them, 5 patients were diagnosed as Leigh-like syndrome, with progressive neurodegenerative course, and symmetrical basal ganglia lesions on brain MRI. Another case was reported in 1982, with developmental delay and various physical malformations without data on his brain MRI. HIBCH gene mutational analysis showed that 4 cases had homozygous mutations, which were c. 950G > A (p. G317E) in two brothers, c. 219 _220insTTGAATAG (p. K73fsX86) and c. 1128_1129insT (p. K377X) respectively. Three of them died before 3 years old. Two cases had compound heterozygous mutations: c. 365A > G (p. Y122C) and IVS2-3C > G (p. R27fsX50); c. 517 + 1G > A and c. 410C > T (p. A137V). They were alive at the time of the report. Patients with HIBCH gene mutation mainly presented as Leigh-like syndrome both in clinical manifestation and in neuroimage. HIBCH gene mutational analysis should be performed on children with Leigh-like syndrome, if the mutations of known genes of Leigh syndrome were negative.

Adult Leigh disease without failure to thrive.

PubMed

Sakushima, Ken; Tsuji-Akimoto, Sachiko; Niino, Masaaki; Saitoh, Shinji; Yabe, Ichiro; Sasaki, Hidenao

2011-07-01

Most Leigh disease (LD) patients die before reaching adulthood, but there are reports of "adult LD." The clinical features of adult LD were quite different from those in infant or childhood cases. Here, we describe a normally developed patient with adult LD, who presented with spastic paraplegia that was followed several years later by acute encephalopathy. We also conducted a systemic literature search on adult LD and integrated its various manifestations to arrive at a diagnostic procedure for adult LD. A 26-year-old woman presented with acute encephalopathy after spastic paraplegia. On her first admission, she exhibited bilateral basal ganglia lesion on magnetic resonance images and normal serum lactate levels. On second admission, she had acute encephalopathy with lactic acidosis and bilateral basal ganglia and brainstem lesions. A muscle biopsy revealed cytochrome c oxidase deficiency, and a diagnosis of adult LD was made. Despite treatment in the intensive care unit, she died 9 days after admission. A review of the literature describing adult LD revealed that developmental delay, COX deficiency, serum lactate elevation, and basal ganglia lesions occurred less frequently than they did in children with LD. Cranial nerve disturbance, pyramidal signs, and cerebellar dysfunction were the primary symptoms in adult LD. Thus, the many differences between childhood and adult LD may be helpful for diagnosing adult LD.

Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients.

PubMed

Ogawa, Erika; Shimura, Masaru; Fushimi, Takuya; Tajika, Makiko; Ichimoto, Keiko; Matsunaga, Ayako; Tsuruoka, Tomoko; Ishige, Mika; Fuchigami, Tatsuo; Yamazaki, Taro; Mori, Masato; Kohda, Masakazu; Kishita, Yoshihito; Okazaki, Yasushi; Takahashi, Shori; Ohtake, Akira; Murayama, Kei

2017-09-01

Leigh syndrome (LS) is a progressive neurodegenerative disorder of infancy and early childhood. It is clinically diagnosed by typical manifestations and characteristic computed tomography (CT) or magnetic resonance imaging (MRI) studies. Unravelling mitochondrial respiratory chain (MRC) dysfunction behind LS is essential for deeper understanding of the disease, which may lead to the development of new therapies and cure. The aim of this study was to evaluate the clinical validity of various diagnostic tools in confirming MRC disorder in LS and Leigh-like syndrome (LL). The results of enzyme assays, molecular analysis, and cellular oxygen consumption rate (OCR) measurements were examined. Of 106 patients, 41 were biochemically and genetically verified, and 34 had reduced MRC activity but no causative mutations. Seven patients with normal MRC complex activities had mutations in the MT-ATP6 gene. Five further patients with normal activity in MRC were identified with causative mutations. Conversely, 12 out of 60 enzyme assays performed for genetically verified patients returned normal results. No biochemical or genetic background was confirmed for 19 patients. OCR was reduced in ten out of 19 patients with negative enzyme assay results. Inconsistent enzyme assay results between fibroblast and skeletal muscle biopsy samples were observed in 33% of 37 simultaneously analyzed cases. These data suggest that highest diagnostic rate is reached using a combined enzymatic and genetic approach, analyzing more than one type of biological materials where suitable. Microscale oxygraphy detected MRC impairment in 50% cases with no defect in MRC complex activities.

Anesthetic Management in Pediatric Patient for Percutaneous Endoscopic Gastrostomy with Mitochondrial Myopathy: Leigh Syndrome

PubMed Central

Kiliç, Ebru Tarikçi; Gerenli, Nelgin; Akdemir, Mehmet Salim; Tastan, Necmi Onur; Atag, Egemen

2018-01-01

Leigh syndrome (LS) is a rare disease mainly affecting the central nervous system due to the abnormalities of mitochondrial energy generation and seen in early childhood with progressive loss of movement, mental abilities, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure. Anesthesia and surgery exacerbate the risks of aspiration, wheezing, and breathing difficulties. Tracheal irritability can be stimulated with the efforts of intubation. We report the anesthetic management of a rare case of an 11-year-old boy with a severe form of LS for percutaneous endoscopic gastrostomy insertion. The patient was closely monitored during the procedure and the postoperative period. Carefully chosen anesthetic agents, good pain control, and close monitoring are essential. PMID:29628597

Leigh-like subacute necrotising encephalopathy in Yorkshire Terriers: neuropathological characterisation, respiratory chain activities and mitochondrial DNA.

PubMed

Baiker, Kerstin; Hofmann, Sabine; Fischer, Andrea; Gödde, Thomas; Medl, Susanne; Schmahl, Wolfgang; Bauer, Matthias F; Matiasek, Kaspar

2009-11-01

Our knowledge of molecular mechanisms underlying mitochondrial disorders in humans has increased considerably during the past two decades. Mitochondrial encephalomyopathies have sporadically been reported in dogs. However, molecular and biochemical data that would lend credence to the suspected mitochondrial origin are largely missing. This study was aimed to characterise a Leigh-like subacute necrotising encephalopathy (SNE) in Yorkshire Terriers and to shed light on its enzymatic and genetic background. The possible resemblance to SNE in Alaskan Huskies and to human Leigh syndrome (LS) was another focus of interest. Eleven terriers with imaging and/or gross evidence of V-shaped, non-contiguous, cyst-like cavitations in the striatum, thalamus and brain stem were included. Neuropathological examinations focussed on muscle, brain pathology and mitochondrial ultrastructure. Further investigations encompassed respiratory-chain activities and the mitochondrial DNA. In contrast to mild non-specific muscle findings, brain pathology featured the stereotypic triad of necrotising grey matter lesions with relative preservation of neurons in the aforementioned regions, multiple cerebral infarcts, and severe patchy Purkinje-cell degeneration in the cerebellar vermis. Two dogs revealed a reduced activity of respiratory-chain-complexes I and IV. Genetic analyses obtained a neutral tRNA-Leu(UUR) A-G-transition only. Neuropathologically, SNE in Yorkshire Terriers is nearly identical to the Alaskan Husky form and very similar to human LS. This study, for the first time, demonstrated that canine SNE can be associated with a combined respiratory chain defect. Mitochondrial tRNA mutations and large genetic rearrangements were excluded as underlying aetiology. Further studies, amongst relevant candidates, should focus on nuclear encoded transcription and translation factors.

Leigh syndrome associated with a novel mutation in the COX15 gene.

PubMed

Miryounesi, Mohammad; Fardaei, Majid; Tabei, Seyed Mohammadbagher; Ghafouri-Fard, Soudeh

2016-06-01

Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with a diverse range of symptoms, such as psychomotor delay or regression, weakness, hypotonia, truncal ataxia, intention tremor as well as lactic acidosis in the blood, cerebrospinal fluid or urine. Both nuclear gene defects and mutations of the mitochondrial genome have been detected in these patients. Here we report a 7-year-old girl with hypotonia, tremor, developmental delay and psychomotor regression. However, serum lactate level as well as brain magnetic resonance imaging were normal. Mutational analysis has revealed a novel mutation in exon 4 of COX15 gene (c.415C>G) which results in p.Leu139Val. Previous studies have demonstrated that COX15 mutations are associated with typical LS as well as fatal infantile hypertrophic cardiomyopathy. Consequently, clinical manifestations of COX15 mutations may be significantly different in patients. Such information is of practical importance in genetic counseling.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome.

PubMed

Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2016-04-01

Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome.

PubMed

Kato, Hiroki; Han, Xu; Yamaza, Haruyoshi; Masuda, Keiji; Hirofuji, Yuta; Sato, Hiroshi; Pham, Thanh Thi Mai; Taguchi, Tomoaki; Nonaka, Kazuaki

2017-11-04

Mitochondrial diseases are the result of aberrant mitochondrial function caused by mutations in either nuclear or mitochondrial DNA. Poor bone health has recently been suggested as a symptom of mitochondrial diseases; however, a direct link between decreased mitochondrial function and poor bone health in mitochondrial disease has not been demonstrated. In this study, stem cells from human exfoliated deciduous teeth (SHED) were isolated from a child with Leigh syndrome (LS), a mitochondrial disease, and the effects of decreased mitochondrial function on poor bone health were analyzed. Compared with control SHED, LS SHED displayed decreased osteoblastic differentiation and calcium mineralization. The intracellular and mitochondrial calcium levels were lower in LS SHED than in control SHED. Furthermore, the mitochondrial activity of LS SHED was decreased compared with control SHED both with and without osteoblastic differentiation. Our results indicate that decreased osteoblast differentiation potential and osteoblast function contribute to poor bone health in mitochondrial diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Fatal breathing dysfunction in a mouse model of Leigh syndrome.

PubMed

Quintana, Albert; Zanella, Sebastien; Koch, Henner; Kruse, Shane E; Lee, Donghoon; Ramirez, Jan M; Palmiter, Richard D

2012-07-01

Leigh syndrome (LS) is a subacute necrotizing encephalomyelopathy with gliosis in several brain regions that usually results in infantile death. Loss of murine Ndufs4, which encodes NADH dehydrogenase (ubiquinone) iron-sulfur protein 4, results in compromised activity of mitochondrial complex I as well as progressive neurodegenerative and behavioral changes that resemble LS. Here, we report the development of breathing abnormalities in a murine model of LS. Magnetic resonance imaging revealed hyperintense bilateral lesions in the dorsal brain stem vestibular nucleus (VN) and cerebellum of severely affected mice. The mutant mice manifested a progressive increase in apnea and had aberrant responses to hypoxia. Electrophysiological recordings within the ventral brain stem pre-Bötzinger respiratory complex were also abnormal. Selective inactivation of Ndufs4 in the VN, one of the principle sites of gliosis, also led to breathing abnormalities and premature death. Conversely, Ndufs4 restoration in the VN corrected breathing deficits and prolonged the life span of knockout mice. These data demonstrate that mitochondrial dysfunction within the VN results in aberrant regulation of respiration and contributes to the lethality of Ndufs4-knockout mice.

Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.

PubMed

Ortigoza-Escobar, Juan Darío; Molero-Luis, Marta; Arias, Angela; Oyarzabal, Alfonso; Darín, Niklas; Serrano, Mercedes; Garcia-Cazorla, Angels; Tondo, Mireia; Hernández, María; Garcia-Villoria, Judit; Casado, Mercedes; Gort, Laura; Mayr, Johannes A; Rodríguez-Pombo, Pilar; Ribes, Antonia; Artuch, Rafael; Pérez-Dueñas, Belén

2016-01-01

Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Atypical presentation of Leigh syndrome associated with a Leber hereditary optic neuropathy primary mitochondrial DNA mutation.

PubMed

Fruhman, Gary; Landsverk, Megan L; Lotze, Timothy E; Hunter, Jill V; Wangler, Michael F; Adesina, Adekunle M; Wong, Lee-Jun C; Scaglia, Fernando

2011-06-01

Leber hereditary optic neuropathy (LHON) is caused by point mutations in mitochondrial DNA (mtDNA), and is characterized by bilateral, painless sub-acute visual loss that develops during the second decade of life. Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON. This case is unusual for age of onset, gender, associated neurological findings and evolution, further expanding the clinical spectrum associated with primary LHON mtDNA mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

Medical treatment with thiamine, coenzyme Q, vitamins E and C, and carnitine improved obstructive sleep apnea in an adult case of Leigh disease.

PubMed

Mermigkis, Charalampos; Bouloukaki, Izolde; Mastorodemos, Vasileios; Plaitakis, Andreas; Alogdianakis, Vangelis; Siafakas, Nikolaos; Schiza, Sophia

2013-12-01

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

50 CFR Figure 5 to Part 679 - Kodiak Island Type 1, 2, and 3 Nonpelagic Trawl Closure Status and Marmot Bay Tanner Crab...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Kodiak Island Type 1, 2, and 3 Nonpelagic Trawl Closure Status and Marmot Bay Tanner Crab Protection Area 5 Figure 5 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE...

Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency.

PubMed

Ribeiro, Carolina; do Carmo Macário, Maria; Viegas, Ana Teresa; Pratas, João; Santos, Maria João; Simões, Marta; Mendes, Cândida; Bacalhau, Mafalda; Garcia, Paula; Diogo, Luísa; Grazina, Manuela

2016-11-01

Leigh syndrome (LS) is a rare, progressive neurodegenerative mitochondrial disorder of infancy. It is a genetically heterogeneous disease. The mutations in SURF1 gene are the most frequently known cause. Here two cases of LS likely caused by SURF1 gene variants are reported: a 39-year-old male patient with a novel homozygous deletion (c.-11_13del), and a case of a 6-year-old boy with the same deletion and a nonsense mutation (c.868dupT), both in heterozygosity. Blue native PAGE showed absence of assembled complex IV. This is the first report of a variant that may abolish the SURF1 gene initiation codon in two LS patients. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Mitochondrial DNA haplogroup Y is associated to Leigh syndrome in Chinese population.

PubMed

Hao, Xiao-Dan; Yang, Yan-Ling; Tang, Nelson Leung Sang; Kong, Qing-Peng; Wu, Shi-Fang; Zhang, Ya-Ping

2013-01-10

Although Leigh syndrome (LS) is a well characterized clinical mitochondrial disorder; the exact mutation is not found in all cases and it is not clear whether matrilineal background has contributed to this disease. To address this issue, we extensively studied and compared the haplogroup composition of a sample of 171 Chinese LS patients with that of 1597 controls. Our results show that haplogroup Y may increase the risk of LS in Chinese by 2.867 fold (95% CI=1.135-7.240, P=0.020). Haplogroup B5 has also this trend (1.737 fold, 95% CI=0.961-3.139), but with a borderline P-value (P=0.065). Both haplogroups belong to macro-haplogroup N and share a common reverse mutation on nucleotide position 10398 (A10398G). In fact, the combined haplogroup N with 10398G is also associated with an increased risk for LS (OR=1.882, 95% CI=1.134-3.124, P=0.013). Copyright © 2012. Published by Elsevier B.V.

The assessment and interpretation of Demirjian, Goldstein and Tanner's dental maturity.

PubMed

Liversidge, Helen M

2012-09-01

A frequently reported advancement in dental maturity compared with the 50(th) percentile of Demirjian, Goldstein and Tanner (1973, Hum Biol 45:211-27) has been interpreted as a population difference. To review the assessment and interpretation of Demirjian et al.'s dental maturity. Dental maturity of boys from published reports was compared as maturity curves and difference to the 50(th) percentile in terms of chronological age and score. Dental maturity, as well as maturity of individual teeth, was compared in the fastest and slowest maturing groups of boys from the Chaillet database. Maturity curves from published reports by age category were broadly similar and differences occurred at the steepest part of the curve. These reduced when expressed as score rather than age. Many studies report a higher than expected score for chronological age and the database contained more than expected children with scores>97(th) percentile. Revised scores for chronological age from this database were calculated (4072 males, 3958 females, aged 2.1-17.9). Most published reports were similar to the database smoothed maturity curve. This method of dental maturity is designed to assess maturity for a single child and is unsuitable to compare groups.

Mortality among retired fur workers. Dyers, dressers (tanners) and service workers.

PubMed

Sweeney, M H; Walrath, J; Waxweiler, R J

1985-08-01

A retrospective cohort mortality study was conducted on 807 fur dyers, fur dressers (tanners), and fur service workers who were pensioned between 1952 and 1977 by the Fur, Leather and Machine Workers Union of New York City. Workplace exposures of fur workers varied with job category. Dyers were exposed to oxidative dyes used in commercial hair dyes; dressers and service workers were exposed to tanning chemicals. In a comparison with the New York City population, no significant increases in mortality were observed among the fur dyers. Among fur dressers, mortality from all malignant neoplasms [standardized mortality ratio (SMR) 151] and lung cancer (SMR 232) was significantly elevated, as was mortality from cardiovascular disease (SMR 126) among fur service workers. When examined by ethnic origin, the elevated SMR values and directly age-adjusted rate ratios suggested that foreign-born fur dressers and eastern European-born fur workers experienced the highest risks for lung and colorectal cancers, respectively. These data support previous findings of increased mortality from colorectal cancer in the foreign-born population of the United States and suggest a possible occupational etiology for the observed lung cancer excess.

A rapid screening with direct sequencing from blood samples for the diagnosis of Leigh syndrome.

PubMed

Shimbo, Hiroko; Takagi, Mariko; Okuda, Mitsuko; Tsuyusaki, Yu; Takano, Kyoko; Iai, Mizue; Yamashita, Sumimasa; Murayama, Kei; Ohtake, Akira; Goto, Yu-Ichi; Aida, Noriko; Osaka, Hitoshi

2014-01-01

Large numbers of genes are responsible for Leigh syndrome (LS), making genetic confirmation of LS difficult. We screened our patients with LS using a limited set of 21 primers encompassing the frequently reported gene for the respiratory chain complexes I (ND1-ND6, and ND4L), IV(SURF1), and V(ATP6) and the pyruvate dehydrogenase E1α-subunit. Of 18 LS patients, we identified mutations in 11 patients, including 7 in mDNA (two with ATP6), 4 in nuclear (three with SURF1). Overall, we identified mutations in 61% of LS patients (11/18 individuals) in this cohort. Sanger sequencing with our limited set of primers allowed us a rapid genetic confirmation of more than half of the LS patients and it appears to be efficient as a primary genetic screening in this cohort.

Thermal alteration of organic matter in recent marine sediments. 1: Pigments. [photosynthetic pigments from Tanner Basin off Southern California

NASA Technical Reports Server (NTRS)

Ikan, R.; Aizenshtat, Z.; Baedecker, M. J.; Kaplan, I. R.

1974-01-01

Sediment from Tanner Basin, the outer continental shelf off Southern California, was analyzed for photosynthetic pigments and their derivatives, namely carotenes and chlorins. Samples of the sediment were also exposed to raised temperatures (65, 100, 150 C) for various periods of time (1 week, 1 month, 2 months). Analysis of the heat-treated sediment revealed the presence of alpha-ionene and 2,6-dimethylnapthalene, thermal degradation products of Betacarotente. Chlorins were converted to nickel porphyrins of both DPEP and etio series. Possible mechanisms of these transformations are presented.

The genetics of Leigh syndrome and its implications for clinical practice and risk management.

PubMed

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient's family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.

The genetics of Leigh syndrome and its implications for clinical practice and risk management

PubMed Central

Ruhoy, Ilene S; Saneto, Russell P

2014-01-01

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient’s family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms. PMID:25419155

A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome

PubMed

Thompson Legault, Julie; Strittmatter, Laura; Tardif, Jessica; Sharma, Rohit; Tremblay-Vaillancourt, Vanessa; Aubut, Chantale; Boucher, Gabrielle; Clish, Clary B; Cyr, Denis; Daneault, Caroline; Waters, Paula J; Vachon, Luc; Morin, Charles; Laprise, Catherine; Rioux, John D; Mootha, Vamsi K; Des Rosiers, Christine

2015-11-03

A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism. It is also associated with common age-associated diseases and the aging process. To gain insight into the systemic, biochemical consequences of respiratory chain dysfunction, we performed a case-control, prospective metabolic profiling study in a genetically homogenous cohort of patients with Leigh syndrome French Canadian variant, a mitochondrial respiratory chain disease due to loss-of-function mutations in LRPPRC. We discovered 45 plasma and urinary analytes discriminating patients from controls, including classic markers of mitochondrial metabolic dysfunction (lactate and acylcarnitines), as well as unexpected markers of cardiometabolic risk (insulin and adiponectin), amino acid catabolism linked to NADH status (α-hydroxybutyrate), and NAD(+) biosynthesis (kynurenine and 3-hydroxyanthranilic acid). Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Clinical and genetic characteristics of children with Leigh syndrome].

PubMed

Fang, F; Shen, Y; Shen, D M; Liu, Z M; Ding, C H; Zhang, W C; Sun, S Z; Lyu, J L; Han, T L; Wang, X H; Zhang, W H; Yang, X Y; Li, J W; Wu, H S

2017-03-02

Objective: To investigate the clinically and genetic characteristics of children with Leigh syndrome. Method: Patients with clinically diagnosed Leigh syndrome(LS)in the department of Neurology, Beijing Children's Hospital from January 2013 to February 2016 underwent the mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) detecting with next generation sequencing (NGS) technology. The clinical data of gene confirmed cases were retrospectively collected and analyzed. The differences in the onset age, clinical manifestations, lactic acid level and MRI results between the mtDNA variation and nDNA variation were compared and analyzed. t test, Chi-square test and Fisher's exact test were used for statistical analysis. Result: Thirty-five cases were diagnosed by gene detection, including 20 males and 15 females. The median onset age was 1 year (ranging from the neonatal period to 4.4 years old). The age of onset within 2 years accounted for 74%(26 cases). The onset age of initial symptoms, including developmental delay, developmental regression, and seizures, were 6 (4, 12) months, 12 (8, 14) months, and 6 (1, 23) months respectively. The onset age of ptosis, extrapyramidal symptoms and ataxia were 26 (18, 44) months, 28 (23, 40) months and 28 (19, 35) months, respectively. There were significant differences in the onset age between the three groups ( H =21.919, P =0.01). Within the 35 cases, 29 were manifested with developmental delay (83%), 26 with dystonia (74%), 18 with growth retardation, 15 with myasthenia, 13 with developmental regression, 11 with dysphagia, 10 with feeding difficulties, 4 with skeletal dysplasia, and 2 with digestive tract symptoms; nystagmus and respiratory abnormalities were observed in 9 cases respectively; extrapyramidal symptoms, peripheral nerve injury, ptosis, seizures were observed in 8 cases respectively; and ataxia, ophthalmoplegia and hypertrichiasis were found in 5 cases respectively.The blood lactic acid was measured in 32 LS patients

A hemizygous GYG2 mutation and Leigh syndrome: a possible link?

PubMed

Imagawa, Eri; Osaka, Hitoshi; Yamashita, Akio; Shiina, Masaaki; Takahashi, Eihiko; Sugie, Hideo; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Ogata, Kazuhiro; Matsumoto, Naomichi; Miyake, Noriko

2014-02-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder characterized by unique, bilateral neuropathological findings in brainstem, basal ganglia, cerebellum and spinal cord. LS is genetically heterogeneous, with the majority of the causative genes affecting mitochondrial malfunction, and many cases still remain unsolved. Here, we report male sibs affected with LS showing ketonemia, but no marked elevation of lactate and pyruvate. To identify their genetic cause, we performed whole exome sequencing. Candidate variants were narrowed down based on autosomal recessive and X-linked recessive models. Only one hemizygous missense mutation (c.665G>C, p.W222S) in glycogenin-2 (GYG2) (isoform a: NM_001079855) in both affected sibs and a heterozygous change in their mother were identified, being consistent with the X-linked recessive trait. GYG2 encodes glycogenin-2 (GYG2) protein, which plays an important role in the initiation of glycogen synthesis. Based on the structural modeling, the mutation can destabilize the structure and result in protein malfunctioning. Furthermore, in vitro experiments showed mutant GYG2 was unable to undergo the self-glucosylation, which is observed in wild-type GYG2. This is the first report of GYG2 mutation in human, implying a possible link between GYG2 abnormality and LS.

Two new mutations in the MTATP6 gene associated with Leigh syndrome.

PubMed

Moslemi, A-R; Darin, N; Tulinius, M; Oldfors, A; Holme, E

2005-10-01

In this study we have analyzed the mtDNA encoded ATPase 6 and 8 genes ( MTATP6 and MTATP8) in two children with Leigh syndrome (LS) and reduced Mg (2+) ATPase activity in muscle mitochondria. In patient 1, with a mild and reversible phenotype, mutational analysis revealed a heteroplasmic T --> C mutation at nt position 9185 (T9185C) in the MTATP6. The mutation resulted in substitution of a highly conserved leucine to proline at codon 220. The proportion of the mutation was > 97 % in the patient's blood and muscle and 85 % in blood of his asymptomatic mother. Patient 2, with severe clinical phenotype and death at 2 years of age, exhibited a novel heteroplasmic T9191C missense mutation in the MTATP6, which converted a highly conserved leucine to a proline at position 222 of the polypeptide. The proportion of the mutation was 90 % in fibroblasts and 94 % muscle tissue. This mutation was absent in the patient's parents and sister suggesting that the mutation was de novo. Our findings expand the spectrum of mutations causing LS and emphasize the role of MTATP6 gene mutations in pathogenesis of LS.

Mitochondrial respiratory chain enzyme assay and DNA analysis in peripheral blood leukocytes for the etiological study of Chinese children with Leigh syndrome due to complex I deficiency.

PubMed

Ma, Yan Yan; Wu, Tong Fei; Liu, Yu Peng; Wang, Qiao; Li, Xi Yuan; Zhang, Yao; Song, Jin Qing; Wang, Yu Jie; Yang, Yan Ling

2013-02-01

Mitochondrial respiratory chain complex I enzyme deficiency is the most commonly seen mitochondrial respiratory chain disorder. Although screening and diagnostic methods are available overseas, clinically feasible diagnostic methods have not yet been established in China. In this study, four Chinese boys with Leigh syndrome due to complex I deficiency were diagnosed by mitochondrial respiratory chain enzyme assay and DNA analysis using peripheral blood leukocytes. Four patients were admitted at the age of 5-14 years because of unexplained progressive neuromuscular symptoms, including motor developmental delay or regression, weakness, and seizures. Their cranial magnetic resonance imaging revealed typical finding as Leigh syndrome. Peripheral leukocyte mitochondrial respiratory chain complex I activities were found decreased to 9.6-33.1 nmol/min/mg mitochondrial protein(control 44.0 ± 5.4 nmol/min/mg). The ratios of complex I to citrate synthase activity were also decreased (8.9-19.8% in patients vs. control 48 ± 11%). Three mtDNA mutations were identified from three out of four patients, supporting the diagnosis of complex I deficiency. Point mutations m.10191T>C in mitochondrial ND3 gene, m.13513G>A in ND5 gene and m.14,453G>A in ND6 gene were detected in three patients.

Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a sibling pair: identification through whole exome sequencing and management strategies.

PubMed

Fraser, Jamie L; Vanderver, Adeline; Yang, Sandra; Chang, Taeun; Cramp, Laura; Vezina, Gilbert; Lichter-Konecki, Uta; Cusmano-Ozog, Kristina P; Smpokou, Patroula; Chapman, Kimberly A; Zand, Dina J

2014-01-01

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of previously lost milestones. The diagnosis of TPK deficiency was difficult due to inconsistent biochemical and diagnostic parameters, rapidity of clinical demise and would not have been made in a timely manner without the use of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary modification with cofactor supplementation which resulted in an improved clinical course.

Long survival in Leigh syndrome: new cases and review of literature.

PubMed

Aulbert, Wiebke; Weigt-Usinger, Katharina; Thiels, Charlotte; Köhler, Cornelia; Vorgerd, Matthias; Schreiner, Anja; Hoffjan, Sabine; Rothoeft, Tobias; Wortmann, Saskia Brigitte; Heyer, Christoph Malte; Podskarbi, Teodor; Lücke, Thomas

2014-12-01

Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and>16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival>14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients. Georg Thieme Verlag KG Stuttgart · New York.

ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.

PubMed

Sakai, Chika; Yamaguchi, Seiji; Sasaki, Masayuki; Miyamoto, Yusaku; Matsushima, Yuichi; Goto, Yu-ichi

2015-02-01

The human ECHS1 gene encodes the short-chain enoyl coenzyme A hydratase, the enzyme that catalyzes the second step of β-oxidation of fatty acids in the mitochondrial matrix. We report on a boy with ECHS1 deficiency who was diagnosed with Leigh syndrome at 21 months of age. The patient presented with hypotonia, metabolic acidosis, and developmental delay. A combined respiratory chain deficiency was also observed. Targeted exome sequencing of 776 mitochondria-associated genes encoded by nuclear DNA identified compound heterozygous mutations in ECHS1. ECHS1 protein expression was severely depleted in the patient's skeletal muscle and patient-derived myoblasts; a marked decrease in enzyme activity was also evident in patient-derived myoblasts. Immortalized patient-derived myoblasts that expressed exogenous wild-type ECHS1 exhibited the recovery of the ECHS1 activity, indicating that the gene defect was pathogenic. Mitochondrial respiratory complex activity was also mostly restored in these cells, suggesting that there was an unidentified link between deficiency of ECHS1 and respiratory chain. Here, we describe the patient with ECHS1 deficiency; these findings will advance our understanding not only the pathology of mitochondrial fatty acid β-oxidation disorders, but also the regulation of mitochondrial metabolism. © 2014 WILEY PERIODICALS, INC.

Gait analysis in a mouse model resembling Leigh disease.

PubMed

de Haas, Ria; Russel, Frans G; Smeitink, Jan A

2016-01-01

Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family.

PubMed

Bestwick, Megan; Jeong, Mi-Young; Khalimonchuk, Oleh; Kim, Hyung; Winge, Dennis R

2010-09-01

Three missense SURF1 mutations identified in patients with Leigh syndrome (LS) were evaluated in the yeast homolog Shy1 protein. Introduction of two of the Leigh mutations, F(249)T and Y(344)D, in Shy1 failed to significantly attenuate the function of Shy1 in cytochrome c oxidase (CcO) biogenesis as seen with the human mutations. In contrast, a G(137)E substitution in Shy1 results in a nonfunctional protein conferring a CcO deficiency. The G(137)E Shy1 mutant phenocopied shy1Delta cells in impaired Cox1 hemylation and low mitochondrial copper. A genetic screen for allele-specific suppressors of the G(137)E Shy1 mutant revealed Coa2, Cox10, and a novel factor designated Coa4. Coa2 and Cox10 are previously characterized CcO assembly factors. Coa4 is a twin CX(9)C motif mitochondrial protein localized in the intermembrane space and associated with the inner membrane. Cells lacking Coa4 are depressed in CcO activity but show no impairment in Cox1 maturation or formation of the Shy1-stabilized Cox1 assembly intermediate. To glean insights into the functional role of Coa4 in CcO biogenesis, an unbiased suppressor screen of coa4Delta cells was conducted. Respiratory function of coa4Delta cells was restored by the overexpression of CYC1 encoding cytochrome c. Cyc1 is known to be important at an ill-defined step in the assembly and/or stability of CcO. This new link to Coa4 may begin to further elucidate the role of Cyc1 in CcO biogenesis.

Effects of Ocean Acidification on Juvenile Red King Crab (Paralithodes camtschaticus) and Tanner Crab (Chionoecetes bairdi) Growth, Condition, Calcification, and Survival

PubMed Central

Long, William Christopher; Swiney, Katherine M.; Harris, Caitlin; Page, Heather N.; Foy, Robert J.

2013-01-01

Ocean acidification, a decrease in the pH in marine waters associated with rising atmospheric CO2 levels, is a serious threat to marine ecosystems. In this paper, we determine the effects of long-term exposure to near-future levels of ocean acidification on the growth, condition, calcification, and survival of juvenile red king crabs, Paralithodes camtschaticus, and Tanner crabs, Chionoecetes bairdi. Juveniles were reared in individual containers for nearly 200 days in flowing control (pH 8.0), pH 7.8, and pH 7.5 seawater at ambient temperatures (range 4.4–11.9 °C). In both species, survival decreased with pH, with 100% mortality of red king crabs occurring after 95 days in pH 7.5 water. Though the morphology of neither species was affected by acidification, both species grew slower in acidified water. At the end of the experiment, calcium concentration was measured in each crab and the dry mass and condition index of each crab were determined. Ocean acidification did not affect the calcium content of red king crab but did decrease the condition index, while it had the opposite effect on Tanner crabs, decreasing calcium content but leaving the condition index unchanged. This suggests that red king crab may be able to maintain calcification rates, but at a high energetic cost. The decrease in survival and growth of each species is likely to have a serious negative effect on their populations in the absence of evolutionary adaptation or acclimatization over the coming decades. PMID:23593357

Ophthalmological manifestations in patients with Leigh syndrome.

PubMed

Han, Jinu; Lee, Young-Mock; Kim, Sang Myung; Han, So Young; Lee, Jong Bok; Han, Sueng-Han

2015-04-01

To describe the ophthalmological manifestations in patients with childhood onset Leigh syndrome (LS) and investigate the correlation between genotypes and phenotypes in patients with LS. Childhood onset LS was clinically and enzymatically confirmed in a total of 63 patients. Among them, 44 patients who underwent ophthalmologic consultation were included in this study. Patients with LS underwent genotyping for the whole genome of mitochondrial DNA and SURF1 mutations. The clinical demographic and ophthalmologic phenotypes were compared between the good prognosis group and the poor prognosis group. Strabismus (40.9%) was the most frequently observed ophthalmologic manifestation, followed by pigmentary retinopathy (22.5%), optic atrophy (22.5%), ptosis (15.9%), and nystagmus (13.6%). Thirteen patients were exotropes and five patients were esotropes. The mean exodeviation was 29.6±12.5 prism dioptres (PD) and the mean esodeviation was 24.0±8.9 PD. All patients with esotropia reported disease onset at <1 year old. Among 26 patients older than 4 years, eight (30.8%) patients had better than 0.4 in the best eye was noted. Eyelid ptosis was a main presenting sign in four patients (9.1%). Among these patients, two patients had m.13513G>A mutation in the MT-ND5 gene. Age at onset was 2.47±2.06 years in the good prognosis group and 0.92±0.98 years in the poor prognosis group (p=0.002). Serum lactate peak concentration was 3.23±1.36 mmol/L in the good prognosis group and 4.54±2.31 mmol/L in the poor prognosis group (p=0.051). LS is a group of mitochondrial disorders with variable ophthalmologic manifestations, the most frequent being strabismus in this study. Ptosis could be an initial sign in patients with LS and these patients can be easily misdiagnosed as having juvenile myasthenia gravis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Sequence conservation from human to prokaryotes of Surf1, a protein involved in cytochrome c oxidase assembly, deficient in Leigh syndrome.

PubMed

Poyau, A; Buchet, K; Godinot, C

1999-12-03

The human SURF1 gene encoding a protein involved in cytochrome c oxidase (COX) assembly, is mutated in most patients presenting Leigh syndrome associated with COX deficiency. Proteins homologous to the human Surf1 have been identified in nine eukaryotes and six prokaryotes using database alignment tools, structure prediction and/or cDNA sequencing. Their sequence comparison revealed a remarkable Surf1 conservation during evolution and put forward at least four highly conserved domains that should be essential for Surf1 function. In Paracoccus denitrificans, the Surf1 homologue is found in the quinol oxidase operon, suggesting that Surf1 is associated with a primitive quinol oxidase which belongs to the same superfamily as cytochrome oxidase.

Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency.

PubMed

Péquignot, M O; Dey, R; Zeviani, M; Tiranti, V; Godinot, C; Poyau, A; Sue, C; Di Mauro, S; Abitbol, M; Marsac, C

2001-05-01

Cytochrome c oxidase (COX) deficiency is one of the major causes of Leigh Syndrome (LS), a fatal encephalopathy of infancy or childhood, characterized by symmetrical lesions in the basal ganglia and brainstem. Mutations in the nuclear genes encoding COX subunits have not been found in patients with LS and COX deficiency, but mutations have been identified in SURF1. SURF1 encodes a factor involved in COX biogenesis. To date, 30 different mutations have been reported in 40 unrelated patients. We aim to provide an overview of all known mutations in SURF1, and to propose a common nomenclature. Twelve of the mutations were insertion/deletion mutations in exons 1, 4, 6, 8, and 9; 10 were missense/nonsense mutations in exons 2, 4, 5, 7, and 8; and eight were detected at splicing sites in introns 3 to 7. The most frequent mutation was 312_321del 311_312insAT which was found in 12 patients out of 40. Twenty mutations have been described only once. We also list all polymorphisms discovered to date. Copyright 2001 Wiley-Liss, Inc.

Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation.

PubMed

van Riesen, A K J; Antonicka, H; Ohlenbusch, A; Shoubridge, E A; Wilichowski, E K G

2006-04-01

Cytochrome c oxidase deficiency (COX) is the most frequent cause of Leigh syndrome (LS), a mitochondrial subacute necrotizing encephalomyelopathy. Most of these LS (COX-) patients show mutations in SURF1 on chromosome 9 (9q34), which encodes a protein essential for the assembly of the COX complex. We describe a family whose first-born boy developed characteristic features of LS. Severe COX deficiency in muscle was caused by a novel homozygous nonsense mutation in SURF1. Segregation analysis of this mutation in the family was incompatible with autosomal recessive inheritance but consistent with a maternal disomy. Haplotype analysis of microsatellite markers confirmed isodisomy involving nearly the complete long arm of chromosome 9 (9q21-9tel). No additional physical abnormalities were present in the boy, suggesting that there are no imprinted genes on the long arm of chromosome 9 which are crucial for developmental processes. This case of segmental isodisomy illustrates that genotyping of parents is crucial for correct genetic counseling.

LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.

PubMed

Stowe, Robert C; Sun, Qin; Elsea, Sarah H; Scaglia, Fernando

2018-05-01

Lipoic acid is an essential cofactor for the mitochondrial 2-ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2-month-old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease. Exome sequencing implicated compound heterozygous LIPT1 pathogenic variants. We describe the fifth case of LIPT1 deficiency, whose phenotype progressed to that of an early infantile epileptic encephalopathy, which is novel compared to previously described patients whom we will review. Due to the significant biochemical and phenotypic overlap that LIPT1 deficiency and mitochondrial energy cofactor disorders have with pyruvate dehydrogenase deficiency and/or nonketotic hyperglycinemia, they are and have been presumptively under-diagnosed without exome sequencing. © 2018 Wiley Periodicals, Inc.

Assessing the skeletal age from a hand radiograph: automating the Tanner-Whitehouse method

NASA Astrophysics Data System (ADS)

Niemeijer, Meindert; van Ginneken, Bram; Maas, Casper A.; Beek, Frederik J. A.; Viergever, Max A.

2003-05-01

The skeletal maturity of children is usually assessed from a standard radiograph of the left hand and wrist. An established clinical method to determine the skeletal maturity is the Tanner-Whitehouse (TW2) method. This method divides the skeletal development into several stages (labelled A, B, ...,I). We are developing an automated system based on this method. In this work we focus on assigning a stage to one region of interest (ROI), the middle phalanx of the third finger. We classify each ROI as follows. A number of ROIs which have been assigned a certain stage by a radiologist are used to construct a mean image for that stage. For a new input ROI, landmarks are detected by using an Active Shape Model. These are used to align the mean images with the input image. Subsequently the correlation between each transformed mean stage image and the input is calculated. The input ROI can be assigned to the stage with the highest correlation directly, or the values can be used as features in a classifier. The method was tested on 71 cases ranging from stage E to I. The ROI was staged correctly in 73.2% of all cases and in 97.2% of all incorrectly staged cases the error was not more than one stage.

Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

PubMed

Piekutowska-Abramczuk, Dorota; Rutyna, Rafał; Czyżyk, Elżbieta; Jurkiewicz, Elżbieta; Iwanicka-Pronicka, Katarzyna; Rokicki, Dariusz; Stachowicz, Sylwia; Strzemecka, Joanna; Guz, Wiesław; Gawroński, Michał; Kosierb, Aneta; Ligas, Joanna; Puchala, Mateusz; Drelich-Zbroja, Anna; Bednarska-Makaruk, Małgorzata; Dąbrowski, Wojciech; Ciara, Elżbieta; Książyk, Janusz B; Pronicka, Ewa

2018-02-01

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO 2 ). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a "hypoventilation" might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation.

PubMed

Debray, François-Guillaume; Lambert, Marie; Lortie, Anne; Vanasse, Michel; Mitchell, Grant A

2007-09-01

Mutations at mitochondrial DNA (mtDNA) nucleotide 8993 can cause neurogenic weakness, ataxia and retinitis pigmentosa (NARP syndrome), or maternally inherited Leigh syndrome (LS), with a correlation between the amount of mutant mtDNA and the severity of the neurological disease. The T8993C mutation is generally considered to be clinically milder than the T8993G mutation but when the level of heteroplasmy exceeds 90%, progressive neurodegeneration has been found. We report on a long-term follow-up of a patient who presented at 4 years of age with typical LS but showed an unexpected resolution of his symptoms and a favorable outcome. At 18 years of age, his neurological examination was near normal, with neither peripheral neuropathy nor retinopathy. mtDNA analysis identified the presence of T8993C mutation at high level (>95%) in the patient's blood leukocytes. This case report and literature review emphasizes the variability of the phenotypic expression of the T8993C mutation and the need for caution in predictive counseling in such patients. (c) 2007 Wiley-Liss, Inc. Copyright 2007 Wiley-Liss, Inc.

Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells

PubMed Central

Fontes-Oliveira, Cibely C.; Steinz, Maarten; Schneiderat, Peter; Mulder, Hindrik; Durbeej, Madeleine

2017-01-01

Skeletal muscle has high energy requirement and alterations in metabolism are associated with pathological conditions causing muscle wasting and impaired regeneration. Congenital muscular dystrophy type 1A (MDC1A) is a severe muscle disorder caused by mutations in the LAMA2 gene. Leigh syndrome (LS) is a neurometabolic disease caused by mutations in genes related to mitochondrial function. Skeletal muscle is severely affected in both diseases and a common feature is muscle weakness that leads to hypotonia and respiratory problems. Here, we have investigated the bioenergetic profile in myogenic cells from MDC1A and LS patients. We found dysregulated expression of genes related to energy production, apoptosis and proteasome in myoblasts and myotubes. Moreover, impaired mitochondrial function and a compensatory upregulation of glycolysis were observed when monitored in real-time. Also, alterations in cell cycle populations in myoblasts and enhanced caspase-3 activity in myotubes were observed. Thus, we have for the first time demonstrated an impairment of the bioenergetic status in human MDC1A and LS muscle cells, which could contribute to cell cycle disturbance and increased apoptosis. Our findings suggest that skeletal muscle metabolism might be a promising pharmacological target in order to improve muscle function, energy efficiency and tissue maintenance of MDC1A and LS patients. PMID:28367954

MPTP intoxication in mice: a useful model of Leigh syndrome to study mitochondrial diseases in childhood.

PubMed

Lagrue, E; Abert, B; Nadal, L; Tabone, L; Bodard, S; Medja, F; Lombes, A; Chalon, S; Castelnau, P

2009-06-01

The basal ganglia, which are interconnected in the striato-nigral dopaminergic network, are affected in several childhood diseases including Leigh syndrome (LS). LS is the most common mitochondrial disorder affecting children and usually arise from inhibition of the respiratory chain. This vulnerability is attributed to a particular susceptibility to energetic stress, with mitochondrial inhibition as a common pathogenic pathway. In this study we developed a LS model for neuroprotection trials in mice by using the complex I inhibitor MPTP. We first verified that MPTP significantly inhibits the mitochondrial complex I in the brain (p = 0.018). This model also reproduced the biochemical and pathological features of LS: MPTP increased plasmatic lactate levels (p = 0.023) and triggered basal ganglia degeneration, as evaluated through dopamine transporter (DAT) autoradiography, tyrosine hydroxylase (TH) immunohistochemistry, and dopamine dosage. Striatal DAT levels were markedly decreased after MPTP treatment (p = 0.003). TH immunoreactivity was reduced in the striatum and substantia nigra (p = 0.005), and striatal dopamine was significantly reduced (p < 0.01). Taken together, these results confirm that acute MPTP intoxication in young mice provides a reproducible pharmacological paradigm of LS, thus opening new avenues for neuroprotection research.

Leigh Syndrome with Nephropathy and CoQ10 Deficiency Due to decaprenyl diphosphate synthase subunit 2 (PDSS2) Mutations

PubMed Central

López, Luis Carlos ; Schuelke, Markus ; Quinzii, Catarina M. ; Kanki, Tomotake ; Rodenburg, Richard J. T. ; Naini, Ali ; DiMauro, Salvatore ; Hirano, Michio 

2006-01-01

Coenzyme Q10 (CoQ10) is a vital lipophilic molecule that transfers electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ10 has been associated with diverse clinical phenotypes, but, in most patients, the molecular cause is unknown. The first defect in a CoQ10 biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and nephrotic syndrome and in a younger sibling with only nephropathy. Here, we describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ10 deficiency in muscle and fibroblasts and compound heterozygous mutations in the PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first enzyme of the CoQ10 biosynthetic pathway. Biochemical assays with radiolabeled substrates indicated a severe defect in decaprenyl diphosphate synthase in the patient’s fibroblasts. This is the first description of pathogenic mutations in PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ10 deficiency. PMID:17186472

Mitochondrial DNA 8993T>G mutation in a child with ornithine transcarbamylase deficiency and leigh syndrome: an unexpected association.

PubMed

Henriques, Margarida; Diogo, Luísa; Garcia, Paula; Pratas, João; Simões, Marta; Grazina, Manuela

2012-08-01

MC, female, is the third child of a nonconsanguineous Portuguese couple, born after an uneventful pregnancy and delivery. A positive family history of ornithine transcarbamylase deficiency, associated with the IVS8+1 G>A mutation in the ornithine transcarbamylase gene, prompted prenatal diagnosis with identification of the same mutation in the proband. During an episode of Klebsiella pneumoniae sepsis at 1.5 months of age, lactic acidosis and moderate hyperammonemia were noticed. After a short asymptomatic period, progressive neurologic symptoms, with normal ammonemia, persistent hyperlactacidemia, and typical lesions in brain computed tomography (CT) scan led to a diagnosis of Leigh syndrome. Mitochondrial respiratory chain complex V was reduced in the liver. The mtDNA 8993T>G mutation was identified in the liver, muscle, and blood (82%-87% heteroplasmy). She died at 6 months of age. This case represents a benign phenotype of ornithine transcarbamylase deficiency, associated with a severe mitochondrial respiratory chain disorder due to an mtDNA pathogenic mutation.

First record of the larvae of tanner crab Chionoecetes bairdi in the Chukchi Sea: A future northward expansion in the Arctic?

NASA Astrophysics Data System (ADS)

Landeira, Jose M.; Matsuno, Kohei; Tanaka, Yuji; Yamaguchi, Atsushi

2018-06-01

In the Bering Sea, warming and reduction of summer sea-ice cover are driving species ranges towards the Arctic. Tanner crab, Chionoecetes bairdi, is a commercially important species in the SE Bering Sea with a northerly range margin in 62ºN. In this paper, using plankton samples collected in the Pacific sub-Arctic/Arctic sector during summer, we report for the first time the presence of larval stages (zoea II) of C. bairdi far from its northern limit of the distribution, in the south of St. Lawrence Island during 1991, and even crossing the Bering Strait into the Chukchi Sea during 1992. We suggest that the long planktonic phase (3-5 months), in combination with the oceanographic circulation, may facilitate eventual long-distance transport.

76 FR 39141 - Post Office Closing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... determination. On June 24, 2011, a second petition for review was filed by Duane O. Davison on behalf of the... Facility at 13 Lafayette Street, Freehold, New Jersey 07728, filed by Duane O. Davison, on behalf of the...

Prediction of adult height by Tanner-Whitehouse method in young Caucasian male athletes.

PubMed

Ostojic, S M

2013-04-01

Although the accuracy of final height prediction using skeletal age development has been confirmed in many studies for children treated for congenital primary hypothyroidism, short normal children, constitutionally tall children, no studies compared the predicted adult height at young age with final stature in athletic population. In this study, the intention was to investigate to what extent the Tanner-Whitehouse (TW) method is adequate for prediction of final stature in young Caucasian male athletes. Prospective observational study. Plain radiographs of the left hand and wrist were obtained from 477 athletic children (ranging in age from 8.0 to 17.9 years) who came to the outpatient clinic between 2000 and 2011 for adult height estimation, with no orthopedic trauma suspected. Adult height was estimated using bone age rates according to TW method. Height was measured both at baseline and follow-up (at the age of 19 years). No significant difference was found between the estimated adult height (184.9 ± 9.7 cm) and final stature (185.6 ± 9.6 cm) [95% confidence interval (CI) 1.61-3.01, P = 0.55]. The relationship between estimated and final adult height was high (r = 0.96). Bland-Altman analysis confirmed that the 95% of differences between estimated adult height and final stature lie between limits of agreement (mean ± 2 SD) (-5.84 and 4.52 cm). TW method is an accurate method of predicting adult height in male normal-growing athletic boys.

Electroosmotic flow of Phan-Thien-Tanner fluids at high zeta potentials: An exact analytical solution

NASA Astrophysics Data System (ADS)

Sarma, Rajkumar; Deka, Nabajit; Sarma, Kuldeep; Mondal, Pranab Kumar

2018-06-01

We present a mathematical model to study the electroosmotic flow of a viscoelastic fluid in a parallel plate microchannel with a high zeta potential, taking hydrodynamic slippage at the walls into account in the underlying analysis. We use the simplified Phan-Thien-Tanner (s-PTT) constitutive relationships to describe the rheological behavior of the viscoelastic fluid, while Navier's slip law is employed to model the interfacial hydrodynamic slip. Here, we derive analytical solutions for the potential distribution, flow velocity, and volumetric flow rate based on the complete Poisson-Boltzmann equation (without considering the frequently used Debye-Hückel linear approximation). For the underlying electrokinetic transport, this investigation primarily reveals the influence of fluid rheology, wall zeta potential as modulated by the interfacial electrochemistry and interfacial slip on the velocity distribution, volumetric flow rate, and fluid stress, as well as the apparent viscosity. We show that combined with the viscoelasticity of the fluid, a higher wall zeta potential and slip coefficient lead to a phenomenal enhancement in the volumetric flow rate. We believe that this analysis, besides providing a deep theoretical insight to interpret the transport process, will also serve as a fundamental design tool for microfluidic devices/systems under electrokinetic influence.

Homozygous p.V116* mutation in C12orf65 results in Leigh syndrome.

PubMed

Imagawa, Eri; Fattal-Valevski, Aviva; Eyal, Ori; Miyatake, Satoko; Saada, Ann; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi

2016-02-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder associated with mitochondrial dysfunction. LS is characterised by elevated lactate and pyruvate and bilateral symmetric hyperintense lesions in the basal ganglia, thalamus, brainstem, cerebral white matter or spinal cord on T2-weighted MRI. LS is a genetically heterogeneous disease, and to date mutations in approximately 40 genes related to mitochondrial function have been linked to the disorder. We investigated a pair of female monozygotic twins diagnosed with LS from consanguineous healthy parents of Indian origin. Their common clinical features included optic atrophy, ophthalmoplegia, spastic paraparesis and mild intellectual disability. High-blood lactate and high-intensity signal in the brainstem on T2-weighted MRI were consistent with a clinical diagnosis of LS. To identify the genetic cause of their condition, we performed whole exome sequencing. We identified a homozygous nonsense mutation in C12orf65 (NM_001143905; c.346delG, p.V116*) in the affected twins. Interestingly, the identical mutation was previously reported in an Indian family with Charcot-Marie Tooth disease type 6, which displayed some overlapping clinical features with the twins. We demonstrate that the identical nonsense mutation in C12orf65 can result in different clinical features, suggesting the involvement of unknown modifiers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Leigh syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing.

PubMed

Da-Rè, Caterina; von Stockum, Sophia; Biscontin, Alberto; Millino, Caterina; Cisotto, Paola; Zordan, Mauro A; Zeviani, Massimo; Bernardi, Paolo; De Pittà, Cristiano; Costa, Rodolfo

2014-10-17

Leigh Syndrome (LS) is the most common early-onset, progressive mitochondrial encephalopathy usually leading to early death. The single most prevalent cause of LS is occurrence of mutations in the SURF1 gene, and LS(Surf1) patients show a ubiquitous and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). SURF1 encodes an inner membrane mitochondrial protein involved in COX assembly. We established a Drosophila melanogaster model of LS based on the post-transcriptional silencing of CG9943, the Drosophila homolog of SURF1. Knockdown of Surf1 was induced ubiquitously in larvae and adults, which led to lethality; in the mesodermal derivatives, which led to pupal lethality; or in the central nervous system, which allowed survival. A biochemical characterization was carried out in knockdown individuals, which revealed that larvae unexpectedly displayed defects in all complexes of the mitochondrial respiratory chain and in the F-ATP synthase, while adults had a COX-selective impairment. Silencing of Surf1 expression in Drosophila S2R(+) cells led to selective loss of COX activity associated with decreased oxygen consumption and respiratory reserve. We conclude that Surf1 is essential for COX activity and mitochondrial function in D. melanogaster, thus providing a new tool that may help clarify the pathogenic mechanisms of LS. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

[Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics].

PubMed

Tsygankova, P G; Mikhaĭlova, S V; Zakharova, E Iu; Pichkur, N A; Il'ina, E S; Nikolaeva, E A; Rudenskaia, G E; Dadali, E L; Kolpakchi, L M; Fedoniuk, I D; Matiushchenko, G N

2010-01-01

Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population.

Advertising vs. Public Service Announcements: The Role of Message Type in Safer-Sex Campaigns and Third-Person Perception.

ERIC Educational Resources Information Center

Chapin, John

Fifteen years ago, W. Davison introduced the third-person effect hypothesis, that individuals believe they are less influenced than others by media messages. Although third-person effect is a perceptual bias, Davison believed that individuals act on such misperceptions. Few studies since have tested the behavioral aspect of the third-person…

The Debate Continues: Are There Gender Differences in Moral Reasoning as Defined by Kohlberg?

ERIC Educational Resources Information Center

Bruess, Brian J.; Pearson, Frances C.

2002-01-01

Examines changes in moral reasoning among college students and seeks to determine whether there are gender differences in the process. Women scored higher than men on both Principled moral reasoning and Davison's moral index and graduating students scored higher than first-year students on Davison's moral index. Discusses whether Kohlberg's theory…

Evolution of skin grafting for treatment of burns: Reverdin pinch grafting to Tanner mesh grafting and beyond.

PubMed

Singh, Mansher; Nuutila, Kristo; Collins, K C; Huang, Anne

2017-09-01

Skin grafting is the current standard care in the treatment of full thickness burns. It was first described around 1500 BC but the vast majority of advancements have been achieved over the past 200 years. An extensive literature review was conducted on Pubmed, Medline and Google Scholar researching the evolution of skin grafting techniques. The authors concentrated on the major landmarks of skin grafting and also provide an overview of ongoing research efforts in this field. The major innovations of skin grafting include Reverdin pinch grafting, Ollier grafting, Thiersch grafting, Wolfe grafting, Padgett dermatome and modifications, Meek-wall microdermatome and Tanner mesh grafting. A brief description of the usage, advantages and limitations of each technique is included in the manuscript. Skin grafting technique have evolved significantly over past 200 years from Reverdin pinch grafting to modern day meshed skin grafts using powered dermatome. Increasing the expansion ratio and improving the cosmetic and functional outcome are the main focus of ongoing skin grafting research and emerging techniques (such as Integra ® , Recell ® , Xpansion ® ) are showing promise. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.

PubMed

Martín, Miguel A; Blázquez, Alberto; Gutierrez-Solana, Luis G; Fernández-Moreira, Daniel; Briones, Paz; Andreu, Antoni L; Garesse, Rafael; Campos, Yolanda; Arenas, Joaquín

2005-04-01

Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect. The proband was a child who displayed the clinical features of LS. Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation. Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.

Association between serum uric acid and metabolic syndrome components in prepubertal obese children (Tanner Stage I) from Nuevo León, Mexico - a preliminary study.

PubMed

Perez, Elizabeth Solis; Medina, Mario Alberto González; Lomeli, Manuel Lopez-Cabanillas; González, Verónica Tijerina; Pérez, Jesús Zacarías Villarreal; Lavalle González, Fernando J; Imrhan, Victorine; Juma, Shanil; Vijayagopal, Parakat; Boonme, Kittipong; Prasad, Chandan

2017-01-01

Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease and diabetes. Previous studies in obese children demonstrating a positive association between serum uric acid (sUA) and components of MetS are confounded by lack of uniformity in age and pubertal status of children. Therefore, we have examined the role of sUA in MetS and its components in pre-pubertal children (Tanner Stage I, age ≤ 9 years). Pre-pubertal obese children (32 boys, 27 girls, age 6-9 years) were recruited from Nuevo Leon, Mexico. For comparison, an equal number of children with normal body mass index (BMI) in the same age range (22 Boys, 39 girls, age 6-9 years) were also recruited from the same community. Presence of MetS and its components was defined according to the criteria of International Diabetes Federation. Fasting blood was analyzed for lipids, glucose, insulin, and uric acid. Among the obese children, sUA was positively associated with insulin resistance and hypertriglyceridemia and negatively associated with high density lipoprotein-cholesterol (HDLc). Subjects were three times more likely to have a MetS diagnosis per one unit (md/dL) difference in sUA. Of the 59 obese pre-pubertal children, 20 were classified as having MetS defined by the presence of abdominal obesity and two or more of other components described under methods. Of these, 57.1% (20/61) had sUA between 5.1 and 7.1 mg/dl. The findings of this study clearly indicate a positive relationship between uric acid and MetS and its components in pre-pubertal obese children with Tanner stage I and ≤9 years of age.

Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.

PubMed

Iyer, Shilpa; Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R; Bennett, James P

2012-06-01

Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ∼1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future.

Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene.

PubMed

Bianciardi, Laura; Imperatore, Valentina; Fernandez-Vizarra, Erika; Lopomo, Angela; Falabella, Micol; Furini, Simone; Galluzzi, Paolo; Grosso, Salvatore; Zeviani, Massimo; Renieri, Alessandra; Mari, Francesca; Frullanti, Elisa

2016-11-01

We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome analysis using autosomal/X-linked recessive or de novo models. Dosage of respiratory chain activity on fibroblasts, but not in muscle, underlined a deficit in complex I. Re-analysis of heterozygous probably pathogenic variants, inherited from one healthy parent, identified the p.Ala178Pro in NDUFAF6, a complex I assembly factor. RNA analysis showed an almost mono-allelic expression of the mutated allele in blood and fibroblasts and puromycin treatment on cultured fibroblasts did not lead to the rescue of the maternal allele expression, not supporting the involvement of nonsense-mediated RNA decay mechanism. Complementation assay underlined a recovery of complex I activity after transduction of the wild-type gene. Since the second mutation was not detected and promoter methylation analysis resulted normal, we hypothesized a non-exonic event in the maternal allele affecting a regulatory element that, in conjunction with the paternal mutation, leads to the autosomal recessive disorder and the different allele expression in various tissues. This paper confirms NDUFAF6 as a genuine morbid gene and proposes the coupling of exome sequencing with mRNA analysis as a method useful for enhancing the exome sequencing detection rate when the simple application of classical inheritance models fails. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular-clinical correlation in a family with a novel heteroplasmic Leigh syndrome missense mutation in the mitochondrial cytochrome c oxidase III gene.

PubMed

Mkaouar-Rebai, Emna; Ellouze, Emna; Chamkha, Imen; Kammoun, Fatma; Triki, Chahnez; Fakhfakh, Faiza

2011-01-01

Cytochrome c oxidase is an essential component of the mitochondrial respiratory chain that catalyzes the reduction of molecular oxygen by reduced cytochrome c. In this study, the authors report the second mutation associated with Leigh syndrome in the blood and buccal mucosa of 2 affected members of a Tunisian family. It was a novel heteroplasmic missense mitochondrial mutation at nucleotide 9478 in the gene specifying subunit III of cytochrome c oxidase substituting the valine at position 91 to alanine in a highly conserved amino acid. It was found with a high mutant load in tissues derived from endoderm (buccal mucosa) and mesoderm (blood). However, it was nearly absent in tissue derived from ectoderm (hair follicles). It was absent in 120 healthy controls, and PolyPhen analysis showed that the hydropathy index changed from +1.276 to +0.242, and the number of structures of the 3D protein decreased from 39 to 32.

[Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage].

PubMed

Gaete, Ximena; García, Roberto; Riquelme, Joel; Codner, Ethel

2015-03-01

A secular trend towards a younger age of puberty onset has been reported in Chilean girls. To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Development and Maintenance of Choice in a Dynamic Environment

ERIC Educational Resources Information Center

Rodewald, Andrew M.; Hughes, Christine E.; Pitts, Raymond C.

2010-01-01

Four pigeons were exposed to a concurrent procedure similar to that used by Davison, Baum, and colleagues (e.g., Davison & Baum, 2000, 2006) in which seven components were arranged in a mixed schedule, and each programmed a different left:right reinforcer ratio (1:27, 1:9, 1:3, 1:1, 3:1, 9:1, 27:1). Components within each session were presented…

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome

PubMed Central

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-01-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4−/− mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4−/− mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs. PMID:28753212

AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome.

PubMed

Di Meo, I; Marchet, S; Lamperti, C; Zeviani, M; Viscomi, C

2017-10-01

Leigh syndrome (LS) is the most common infantile mitochondrial encephalopathy. No treatment is currently available for this condition. Mice lacking Ndufs4, encoding NADH: ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) recapitulates the main findings of complex I (cI)-related LS, including severe multisystemic cI deficiency and progressive neurodegeneration. In order to develop a gene therapy approach for LS, we used here an AAV2/9 vector carrying the human NDUFS4 coding sequence (hNDUFS4). We administered AAV2/9-hNDUFS4 by intravenous (IV) and/or intracerebroventricular (ICV) routes to either newborn or young Ndufs4 -/- mice. We found that IV administration alone was only able to correct the cI deficiency in peripheral organs, whereas ICV administration partially corrected the deficiency in the brain. However, both treatments failed to improve the clinical phenotype or to prolong the lifespan of Ndufs4 -/- mice. In contrast, combined IV and ICV treatments resulted, along with increased cI activity, in the amelioration of the rotarod performance and in a significant prolongation of the lifespan. Our results indicate that extraneurological organs have an important role in LS pathogenesis and provide an insight into current limitations of adeno-associated virus (AAV)-mediated gene therapy in multisystem disorders. These findings warrant future investigations to develop new vectors able to efficiently target multiple organs.

Ophthalmological characteristics in children with Leigh syndrome - A long-term follow-up.

PubMed

Åkebrand, Rebecka; Andersson, Susann; Seyedi Honarvar, Antovan K; Sofou, Kalliopi; Darin, Niklas; Tulinius, Mar; Grönlund, Marita Andersson

2016-09-01

To describe ophthalmological characteristics in children with Leigh syndrome (LS), an inherited, progressive, mitochondrial encephalomyopathy, at diagnosis and over time, and relate the results to causative genetic mutations. Forty-four children with LS (19 females), with a median age of 2.4 years (range: 0.6-14.2 years) at diagnosis, were studied at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Twenty-eight children had known genetic defects. The children underwent an ophthalmological examination, including visual acuity (VA), eye motility, refraction, slit lamp examination, ophthalmoscopy and a full-field electroretinogram (ff-ERG). Seventeen children were available for follow-up over a mean time of 5.4 years (range: 0.3-14.8 years). The results of these children were compared with an age- and sex-matched reference group of healthy children (n = 119). Altogether 36/44 of the children (82%) had ophthalmological abnormalities. The most common findings were refractive errors (n = 16/25), low VA (n = 9/36), strabismus (n = 8/42), reduced eye motility (n = 8/40), optic atrophy (n = 7/41), retinal pigmentation (n = 6/40) and nystagmus (n = 6/42). Several ophthalmological manifestations appeared over time. In 5/22 children, ff-ERG showed retinal dystrophy. No significant correlation between phenotype and genotype was found. The children with LS had significantly lower VA (p < 0.0001, Mantel-Haenszel chi-square exact test), more astigmatism (p = 0.012, Fisher's exact test) and higher incidence of strabismus (p = 0.0002) compared to controls at follow-up. In this unique cohort of children with LS, the vast majority showed ophthalmological findings at diagnosis, which increased over time. Therefore, we recommend that all children diagnosed with LS should be followed up with regular ophthalmological examinations. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Short-term secular change in height, body mass and Tanner-Whitehouse 3 skeletal maturity of Madeira youth, Portugal.

PubMed

Freitas, Duarte; Malina, Robert M; Maia, José; Lefevre, Johan; Stasinopoulos, Mikis; Gouveia, Élvio; Claessens, Albrecht; Thomis, Martine; Lausen, Berthold

2012-05-01

Secular trends in height and weight are reasonably well documented in Europe. Corresponding observations for skeletal maturation are lacking. To assess secular trends in height, body mass and skeletal maturity of Portuguese children and adolescents and to provide updated reference values for skeletal maturity scores (SMSs). Data for 2856 children and adolescents of 4-17 years, 1412 boys and 1444 girls, from The 'Madeira Growth Study' (MGS; 1996-1998) and from the'Healthy Growth of Madeira Children Study' (CRES; 2006) were used. Height and body mass were measured. Skeletal maturity was assessed with the Tanner-Whitehouse 2 and 3 methods. Children from CRES were taller and heavier than peers from MGS. Differences in height reached 5.8 cm in boys and 5.5 cm in girls. RUS SMSs did not differ consistently between surveys boys, while higher RUS scores were observed in CRES girls. Adult RUS SMSs for MGS and CRES combined were attained at 15.8 years in boys and 14.8 years in girls. Corresponding ages for adult Carpal SMSs were 14.4 and 14.0, respectively. The short-term trends for height and mass were not entirely consistent with the trends in RUS and Carpal SMSs and SAs.

SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome.

PubMed

Janer, Alexandre; Prudent, Julien; Paupe, Vincent; Fahiminiya, Somayyeh; Majewski, Jacek; Sgarioto, Nicolas; Des Rosiers, Christine; Forest, Anik; Lin, Zhen-Yuan; Gingras, Anne-Claude; Mitchell, Grant; McBride, Heidi M; Shoubridge, Eric A

2016-09-01

Mitochondria form a dynamic network that responds to physiological signals and metabolic stresses by altering the balance between fusion and fission. Mitochondrial fusion is orchestrated by conserved GTPases MFN1/2 and OPA1, a process coordinated in yeast by Ugo1, a mitochondrial metabolite carrier family protein. We uncovered a homozygous missense mutation in SLC25A46, the mammalian orthologue of Ugo1, in a subject with Leigh syndrome. SLC25A46 is an integral outer membrane protein that interacts with MFN2, OPA1, and the mitochondrial contact site and cristae organizing system (MICOS) complex. The subject mutation destabilizes the protein, leading to mitochondrial hyperfusion, alterations in endoplasmic reticulum (ER) morphology, impaired cellular respiration, and premature cellular senescence. The MICOS complex is disrupted in subject fibroblasts, resulting in strikingly abnormal mitochondrial architecture, with markedly shortened cristae. SLC25A46 also interacts with the ER membrane protein complex EMC, and phospholipid composition is altered in subject mitochondria. These results show that SLC25A46 plays a role in a mitochondrial/ER pathway that facilitates lipid transfer, and link altered mitochondrial dynamics to early-onset neurodegenerative disease and cell fate decisions. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.

PubMed

Balasubramaniam, S; Riley, L G; Bratkovic, D; Ketteridge, D; Manton, N; Cowley, M J; Gayevskiy, V; Roscioli, T; Mohamed, M; Gardeitchik, T; Morava, E; Christodoulou, J

2017-09-01

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.

Simplified radius, ulna, and short bone-age assessment procedure using grouped-Tanner-Whitehouse method.

PubMed

Hsieh, Chi-Wen; Liu, Tzu-Chiang; Wang, Jui-Kai; Jong, Tai-Lang; Tiu, Chui-Mei

2011-08-01

The Tanner-Whitehouse III (TW3) method is popular for assessing children's bone age, but it is time-consuming in clinical settings; to simplify this, a grouped-TW algorithm (GTA) was developed. A total of 534 left-hand roentgenograms of subjects aged 2-15 years, including 270 training and 264 testing datasets, were evaluated by a senior pediatrician. Next, GTA was used to choose the appropriate candidate of radius, ulna, and short bones and to classify the bones into three groups by data mining. Group 1 was composed of the maturity pattern of the radius and the middle phalange of the third and fifth digits and three weights were obtained by data mining, yielding a result similar to that of TW3. Subsequently, new bone-age assessment tables were constructed for boys and girls by linear regression and fuzzy logic. In addition, the Bland-Altman plot was utilized to compare accuracy between the GTA, the Greulich-Pyle (GP), and the TW3 method. The relative accuracy between the GTA and the TW3 was 96.2% in boys and 95% in girls, with an error of 1 year, while that between the assessment results of the GP and TW3 was about 87%, with an error of 1 year. However, even if the three weights were not optimally processed, GTA yielded a marginal result with an accuracy of 78.2% in boys and 79.6% in girls. GTA can efficiently simplify the complexity of the TW3 method, while maintaining almost the same accuracy. The relative accuracy between the assessment results of GTA and GP can also be marginal. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Low-concentration methylene blue maintains energy production and strongly improves survival of Leigh syndrome French Canadian skin fibroblasts.

PubMed

Legault, Jean; Larouche, Pierre-Luc; Côté, Isabelle; Bouchard, Line; Pichette, André; Robinson, Brian H; Morin, Charles

2011-01-01

Leigh syndrome French Canadian (LSFC) is a recessive disease caused by mutations in the LRPPRC gene (leucine-rich pentatricopeptide repeat containing protein). These mutations induce a cytochrome c oxidase (COX) deficiency resulting in episodes of acute acidotic crisis that will often lead to death. There is no effective treatment. Methylene blue (MB) is a redox dye that increases COX content and activity in vitro and in vivo suggesting that MB could prevent and treat LSFC. In this study, the protective effect of low-concentration MB was tested on two LSFC cell lines, including LSFC-F1, homozygous for the mutation A354V, and LSFC-F2 a compound heterozygous for the mutations A354V and C12775STOP. MB effect on metabolic activity was assessed on both LSFC cells in stable and acidotic conditions. For LSFC-F1, results showed that metabolic activity drastically decline after 96 hours in both conditions but not LSFC-F2 and normal cells. MB completely prevents the decrease of metabolic activity in LSFC-F1. Intracellular ATP content was also measured in both culture media. After 96 hours in acidotic medium, ATP content was almost completely depleted for both LSFC cells. Interestingly, MB completely restores ATP content in LSFC-F1 and LSFC-F2 cells. Finally, MB strongly improves the survival of both LSFC cells.

A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome.

PubMed

Duff, Rachael M; Shearwood, Anne-Marie J; Ermer, Judith; Rossetti, Giulia; Gooding, Rebecca; Richman, Tara R; Balasubramaniam, Shanti; Thorburn, David R; Rackham, Oliver; Lamont, Phillipa J; Filipovska, Aleksandra

2015-11-01

Leigh syndrome (LS) is a progressive mitochondrial neurodegenerative disorder, whose symptoms most commonly include psychomotor delay with regression, lactic acidosis and a failure to thrive. Here we describe three siblings with LS, but with additional manifestations including hypertrophic cardiomyopathy, hepatosplenomegaly, cholestatic hepatitis, and seizures. All three affected siblings were found to be homoplasmic for an m. 5559A>G mutation in the T stem of the mitochondrial DNA-encoded MT-TW by next generation sequencing. The m.5559A>G mutation causes a reduction in the steady state levels of tRNA(Trp) and this decrease likely affects the stability of other mitochondrial RNAs in the patient fibroblasts. We observe accumulation of an unprocessed transcript containing tRNA(Trp), decreased de novo protein synthesis and consequently lowered steady state levels of mitochondrial DNA-encoded proteins that compromise mitochondrial respiration. Our results show that the m.5559A>G mutation at homoplasmic levels causes LS in association with severe multi-organ disease (LS-plus) as a consequence of dysfunctional mitochondrial RNA metabolism. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients.

PubMed

Poyau, A; Buchet, K; Bouzidi, M F; Zabot, M T; Echenne, B; Yao, J; Shoubridge, E A; Godinot, C

2000-02-01

We have studied the fibroblasts of three patients suffering from Leigh syndrome associated with cytochrome c oxidase deficiency (LS-COX-). Their mitochondrial DNA was functional and all nuclear COX subunits had a normal sequence. The expression of transcripts encoding mitochondrial and nuclear COX subunits was normal or slightly increased. Similarly, the OXA1 transcript coding for a protein involved in COX assembly was increased. However, several COX-protein subunits were severely depressed, indicating deficient COX assembly. Surf1, a factor involved in COX biogenesis, was recently reported as mutated in LS-COX- patients, all mutations predicting a truncated protein. Sequence analysis of SURF1 gene in our three patients revealed seven heterozygous mutations, six of which were new : an insertion, a nonsense mutation, a splicing mutation of intron 7 in addition to three missense mutations. The mutation G385 A (Gly124-->Glu) changes a Gly that is strictly conserved in Surfl homologs of 12 species. The substitution G618 C (Asp202-->His), changing an Asp that is conserved only in mammals, appears to be a polymorphism. The mutation T751 C changes Ile246 to Thr, a position at which a hydrophobic amino acid is conserved in all eukaryotic and some bacterial species. Replacing Ile246 by Thr disrupts a predicted beta sheet structure present in all higher eukaryotes. COX activity could be restored in fibroblasts of the three patients by complementation with a retroviral vector containing normal SURF1 cDNA. These mutations identify domains essential to Surf1 protein structure and/or function.

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers (in protective clothing) brief STS-117 Mission Specialist James Reilly (center) and STS-115 Mission Specialist Joseph Tanner (right) about the Japanese Experiment Module (JEM). Equipment familiarization is a routine part of astronaut training and launch preparations.

NASA Image and Video Library

2003-10-21

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers (in protective clothing) brief STS-117 Mission Specialist James Reilly (center) and STS-115 Mission Specialist Joseph Tanner (right) about the Japanese Experiment Module (JEM). Equipment familiarization is a routine part of astronaut training and launch preparations.

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

PubMed

Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

2016-01-01

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy.

PubMed

Hallmann, Kerstin; Kudin, Alexei P; Zsurka, Gábor; Kornblum, Cornelia; Reimann, Jens; Stüve, Burkhard; Waltz, Stephan; Hattingen, Elke; Thiele, Holger; Nürnberg, Peter; Rüb, Cornelia; Voos, Wolfgang; Kopatz, Jens; Neumann, Harald; Kunz, Wolfram S

2016-02-01

Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

The relationship between circulating ecdysteroids and chela allometry in male tanner crabs: Evidence for a terminal molt in the genus Chionoecetes

USGS Publications Warehouse

Tamone, S.L.; Taggart, S. James; Andrews, A.G.; Mondragon, Jennifer; Nielsen, J.K.

2007-01-01

Whether male Tanner crabs, Chionoecetes bairdi, undergo a terminal molt associated with a change in claw allometry has long been debated. We measured molting hormone levels in captured male C. bairdi to assess the potential for molting. We plotted a frequency histogram of chela height to carapace width ratios and found a bimodal distribution of crabs with a ratio of approximately 0.18 separating the two modes. Male crabs with a ratio less than 0.18 were classified as "small-clawed" (SC) while crabs with a ratio greater than 0.18 were classified as "large-clawed" (LC). Circulating molting hormones between SC and LC crabs were compared. Significantly lower ecdysteroid levels were found in LC crabs, indicating that this morphotype had negligible potential for molting. Circulating ecdysteroids were measured in SC males of different shell conditions (soft, new, old, and very old) and no significant differences were found. This research suggests that the molt to LC morphology is a terminal molt. The results from this study have important implications for fisheries management because sub-legal LC males will not recruit into the fishery and removal of larger males may have long term effects on population size structure.

Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome.

PubMed

Chen, Byron; Hui, Jessica; Montgomery, Kelsey S; Gella, Alejandro; Bolea, Irene; Sanz, Elisenda; Palmiter, Richard D; Quintana, Albert

2017-01-01

Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4 , a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

Tanner-Whitehouse Skeletal Ages in Male Youth Soccer Players: TW2 or TW3?

PubMed

Malina, Robert M; Coelho-E-Silva, Manuel J; Figueiredo, António J; Philippaerts, Renaat M; Hirose, Norikazu; Peña Reyes, Maria Eugenia; Gilli, Giulio; Benso, Andrea; Vaeyens, Roel; Deprez, Dieter; Guglielmo, Luiz F; Buranarugsa, Rojapon

2018-04-01

The Tanner-Whitehouse radius-ulna-short bone protocol (TW2 RUS) for the assessment of skeletal age (SA) is widely used to estimate the biological (skeletal) maturity status of children and adolescents. The scale for converting TW RUS ratings to an SA has been revised (TW3 RUS) and has implications for studies of youth athletes in age-group sports. The aim of this study was to compare TW2 and TW3 RUS SAs in an international sample of male youth soccer players and to compare distributions of players by maturity status defined by each SA protocol. SA assessments with the TW RUS method were collated for 1831 male soccer players aged 11-17 years from eight countries. RUS scores were converted to TW2 and TW3 SAs using the appropriate tables. SAs were related to chronological age (CA) in individual athletes and compared by CA groups. The difference of SA minus CA with TW2 SA and with TW3 SA was used to classify players as late, average, or early maturing with each method. Concordance of maturity classifications was evaluated with Cohen's Kappa coefficients. For the same RUS score, TW3 SAs were systematically and substantially reduced compared with TW2 SAs; mean differences by CA group ranged from - 0.97 to - 1.16 years. Kappa coefficients indicated at best fair concordance of TW2 and TW3 maturity classifications. Across the age range, 42% of players classified as average with TW2 SA were classified as late with TW3 SA, and 64% of players classified as early with TW2 SA were classified as average with TW3 SA. TW3 SAs were systematically lower than corresponding TW2 SAs in male youth soccer players. The differences between scales have major implications for the classification of players by maturity status, which is central to some talent development programs.

Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh syndrome patient.

PubMed

Miller, David K; Menezes, Minal J; Simons, Cas; Riley, Lisa G; Cooper, Sandra T; Grimmond, Sean M; Thorburn, David R; Christodoulou, John; Taft, Ryan J

2014-01-01

Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical's phase 2B clinical trial of EPI-743. SNP-arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high-depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively causal mutations were identified in nuclear-encoded genes. Analysis of low-coverage off-target mitochondrial reads revealed a previously unreported mitochondrial mutation in the proband in MT-ND3 (m.10134C>A, p.Q26K), a Complex I mitochondrial gene previously associated with LS. Targeted investigations demonstrated that this mutation was 1% heteroplasmic in the mother's blood and homoplasmic in the proband's blood, fibroblasts, liver and muscle. Enzyme assays revealed decreased Complex I activity. The identification of this novel LS MT-ND3 variant, the genomics of which was accomplished in less than 3.5 weeks, indicates that rapid genomic approaches may prove useful in time-sensitive cases with an unresolved genetic diagnosis.

Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis.

PubMed

Yamada, Kenichiro; Naiki, Misako; Hoshino, Shin; Kitaura, Yasuyuki; Kondo, Yusuke; Nomura, Noriko; Kimura, Reiko; Fukushi, Daisuke; Yamada, Yasukazu; Shimozawa, Nobuyuki; Yamaguchi, Seiji; Shimomura, Yoshiharu; Miura, Kiyokuni; Wakamatsu, Nobuaki

2014-01-01

3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is an autosomal recessive disorder characterized by episodes of ketoacidosis and a Leigh-like basal ganglia disease, without high concentrations of pyruvate and lactate in the cerebrospinal fluid. Only 4 cases of HIBCH deficiency have been reported. However, clinical-biochemical correlation in HIBCH deficiency by determining the detailed residual enzyme activities has not yet been elucidated. Here, we report a case of two Japanese siblings with HIBCH deficiency carrying a new homozygous missense mutation (c.287C > A, [p.A96D]) at the substrate-binding site. A transfection study using HIBCH expression vectors harboring wild type or 4 reported mutations, including the newly identified mutation (p.A96D, p.Y122C, p.G317E, and p.K74Lfs*13), revealed a correlation between residual HIBCH activities and the severity of the disease. All HIBCH mutants, except p.K74Lfs*13, showed residual enzyme activity and only the patient with p.K74Lfs*13 had congenital anomalies. p.G317E showed only low enzyme activity (~ 3%) of that of wild-type HIBCH. Although p.A96D had approximately 7 times higher enzyme activity than p.G317E, patients with p.A96D died during childhood. These findings are essential for clinical management, genetic counseling, and specific meal and concomitant drug considerations as part of the treatment for patients with HIBCH deficiency.

A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome.

PubMed

Lebon, Sophie; Minai, Limor; Chretien, Dominique; Corcos, Johanna; Serre, Valérie; Kadhom, Noman; Steffann, Julie; Pauchard, Jean-Yves; Munnich, Arnold; Bonnefont, Jean-Paul; Rötig, Agnès

2007-01-01

Complex I deficiency is a frequent cause of mitochondrial disease as it accounts for one third of these disorders. By genotyping several putative disease loci using microsatellite markers we were able to describe a new NDUFS7 mutation in a consanguineous family with Leigh syndrome and isolated complex I deficiency. This mutation lies in the first intron of the NDUFS7 gene (c.17-1167 C>G) and creates a strong donor splice site resulting in the generation of a cryptic exon. This mutation is predicted to result in a shortened mutant protein of 41 instead of 213 amino acids containing only the first five amino acids of the normal protein. Analysis of the assembly state of the respiratory chain complexes under native condition revealed a marked decrease of fully assembled complex I while the quantity of the other complexes was not altered. These results report the first intronic NDUFS7 gene mutation and demonstrate the crucial role of NDUFS7 in the biogenesis of complex I.

The Office of the Secretary of the Air Force 1947-1965

DTIC Science & Technology

1993-01-01

for Air. He had learned to fly during the summer of 1916 while staying at the Davison home in New York.* Like Davison, Lovett had served in the Naval...turned her New York summer home at Locust Valley on Long Island into a camp for her son and his friends from Yale so they could attend a nearby flying ...activated its first air refueling squadrons, the 43d and 509th, at Davis-Monthan and Roswell Air Force Bases. Because new engines were needed to power jet

Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome.

PubMed

Lake, Nicole J; Webb, Bryn D; Stroud, David A; Richman, Tara R; Ruzzenente, Benedetta; Compton, Alison G; Mountford, Hayley S; Pulman, Juliette; Zangarelli, Coralie; Rio, Marlene; Boddaert, Nathalie; Assouline, Zahra; Sherpa, Mingma D; Schadt, Eric E; Houten, Sander M; Byrnes, James; McCormick, Elizabeth M; Zolkipli-Cunningham, Zarazuela; Haude, Katrina; Zhang, Zhancheng; Retterer, Kyle; Bai, Renkui; Calvo, Sarah E; Mootha, Vamsi K; Christodoulou, John; Rötig, Agnes; Filipovska, Aleksandra; Cristian, Ingrid; Falk, Marni J; Metodiev, Metodi D; Thorburn, David R

2017-08-03

The synthesis of all 13 mitochondrial DNA (mtDNA)-encoded protein subunits of the human oxidative phosphorylation (OXPHOS) system is carried out by mitochondrial ribosomes (mitoribosomes). Defects in the stability of mitoribosomal proteins or mitoribosome assembly impair mitochondrial protein translation, causing combined OXPHOS enzyme deficiency and clinical disease. Here we report four autosomal-recessive pathogenic mutations in the gene encoding the small mitoribosomal subunit protein, MRPS34, in six subjects from four unrelated families with Leigh syndrome and combined OXPHOS defects. Whole-exome sequencing was used to independently identify all variants. Two splice-site mutations were identified, including homozygous c.321+1G>T in a subject of Italian ancestry and homozygous c.322-10G>A in affected sibling pairs from two unrelated families of Puerto Rican descent. In addition, compound heterozygous MRPS34 mutations were identified in a proband of French ancestry; a missense (c.37G>A [p.Glu13Lys]) and a nonsense (c.94C>T [p.Gln32 ∗ ]) variant. We demonstrated that these mutations reduce MRPS34 protein levels and the synthesis of OXPHOS subunits encoded by mtDNA. Examination of the mitoribosome profile and quantitative proteomics showed that the mitochondrial translation defect was caused by destabilization of the small mitoribosomal subunit and impaired monosome assembly. Lentiviral-mediated expression of wild-type MRPS34 rescued the defect in mitochondrial translation observed in skin fibroblasts from affected subjects, confirming the pathogenicity of MRPS34 mutations. Our data establish that MRPS34 is required for normal function of the mitoribosome in humans and furthermore demonstrate the power of quantitative proteomic analysis to identify signatures of defects in specific cellular pathways in fibroblasts from subjects with inherited disease. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.

PubMed

Wortmann, S; Rodenburg, R J T; Huizing, M; Loupatty, F J; de Koning, T; Kluijtmans, L A J; Engelke, U; Wevers, R; Smeitink, J A M; Morava, E

2006-05-01

In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (left) and STS-117 Mission Specialist James Reilly (right) are donning protective clothing to interface with the Japanese Experiment Module (JEM), in the background. Equipment familiarization is a routine part of astronaut training and launch preparations.

NASA Image and Video Library

2003-10-21

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (left) and STS-117 Mission Specialist James Reilly (right) are donning protective clothing to interface with the Japanese Experiment Module (JEM), in the background. Equipment familiarization is a routine part of astronaut training and launch preparations.

Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer optical fiber coating analysis with Slip Conditions

NASA Astrophysics Data System (ADS)

Khan, Zeeshan; Shah, Rehan Ali; Islam, Saeed; Jan, Bilal; Imran, Muhammad; Tahir, Farisa

2016-10-01

Modern optical fibers require double-layer coating on the glass fiber to provide protection from signal attenuation and mechanical damage. The most important plastic resins used in wires and optical fibers are plastic polyvinyl chloride (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In this paper, double-layer optical fiber coating is performed using melt polymer satisfying PTT fluid model in a pressure type die using wet-on-wet coating process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid model, two-layer liquid flows of an immiscible fluid is modeled in an annular die, where the fiber is dragged at a higher speed. The equations characterizing the flow and heat transfer phenomena are solved exactly and the effects of emerging parameters (Deborah and slip parameters, characteristic velocity, radii ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated fiber optics, and temperature distribution) are reported in graphs. It is shown that an increase in the non-Newtonian parameters increase the velocity in the absence or presence of slip parameters which coincides with related work. The comparison is done with experimental work by taking λ → 0 (non-Newtonian parameter).

Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer optical fiber coating analysis with Slip Conditions.

PubMed

Khan, Zeeshan; Shah, Rehan Ali; Islam, Saeed; Jan, Bilal; Imran, Muhammad; Tahir, Farisa

2016-10-06

Modern optical fibers require double-layer coating on the glass fiber to provide protection from signal attenuation and mechanical damage. The most important plastic resins used in wires and optical fibers are plastic polyvinyl chloride (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In this paper, double-layer optical fiber coating is performed using melt polymer satisfying PTT fluid model in a pressure type die using wet-on-wet coating process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid model, two-layer liquid flows of an immiscible fluid is modeled in an annular die, where the fiber is dragged at a higher speed. The equations characterizing the flow and heat transfer phenomena are solved exactly and the effects of emerging parameters (Deborah and slip parameters, characteristic velocity, radii ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated fiber optics, and temperature distribution) are reported in graphs. It is shown that an increase in the non-Newtonian parameters increase the velocity in the absence or presence of slip parameters which coincides with related work. The comparison is done with experimental work by taking λ → 0 (non-Newtonian parameter).

Steady flow and heat transfer analysis of Phan-Thein-Tanner fluid in double-layer optical fiber coating analysis with Slip Conditions

PubMed Central

Khan, Zeeshan; Shah, Rehan Ali; Islam, Saeed; Jan, Bilal; Imran, Muhammad; Tahir, Farisa

2016-01-01

Modern optical fibers require double-layer coating on the glass fiber to provide protection from signal attenuation and mechanical damage. The most important plastic resins used in wires and optical fibers are plastic polyvinyl chloride (PVC) and low-high density polyethylene (LDPE/HDPE), nylon and Polysulfone. In this paper, double-layer optical fiber coating is performed using melt polymer satisfying PTT fluid model in a pressure type die using wet-on-wet coating process. The assumption of fully developed flow of Phan-Thien-Tanner (PTT) fluid model, two-layer liquid flows of an immiscible fluid is modeled in an annular die, where the fiber is dragged at a higher speed. The equations characterizing the flow and heat transfer phenomena are solved exactly and the effects of emerging parameters (Deborah and slip parameters, characteristic velocity, radii ratio and Brinkman numbers on the axial velocity, flow rate, thickness of coated fiber optics, and temperature distribution) are reported in graphs. It is shown that an increase in the non-Newtonian parameters increase the velocity in the absence or presence of slip parameters which coincides with related work. The comparison is done with experimental work by taking λ → 0 (non-Newtonian parameter). PMID:27708412

HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase.

PubMed

Ferdinandusse, Sacha; Waterham, Hans R; Heales, Simon J R; Brown, Garry K; Hargreaves, Iain P; Taanman, Jan-Willem; Gunny, Roxana; Abulhoul, Lara; Wanders, Ronald J A; Clayton, Peter T; Leonard, James V; Rahman, Shamima

2013-12-04

Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme deficiencies can arise from a number of mechanisms, including defective maintenance or expression of mitochondrial DNA. Impaired biosynthesis of iron-sulphur clusters and lipoic acid can lead to pyruvate dehydrogenase complex (PDHc) deficiency in addition to multiple RC deficiencies, known as the multiple mitochondrial dysfunctions syndrome. Two brothers born to distantly related Pakistani parents presenting in early infancy with a progressive neurodegenerative disorder, associated with basal ganglia changes on brain magnetic resonance imaging, were investigated for suspected Leigh-like mitochondrial disease. The index case had deficiencies of multiple RC enzymes and PDHc in skeletal muscle and fibroblasts respectively, but these were normal in his younger brother. The observation of persistently elevated hydroxy-C4-carnitine levels in the younger brother led to suspicion of HIBCH deficiency, which was investigated by biochemical assay in cultured skin fibroblasts and molecular genetic analysis. Specific spectrophotometric enzyme assay revealed HIBCH activity to be below detectable limits in cultured skin fibroblasts from both brothers. Direct Sanger sequence analysis demonstrated a novel homozygous pathogenic missense mutation c.950G

Mitochondrial Vulnerability and Increased Susceptibility to Nutrient-Induced Cytotoxicity in Fibroblasts from Leigh Syndrome French Canadian Patients

PubMed Central

Burelle, Yan; Thompson Legault, Julie; Boucher, Gabrielle; Morin, Charles; Coderre, Lise; Des Rosiers, Christine

2015-01-01

Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC), a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX) and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol), or modulate fatty acid (L-carnitine) or Krebs cycle metabolism (propionate) are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol) exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise questions about the

A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome.

PubMed

Lim, Sze Chern; Smith, Katherine R; Stroud, David A; Compton, Alison G; Tucker, Elena J; Dasvarma, Ayan; Gandolfo, Luke C; Marum, Justine E; McKenzie, Matthew; Peters, Heidi L; Mowat, David; Procopis, Peter G; Wilcken, Bridget; Christodoulou, John; Brown, Garry K; Ryan, Michael T; Bahlo, Melanie; Thorburn, David R

2014-02-06

Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic bilateral lesions, typically in the brainstem and basal ganglia. It usually presents in infancy and is genetically heterogeneous, but most individuals with mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals from six families of Lebanese origin. They differed from individuals with SURF1 mutations in having seizures as a prominent feature. Complementation analysis suggested they had mutation(s) in the same gene but targeted massively parallel sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to identify a likely candidate. Linkage and haplotype analyses mapped the location of the gene to chromosome 19 and targeted MPS of the linkage region identified a homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon could potentially still allow initiation at a downstream methionine residue but we showed that this would not result in a functional protein. We confirmed that mutation of this gene was causative by lentiviral-mediated phenotypic correction. C19orf79 was recently renamed PET100 and predicted to encode a complex IV biogenesis factor. We showed that it is located in the mitochondrial inner membrane and forms a ∼300 kDa subcomplex with complex IV subunits. Previous proteomic analyses of mitochondria had overlooked PET100 because its small size was below the cutoff for annotating bona fide proteins. The mutation was estimated to have arisen at least 520 years ago, explaining how the families could have different religions and different geographic origins within Lebanon. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Mitochondrial vulnerability and increased susceptibility to nutrient-induced cytotoxicity in fibroblasts from leigh syndrome French canadian patients.

PubMed

Burelle, Yan; Bemeur, Chantal; Rivard, Marie-Eve; Thompson Legault, Julie; Boucher, Gabrielle; Morin, Charles; Coderre, Lise; Des Rosiers, Christine

2015-01-01

Mutations in LRPPRC are responsible for the French Canadian variant of Leigh Syndrome (LSFC), a severe disorder characterized biochemically by a tissue-specific deficiency of cytochrome c oxidase (COX) and clinically by the occurrence of severe and deadly acidotic crises. Factors that precipitate these crises remain unclear. To better understand the physiopathology and identify potential treatments, we performed a comprehensive analysis of mitochondrial function in LSFC and control fibroblasts. Furthermore, we have used this cell-based model to screen for conditions that promote premature cell death in LSFC cells and test the protective effect of ten interventions targeting well-defined aspects of mitochondrial function. We show that, despite maintaining normal ATP levels, LSFC fibroblasts present several mitochondrial functional abnormalities under normal baseline conditions, which likely impair their capacity to respond to stress. This includes mitochondrial network fragmentation, impaired oxidative phosphorylation capacity, lower membrane potential, increased sensitivity to Ca2+-induced permeability transition, but no changes in reactive oxygen species production. We also show that LSFC fibroblasts display enhanced susceptibility to cell death when exposed to palmitate, an effect that is potentiated by high lactate, while high glucose or acidosis alone or in combination were neutral. Furthermore, we demonstrate that compounds that are known to promote flux through the electron transport chain independent of phosphorylation (methylene blue, dinitrophenol), or modulate fatty acid (L-carnitine) or Krebs cycle metabolism (propionate) are protective, while antioxidants (idebenone, N-acetyl cysteine, resveratrol) exacerbate palmitate plus lactate-induced cell death. Collectively, beyond highlighting multiple alterations in mitochondrial function and increased susceptibility to nutrient-induced cytotoxicity in LSFC fibroblasts, these results raise questions about the

The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome.

PubMed

Kanabus, Marta; Fassone, Elisa; Hughes, Sean David; Bilooei, Sara Farahi; Rutherford, Tricia; Donnell, Maura O'; Heales, Simon J R; Rahman, Shamima

2016-05-01

There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis. The effects of C10 were investigated in primary fibroblasts from a cohort of patients with Leigh syndrome (LS) caused by nuclear-encoded defects of respiratory chain complex I, using mitochondrial respiratory chain enzyme assays, gene expression microarray, qPCR and flow cytometry. Treatment with C10 increased citrate synthase activity, a marker of cellular mitochondrial content, in 50 % of fibroblasts obtained from individuals diagnosed with LS in a PPAR-γ-mediated manner. Gene expression analysis and qPCR studies suggested that treating cells with C10 supports fatty acid metabolism, through increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism (PDK3, PDK4). PCK2, involved in blocking glucose metabolism, was upregulated, as was CAT, encoding catalase. Moreover, treatment with C10 also decreased oxidative stress in complex I deficient (rotenone treated) cells. However, since not all cells from subjects with LS appeared to respond to C10, prior cellular testing in vitro could be employed as a means for selecting individuals for subsequent clinical studies involving C10 preparations.

Human mitochondrial NDUFS3 protein bearing Leigh syndrome mutation is more prone to aggregation than its wild-type.

PubMed

Jaokar, Tulika M; Patil, Deepak P; Shouche, Yogesh S; Gaikwad, Sushama M; Suresh, C G

2013-12-01

NDUFS3 is an integral subunit of the Q module of the mitochondrial respiratory Complex-I. The combined mutation (T145I + R199W) in the subunit is reported to cause optic atrophy and Leigh syndrome accompanied by severe Complex-I deficiency. In the present study, we have cloned and overexpressed the human NDUFS3 subunit and its double mutant in a soluble form in Escherichia coli. The wild-type (w-t) and mutant proteins were purified to homogeneity through a serial two-step chromatographic purification procedure of anion exchange followed by size exclusion chromatography. The integrity and purity of the purified proteins was confirmed by Western blot analysis and MALDI-TOF/TOF. The conformational transitions of the purified subunits were studied through steady state as well as time resolved fluorescence and CD spectroscopy under various denaturing conditions. The mutant protein showed altered polarity around tryptophan residues, changed quenching parameters and also noticeably altered secondary and tertiary structure compared to the w-t protein. Mutant also exhibited a higher tendency than the w-t protein for aggregation which was examined using fluorescent (Thioflavin-T) and spectroscopic (Congo red) dye binding techniques. The pH stability of the w-t and mutant proteins varied at extreme acidic pH and the molten globule like structure of w-t at pH1 was absent in case of the mutant protein. Both the w-t and mutant proteins showed multi-step thermal and Gdn-HCl induced unfolding. Thus, the results provide insight into the alterations of NDUFS3 protein structure caused by the mutations, affecting the overall integrity of the protein and finally leading to disruption of Complex-I assembly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome.

PubMed

Schwartzentruber, Jeremy; Buhas, Daniela; Majewski, Jacek; Sasarman, Florin; Papillon-Cavanagh, Simon; Thiffault, Isabelle; Thiffaut, Isabelle; Sheldon, Katherine M; Massicotte, Christine; Patry, Lysanne; Simon, Mariella; Zare, Amir S; McKernan, Kevin J; Michaud, Jacques; Boles, Richard G; Deal, Cheri L; Desilets, Valerie; Shoubridge, Eric A; Samuels, Mark E

2014-11-01

Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are associated with a range of clinical phenotypes. Here, we report a novel disorder in three adult patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome sequencing, we identified a single likely causal variant, a missense mutation in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level was reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of clinical findings associated with IARS2 mutations. © 2014 WILEY PERIODICALS, INC.

A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome.

PubMed

Ngu, Lock Hock; Nijtmans, Leo G; Distelmaier, Felix; Venselaar, Hanka; van Emst-de Vries, Sjenet E; van den Brand, Mariël A M; Stoltenborg, Berendien J M; Wintjes, Liesbeth T; Willems, Peter H; van den Heuvel, Lambertus P; Smeitink, Jan A; Rodenburg, Richard J T

2012-02-01

In this study, we investigated the pathogenicity of a homozygous Asp446Asn mutation in the NDUFS2 gene of a patient with a mitochondrial respiratory chain complex I deficiency. The clinical, biochemical, and genetic features of the NDUFS2 patient were compared with those of 4 patients with previously identified NDUFS2 mutations. All 5 patients presented with Leigh syndrome. In addition, 3 out of 5 showed hypertrophic cardiomyopathy. Complex I amounts in the patient carrying the Asp446Asn mutation were normal, while the complex I activity was strongly reduced, showing that the NDUFS2 mutation affects complex I enzymatic function. By contrast, the 4 other NDUFS2 patients showed both a reduced amount and activity of complex I. The enzymatic defect in fibroblasts of the patient carrying the Asp446Asn mutation was rescued by transduction of wild type NDUFS2. A 3-D model of the catalytic core of complex I showed that the mutated amino acid residue resides near the coenzyme Q binding pocket. However, the K(M) of complex I for coenzyme Q analogs of the Asp446Asn mutated complex I was similar to the K(M) observed in other complex I defects and in controls. We propose that the mutation interferes with the reduction of coenzyme Q or with the coupling of coenzyme Q reduction with the conformational changes involved in proton pumping of complex I. Copyright © 2011 Elsevier B.V. All rights reserved.

Global Logistics Management

DTIC Science & Technology

2011-07-21

Phillips, Richard Spencer, and Leigh Warner. Catherine Whittington served as the Board Staff Analyst. PROCESS The Task Group conducted more than...Chair) Mr. Pierre Chao Mr. William Phillips Mr. Richard Spencer Ms. Leigh Warner DBB Staff Analyst Catherine Whittington 2 Methodology

Report To The Secretary Of Defense - Global Logistics Management

DTIC Science & Technology

2011-07-01

Spencer, and Leigh Warner. Catherine Whittington served as the Board’s Staff Analyst. PROCESS The Task Group conducted more than 30 interviews...Phillips Mr. Richard Spencer Ms. Leigh Warner DBB Staff Analyst Ms. Catherine Whittington 2 Methodology  Reviewed DoD Directives and

Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene.

PubMed

Koga, Yasutoshi; Povalko, Nataliya; Katayama, Koujyu; Kakimoto, Noriko; Matsuishi, Toyojiro; Naito, Etsuo; Tanaka, Masashi

2012-02-01

Leigh syndrome (LS) is a progressive untreatable degenerating mitochondrial disorder caused by either mitochondrial or nuclear DNA mutations. A patient was a second child of unconsanguineous parents. On the third day of birth, he was transferred to neonatal intensive care units because of severe lactic acidosis. Since he was showing continuous lactic acidosis, the oral supplementation of dichloroacetate (DCA) was introduced on 31st day of birth at initial dose of 50 mg/kg, followed by maintenance dose of 25 mg/kg/every 12 h. The patient was diagnosed with LS due to a point mutation of an A-C at nucleotide 599 in exon 6 in the pyruvate dehydrogenase E1α gene, resulting in the substitution of aspartate for threonine at position 200 (N200T). Although the concentrations of lactate and pyruvate in blood were slightly decreased, his clinical conditions were deteriorating progressively. In order to overcome the mitochondrial or cytosolic energy crisis indicated by lactic acidosis as well as clinical symptoms, we terminated the DCA and administered 0.5 g/kg/day TID of sodium pyruvate orally. We analyzed the therapeutic effects of DCA or sodium pyruvate in the patient, and found that pyruvate therapy significantly decreased lactate, pyruvate and alanine levels, showed no adverse effects such as severe neuropathy seen in DCA, and had better clinical response on development and epilepsy. Though the efficacy of pyruvate on LS will be evaluated by randomized double-blind placebo-controlled study design in future, pyruvate therapy is a possible candidate for therapeutic choice for currently incurable mitochondrial disorders such as LS. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Investigation of blood flow rheology using second-grade viscoelastic model (Phan-Thien-Tanner) within carotid artery.

PubMed

Ramiar, Abas; Larimi, Morsal Momenti; Ranjbar, Ali Akbar

2017-01-01

Hemodynamic factors, such as Wall Shear Stress (WSS), play a substantial role in arterial diseases. In the larger arteries, such as the carotid artery, interaction between the vessel wall and blood flow affects the distribution of hemodynamic factors. The fluid is considered to be non-Newtonian, whose flow is governed by the equation of a second-grade viscoelastic fluid and the effects of viscoelastic on blood flow in carotid artery is investigated. Pulsatile flow studies were carried out in a 3D model of carotid artery. The governing equations were solved using finite volume C++ based on open source code, OpenFOAM. To describe blood flow, conservation of mass and momentum, a constitutive relation of simplified Phan-Thien-Tanner (sPTT), and appropriate relations were used to explain shear thinning behavior. The first recirculation was observed at t = 0.2 s, in deceleration phase. In the acceleration phase from t = 0.3 s to t = 0.5 s, vortex and recirculation sizes in bulb regions in both ECA and ICA gradually increased. As is observed in the line graphs based on extracted data from ICA, at t = 0.2 s, τyy is the maximum amount of wall shear stress and τxy the minimum one. The maximum shear stress occurred in the inner side of the main branch (inner side of ICA and ECA) because the velocity of blood flow in the inner side of the bulb region was maximum due to the created recirculation zone in the opposite side in this area. The rheology of blood flow and shear stress in various important parts (the area that are in higher rates of WSS such as bifurcation region and the regions after bulb areas in both branches, Line1-4 in Fig. 7) were also analyzed. The investigation of velocity stream line, velocity profile and shear stress in various sections of carotid artery showed that the maximum shear stress occurred in acceleration phase and in the bifurcation region between ECA and ICA which is due to velocity gradients and changes in thinning behavior of blood and

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

PubMed

Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Adult Onset Leigh Syndrome in the Intensive Care Setting: A Novel Presentation of a C12orf65 Related Mitochondrial Disease.

PubMed

Wesolowska, Maria; Gorman, Grainne S; Alston, Charlotte L; Pajak, Aleksandra; Pyle, Angela; He, Langping; Griffin, Helen; Chinnery, Patrick F; Miller, James A L; Schaefer, Andrew M; Taylor, Robert W; Lightowlers, Robert N; Chrzanowska-Lightowlers, Zofia M

2015-10-07

Mitochondrial disease can present at any age, with dysfunction in almost any tissue making diagnosis a challenge. It can result from inherited or sporadic mutations in either the mitochondrial or the nuclear genome, many of which affect intraorganellar gene expression. The estimated prevalence of 1/4300 indicates these to be amongst the commonest inherited neuromuscular disorders, emphasising the importance of recognition of the diagnostic clinical features. Despite major advances in our understanding of the molecular basis of mitochondrial diseases, accurate and early diagnoses are critically dependent on the fastidious clinical and biochemical characterisation of patients. Here we describe a patient harbouring a previously reported homozygous mutation in C12orf65, a mitochondrial protein of unknown function, which does not adhere to the proposed distinct genotype-phenotype relationship. We performed clinical, biochemical and molecular analysis including whole exome sequencing on patient samples and cell lines. We report an extremely rare case of an adult presenting with Leigh-like disease, in intensive care, in the 5th decade of life, harbouring a recessively inherited mutation previously reported in children. A global reduction in intra-mitochondrial protein synthesis was observed despite normal or elevated levels of mt-RNA, leading to an isolated complex IV deficiency. All the reported C12orf65 mutations have shown an autosomal recessive pattern of inheritance. Mitochondrial disease causing mutations inherited in this manner are usually of early onset and associated with a severe, often fatal clinical phenotype. Presentations in adulthood are usually less severe. This patient's late adulthood presentation is in sharp contrast emphasising the clinical variability that is characteristic of mitochondrial disease and illustrates why making a definitive diagnosis remains a formidable challenge.

Eliminate the "Bounce"!

ERIC Educational Resources Information Center

Leigh, Susan

2016-01-01

The "bounce" (coined by students at Susan Leigh's last campus) refers to the amount of time students spent chasing signatures and removing often-unnecessary registration "holds" in order to attend their classes. Leigh explains that all this chaos from complex, separately housed transactional business processes has led to the…

Passive Detection of Misbehaving Name Servers

DTIC Science & Technology

2013-10-01

Passive Detection of Misbehaving Name Servers Leigh B. Metcalf Jonathan M. Spring October 2013 TECHNICAL REPORT CMU/SEI-2013-TR-010 ESC-TR...Detection of Misbehaving Name Servers 5. FUNDING NUMBERS FA8721-05-C-0003 6. AUTHOR(S) Leigh B. Metcalf and Jonathan M. Spring 7. PERFORMING

Metabolic rescue in pluripotent cells from patients with mtDNA disease.

PubMed

Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

2015-08-13

Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leshinsky-Silver, E.; Mitochondrial Disease Center, Wolfson Medical Center, Holon; E-mail: leshinsky@wolfson.health.gov.il

Leigh syndrome can result from both nuclear and mitochondrial DNA defects. Mutations in complex V genes of the respiratory chain were considered until recently as the most frequent cause for mitochondrial inherited Leigh syndrome, while gene defects in complex I were related to recessive Leigh syndrome. Recently few reports of mutations in the mitochondrial-encoded complex I subunit genes causing Leigh syndrome have been reported. We describe a 1-month-old baby who acutely deteriorated, with abrupt onset of brainstem dysfunction, due to basal ganglia lesions extending to the brainstem. A muscle biopsy demonstrated complex I deficiency. Subsequent analysis of the mitochondrial genomemore » revealed a homoplastic T10191C mutation in the ND3 gene (in blood and muscle), resulting in a substitution of serine to proline. Hair root analysis revealed a 50% mutant load, reflecting heteroplasmy in early embryonic stages. The mutation was also detected in his mother (5%). Western blot analysis revealed a decrease of the 20 kDa subunit (likely ND6) and of the 30 kDa subunit (NDUFA9), which is probably due to instability attributed to the inability to form subcomplexes with ND3. This is the first description of infantile Leigh syndrome due to a maternally transmitted T10191C substitution in ND3 and not due to a de novo mutation. This mutation is age and tissue dependent and therefore may not be amenable to prenatal testing.« less

Mortality of tanners.

PubMed Central

Pippard, E C; Acheson, E D; Winter, P D

1985-01-01

The mortality of 833 male tannery workers known to have been employed in the industry in 1939 and who were followed up to the end of 1982 was studied. A total of 573 men had been employed in making leather tanned by vegetable extracts for soles and heels, and 260 men had used chrome tanning to make leather for the upper parts of shoes. No significant excesses of deaths were found for any of the common sites of cancer in either group of workers. One death from nasal cancer (0.21 expected) was reported among the men who worked with sole and heel leather. PMID:3978050

50 CFR Table 16 to Part 679 - Area Codes and Descriptions for Use With State of Alaska ADF&G Commercial Operator's Annual...

Code of Federal Regulations, 2011 CFR

2011-10-01

... Shrimp Outer Cook Inlet Shrimp Dungeness Crab King Crab Tanner Crab Miscellaneous Shellfish Salmon HH H H...) (K) GroundfishHerring King Crab Salmon Shrimp Dungeness Crab Tanner Crab Miscellaneous Shellfish KK K... 04.100 Prince William Sound (E) GroundfishHerring Shrimp Dungeness Crab King Crab Tanner Crab...

Friendly tanning: young adults' engagement with friends around indoor tanning.

PubMed

Rodríguez, Vivian M; Daniel, Casey L; Welles, Brooke Foucault; Geller, Alan C; Hay, Jennifer L

2017-08-01

Indoor tanning (IT), particularly during early adulthood, increases risk for melanoma and is exceedingly common among youth. Social influence, including social norms, promotes IT but little is known about young adults' engagement with friends around tanning. We examined IT behaviors and tanning-related communication with friends at three universities. Of 837 participants, 261 (31%) reported ever tanning (90% female, 85% White). Of those, 113 (43%) were former tanners and 148 (57%) current tanners. Current tanners reported more social tanning and discussions with friends about tanning, more frequent outdoor tanning, high propensity to tan, and greater lifetime IT exposure than former tanners. Risks-to-benefits discussion ratios were greater for former tanners. In adjusted analyses, current tanners were more likely to make plans to tan and to talk about tanning benefits with friends. Findings confirm IT is a social experience. Future work should examine social tanning's role in the promotion and reduction of IT among youth.

Innovative Methods for Engine Health Monitoring

DTIC Science & Technology

2006-11-30

ELEMENT NUMBER 6. AUTHOR(S) 6d. PROJECT NUMBER C. L. Philip Chen, Z. Pantic-Tanner, H. Millwater , S. Hudak, Y. Huang, P. Cotae, D. Tanner, E. John, K. Chan...Philip Chen’, Z. Pantic-Tanner 2, H. Millwater 3, S. Hudak 4, Y. Huang5, P. Cotae6, D. Tanner 7, E. Johns, K.Chan9, X. Wang𔃺 1 - Professor and Chair... Millwater , R.C. McClung, M.P. Enright, "A new tool for design and certification of aircraft turbine rotors," Journal of Engineering for Gas Turbines

Isolated case of mental retardation and ataxia due to a de novo mitochondrial T8993G mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Coo, I.F.M.; Smeets, H.J.M.; Oost, B.A. van

1996-03-01

Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and subacute necrotizing encephalomyelopathy (Leigh disease) are both associated with an alteration of nt 8993 in the mitochondrial ATPase 6 gene. In NARP, the T-to-G transversion at that position changes leucine into arginine. In Leigh syndrome, the same mutation can be found, as can a T-to-C transition, which changes this leucine into proline. Clinical manifestations occur for NARP when {approximately}60%-90% mutated mtDNA is present. In case of Leigh, these percentages usually exceed 95%. It is known that this mutation can segregate very rapidly within pedigrees. Here we report on a sporadic casemore » with mental retardation and ataxia without retinitis pigmentosa in which the T8993G mutation was found. 13 refs., 1 fig.« less

Method of Breast Reconstruction Determines Venous Thromboembolism Risk Better Than Current Prediction Models

PubMed Central

Patel, Niyant V.; Wagner, Douglas S.

2015-01-01

Background: Venous thromboembolism (VTE) risk models including the Davison risk score and the 2005 Caprini risk assessment model have been validated in plastic surgery patients. However, their utility and predictive value in breast reconstruction has not been well described. We sought to determine the utility of current VTE risk models in this population and the VTE rate observed in various methods of breast reconstruction. Methods: A retrospective review of breast reconstructions by a single surgeon was performed. One hundred consecutive transverse rectus abdominis myocutaneous (TRAM) patients, 100 consecutive implant patients, and 100 consecutive latissimus dorsi patients were identified over a 10-year period. Patient demographics and presence of symptomatic VTE were collected. 2005 Caprini risk scores and Davison risk scores were calculated for each patient. Results: The TRAM reconstruction group was found to have a higher VTE rate (6%) than the implant (0%) and latissimus (0%) reconstruction groups (P < 0.01). Mean Davison risk scores and 2005 Caprini scores were similar across all reconstruction groups (P > 0.1). The vast majority of patients were stratified as high risk (87.3%) by the VTE risk models. However, only TRAM reconstruction patients demonstrated significant VTE risk. Conclusions: TRAM reconstruction appears to have a significantly higher risk of VTE than both implant and latissimus reconstruction. Current risk models do not effectively stratify breast reconstruction patients at risk for VTE. The method of breast reconstruction appears to have a significant role in patients’ VTE risk. PMID:26090287

Dopamine efflux in response to ultraviolet radiation in addicted sunbed users

PubMed Central

Aubert, Pamela M.; Seibyl, John P.; Price, Julianne L.; Harris, Thomas S.; Filbey, Francesca M.; Jacobe, Heidi; Devous, Michael D.; Adinoff, Bryon

2017-01-01

Compulsive tanning despite awareness of ultraviolet radiation (UVR) carcinogenicity may represent an “addictive” behavior. Many addictive disorders are associated with alterations in dopamine (D2/D3) receptor binding and dopamine reactivity in the brain’s reward pathway. To determine if compulsive tanners exhibited neurobiologic responses similar to other addictive disorders, this study assessed basal striatal D2/D3 binding and UVR-induced striatal dopamine efflux in ten addicted and ten infrequent tanners. In a double-blind crossover trial, UVR or sham UVR was administered in separate sessions during brain imaging with single photon emission computerized tomography (SPECT). Basal D2/D3 receptor density and UVR-induced dopamine efflux in the caudate were assessed using 123I-iodobenzamide (123I-IBZM) binding potential non-displaceable (BPnd). Basal BPnd did not significantly differ between addicted and infrequent tanners. Whereas neither UVR nor sham UVR induced significant changes in bilateral caudate BPnd in either group, post-hoc analyses revealed left caudate BPnd significantly decreased (reflecting increased dopamine efflux) in the addicted tanners – but not the infrequent tanners –during the UVR session only. Bilateral ΔBPnd correlated with tanning severity only in the addicted tanners. These preliminary findings are consistent with a stronger neural rewarding response to UVR in addicted tanners, supporting a cutaneous-neural connection driving excessive sunbed use. PMID:27085608

Obesity and Sex Steroid Changes Across Puberty: Evidence for Marked Hyperandrogenemia in Pre- and Early Pubertal Obese Girls*

PubMed Central

McCartney, Christopher R.; Blank, Susan K.; Prendergast, Kathleen A.; Chhabra, Sandhya; Eagleson, Christine A.; Helm, Kristin D.; Yoo, Richard; Chang, R. Jeffrey; Foster, Carol M.; Caprio, Sonia; Marshall, John C.

2008-01-01

Context Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear. Objective To assess the degree of hyperandrogenemia across puberty in obese girls, and to assess overnight sex steroid changes in Tanner 1–3 girls. Design Cross-sectional analysis. Setting General Clinical Research Centers. Subjects Thirty normal weight (BMI-for-age < 85%) and 74 obese (BMI-for-age ≥ 95%) peripubertal girls. Intervention Blood samples (circa 0500–0700 h) while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1–3 girls. Main outcome measures Hormone concentrations stratified by Tanner stage. Results Compared to normal weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, while fasting insulin was 3-fold elevated in obese Tanner 1–3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05), but not in more mature girls. In a subgroup of normal weight Tanner 1–3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P ≤ 0.001). In obese Tanner 1–3 girls (n = 6), evening P and T were elevated, and both tended to increase overnight (mean 1.4- and 1.6-fold, respectively [P = 0.06]). Conclusions Peripubertal obesity is associated with hyperandrogenemia and hyperinsulinemia throughout puberty, being especially marked shortly before and during early puberty. Progesterone and testosterone concentrations in normal weight Tanner 1–3 girls increase overnight, with similar but less evident changes in obese girls. PMID:17118995

Leigh's Disease

MedlinePlus

... genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of ... primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance ...

Prevalence and Correlates of Skin Cancer Screening Among Indoor Tanners and Nontanners.

PubMed

Heckman, Carolyn J; Handorf, Elizabeth; Auerbach, Melissa V

2018-04-04

The US Food and Drug Administration recommends that indoor tanners (ITs) be screened regularly for skin cancer (SC). To investigate the association between indoor tanning and SC screening. The 2015 National Health Interview Survey was a multistage, clustered, cross-sectional design with 30 352 US adults participating. The response rate for the sample adult data used in this study was 55.20% after excluding 1099 individuals who reported a history of SC and 2221 individuals with unknown SC screening or indoor tanning history. To examine the independent correlates of screening, we conducted multiple logistic regressions separately for ITs and nontanners (NTs), simultaneously including all preselected variables of interest as potential predictors. Formal interaction analyses were also performed to determine if the covariate effects differed significantly between ITs and NTs. Indoor tanning as well as sociodemographic, health care, and SC risk and sun protection factors. The primary outcome was self-reported full-body SC screening by a physician. Univariable and multivariable analyses were conducted to determine the secondary outcome, correlates of SC screening among ITs and NTs. A total of 15 777 participants (51.98%) were female, and 23 823 (78.49%) were white; 4987 (16.43%) of the sample had indoor tanned, and 1077 (21.59%) of these had tanned last year. A total of 1505 ITs (30.18%) and 4951 NTs (19.52%) had been screened for SC. Correlates of screening for ITs and NTs were older age (ITs: odds ratio [OR], 4.29 [95% CI, 2.72-6.76]; NTs, OR, 5.14 [95% CI, 4.01-6.58], age ≥65 years vs 18-29 years), higher income (ITs: OR, 2.08 [95% CI, 1.50-2.88]; NTs: OR, 1.79 [95% CI, 1.51-2.12]; >$100 000 vs $0-34 999), seeking online health information (ITs, OR, 0.71 [95% CI. 0.56-0.91; NTs, OR, 0.65 [95% CI, 0.58-0.72], for not looking up health info online), family history of melanoma (ITs: OR, 1.92 [95% CI, 1.26-2.93]; NTs: OR, 1.58 [95% CI, 1.21-2.05]) or SC (ITs

CO2 Capacity Sorbent Analysis Using Volumetric Measurement Approach

NASA Technical Reports Server (NTRS)

Huang, Roger; Richardson, Tra-My Justine; Belancik, Grace; Jan, Darrell; Knox, Jim

2017-01-01

In support of air revitalization system sorbent selection for future space missions, Ames Research Center (ARC) has performed CO2 capacity tests on various solid sorbents to complement structural strength tests conducted at Marshall Space Flight Center (MSFC). The materials of interest are: Grace Davison Grade 544 13X, Honeywell UOP APG III, LiLSX VSA-10, BASF 13X, and Grace Davison Grade 522 5A. CO2 capacity was for all sorbent materials using a Micromeritics ASAP 2020 Physisorption Volumetric Analysis machine to produce 0C, 10C, 25C, 50C, and 75C isotherms. These data are to be used for modeling data and to provide a basis for continued sorbent research. The volumetric analysis method proved to be effective in generating consistent and repeatable data for the 13X sorbents, but the method needs to be refined to tailor to different sorbents.

CO2 Capacity Sorbent Analysis Using Volumetric Measurement Approach

NASA Technical Reports Server (NTRS)

Huang, Roger; Richardson, Tra-My Justine; Belancik, Grace; Jan, Darrell; Knox, James; Cmarik, Gregory E.; Ebner, Armin; Ritter, James

2017-01-01

In support of air revitalization system sorbent selection for future space missions, Ames Research Center (ARC) has performed CO2 capacity tests on various solid sorbents to complement structural strength tests conducted at Marshall Space Flight Center (MSFC). The materials of interest are: Grace Davison Grade 544 13X, Honeywell UOP APG III, LiLSX VSA-10, BASF 13X, and Grace Davison Grade 522 5A. CO2 capacity was for all sorbent materials using a Micromeritics ASAP 2020 Physisorption Volumetric Analysis machine to produce 0 C, 10 C, 25 C, 50 C, and 75 C isotherms. These data are to be used for modeling data and to provide a basis for continued sorbent research. The volumetric analysis method proved to be effective in generating consistent and repeatable data for the 13X sorbents, but the method needs to be refined to tailor to different sorbents.

Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase

PubMed Central

2013-01-01

Background Synthesis and apoenzyme attachment of lipoic acid have emerged as a new complex metabolic pathway. Mutations in several genes involved in the lipoic acid de novo pathway have recently been described (i.e., LIAS, NFU1, BOLA3, IBA57), but no mutation was found so far in genes involved in the specific process of attachment of lipoic acid to apoenzymes pyruvate dehydrogenase (PDHc), α-ketoglutarate dehydrogenase (α-KGDHc) and branched chain α-keto acid dehydrogenase (BCKDHc) complexes. Methods Exome capture was performed in a boy who developed Leigh disease following a gastroenteritis and had combined PDH and α-KGDH deficiency with a unique amino acid profile that partly ressembled E3 subunit (dihydrolipoamide dehydrogenase / DLD) deficiency. Functional studies on patient fibroblasts were performed. Lipoic acid administration was tested on the LIPT1 ortholog lip3 deletion strain yeast and on patient fibroblasts. Results Exome sequencing identified two heterozygous mutations (c.875C > G and c.535A > G) in the LIPT1 gene that encodes a mitochondrial lipoyltransferase which is thought to catalyze the attachment of lipoic acid on PDHc, α-KGDHc, and BCKDHc. Anti-lipoic acid antibodies revealed absent expression of PDH E2, BCKDH E2 and α-KGDH E2 subunits. Accordingly, the production of 14CO2 by patient fibroblasts after incubation with 14Cglucose, 14Cbutyrate or 14C3OHbutyrate was very low compared to controls. cDNA transfection experiments on patient fibroblasts rescued PDH and α-KGDH activities and normalized the levels of pyruvate and 3OHbutyrate in cell supernatants. The yeast lip3 deletion strain showed improved growth on ethanol medium after lipoic acid supplementation and incubation of the patient fibroblasts with lipoic acid decreased lactate level in cell supernatants. Conclusion We report here a putative case of impaired free or H protein-derived lipoic acid attachment due to LIPT1 mutations as a cause of PDH and α-KGDH deficiencies. Our

Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase.

PubMed

Soreze, Yohan; Boutron, Audrey; Habarou, Florence; Barnerias, Christine; Nonnenmacher, Luc; Delpech, Hélène; Mamoune, Asmaa; Chrétien, Dominique; Hubert, Laurence; Bole-Feysot, Christine; Nitschke, Patrick; Correia, Isabelle; Sardet, Claude; Boddaert, Nathalie; Hamel, Yamina; Delahodde, Agnès; Ottolenghi, Chris; de Lonlay, Pascale

2013-12-17

Synthesis and apoenzyme attachment of lipoic acid have emerged as a new complex metabolic pathway. Mutations in several genes involved in the lipoic acid de novo pathway have recently been described (i.e., LIAS, NFU1, BOLA3, IBA57), but no mutation was found so far in genes involved in the specific process of attachment of lipoic acid to apoenzymes pyruvate dehydrogenase (PDHc), α-ketoglutarate dehydrogenase (α-KGDHc) and branched chain α-keto acid dehydrogenase (BCKDHc) complexes. Exome capture was performed in a boy who developed Leigh disease following a gastroenteritis and had combined PDH and α-KGDH deficiency with a unique amino acid profile that partly ressembled E3 subunit (dihydrolipoamide dehydrogenase / DLD) deficiency. Functional studies on patient fibroblasts were performed. Lipoic acid administration was tested on the LIPT1 ortholog lip3 deletion strain yeast and on patient fibroblasts. Exome sequencing identified two heterozygous mutations (c.875C > G and c.535A > G) in the LIPT1 gene that encodes a mitochondrial lipoyltransferase which is thought to catalyze the attachment of lipoic acid on PDHc, α-KGDHc, and BCKDHc. Anti-lipoic acid antibodies revealed absent expression of PDH E2, BCKDH E2 and α-KGDH E2 subunits. Accordingly, the production of 14CO2 by patient fibroblasts after incubation with 14Cglucose, 14Cbutyrate or 14C3OHbutyrate was very low compared to controls. cDNA transfection experiments on patient fibroblasts rescued PDH and α-KGDH activities and normalized the levels of pyruvate and 3OHbutyrate in cell supernatants. The yeast lip3 deletion strain showed improved growth on ethanol medium after lipoic acid supplementation and incubation of the patient fibroblasts with lipoic acid decreased lactate level in cell supernatants. We report here a putative case of impaired free or H protein-derived lipoic acid attachment due to LIPT1 mutations as a cause of PDH and α-KGDH deficiencies. Our study calls for renewed efforts to

Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome.

PubMed

Uittenbogaard, Martine; Brantner, Christine A; Fang, ZiShui; Wong, Lee-Jun C; Gropman, Andrea; Chiaramello, Anne

2018-03-27

In this study, we report a novel perpective of metabolic consequences for the m.8993T>G variant using fibroblasts from a proband with clinical symptoms compatible with Maternally Inherited Leigh Syndrome (MILS). Definitive diagnosis was corroborated by mitochondrial DNA testing for the pathogenic variant m.8993T>G in MT-ATP6 subunit by Sanger sequencing. The long-range PCR followed by massively parallel sequencing method detected the near homoplasmic m.8993T>G variant at 83% in the proband's fibroblasts and at 0.4% in the mother's fibroblasts. Our results are compatible with very low levels of germline heteroplasmy or an apparent de novo mutation. Our mitochondrial morphometric analysis reveals severe defects in mitochondrial cristae structure in the proband's fibroblasts. Our live-cell mitochondrial respiratory analyses show impaired oxidative phosphorylation with decreased spare respiratory capacity in response to energy stress in the proband's fibroblasts. We detected a diminished glycolysis with a lessened glycolytic capacity and reserve, revealing a stunted ability to switch to glycolysis upon full inhibition of OXPHOS activities. This dysregulated energy reprogramming results in a defective interplay between OXPHOS and glycolysis during an energy crisis. Our study sheds light on the potential pathophysiologic mechanism leading to chronic energy crisis in this MILS patient harboring the m.8993T>G variant. Copyright © 2018 Elsevier Inc. All rights reserved.

Photographic coverage of STS-115 Egress Training. Bldg.9NW, CTT

NASA Image and Video Library

2002-12-03

JSC2002-02121 (3 December 2002) --- Astronaut Joseph R. (Joe) Tanner, STS-115 mission specialist, uses the Sky-genie to lower himself from a simulated trouble-plagued shuttle in an emergency egress training session in the Space Vehicle Mockup Facility at the Johnson Space Center (JSC). Tanner is wearing a training version of the shuttle launch and entry suit. United Space Alliance (USA) crew trainer David Pogue assisted Tanner.

Evaluation of Dimensionality in the Assessment of Internal Consistency Reliability: Coefficient Alpha and Omega Coefficients

ERIC Educational Resources Information Center

Green, Samuel B.; Yang, Yanyun

2015-01-01

In the lead article, Davenport, Davison, Liou, & Love demonstrate the relationship among homogeneity, internal consistency, and coefficient alpha, and also distinguish among them. These distinctions are important because too often coefficient alpha--a reliability coefficient--is interpreted as an index of homogeneity or internal consistency.…

Delimiting Coefficient a from Internal Consistency and Unidimensionality

ERIC Educational Resources Information Center

Sijtsma, Klaas

2015-01-01

I discuss the contribution by Davenport, Davison, Liou, & Love (2015) in which they relate reliability represented by coefficient a to formal definitions of internal consistency and unidimensionality, both proposed by Cronbach (1951). I argue that coefficient a is a lower bound to reliability and that concepts of internal consistency and…

Did the Moral Education Establishment Kill Character? An Autopsy of "The Death of Character."

ERIC Educational Resources Information Center

Glanzer, Perry L.

2003-01-01

Examines James Davison Hunter's claim that the moral education establishment is responsible for the death of character. Declares that moral education must grapple with Hunter's finding that effective moral education requires coherent moral culture with a clear conception of public and private good. Compares post-Soviet and current U.S. moral…

Employability in the First Degree: The Role of Work Placements on Students' Perceptions of Graduate Employability

ERIC Educational Resources Information Center

Mahmood, Lynsey; Slabu, Letitia; de Moura, Georgina Randsley; Hopthrow, Tim

2014-01-01

Employers often claim that graduates are not ready for the world of work as they lack employability skills (Archer & Davison, 2008). One policy response to this claim has been to encourage students to undertake a work placement to enhance success in the competitive job market (The Dearing Report, 1997). The present research investigated…

Easier Said than Done: Rejoinder on Sijtsma and on Green and Yang

ERIC Educational Resources Information Center

Davenport, Ernest C.; Davison, Mark L.; Liou, Pey-Yan; Love, Quintin U.

2016-01-01

The main points of Sijtsma and Green and Yang in Educational Measurement: Issues and Practice (34, 4) are that reliability, internal consistency, and unidimensionality are distinct and that Cronbach's alpha may be problematic. Neither of these assertions are at odds with Davenport, Davison, Liou, and Love in the same issue. However, many authors…

Content Area Reading Instruction for Secondary Teacher Candidates: A Case Study of a State-Required Online Content Area Reading Course

ERIC Educational Resources Information Center

Biggs, Brad

2014-01-01

This dissertation examined in a state-required, online preservice teacher course in content area reading instruction (CARI) at a large land-grant university in Minnesota. Few studies have been published to date on revitalized literacy teacher preparation efforts in CARI (See Vagle, Dillon, Davison-Jenkins, & LaDuca, 2005; Dillon, O'Brien,…

The Experiences of Disabled Pupils and Their Families

ERIC Educational Resources Information Center

Lewis, Ann; Davison, Ian; Ellins, Jean; Niblett, Louise; Parsons, Sarah; Robertson, Christopher; Sharpe, Jeremy

2007-01-01

In this article, Ann Lewis, Professor of Education at the University of Birmingham, and Ian Davison, Jean Ellins, Louise Niblett, Sarah Parsons, Christopher Robertson and Jeremy Sharpe from the research team provide a summary of discussions and selected recommendations arising from four linked projects run between 2004 and 2006. The projects were…

Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome*

PubMed Central

Piroli, Gerardo G.; Manuel, Allison M.; Clapper, Anna C.; Walla, Michael D.; Baatz, John E.; Palmiter, Richard D.; Quintana, Albert; Frizzell, Norma

2016-01-01

Elevated fumarate concentrations as a result of Krebs cycle inhibition lead to increases in protein succination, an irreversible post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). Metabolic events that reduce NADH re-oxidation can block Krebs cycle activity; therefore we hypothesized that oxidative phosphorylation deficiencies, such as those observed in some mitochondrial diseases, would also lead to increased protein succination. Using the Ndufs4 knockout (Ndufs4 KO) mouse, a model of Leigh syndrome, we demonstrate for the first time that protein succination is increased in the brainstem (BS), particularly in the vestibular nucleus. Importantly, the brainstem is the most affected region exhibiting neurodegeneration and astrocyte and microglial proliferation, and these mice typically die of respiratory failure attributed to vestibular nucleus pathology. In contrast, no increases in protein succination were observed in the skeletal muscle, corresponding with the lack of muscle pathology observed in this model. 2D SDS-PAGE followed by immunoblotting for succinated proteins and MS/MS analysis of BS proteins allowed us to identify the voltage-dependent anion channels 1 and 2 as specific targets of succination in the Ndufs4 knockout. Using targeted mass spectrometry, Cys77 and Cys48 were identified as endogenous sites of succination in voltage-dependent anion channels 2. Given the important role of voltage-dependent anion channels isoforms in the exchange of ADP/ATP between the cytosol and the mitochondria, and the already decreased capacity for ATP synthesis in the Ndufs4 KO mice, we propose that the increased protein succination observed in the BS of these animals would further decrease the already compromised mitochondrial function. These data suggest that fumarate is a novel biochemical link that may contribute to the progression of the neuropathology in this mitochondrial disease model

Factors in Adult Learning and Instruction. Theory, Innovation, and Practice in Andragogy. No. 1.

ERIC Educational Resources Information Center

Adam, Felix, Ed.; Aker, George F., Ed.

This publication, the first in a series on theory, innovation, and practice in andragogy, is a reproduction of two papers first published in 1971 by Coolie Verner and Catherine V. Davison. The first paper in this booklet explores psychological factors in adult learning and instruction, while the second discusses physiological factors. In the five…

41 CFR 50-201.2 - Administration of the Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 790). Furthermore, these interpretations are intended to indicate the construction of the law which... Company v. United States,” 374 F. 2d 689, 692 (C.A. 4, 1967); see also “United States v. Davison Fuel and... employees but also the competitive interest of all firms qualified to compete for covered contracts. [43 FR...

41 CFR 50-201.2 - Administration of the Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 790). Furthermore, these interpretations are intended to indicate the construction of the law which... Company v. United States,” 374 F. 2d 689, 692 (C.A. 4, 1967); see also “United States v. Davison Fuel and... employees but also the competitive interest of all firms qualified to compete for covered contracts. [43 FR...

Harry Potter's Provocative Moral World: Is There a Place for Good and Evil in Moral Education?

ERIC Educational Resources Information Center

Glanzer, Perry L.

2008-01-01

In a challenging critique of moral education in public schools, James Davison Hunter argues that the unspoken imperative of all moral education is to teach only those virtues, principles, and other moral teachings about which there is essentially no disagreement in American society. Hunter claims that almost every major form of moral education in…

Applying Clinical Neuropsychology in the Public Schools.

ERIC Educational Resources Information Center

Federhar, David B.

Neuropsychology is an area in which the functioning or integrity of the brain is linked to measurable human behavior. This paper describes the use of the Reitan batteries (Reitan and Davison; 1974) in public school settings for documenting and prescribing appropriate academic programs. Three individual case studies are presented. Case 1 is a 16…

Principles for Large-Scale Classroom-Based Teacher Assessment of English Learners' Language: An Initial Framework from School-Based Assessment in Hong Kong

ERIC Educational Resources Information Center

Hamp-Lyons, Liz

2009-01-01

Davison and Leung (this issue) describe the field of teacher-based English language assessment as having "much variability, a lack of systematic principles and procedures and a dearth of information as to the impact of teacher-based assessments on learning and teaching" (p. 389). In this article, the author briefly explores an example of…

A Critical Test of Self-Enhancement, Exposure, and Self-Categorization Explanations for First- and Third-Person Perceptions

ERIC Educational Resources Information Center

Reid, Scott A.; Byrne, Sahara; Brundidge, Jennifer S.; Shoham, Mirit D.; Marlow, Mikaela L.

2007-01-01

The third-person perception is the tendency for people to believe that others are more influenced by media content than themselves (W. P. Davison, 1983). The current study provides a critical test of self-enhancement, exposure, and self-categorization explanations for first- (i.e., self more influenced than others) and third-person perceptions.…

Age of onset of pubertal maturation of Thai boys.

PubMed

Jaruratanasirikul, Somchit; Yuenyongwiwat, Sakdawut; Kreetapirom, Piyavut; Sriplung, Hutcha

2014-03-01

Data regarding sexual maturation in Thai boys are limited to only one 1999 study done in Bangkok which found that the ages of onset of Tanner 2 testicular enlargement and pubic hair were 10.8 and 12.4 years, respectively. To determine the age of onset of pubertal maturation and the physical growth of Thai boys at Hat Yai municipality, southern Thailand, in the year 2012. A cross-sectional study was conducted in 1320 healthy boys, aged 6-19 years, during June 2011 to March 2012. Testicular volume and pubic hair development were assessed according to the Tanner staging method. Probit analysis was used to calculate the median age of different stages of testicular enlargement and pubic hair development. The median ages of boys having Tanner 2 testicular enlargement and Tanner 2 pubic hair were 10.6 [95% confidence interval (CI), 10.4-10.7] and 12.0 (95% CI, 11.8-12.2) years, respectively. The youngest ages of boys who had Tanner 2 testicular enlargement and Tanner 2 pubic hair were 8.2 and 9.7 years, respectively. The final height was attained at age 18 years at 170.3 cm, 3.3 cm greater than the 167.0 cm final height of Hat Yai boys studied in 1994. The age of onset of puberty in Hat Yai schoolboys in 2012 was 0.2 years earlier than that of Bangkok schoolboys in 1999. The final adult height of Thai boys increased 3 cm during the two decades.

A Huge Responsibility: Three Keys to Teaching Elementary Students

ERIC Educational Resources Information Center

Davison, Leslie

2014-01-01

Based on her 20 years of teaching Spanish, Leslie Davison strives for a holistic approach to teaching and learning that is authentic and relevant to her young language learners. Herein, she shares three keys to teaching elementary level students in a way that ensures they will have a "Can Do" attitude in terms of language proficiency and…

NREL's Thermochemical Conversion Facility Video Text Version | Bioenergy |

Science.gov Websites

steady-state. We use a tandem fast pyrolysis reactor and Davison recirculating reactor system to study ex be continually added and withdrawn so we can study catalyst activity and product composition at catalyst. Here we can study the impact of catalyst formulation and processing conditions on bio-oil

Genome Sequence of an Alphaherpesvirus from a Beluga Whale (Delphinapterus leucas).

PubMed

Davison, Andrew J; Nielsen, Ole; Subramaniam, Kuttichantran; Jacob, Jessica M; Romero, Carlos H; Burek-Huntington, Kathy A; Waltzek, Thomas B

2017-10-19

Beluga whale alphaherpesvirus 1 was isolated from a blowhole swab taken from a juvenile beluga whale. The genome is 144,144 bp in size and contains 86 putative genes. The virus groups phylogenetically with members of the genus Varicellovirus in subfamily Alphaherpesvirinae and is the first alphaherpesvirus sequenced from a marine mammal. Copyright © 2017 Davison et al.

Introducing the human Leigh syndrome mutation T9176G into Saccharomyces cerevisiae mitochondrial DNA leads to severe defects in the incorporation of Atp6p into the ATP synthase and in the mitochondrial morphology.

PubMed

Kucharczyk, Roza; Salin, Bénédicte; di Rago, J-P

2009-08-01

The Leigh syndrome is a severe neurological disorder that has been associated with mutations affecting the mitochondrial energy transducing system. One of these mutations, T9176G, has been localized in the mitochondrial ATP6 gene encoding the Atp6p (or a) subunit of the ATP synthase. This mutation converts a highly conserved leucine residue into arginine within a presumed trans-membrane alpha-helical segment, at position 217 of Atp6p. The T9176G mutation was previously shown to severely reduce the rate of mitochondrial ATP production in cultured human cells containing high loads of this mutation. However, the underlying mechanism responsible for the impaired ATP production is still unknown. To better understand how T9176G affects the ATP synthase, we have created and analyzed the properties of a yeast strain bearing an equivalent of this mutation. We show that incorporation of Atp6p within the ATP synthase was almost completely prevented in the modified yeast. Based on previous partial biochemical characterization of human T9176G cells, it is likely that this mutation similarly affects the human ATP synthase instead of causing a block in the rotary mechanism of this enzyme as it had been suggested. Interestingly, the T9176G yeast exhibits important anomalies in mitochondrial morphology, an observation which indicates that the pathogenicity of T9176G may not be limited to a bioenergetic deficiency.

Correspondence between Gonadal Steroid Hormone Concentrations and Secondary Sexual Characteristics Assessed by Clinicians, Adolescents, and Parents

ERIC Educational Resources Information Center

Huang, Bin; Hillman, Jennifer; Biro, Frank M.; Ding, Lili; Dorn, Lorah D.; Susman, Elizabeth J.

2012-01-01

Adolescent sexual maturation is staged using Tanner criteria assessed by clinicians, parents, or adolescents. The physiology of sexual maturation is driven by gonadal hormones. We investigate Tanner stage progression as a function of increasing gonadal hormone concentration and compare performances of different raters. Fifty-six boys (mean age,…

Thiamine transporter-2 deficiency: outcome and treatment monitoring.

PubMed

Ortigoza-Escobar, Juan Darío; Serrano, Mercedes; Molero, Marta; Oyarzabal, Alfonso; Rebollo, Mónica; Muchart, Jordi; Artuch, Rafael; Rodríguez-Pombo, Pilar; Pérez-Dueñas, Belén

2014-06-23

The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10-40 mg/kg/day) and biotin (1-2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.

EVA 2 activity on Flight Day 5 to service the Hubble Space Telescope

NASA Image and Video Library

1997-02-15

STS082-742-047 (11-21 Feb. 1997) --- On Flight Day 5, astronaut Joseph R. Tanner (left) holds a 500 pound piece of hardware as he stands on the end of the Space Shuttle Discovery's Remote Manipulator System (RMS) arm, as tethered astronaut Gregory J. Harbaugh works nearby. The piano-shaped object held aloft by Tanner is actually the Fine Guidance Sensor 1 (FGS-1), which Tanner had just removed from the Hubble Space Telescope (HST). Harbaugh is inspecting the FGS' bay to set the stage for the two to insert the replacement hardware. EDITOR'S NOTE: For orientation purposes, the picture should be held with Space Shuttle's OMS pods at top.

Multi-Robot FastSLAM for Large Domains

DTIC Science & Technology

2007-03-01

Derr, D. Fox, A.B. Cremers , Integrating global position estimation and position tracking for mobile robots: The dynamic markov localization approach...Intelligence (AAAI), 2000. 53. Andrew J. Davison and David W. Murray. Simultaneous Localization and Map- Building Using Active Vision. IEEE...Wyeth, Michael Milford and David Prasser. A Modified Particle Filter for Simultaneous Robot Localization and Landmark Tracking in an Indoor

Peer Relationships and Depressive Symptomatology in Boys at Puberty

ERIC Educational Resources Information Center

Mendle, Jane; Harden, K. Paige; Brooks-Gunn, Jeanne; Graber, Julia A.

2012-01-01

The physical changes of puberty coincide with an increase in the salience of peer relationships and a growing risk for depression and other forms of psychopathology. Previously, we reported that pubertal tempo, defined as a child's rate of intraindividual change in pubertal status (measured using parent-reported Tanner stages; Marshall & Tanner,…

Teaching More by Grading Less (or Differently)

ERIC Educational Resources Information Center

Schinske, Jeffrey; Tanner, Kimberly

2014-01-01

This article explores a brief history of grading in higher education in the United States. Authors, Schinske and Tanner then follow up with considerations of the potential purposes of grading and insights from research literature that has explored the influence of grading on teaching and learning. Schinske and Tanner then ask: Does grading provide…

Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome.

PubMed

Piroli, Gerardo G; Manuel, Allison M; Clapper, Anna C; Walla, Michael D; Baatz, John E; Palmiter, Richard D; Quintana, Albert; Frizzell, Norma

2016-02-01

Elevated fumarate concentrations as a result of Krebs cycle inhibition lead to increases in protein succination, an irreversible post-translational modification that occurs when fumarate reacts with cysteine residues to generate S-(2-succino)cysteine (2SC). Metabolic events that reduce NADH re-oxidation can block Krebs cycle activity; therefore we hypothesized that oxidative phosphorylation deficiencies, such as those observed in some mitochondrial diseases, would also lead to increased protein succination. Using the Ndufs4 knockout (Ndufs4 KO) mouse, a model of Leigh syndrome, we demonstrate for the first time that protein succination is increased in the brainstem (BS), particularly in the vestibular nucleus. Importantly, the brainstem is the most affected region exhibiting neurodegeneration and astrocyte and microglial proliferation, and these mice typically die of respiratory failure attributed to vestibular nucleus pathology. In contrast, no increases in protein succination were observed in the skeletal muscle, corresponding with the lack of muscle pathology observed in this model. 2D SDS-PAGE followed by immunoblotting for succinated proteins and MS/MS analysis of BS proteins allowed us to identify the voltage-dependent anion channels 1 and 2 as specific targets of succination in the Ndufs4 knockout. Using targeted mass spectrometry, Cys(77) and Cys(48) were identified as endogenous sites of succination in voltage-dependent anion channels 2. Given the important role of voltage-dependent anion channels isoforms in the exchange of ADP/ATP between the cytosol and the mitochondria, and the already decreased capacity for ATP synthesis in the Ndufs4 KO mice, we propose that the increased protein succination observed in the BS of these animals would further decrease the already compromised mitochondrial function. These data suggest that fumarate is a novel biochemical link that may contribute to the progression of the neuropathology in this mitochondrial disease

50 CFR 100.28 - Subsistence taking of shellfish.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Federally-qualified subsistence user; (ii) The gear has been marked with the client's or guest's name and... March 15; (B) The daily harvest and possession limit is 5 male Tanner crabs; (C) Only male Tanner crabs... boundaries of Womens Bay, Gibson Cove, and an area defined by a line1/2mile on either side of the mouth of...

36 CFR 242.28 - Subsistence taking of shellfish.

Code of Federal Regulations, 2010 CFR

2010-07-01

... subsistence user; (ii) The gear has been marked with the client's or guest's name and address; and (iii) The... Tanner crab: (A) Male Tanner crab may be taken only from July 15 through March 15; (B) The daily harvest...) The waters of the Pacific Ocean enclosed by the boundaries of Womens Bay, Gibson Cove, and an area...

Bioengineering/Biophysicist Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A post-doctoral fellow position is available in the Tissue Morphodynamics Unit headed by Dr. Kandice Tanner at the National Cancer Institute. The Tanner lab combines biophysical and cell biological approaches to understand the interplay between tissue architecture and metastasis. We use a combination of imaging modalities, cell biology and animal models. It is expected that as

Bioengineering/Biophysicist Post-doctoral Fellow | Center for Cancer Research

Cancer.gov

A post-doctoral fellow position is available in the Tissue Morphodynamics Unit headed by Dr. Kandice Tanner at the National Cancer Institute. The Tanner lab combines biophysical and cell biological approaches to understand the interplay between tissue architecture and metastasis. We use a combination of imaging modalities, cell biology and animal models. It is expected that as

Thiamine transporter-2 deficiency: outcome and treatment monitoring

PubMed Central

2014-01-01

Background The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse. Methods We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature. Results At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10–40 mg/kg/day) and biotin (1–2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring. Conclusions ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients. PMID:24957181

Improving the Emergency Manager’s Hurricane Evacuation Decision Making Through Serious Gaming

DTIC Science & Technology

2016-06-17

Serious Gaming Hayley J. Davison Reynolds, Maxwell H. Perlman Darren P. Wilson MIT Lincoln Laboratory DHS Science and Technology Directorate...transfer it to an actual evacuation event. Through this work, a web-based, ‘serious gaming ’ approach was used to develop hurricane evacuation decision...training for the emergency manager. This paper describes the iterative design approach to developing a training game and collect initial feedback

Operational Design: The Importance of Getting the Fundamentals Right

DTIC Science & Technology

2010-04-01

problems require only a simple form of Aristotelian mission analysis. They can be broken down into parts and treated accordingly. Davison 44...collection of subtly alternative but essentially derivative theories have promised to break through into mainstream doctrine. SOD itself has matured...desired system frame. This is the theory of action that informs the rest of the planning process. This transitional step is commander led, as it

Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA.

PubMed

Sgarbi, Gianluca; Baracca, Alessandra; Lenaz, Giorgio; Valentino, Lucia M; Carelli, Valerio; Solaini, Giancarlo

2006-05-01

Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause several different neurological disorders. The product of this gene is ATPase 6, an essential component of the F1F0-ATPase. In the present study we show that the function of the F1F0-ATPase is impaired in lymphocytes from ten individuals harbouring the mtDNA T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) and Leigh syndrome. We show that the impaired function of both the ATP synthase and the proton transport activity of the enzyme correlates with the amount of the mtDNA that is mutated, ranging from 13-94%. The fluorescent dye RH-123 (Rhodamine-123) was used as a probe to determine whether or not passive proton flux (i.e. from the intermembrane space to the matrix) is affected by the mutation. Under state 3 respiratory conditions, a slight difference in RH-123 fluorescence quenching kinetics was observed between mutant and control mitochondria that suggests a marginally lower F0 proton flux capacity in cells from patients. Moreover, independent of the cellular mutant load the specific inhibitor oligomycin induced a marked enhancement of the RH-123 quenching rate, which is associated with a block in proton conductivity through F0 [Linnett and Beechey (1979) Inhibitors of the ATP synthethase system. Methods Enzymol. 55, 472-518]. Overall, the results rule out the previously proposed proton block as the basis of the pathogenicity of the mtDNA T8993G mutation. Since the ATP synthesis rate was decreased by 70% in NARP patients compared with controls, we suggest that the T8993G mutation affects the coupling between proton translocation through F0 and ATP synthesis on F1. We discuss our findings in view of the current knowledge regarding the rotary mechanism of catalysis of the enzyme.

Socioeconomic Impact Analysis Study. Disposal and Reuse of Loring Air Force Base, Maine

DTIC Science & Technology

1994-03-01

Regional Airport by approximately 23.2 percent ( Hoyle , Tanner and Associates, Inc., 1993). 3.7.3 Rail Recent Trends Rail service is provided to Loring...1993. Personal communication with Chief Hotelling, Volunteer Fire Department, Town of Stockholm. Hoyle , Tanner & Associates, Inc., 1993. Regional...with Linda Richardson, Administrative Assistant, Aroostook County Government. St. Pierre, F., 1993. Personal communication with Fred St. Pierre, 1st

Velocities of Bone Mineral Accrual in Black and White American Children

PubMed Central

Hui, Siu L; Perkins, Anthony J; Harezlak, Jaroslaw; Peacock, Munro; McClintock, Cindy L; Johnston, C Conrad

2010-01-01

Black adults have higher bone mass than whites in the United States, but it is not clear when black children gain bone mineral faster than white children. We performed a cohort study to compare the growth velocity of total-body bone mineral content (TBMC) between black and white children of the same sex at different ages and stages of sexual maturity. TBMC and total-body area were measured in a cohort of 188 black and white boys and girls aged 5 to 15 years annually for up to 4 years. Rates of change in TBMC and area were found to vary with age and with Tanner stage. For both TBMC and area, growth velocities between black and white children differed significantly across Tanner stages. Age-specific velocities were higher in black children during prepuberty and initial entry into puberty but reversed in subsequent Tanner stages. Despite earlier entry into each Tanner stage, black children spent only an average of only 0.2 year longer in Tanner stages II through IV, and total gain in TBMC from age 5 to 15 was not higher in whites. In conclusion, the higher bone mass in black adults compared with whites cannot be attributed to faster accrual during puberty. It is due to black children's higher rate of bone mineral accrual in prepuberty and plausibly in postpuberty. Most of the racial difference in TBMC velocity can be explained by growth in size. © 2010 American Society for Bone and Mineral Research. PMID:20200959

Content analysis of Twitter chatter about indoor tanning.

PubMed

Waring, Molly E; Baker, Katie; Peluso, Anthony; May, Christine N; Pagoto, Sherry L

2018-02-21

Twitter may be useful for learning about indoor tanning behavior and attitudes. The objective of this study was to analyze the content of tweets about indoor tanning to determine the extent to which tweets are posted by people who tan, and to characterize the topics of tweets. We extracted 4,691 unique tweets from Twitter using the terms "tanning bed" or "tanning salon" over 7 days in March 2016. We content analyzed a random selection of 1,000 tweets, double-coding 20% of tweets (κ = 0.74, 81% agreement). Most tweets (71%) were by tanners (n = 699 individuals) and included tweets expressing positive sentiment about tanning (57%), and reports of a negative tanning experience (17%), burning (15%), or sleeping in a tanning bed (9%). Four percent of tweets were by tanning salon employees. Tweets posted by people unlikely to be tanners (15%) included tweets mocking tanners (71%) and health warnings (29%). The term "tanning bed" had higher precision for identifying individuals who engage in indoor tanning than "tanning salon"; 77% versus 45% of tweets captured by these search terms were by individuals who engaged in indoor tanning, respectively. Extrapolating to the full data set of 4,691 tweets, findings suggest that an average of 468 individuals who engage in indoor tanning can be identified by their tweets per day. The majority of tweets were from tanners and included reports of especially risky habits (e.g., burning, falling asleep). Twitter provides opportunity to identify indoor tanners and examine conversations about indoor tanning.

Wartime Stress: Family Adjustment to Loss

DTIC Science & Technology

1981-07-31

effect on family functioning. In R . C . Spaulding (Ed.), Proceedings of the Third Annual Joint Medical Meeting Concerning POW/MIA Matters. San Diego, CA...Military Family Research Conference, Naval Health Research Center, San Diego, CA, September 1977. BROWN, 0., CATALDO, J., DAVISON, R ., & HUYCKE, E ...an overview and assessment. In R . C . Spaulding (Ed.), Proceedings of the Third Annual Joint Medical Meeting Concerning POW/MIA Matters. San Diego, CA

Papers from the Fifth Regional Meeting of the Chicago Linguistic Society, April 18-19, 1969.

ERIC Educational Resources Information Center

Binnick, Robert I., Ed.; And Others

The topics covered in this volume range over the entire field of linguistics. The authors are: A.L. Becker and D.G. Arms, W.R. Cantrall, G. Cohen, D.J. Darden, A. Davison, D. Elliott and others, J.E. Emonds, B. Fraser, G.M. Green, J.T. Heringer, L.R. Horn, L. Kartunnen, G. Lakoff, R. Lakoff, J.M. Lindholm, V.B. Makkai, J.L. Morgan, Y.C. Morin and…

Computational Investigation of Structured Shocks in Al/SiC-Particulate Metal-Matrix Composites

DTIC Science & Technology

2011-06-01

used to implement the dynamic-mixture model into the VUMAT user-material subroutine of ABAQUS /Explicit. Owing to the attendant large strains and...that the residual thermal - expansion effects are more pronounced in the aluminium-matrix than in SiC-particulates. This finding is consistent with the...simple waves (CSWs) (Davison, 2008). . In accordance with the previously observed larger thermal - expansion effects in Al, Figure 5(b) shows that the

Internet-Based Education for Prostrate Cancer Screening. Addendum

DTIC Science & Technology

2010-12-01

a randomized trial among primary care patients with low health literacy . Patient Education and Counseling, 73(3), 482-489. Appendix 1) Complete...patients with low health literacy . Patient Educ Couns 2008, 73:482-489. 39. Davison BJ, Kirk P, Degner LF, Hassard TH: Information and patient...Carey LA, et al: Retention and use of breast cancer recurrence risk information from genomic tests: the role of health literacy . Cancer Epidemiol

Long-term secular trend of skeletal maturation of Taiwanese children between agricultural (1960s) and contemporary (after 2000s) generations using the Tanner-Whitehouse 3 (TW3) method.

PubMed

Hsieh, Chi-Wen; Liu, Tzu-Chiang; Jong, Tai-Lang; Tiu, Chui-Mei

2013-01-01

The Tanner-Whitehouse (TW) method is one of the well-known techniques in determining the bone age. According to the objectivity of TW3, the secular trend was investigated to discover whether the skeletal maturation of Taiwanese children between two generations was different. The large-scale database of Taiwan was collected. The first group, called mid-1960s, included 265 boys and 295 girls in the agricultural generation (between 1966 and 1967). The second group, called mid-2000s, includes 114 boys and 616 girls in the contemporary generation (after 2000s). The bone age was determined by three radiologists using the carpals-only system of the TW3 method and by two physicians using the Greulich and Pyle method. A comparison of the means (independent-samples t-test) was applied by examining the difference of the children's skeletal maturation between the two generations in the same chronological age. The significant difference was considered while the p-value was 0.05 or less (95% confidence interval). A significant difference of the mean bone age (by, on average, three radiologists using the TW3 method) between the mid-1960s and mid-2000s in the same gender and chronological age was presented by the independent-samples t-test (p<0.001 with 95% confidence interval), and the bone age, determined by the TW3 method, of the mid-2000s group was higher than that of the mid-1960s group. This scenario corresponded with the children's bone age determined by pediatricians. Besides, it deserved to notice that the bone age of boys in the mid-2000s was larger than that of the girls in the mid-1960s. Furthermore, by comparing the environmental condition, we suspect that the difference of bone age of children between the two generations was attributed to the discrepancy in nutrition and socioeconomic variation during the four decades in Taiwan. The study presents that the secular trend of skeletal maturation of children in the mid-2000s is faster than that in the mid-1960s.

P6 Truss, starboard PV solar array wing deployment

NASA Image and Video Library

2000-12-03

STS097-373-005 (3 December 2000) --- Backdropped against the blackness of space, the deployment of International Space Station (ISS) solar array was photographed with a 35mm camera by astronaut Carlos I. Noriega, mission specialist. Part of the extravehicular mobility unit (EMU) attached to astronaut Joseph R. Tanner, mission specialist, is visible at bottom center. Tanner and Noriega went on to participate together in three separate space walks.

The Chinese Air Force: Evolving Concepts, Roles, and Capabilities

DTIC Science & Technology

2012-01-01

5 The Missions of the People’s Liberation Army Air Force . . . 133 Murray Scot Tanner Chapter 6 The Development of the PLAAF’s Doctrine...the Military Region (MR) Headquarters. There are no indications this pattern of army domination will change in the next decade.” Murray Scot Tanner, a...his- tory, one can find remarkable threads of continuity. Early aircraft, though but fragile contraptions of wood and canvas, exploited the same

WILDLIFE - ALLIGATOR STRADDLES TWO PARKING SPACES IN FRONT OF OFFICE TRAILER

NASA Technical Reports Server (NTRS)

1982-01-01

Double-parked, an angry alligator straddles two parking spaces outside an office trailer at NASA's Launch Complex 17. Hank Curtin of Pan Am watches from a safe perch as John Tanner gets ready to wrap a rope around the snout of the 10-foot, 9-inch beast. It's all in a day's work for Tanner, who has a contract with the state of Florida to remove nuisance alligators.

Accurate 3D Modeling of Breast Deformation for Temporal Mammogram Registration

DTIC Science & Technology

2008-09-01

Julia A. Schnabel, Christine Tanner, Andy D. Castellano Smith, Martin O. Leach, Carmel Hayes, Andreas Degenhard, Rodney Hose, Derek L. G. Hill, and...David J. Hawkes, “Validation of Non- Rigid Registration using Finite Element Methods” [41]. Julia A. Schnabel, Christine Tanner, Andy D. Castellano...IMAGING FOR BREAST CANCER DETECTION Mohammad Alrubaiee, Swapan Kumar Gayen, and Robert R. Alfano City University of New York, City College of New York

Leaf Proteome Analysis Reveals Prospective Drought and Heat Stress Response Mechanisms in Soybean.

PubMed

Das, Aayudh; Eldakak, Moustafa; Paudel, Bimal; Kim, Dea-Wook; Hemmati, Homa; Basu, Chhandak; Rohila, Jai S

2016-01-01

Drought and heat are among the major abiotic stresses that affect soybean crops worldwide. During the current investigation, the effect of drought, heat, and drought plus heat stresses was compared in the leaves of two soybean varieties, Surge and Davison, combining 2D-DIGE proteomic data with physiology and biochemical analyses. We demonstrated how 25 differentially expressed photosynthesis-related proteins affect RuBisCO regulation, electron transport, Calvin cycle, and carbon fixation during drought and heat stress. We also observed higher abundance of heat stress-induced EF-Tu protein in Surge. It is possible that EF-Tu might have activated heat tolerance mechanisms in the soybean. Higher level expressions of heat shock-related protein seem to be regulating the heat tolerance mechanisms. This study identifies the differential expression of various abiotic stress-responsive proteins that regulate various molecular processes and signaling cascades. One inevitable outcome from the biochemical and proteomics assays of this study is that increase of ROS levels during drought stress does not show significant changes at the phenotypic level in Davison and this seems to be due to a higher amount of carbonic anhydrase accumulation in the cell which aids the cell to become more resistant to cytotoxic concentrations of H2O2.

Leaf Proteome Analysis Reveals Prospective Drought and Heat Stress Response Mechanisms in Soybean

PubMed Central

Das, Aayudh; Eldakak, Moustafa; Paudel, Bimal; Kim, Dea-Wook; Hemmati, Homa; Basu, Chhandak

2016-01-01

Drought and heat are among the major abiotic stresses that affect soybean crops worldwide. During the current investigation, the effect of drought, heat, and drought plus heat stresses was compared in the leaves of two soybean varieties, Surge and Davison, combining 2D-DIGE proteomic data with physiology and biochemical analyses. We demonstrated how 25 differentially expressed photosynthesis-related proteins affect RuBisCO regulation, electron transport, Calvin cycle, and carbon fixation during drought and heat stress. We also observed higher abundance of heat stress-induced EF-Tu protein in Surge. It is possible that EF-Tu might have activated heat tolerance mechanisms in the soybean. Higher level expressions of heat shock-related protein seem to be regulating the heat tolerance mechanisms. This study identifies the differential expression of various abiotic stress-responsive proteins that regulate various molecular processes and signaling cascades. One inevitable outcome from the biochemical and proteomics assays of this study is that increase of ROS levels during drought stress does not show significant changes at the phenotypic level in Davison and this seems to be due to a higher amount of carbonic anhydrase accumulation in the cell which aids the cell to become more resistant to cytotoxic concentrations of H2O2. PMID:27034942

High HOMA-IR, adjusted for puberty, relates to the metabolic syndrome in overweight and obese Chilean youths.

PubMed

Burrows, Raquel A; Leiva, Laura B; Weisstaub, Gerardo; Lera, Lydia M; Albala, Cecilia B; Blanco, Estela; Gahagan, Sheila

2011-05-01

To determine how the homeostasis model assessment of insulin resistance (HOMA-IR) is related to metabolic risk in a sample of overweight and obese Chilean youths accounting for Tanner stage. A cross-sectional study assessing 486 overweight and obese youths (aged 5-15 years) recruited from the University of Chile, Pediatric Obesity Clinic. We measured anthropometry, Tanner stage, HOMA-IR, and laboratory tests related to metabolic risk. HOMA-IR was categorized by quartile for children (Tanner stages I and II) and adolescents (Tanner stage III and above) from a normative Chilean sample. Children and adolescents with HOMA-IR in the highest quartile were likely to have higher body mass index (BMI) Z-scores, elevated waist circumference, systolic and diastolic blood pressure, and triglycerides and low high-density lipoprotein. HOMA-IR had good negative predictive value for characteristics of the metabolic syndrome (MetS; 0.82). In a multivariate regression model, BMI Z-score [odds ratio (OR) 1.5] and HOMA-IR (OR 3.3) predicted 22% of the variance for the MetS, with 36% of the explained variance attributed to HOMA-IR. In a large clinical sample of overweight and obese Chilean youths, HOMA-IR ≥ 75th percentile was significantly associated with the cluster of factors referred to as the MetS. We emphasize the importance of establishing percentiles for HOMA-IR based on a normative sample and taking Tanner stage into account. Although BMI is easy to assess and interpret with minimal costs in a clinical setting, adding HOMA-IR explains more of the variance in the MetS than BMI Z-score alone. © 2011 John Wiley & Sons A/S.

Adaptive Integration and Optimization of Automated and Neural Processing Systems - Establishing Neural and Behavioral Benchmarks of Optimized Performance

DTIC Science & Technology

2012-07-01

detection only condition followed either face detection only or dual task, thus ensuring that participants were practiced in face detection before...1 ARMY RSCH LABORATORY – HRED RDRL HRM C A DAVISON 320 MANSCEN LOOP STE 115 FORT LEONARD WOOD MO 65473 2 ARMY RSCH LABORATORY...HRED RDRL HRM DI T DAVIS J HANSBERGER BLDG 5400 RM C242 REDSTONE ARSENAL AL 35898-7290 1 ARMY RSCH LABORATORY – HRED RDRL HRS

Topics in Statistical Calibration

DTIC Science & Technology

2014-03-27

on a parametric bootstrap where, instead of sampling directly from the residuals , samples are drawn from a normal distribution. This procedure will...addition to centering them (Davison and Hinkley, 1997). When there are outliers in the residuals , the bootstrap distribution of x̂0 can become skewed or...based and inversion methods using the linear mixed-effects model. Then, a simple parametric bootstrap algorithm is proposed that can be used to either

STS-66 Official pre-flight crew portrait

NASA Technical Reports Server (NTRS)

1994-01-01

The STS-66 Official crew portrait includes the following: Donald R. McMonagle (front right) is mission commander, and Curtis L. Brown (front center) is pilot. Other crewmembers include Ellen S. Ochoa, payload commander; Scott E. Parazynski (rear left), and Joseph R. Tanner (rear center), mission specialists, along with ESA astronaut Jean-Francois Clevoy (front left), mission specialist. Clervoy, Parazynski and Tanner, members of the 1992 astronaut class, are making their initial flights in space.

Development of Acceptance Plans for Airport Pavement Materials. Volume 1. Development

DTIC Science & Technology

1990-05-01

Robert A. Bacza Mr. Kenneth P. Knoll Mr. Timothy Dyer Mr. John Moretto 04/08/87 Harrisburg ADO Mr. Dan Cassidy Mr. Fred Waldmer *04/10/87 Beckley AFO... Hoyle , Tanner & Associates, Inc., Bedford, NH *06/24/87 Calcerinos-Spina, Liverpool, NY *06/25/87 Nigara Frontier Transportation Authority, Buffalo, NY...VA; Suffolk Municipal Airport, Suffolk, VA. 13. Hoyle , Tanner & Asociates, Inc., Bedford, NH, Barry W. Lussier; East Hampton Airport, East Hampton, NY

Nutritional and Genetic Determinants of Early Puberty

DTIC Science & Technology

2006-06-01

between the CYP3A4 *1B polymorphism with pubic hair Tanner stage (p=0.01), but no association of this variant with breast Tanner stage or age at...Vitamin D receptor gene polymorphism is associated with birth height, growth to adolescence, and adult stature in healthy Caucasian men: a cross...to a greater extent to adverse HDL cholesterol , triglyceride, and insulin resistance levels (12). Our study showed that, although Asian adolescent

Predictors of Sun-Related Behaviors among Young Women: Comparisons between Outdoor Tanners, Fake Tanners, and Tan Avoiders

ERIC Educational Resources Information Center

Day, Ashley K.; Oxlad, Melissa; Roberts, Rachel M.

2013-01-01

Objective: Skin cancer incidence continues to rise as a tanned appearance remains desirable, particularly among young women. Fake tanning provides a tanned appearance without exposure to ultraviolet radiation. In order to advance our understanding of the factors that contribute to long-term behavior change, this study explores determinants…

Lifetime history of indoor tanning in young people: a retrospective assessment of initiation, persistence, and correlates

PubMed Central

2012-01-01

Background Despite educational and public health campaigns to convey the risks of indoor tanning, many individuals around the world continue to engage in this behavior. Few descriptive studies of indoor tanning have collected information pertaining to the lifetime history of indoor tanning, thereby limiting our ability to understand indoor tanning patterns and potentially target interventions for individuals who not only initiate, but continue to persistently engage in indoor tanning. Methods In-person interviews elicited detailed retrospective information on lifetime history of indoor tanning among white individuals (n = 401) under age 40 seen by a dermatologist for a minor benign skin condition. These individuals were controls in a case-control study of early-onset basal cell carcinoma. Outcomes of interest included ever indoor tanning in both males and females, as well as persistent indoor tanning in females - defined as females over age 31 who tanned indoors at least once in the last three or all four of four specified age periods (ages 11-15, 16-20, 21-30 and 31 or older). Multivariate logistic regression was used to identify sociodemographic and lifestyle correlates of ever and persistent indoor tanning in females. Results Approximately three-quarters (73.3%) of females and 38.3% of males ever tanned indoors, with a median age of initiation of 17.0 and 21.5, respectively. Among indoor tanners, 39.3% of females and 21.7% of males reported being burned while indoor tanning. Female ever indoor tanners were younger, had darker color eyes, and sunbathed more frequently than females who never tanned indoors. Using unique lifetime exposure data, 24.7% of female indoor tanners 31 and older persistently tanned indoors starting as teenagers. Female persistent indoor tanners drank significantly more alcohol, were less educated, had skin that tanned with prolonged sun exposure, and sunbathed outdoors more frequently than non-persistent tanners. Conclusions Indoor tanning

Genetics Home Reference: mitochondrial complex V deficiency

MedlinePlus

... can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and ... have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss. A condition called Leigh ...

The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development.

PubMed

Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente; Hangartner, Thomas; Kalkwarf, Heidi J; Oberfield, Sharon; Shepherd, John; Winer, Karen K; Zemel, Babette

2015-01-01

Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed-effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. © 2014 American

Indian girls have higher bone mineral content per unit of lean body than boys through puberty.

PubMed

Khadilkar, Anuradha V; Sanwalka, Neha; Mughal, M Zulf; Chiplonkar, Shashi; Khadilkar, Vaman

2018-05-01

Our aim is to describe changes in the muscle-bone unit assessed as a ratio of bone mineral content (BMC) to lean body mass (LBM) through puberty at total body and various skeletal sites in Indian boys and girls. A cross-sectional study was conducted (888 children, 480 boys, aged 5-17 years) in Pune, India. Pubertal staging was assessed. BMC, LBM and fat percentage at the arms, legs, android, gynoid and total body (less the head) were assessed by dual energy X-ray absorptiometry. The amount of BMC per unit LBM (BMC/LBM) was computed. Changes in mean BMC/LBM at 5 Tanner (pubertal) stages after adjustment for age and fat percentage were calculated. In boys, adjusted BMC/LBM was significantly higher with successive Tanner stages [legs (TS-II vs TS-I), android (TS-III vs TS-II, TS-IV vs TS-III) and gynoid region (TS-III vs TS-II and TS-II vs TS-I) (p < 0.05)]. In girls, adjusted BMC/LBM was significantly higher with successive Tanner stages at total body, legs and gynoid (TS-III vs TS-II; TS-II vs TS-I; TS-V vs TS-IV), arms (TS-I to TS-V) and android regions (TS-V vs TS-IV) (p < 0.05). Boys had significantly higher adjusted BMC/LBM than girls at earlier Tanner stages (TS-I to TS-III), whereas girls had significantly higher adjusted BMC/LBM than boys at later Tanner stages (TS-IV, TS-V) (p < 0.05). Indian boys and girls showed higher total and regional body, and age- and fat percentage-adjusted BMC/LBM with successive pubertal stages. Girls had higher BMC/LBM than boys which may possibly act as a reservoir for later demands of pregnancy and lactation.

[Update on pubertal development among primary school students in Shanghai, 2014].

PubMed

Chen, Y; Zhang, Y T; Chen, C; Jiang, Y R; Song, Y J; Liu, S J; Jiang, F

2016-11-06

Objective: To investigate the current prevalence of pubertal development in healthy Shanghai schoolchildren. Methods: This study was a cross-sectional investigation focused on current pubertal development conducted in healthy Shanghai schoolchildren by multi-stage cluster sampling. The sample included 17 571 children in grades 1-5 investigated in June 2014. The data were weighted by inverse probability weighting (IPW) to make them more representative. At examination, stages of breast and pubic hair development were rated according to the Tanner method. Testicular volume was determined. Data on menarche and spermatorrhea were collected by the status quo method. The rates of precocious puberty, breast, and pubic hair development of Tanner stage ≥Ⅱ in girls aged 6-7 years, menarche in girls aged 6-9 years, and testicular volume ≥4 ml and pubic hair development of Tanner stage ≥Ⅱ in boys aged 6-8 years were calculated. All the data were weighted by IPW. Results: After data processing, 16 197 children's data were analyzed. In girls aged 6-7 years, 17.2% and 2.5% showed evidence of breast and pubic hair development at Tanner stage ≥Ⅱ, respectively. In girls aged 6-9 years, 0.3% had experienced menarche. Schoolgirls' rate of menarche was 4.7%. In girls aged 6-7 years, 19.0% were diagnosed with precocious puberty according to the classic criteria. In boys aged 6-8 years, 1.7% had testicular volume ≥4 ml, and 0.6% showed evidence of pubic hair development at Tanner stage ≥Ⅱ. Schoolboys' incidence rate of spermatorrhea was 0.1%. In boys aged 6-8 years, 2.3% were diagnosed with precocious puberty according to the classic criteria. All the numbers above were weighted. Conclusion: Proper education on adolescence and sex is essential for Shanghai schoolchildren.

The Synthesis of 1,1’-Bicobaltocene Salts of Tetracyano-P-Quinodimethanide and the Sturcture of 1,1’-Bicobaltocene (Co (III) Co (III)) (TCNQ)3,

DTIC Science & Technology

1981-06-03

Salts of Bicobaltocenet-The hexafluorophosphate salt of bicobaltocene(III,III) was prepared by the method of Davison and Smart 4 and the orange product...tetrahydrofuran. The lithium salt of TCNO was prepared by adding a boiling solution of lithium iodide in acetonitrile to a boiling solution of TCNQ in...compound 1,1’-bicobaltocene[Co(III)Co(III)[TCNQJ 3 resulted from the reaction of the mixed valence hexafluorophosphate salt with a mixture of [Et3NH

Effects of Cue Reliability on Target Detection and Visual Scanning

DTIC Science & Technology

2010-12-01

instruction on how to rate his workload experience using the NASA-TLX. The participant then completed one 3-min practice ride in each of the four...participant practiced completing the NASA-TLX to rate his workload experience. 3.4.2 Test Procedures After a 5-min rest break, the test period...RDRL HRM A J MARTIN MYER CENTER BLDG 2700 RM 2D311 FORT MONMOUTH NJ 07703-5601 1 ARMY RSCH LABORATORY – HRED RDRL HRM C A DAVISON

Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach

PubMed Central

Hillhouse, Joel; Turrisi, Rob; Cleveland, Michael J.; Scaglione, Nichole M.; Baker, Katie; Florence, L. Carter

2015-01-01

Background Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. Purpose This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. Methods Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. Results Three subgroups were identified: a low-risk, Anti-Tanning subgroup (18.6%) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate-risk Aware Social Tanner subgroup (47.2%) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high-risk Risky Relaxation Tanner subgroup (34.2%) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the Aware Social Tanner and Risky Relaxation Tanner subgroups were significantly more likely to initiate indoor tanning in the following year. Conclusions These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful. PMID:26370893

Measurement of pubertal status with a Chinese self-report Pubertal Development Scale.

PubMed

Chan, Noel P T; Sung, Rita Y T; Nelson, E Anthony S; So, Hung K; Tse, Yee K; Kong, Alice P S

2010-05-01

This cross sectional study of 290 Chinese children aged 8-18 years, evaluated a Chinese version of the self-reported Pubertal Development Scale (PDS) against both raters' and self-reported Tanner assessment of pubertal status. Children completed both the self-reported PDS and self-reported Tanner pubertal questionnaire prior to physical examination through visual depiction by a same gender rater. Puberty Category Scores (PCS) which were derived from the PDS, was used to categorize children into one of five pubertal development stages. Tanner derived composite stage (TDCS) which was derived from the Tanner pubertal questionnaires, was used to compare with PCS to obtain the inter-rater agreement. Moderately high agreements were found between raters' TDCS and PCS in girls [weighted kappa (WK) 0.57 (0.44, 0.71); Kendalltau-b 0.60 (0.51, 0.69)] and in boys [WK 0.58 (0.47, 0.69), Kendalltau-b 0.50 (0.38, 0.62)]. The correlation between self-reported PDS and rater's assessment was substantial in girls [Kendalltau-b 0.61 (0.54, 0.69)] and moderate in boys [Kendalltau-b 0.49 (0.38, 0.61)]. The Hong Kong Chinese children and adolescents were able to reliably estimate their own sexual maturation status (SMS) using a Chinese version PDS. This instrument may be useful in epidemiological studies when cost, privacy and other concerns preclude the use of other SMS assessment tools.

Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach.

PubMed

Hillhouse, Joel; Turrisi, Rob; Cleveland, Michael J; Scaglione, Nichole M; Baker, Katie; Florence, L Carter

2016-02-01

Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. Three subgroups were identified: a low risk, anti-tanning subgroup (18.6 %) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate risk aware social tanner subgroup (47.2 %) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high risk risky relaxation tanner subgroup (34.2 %) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the aware social tanner and risky relaxation tanner subgroups were significantly more likely to initiate indoor tanning in the following year. These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful.

78 FR 68375 - Removal of Procedures for Closeout of Grants and Cooperative Agreements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

..., Contract Management Division, Washington, DC 20546. Comments may also be submitted by email to: leigh... Procurement, Contract Management Division (Room 2P77); Telephone: (202) 358-0592; Email: [email protected] encouraged to perform retrospective analysis, reviewing existing regulation for outmoded, ineffective...

Persistent hyperlactacidaemia: about a clinical case.

PubMed

Oliveira, Ana Rita Saraiva; Valente, Rosalina; Ramos, José; Ventura, Lurdes

2013-05-22

Lactate is the endogenous end product of the anaerobic glycolysis, whose production is favoured in situations of hypoperfusion or mitochondrial dysfunction. Leigh syndrome is a rare, progressive encephalomyopathy that represents a spectrum of mitochondrial genetic diseases phenotypically distinct, but with neuroradiological and pathological uniform presentation. We present the case of a 7-month-old infant, with a history of prematurity, psychomotor retardation and epilepsy, admitted to the paediatric intensive care unit (PICU) due to cardio-respiratory arrest because of respiratory infection. Hyperlactacidaemia was detected and was persistent. The study of redox potential was normal but MRI with spectroscopy identified bilateral and symmetrical lesions involving thalamic and basal ganglia, with small lactate peaks at T2 flair, findings that were suggestive of Leigh syndrome. Subsequent enzymatic study identified lack of pyruvate dehydrogenase. Persistent hyperlactacidaemia, in the appropriate clinical context, should lead to the screening of mitochondrial diseases.

STS-97 (4A) EVA training in NBL pool

NASA Image and Video Library

2000-10-23

JSC2000-07082 (October 2000)--- Wearing a training version of the shuttle extravehicular mobility unit (EMU) space suit, astronaut Joseph R. Tanner, STS-97 mission specialist, simulates a space walk underwater in the giant Neutral Buoyancy Laboratory (NBL). Tanner was there, along with astronaut Carlos I. Noriega, to rehearse one of three scheduled space walks to make additions to the International Space Station (ISS). The five-man crew in early December will deliver the P6 Integrated Truss Segment, which includes the first US Solar arrays and a power distribution system.

EVA 4 activity on Flight Day 7 to service the Hubble Space Telescope

NASA Image and Video Library

1997-02-17

S82-E-5606 (17 Feb. 1997) --- Astronaut Gregory J. Harbaugh at work on Hubble Space Telescope (HST), with the assistance of astronaut Joseph R. Tanner (out of frame) on Remote Manipulator System (RMS). After replacing the HST's Solar Array Drive Electronics (SADE), Harbaugh and Tanner replaced the Magnetic Sensing System (MSS) protective lids with new, permanent covers; and they installed pre-cut insulation pieces to correct tears in the HST's protective covering caused by temperature changes in space. This view was taken with an Electronic Still Camera (ESC).

Commuter Air Carrier Symposium (2nd) January 15-16, 1981 .

DTIC Science & Technology

1981-01-16

AJAN B1 UNCLASSIFIED FAA-ASF-300-81-b NL J , E EEEIEEEI mIhIhhEIhEEEI EEIhIhEIhEEIhE IIIIIIIIIIIIIu IIIEII~lElI Second ot Denrpotmn A Fodeol~(ntiorpom...Kathryn B. Creedy AVMARK, Inc. Commuter Air 1120 19th St., N.W. 4827 Rugby Ave. Washington, D.C. 20002 Bethesda, MD 20008 J. Keith Carter Albert J...Commuter Air Piper Aircraft Corp. 4823 Rugby Rd. 3000 Medulla Rd. Bethesda, MD 20014 Lakeland, Florida 33803 -Calvin Davison ’ Crowell & Moring 1100

76 FR 72327 - NASA Federal Acquisition Regulation Supplement; Responsibility, Suspension and Debarment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

.... chapter 35). List of Subjects in 48 CFR Part 1809 Government procurement. Sheryl Goddard, Director... Space Administration (NASA). ACTION: Final rule. SUMMARY: NASA has adopted as final, without change, a... INFORMATION CONTACT: Leigh Pomponio, Procurement Analyst, at (202) 358-0592 or [email protected

76 FR 41487 - Macy's, Inc., Provisional Acceptance of a Settlement Agreement and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

...; telephone (301) 504-7612. SUPPLEMENTARY INFORMATION: The text of the Agreement and Order appears below. July... products with drawstrings at the neck: Quiksilver, Inc.--Hide & Seek hooded sweatshirts; Jerry Leigh of... Children's Upper Outerwear (``Guidelines'') to help prevent children from strangling or entangling on neck...

A review on management of chrome-tanned leather shavings: a holistic paradigm to combat the environmental issues.

PubMed

Pati, Anupama; Chaudhary, Rubina; Subramani, Saravanabhavan

2014-10-01

Raw hide/skins come to the tanners as a by-product of meat industry which is converted into value-added leather as product for fashion market. Leather manufacturing is a chemical process of natural biological matrix. It employs a huge quantity of water and inorganic and organic chemicals for processing and thereby discharges solid and liquid wastes into the environment. One of the potential solid wastes generated from leather industry is chrome-tanned leather shavings (CTLSs), and its disposal is increasingly becoming a huge challenge on disposal to tanners due to presence of heavy metal chromium. Hence, finding a sustainable solution to the CTLS disposal problem is a prime challenge for global tanners and researchers. This paper aims to the deeper review of various disposal methods on CTLS such as protein, chromium, and energy recovery processes and its utilization methodologies. Sustainable technologies have been developed to overcome CTLS solid wastes emanating from leather processing operations. Further, this review paper brings a broader classification of developed methodologies for treatment of CTLSs.

Review of interventions to reduce ultraviolet tanning: Need for treatments targeting excessive tanning, an emerging addictive behavior.

PubMed

Stapleton, Jerod L; Hillhouse, Joel; Levonyan-Radloff, Kristine; Manne, Sharon L

2017-12-01

Millions of Americans engage in tanning each year, defined as intentional ultraviolet radiation (UVR) exposure in the form of sunbathing or the use of indoor tanning beds. An emerging body of research suggests that UVR has addictive properties and some tanners engage in excessive tanning. This article provides an overview of the evidence of tanning addiction and a systematic review of existing tanning interventions with the goal of evaluating their potential to impact addicted tanners. Our search identified 24 intervention studies that were summarized and discussed according to 3 primary themes. First, there is a dearth of tanning interventions that target excessive tanning or are designed as treatments for tanning addiction. Second, tanning interventions are primarily educational interventions designed to increase knowledge of the risks of tanning. Third, there are notable aspects of existing tanning interventions that are relevant to addiction science, including the use of brief motivational and cognitive-behavioral-based interventions. Future directions are considered including recommendations for utilizing the existing evidence base to formulate interventions targeting excessive tanners. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Staff Views of the Importance of Relationships for Knowledge Development: Is Training by Specialists a Waste of Money?

ERIC Educational Resources Information Center

Bradshaw, Jill; Goldbart, Juliet

2013-01-01

Background: The provision of skilled support is dependent on staff knowledge and understanding (Beadle-Brown J., Beecham J., Mansell J., Baumker T., Leigh J., Whelton R. & Richardson L, unpublished data). Influencing staff knowledge and understanding is an important component of interventions. Materials and Methods: Fourteen individual…

Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

PubMed

Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

2015-11-01

Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.

PubMed

DeWire, Mariko; Green, Daniel M; Sklar, Charles A; Merchant, Thomas E; Wallace, Dana; Lin, Tong; Vern-Gross, Tamara; Kun, Larry E; Krasin, Matthew J; Boyett, James M; Wright, Karen D; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar

2015-02-01

Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy. Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention. Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%. Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Associations between neuromuscular function and levels of physical activity differ for boys and girls during puberty.

PubMed

Rudroff, Thorsten; Kelsey, Megan M; Melanson, Edward L; McQueen, Matthew B; Enoka, Roger M

2013-08-01

To compare the associations between neuromuscular performance and anthropometric characteristics with habitual levels of physical activity in boys and girls during the initial stages of puberty. In a cross-sectional study of 72 healthy children (39 boys and 33 girls) ranging in age from 8 to 14 years, sex differences in anthropometric and motor performance characteristics were compared at 3 Tanner stages (T1-T3). Outcome variables included dual-energy x-ray absorptiometry measurements of body composition, assessments of neuromuscular function, and levels of physical activity (steps/day) measured by accelerometry. Physical activity was lower in girls than boys at T2 and T3, but there was no sex difference at T1. Physical activity increased with Tanner stage for boys but did not differ between Tanner stages in girls. Physical activity at each Tanner stage was strongly associated (R(2) > 0.85) with neuromuscular characteristics for both boys and girls, but percentage of body fat also was associated with physical activity for T3 girls. The attenuated gains in neuromuscular function experienced by girls in early stages of puberty were strongly associated with lower levels of physical activity, whereas the increase in physical activity exhibited by boys was mostly related to increases in the strength and endurance of leg muscles. Because sedentary activity is a known contributor to the development of obesity and type 2 diabetes in youth, this study helps to identify possible contributors to decreases in physical activity in young girls and provides potential targets for early intervention. Copyright © 2013 Mosby, Inc. All rights reserved.

Contrast discrimination: Second responses reveal the relationship between the mean and variance of visual signals

PubMed Central

Solomon, Joshua A.

2007-01-01

To explain the relationship between first- and second-response accuracies in a detection experiment, Swets, Tanner, and Birdsall [Swets, J., Tanner, W. P., Jr., & Birdsall, T. G. (1961). Decision processes in perception. Psychological Review, 68, 301–340] proposed that the variance of visual signals increased with their means. However, both a low threshold and intrinsic uncertainty produce similar relationships. I measured the relationship between first- and second-response accuracies for suprathreshold contrast discrimination, which is thought to be unaffected by sensory thresholds and intrinsic uncertainty. The results are consistent with a slowly increasing variance. PMID:17961625

Operation Watchtower: The Battle for Guadalcanal -- A Foundation for Future USAF Expeditionary Aerospace Force (EAF) Logistics Transformation

DTIC Science & Technology

2000-01-01

1 Colonel Dave Gillett , “Operation Allied Force After-Action,” lecture presented at...Force Commander, Rear Admiral Leigh Noyes, Carrier Forces Commander, and Rear Admiral John McCain, Shore-Based Aircraft Commander. The sole Marine...17 John Miller Jr. Guadalcanal: The First Offensive (Washington D.C.: Center of

Identity Development and Mentoring in Doctoral Education

ERIC Educational Resources Information Center

Hall, Leigh A.; Burns, Leslie D.

2009-01-01

In this essay, Leigh Hall and Leslie Burns use theories of identity to understand mentoring relationships between faculty members and doctoral students who are being prepared as educational researchers. They suggest that becoming a professional researcher requires students to negotiate new identities and reconceptualize themselves both as people…

Writing across the Curriculum.

ERIC Educational Resources Information Center

Smith, Barbara Leigh, Ed.

1983-01-01

The writing across the curriculum movement is discussed in six articles. Barbara Leigh Smith's introductory article, "Writing Across the Curriculum: What's at Stake?" reviews the rationale for this movement, including the declining emphasis on writing in high schools and colleges. In the "Winds of Change: Thomas Kuhn and the…

Local Workforce Development Boards: Alignment with Operational Indicators and Behavioral Characteristics

ERIC Educational Resources Information Center

Johnson, Sharon Humphreys

2017-01-01

The ability of a region to remain competitively viable is dependent upon attracting new business and retaining existing businesses (Good & Strong, 2015). In many instances, regional growth depends on the workforce and the region's ability to develop a talent pipeline of existing or accessible workers (Blakely & Leigh, 2010). The passage of…

The Impact of Maternal Deafness on Cradling Laterality with Deaf and Hearing Infants

ERIC Educational Resources Information Center

Sieratzki, Jechil S.; Woll, Bencie

2004-01-01

A recent article in the "Journal of Deaf Studies and Deaf Education" (Leigh, Brice, & Meadow-Orlans, 2004) explored attachment between deaf mothers and their 18-month-old children and reported relationship patterns similar to those for hearing dyads. The study reported here explores a marker of early mother-child relationships: cradling…

Development and validation of the Comprehensive Indoor Tanning Expectations Scale.

PubMed

Noar, Seth M; Myrick, Jessica Gall; Morales-Pico, Brenda; Thomas, Nancy E

2014-05-01

Strong links between indoor tanning behavior and skin cancer have been demonstrated across several studies. Understanding the complex belief systems that underlie indoor tanning in young women is a crucial first step in developing interventions to deter this behavior. To develop and validate a comprehensive, multidimensional, theory-based outcome expectations measure to advance an understanding of the sets of beliefs that underlie indoor tanning behavior among young women. Cross-sectional study comprising a web-based survey of 11 sororities at a large university in the southeastern United States. Study participants (n = 706) were aged 18 to 25 years; 45.3% had tanned indoors in their lifetime and 30.3% in the past year. Intention to tan indoors, frequency of indoor tanning behavior in the past year, and indoor tanner type (nontanner, former tanner, or current tanner). A comprehensive scale assessing indoor tanning outcome expectations was developed. In total, 6 positive outcome expectations factors and 5 negative outcome expectations factors were identified. These subscales were reliable (coefficient α range, 0.86-0.95) and were significantly (mostly at P < .001) correlated with a set of established measures, including appearance motivation, indoor tanning attitudes and norms, and intention to tan indoors. Examination of subscales across the 3 indoor tanning groups also revealed significant (P < .001) differences on all 11 subscales. Current tanners had the most positive and least negative perceptions about indoor tanning, while nontanners had the most negative and least positive perceptions. Former tanners tended to fall in between these 2 groups. The 2 subscales with the largest differences across the groups were mood enhancement (positive outcome expectation) and psychological/physical discomfort (negative outcome expectation). Multiple linear regression analyses demonstrated several outcome expectations subscales to be significantly associated with

Evaluation of Microbial Load in Oropharyngeal Mucosa from Tannery Workers

PubMed Central

Castellanos-Arévalo, Diana C.; Castellanos-Arévalo, Andrea P.; Camarena-Pozos, David A.; Colli-Mull, Juan G.; Maldonado-Vega, María

2014-01-01

Background Animal skin provides an ideal medium for the propagation of microorganisms and it is used like raw material in the tannery and footware industry. The aim of this study was to evaluate and identify the microbial load in oropharyngeal mucosa of tannery employees. Methods The health risk was estimated based on the identification of microorganisms found in the oropharyngeal mucosa samples. The study was conducted in a tanners group and a control group. Samples were taken from oropharyngeal mucosa and inoculated on plates with selective medium. In the samples, bacteria were identified by 16S ribosomal DNA analysis and the yeasts through a presumptive method. In addition, the sensitivity of these microorganisms to antibiotics/antifungals was evaluated. Results The identified bacteria belonged to the families Enterobacteriaceae, Pseudomonadaceae, Neisseriaceae, Alcaligenaceae, Moraxellaceae, and Xanthomonadaceae, of which some species are considered as pathogenic or opportunistic microorganisms; these bacteria were not present in the control group. Forty-two percent of bacteria identified in the tanners group are correlated with respiratory diseases. Yeasts were also identified, including the following species: Candida glabrata, Candida tropicalis, Candida albicans, and Candida krusei. Regarding the sensitivity test of bacteria identified in the tanners group, 90% showed sensitivity to piperacillin/tazobactam, 87% showed sensitivity to ticarcillin/clavulanic acid, 74% showed sensitivity to ampicillin/sulbactam, and 58% showed sensitivity to amoxicillin/clavulanic acid. Conclusion Several of the bacteria and yeast identified in the oropharyngeal mucosa of tanners have been correlated with infections in humans and have already been reported as airborne microorganisms in this working environment, representing a health risk for workers. PMID:25830072

STS-97 Crew Activity Report/Flight Day 11 Highlights

NASA Technical Reports Server (NTRS)

2000-01-01

On this eleventh day of the STS-97 mission, Commander Brent W. Jett, Pilot Michael J. Bloomfield, and Mission Specialists Joseph R. Tanner, Carlos I. Noriega, and Marc Garneau remain docked with the International Space Station (ISS) on board the Endeavour Orbiter. Jett and Bloomfield are seen performing a check of the shuttle flight controls in preparation for tomorrow's landing. Jett, Noriega, and Tanner answer questions about the mission and the goals fulfilled. Footage shows the Earth at night as the camera on Endeavour sweeps the Mediterranean coastline, outlined by city lights, showing Spanish/French border, the French Riviera, the Alps, Italy, Switzerland, and the German/Austrian border.

STS-97 ascent team in WFCR

NASA Image and Video Library

2000-11-20

JSC2000-07294 (20 November 2000) --- The 40-odd flight controllers assigned to the STS-97 ascent team and some special guests pose for a group portrait in the shuttle flight control room in Houston's Mission Control Center (JSC). The five guests attired in the blue and white shirts are the flight crew members for the STS-97 crew, scheduled to be launched from Florida on the last day of this month. The astronauts are, from the left, Joseph R. Tanner, Carlos I. Noriega, Brent W. Jett, Jr., Michael J. Bloomfield and Marc Garneau, who represents the Canadian Space Agency (CSA). Ascent shift flight director Wayne Hale stands next to Tanner.

Exploring Gender Norms through the "Colour Blind" Initiative

ERIC Educational Resources Information Center

Niblett, Blair; Potvin, Leigh

2010-01-01

Recently, the authors have been collecting data for a research project that explores secondary school boys' perceptions of masculinity. They spent a week in Leigh's grade 11 philosophy class discussing gender while observing and video recording students' perception for analysis. In their research, they used Colour Blind as a vehicle for unearthing…

Interrelationships Between Landscape Art and Geography in Latin America: First Response to a Challenge.

ERIC Educational Resources Information Center

Martinson, Tom L.

Interrelationships between geography and art are explored and ways of integrating an appreciation of landscape art in Latin America into geography instruction are suggested. That geographers have long recognized the usefulness of landscape painting in the study of places is exemplified by the remark by geographer John Leighly in 1937 that "art…

Transformative Learning: Patterns of Psychophysiologic Response and Technology-Enabled Learning and Intervention Systems

DTIC Science & Technology

2008-09-01

Psychophysiologic Response and Technology -Enabled Learning and Intervention Systems PRINCIPAL INVESTIGATOR: Leigh W. Jerome, Ph.D...NUMBER Transformative Learning : Patterns of Psychophysiologic Response and Technology - Enabled Learning and Intervention Systems 5b. GRANT NUMBER...project entitled “Transformative Learning : Patterns of Psychophysiologic Response in Technology Enabled Learning and Intervention Systems.” The

Bennington College: in the Beginning.

ERIC Educational Resources Information Center

Brockway, Thomas P.

The early history of Bennington College, Vermont, beginning with initial endeavors by Vincent Ravi Booth in 1923, is examined. Topics include: granting of a satisfactory charter to the college; the role of educators such as Amy Kelly and William Heard Kilpatrick in initial curriculum recommendations; electing Robert Devore Leigh as president;…

Adult Education and Social Sustainability: Harnessing the "Red Queen Effect"

ERIC Educational Resources Information Center

Easton, Peter

2007-01-01

In 1973, the evolutionary biologist Leigh Van Valen of the University of Chicago devised what he called the "Red Queen Effect" to describe the growth and development of species. It stipulated that an evolutionary system must continue to develop just to maintain its fitness relative to others evolving in its environment. The literary reference is…

Gender, the City and the Politics of Schooling: Towards a Collective Biography of Women "Doing Good" as Public Moralists in Victorian London

ERIC Educational Resources Information Center

Martin, Jane

2005-01-01

This article tells the stories of four middle class, white, English women whose participation in educational policy making is little known: Annie Leigh Browne (1851-1936), Margaret MacDonald (1870-1911), Hilda Miall-Smith (born 1861) and Honnor Morten (1861-1913). In doing so, it provides a perspective on the circumstances that enabled or…

Transient neonatal renal failure and massive polyuria in MEGDEL syndrome.

PubMed

Harbulot, Carole; Paquay, Stéphanie; Dorboz, Imen; Pichard, Samia; Bourillon, Agnès; Benoist, Jean-François; Jardel, Claude; Ogier de Baulny, Hélène; Boespflug-Tanguy, Odile; Schiff, Manuel

2016-06-01

MEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome) syndrome is a mitochondrial disorder associated with recessive mutations in SERAC1. To report transient neonatal renal findings in MEGDEL syndrome. This 7 year-old girl was the first child of consanguineous Turkish parents. She exhibited an acute neonatal deterioration with severe lactic acidosis and liver failure. Initial evaluation revealed massive polyuria and renal failure with 3-methylglutaconic aciduria. Symptoms and biological findings progressively improved with symptomatic treatment but lactic acidosis and high lactate to pyruvate ratio along with 3-methylglutaconic aciduria persisted. At 8 months of age, a subacute neurological degradation occurred with severe hypotonia, dystonia with extrapyramidal movements and failure to thrive. Brain MRI revealed basal ganglia lesions suggestive of Leigh syndrome. At 3 years of age, sensorineural deafness was documented. MEGDEL syndrome was further confirmed by the identification of an already reported homozygous mutation in SERAC1. Transient neonatal polyuria and renal failure have not been reported to date in SERAC1 defective patients. Such neonatal kidney findings expand the clinical spectrum of MEGDEL syndrome.

Multivariable PID controller design tuning using bat algorithm for activated sludge process

NASA Astrophysics Data System (ADS)

Atikah Nor’Azlan, Nur; Asmiza Selamat, Nur; Mat Yahya, Nafrizuan

2018-04-01

The designing of a multivariable PID control for multi input multi output is being concerned with this project by applying four multivariable PID control tuning which is Davison, Penttinen-Koivo, Maciejowski and Proposed Combined method. The determination of this study is to investigate the performance of selected optimization technique to tune the parameter of MPID controller. The selected optimization technique is Bat Algorithm (BA). All the MPID-BA tuning result will be compared and analyzed. Later, the best MPID-BA will be chosen in order to determine which techniques are better based on the system performances in terms of transient response.

Self-Tanners, Tanning Pills, Tanning Booths, and Pregnancy

MedlinePlus

... 3 fatty acid found in some foods and dietary supplements.) DHA often comes from plant sources such as sugar beets and sugar cane, and is considered a non-harmful skin- coloring agent. The Food and Drug Administration ( ...

Make an Alarm! Grades 3-5.

ERIC Educational Resources Information Center

Rushton, Erik; Ryan, Emily; Swift, Charles

After reading the story "Dear Mr. Henshaw" by Beverly Cleary, students build an alarm system for something in the classroom as the main character, Leigh, does to protect his lunchbox from thieves. Students learn about alarms and use their creativity to create an alarm system to protect their lockers, desk, or classroom door. This activity uses a…

Operations Events Census Report: Volume IV. 1981 through 1985. Sanitized Version.

DTIC Science & Technology

1991-04-01

TAYLOR , ALLEN D. 0962 TAYLOR ...CLIFFORD 0640 TAYLOR , JIMMIE L. 0935 TAYLOR , JOHN W. 0935 TAYLOR , MAX W. V TAYLOR , MICHAEL L. 0935 TAYLOR , PETER J. 0935 TAYLOR , REEDE L., JR. 0874 TAYLOR ...RODNEY M. 0916 TALPIS, NATHAN ALEX 0688 TANGE, LEIGH H. 0930 TASCA, DANTE M. 0637 TATE, JAMES B., JR. 0890 TAYLOR , ALLEN D. 0962 TAYLOR , CHARLES

Parenting a Precocious Preschooler: Breaking the Silence

ERIC Educational Resources Information Center

Fish, Leigh Ann

2016-01-01

Precocity in the very young should be a valid topic of discussion in parental and educational circles, yet too frequently those conversations are slow to occur or are absent altogether. Many parents and educators remain silent about raising and nurturing precocious preschoolers, and author Leigh Ann Fish believe that the silence is due to a lack…

STS-97 crew arrives at KSC for launch

NASA Technical Reports Server (NTRS)

2000-01-01

At the Shuttle Landing Facility, STS-97 Mission Specialist Joseph Tanner (left) is greeted by Center Director Roy Bridges on his arrival at KSC from Johnson Space Center. Tanner and the rest of the crew have returned to KSC for the launch, scheduled for Nov. 30 at about 10:06 p.m. EST. Mission STS-97is the sixth construction flight to the International Space Station. Its payload includes the P6 Integrated Truss Structure and a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission includes two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST.

KSC-00pp1756

NASA Image and Video Library

2000-11-27

At the Shuttle Landing Facility, STS-97 Mission Specialist Joseph Tanner (left) is greeted by Center Director Roy Bridges on his arrival at KSC from Johnson Space Center. Tanner and the rest of the crew have returned to KSC for the launch, scheduled for Nov. 30 at about 10:06 p.m. EST. Mission STS-97is the sixth construction flight to the International Space Station. Its payload includes the P6 Integrated Truss Structure and a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission includes two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST

KSC00pp1756

NASA Image and Video Library

2000-11-27

At the Shuttle Landing Facility, STS-97 Mission Specialist Joseph Tanner (left) is greeted by Center Director Roy Bridges on his arrival at KSC from Johnson Space Center. Tanner and the rest of the crew have returned to KSC for the launch, scheduled for Nov. 30 at about 10:06 p.m. EST. Mission STS-97is the sixth construction flight to the International Space Station. Its payload includes the P6 Integrated Truss Structure and a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission includes two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST

KSC-00pp1663

NASA Image and Video Library

2000-11-07

In the Space Station Processing Facility, workers applaud the turnover of the P6 Integrated Truss Structure by International Space Station ground operations to the NASA shuttle integration team in a special ceremony. Standing in front are STS-97 Mission Specialists Joe Tanner and Carlos Noriega plus Pilot Mike Broomfield. Behind and left of Tanner is Mission Specialist Marc Garneau. Mission STS-97is the sixth construction flight to the International Space Station. Its payload includes a photovoltaic (PV) module, with giant solar arrays that will provide power to the Station. The mission involves two spacewalks to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at 10:05 p.m. EST

Astronaut Scott Parazynski during egress training

NASA Image and Video Library

1994-06-23

S94-40083 (23 June 1994) --- Astronaut Scott E. Parazynski looks at fellow STS-66 mission specialist Joseph R. Tanner, (foreground) during a rehearsal of procedures to be followed during launch and entry phases of the their scheduled November flight. This rehearsal, held in the Crew Compartment Trainer (CCT) of the Johnson Space Center's (JSC) Shuttle Mockup and Integration Laboratory, was followed by a training session on emergency egress procedures. In November, Parazynski and Tanner will join three other NASA astronauts and a European mission specialist for a week and a half aboard the Space Shuttle Atlantis in Earth-orbit in support of the Atmospheric Laboratory for Applications and Science (ATLAS-3).

Astronaut Scott Parazynski during egress training

NASA Image and Video Library

1994-06-23

S94-40079 (23 June 1994) --- Astronaut Scott E. Parazynski looks at fellow STS-66 mission specialist Joseph R. Tanner, (partially visible in foreground) during a rehearsal of procedures to be followed during launch and entry phases of the their scheduled November flight. This rehearsal, held in the Crew Compartment Trainer (CCT) of the Johnson Space Center's (JSC) Shuttle Mockup and Integration Laboratory, was followed by a training session on emergency egress procedures. In November, Parazynski and Tanner will join three other NASA astronauts and a European mission specialist for a week and a half aboard the Space Shuttle Atlantis in Earth-orbit in support of the Atmospheric Laboratory for Applications and Science (ATLAS-3).

Prepubertal Serum Concentrations of Organochlorine Pesticides and Age at Sexual Maturity in Russian Boys.

PubMed

Lam, Thuy; Williams, Paige L; Lee, Mary M; Korrick, Susan A; Birnbaum, Linda S; Burns, Jane S; Sergeyev, Oleg; Revich, Boris; Altshul, Larisa M; Patterson, Donald G; Hauser, Russ

2015-11-01

Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys. From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: -1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: -3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: -1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of βHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6-9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), βHCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. Higher prepubertal serum HCB and βHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation. Lam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O, Revich B, Altshul LM, Patterson DG Jr, Hauser R. 2015. Prepubertal serum

Emergent supersymmetry in the marginal deformations of $$\\mathcal{N}=4$$ SYM

DOE PAGES

Jin, Qingjun

2016-10-24

Here, we study the one loop renormalization group flow of the marginal deformations ofmore » $$\\mathcal{N}=4$$ SYM theory using the a-function. We found that in the planar limit some non-supersymmetric deformations flow to the supersymmetric infrared fixed points described by the Leigh-Strassler theory. This means supersymmetry emerges as a result of renormalization group flow.« less

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (second from left, foreground) works with technicians to learn more about the Japanese Experiment Module (JEM), known as Kibo. The JEM consists of six components: two research facilities - the Pressurized Module and the Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. Equipment familiarization is a routine part of astronaut training and launch preparations.

NASA Image and Video Library

2003-10-22

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (second from left, foreground) works with technicians to learn more about the Japanese Experiment Module (JEM), known as Kibo. The JEM consists of six components: two research facilities - the Pressurized Module and the Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. Equipment familiarization is a routine part of astronaut training and launch preparations.

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (center, foreground) works with technicians to learn more about the Japanese Experiment Module (JEM), known as Kibo. The JEM consists of six components: two research facilities - the Pressurized Module and the Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. Equipment familiarization is a routine part of astronaut training and launch preparations.

NASA Image and Video Library

2003-10-22

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, STS-115 Mission Specialist Joseph Tanner (center, foreground) works with technicians to learn more about the Japanese Experiment Module (JEM), known as Kibo. The JEM consists of six components: two research facilities - the Pressurized Module and the Exposed Facility; a Logistics Module attached to each of them; a Remote Manipulator System; and an Inter-Orbit Communication System unit. Kibo also has a scientific airlock through which experiments are transferred and exposed to the external environment of space. The various components of JEM will be assembled in space over the course of three Space Shuttle missions. Equipment familiarization is a routine part of astronaut training and launch preparations.

36 CFR 13.1136 - How can an individual apply for a commercial fishing lifetime access permit?

Code of Federal Regulations, 2011 CFR

2011-07-01

... statistical areas 114-70 through 114-77. For salmon, the Superintendent may need additional documentation that supports the applicant's declaration of Glacier Bay salmon landings. For halibut and Tanner crab, the...

Recruitment variation of eastern Bering Sea crabs: Climate-forcing or top-down effects?

NASA Astrophysics Data System (ADS)

Zheng, Jie; Kruse, Gordon H.

2006-02-01

During the last three decades, population abundances of eastern Bering Sea (EBS) crab stocks fluctuated greatly, driven by highly variable recruitment. In recent years, abundances of these stocks have been very low compared to historical levels. This study aims to understand recruitment variation of six stocks of red king ( Paralithodes camtschaticus), blue king ( P. platypus), Tanner ( Chionoecetes bairdi), and snow ( C. opilio) crabs in the EBS. Most crab recruitment time series are not significantly correlated with each other. Spatial distributions of three broadly distributed crab stocks (EBS snow and Tanner crabs and Bristol Bay red king crab) have changed considerably over time, possibly related in part to the regime shift in climate and physical oceanography in 1976-1977. Three climate-forcing hypotheses on larval survival have been proposed to explain crab recruitment variation of Bristol Bay red king crab and EBS Tanner and snow crabs. Some empirical evidence supports speculation that groundfish predation may play an important role in crab recruitment success in the EBS. However, spatial dynamics in the geographic distributions of groundfish and crabs over time make it difficult to relate crab recruitment strength to groundfish biomass. Comprehensive field and spatially explicit modeling studies are needed to test the hypotheses and better understand the relative importance and compound effects of bottom-up and top-down controls on crab recruitment.

A Pilot Study of the Normative Range of Overnight Urinary Free Cortisol Corrected for Creatinine in Children.

PubMed

Wolthers, Ole D; Mersmann, Sabine; Dissanayake, Sanjeeva

2018-04-01

For more than a decade, urinary free cortisol corrected for creatinine (OUFCC) has been used to assess the systemic bioactivity of inhaled corticosteroids in children with asthma. Paediatric normative ranges, however, have not been established. The aim of the present study was to define a preliminary range for OUFCC in Tanner stage 1 children. A post hoc analysis was performed of 26 Tanner stage one children (aged 5-11 years) with mild asthma only requiring prn (pro re nata) treatment with short-acting β 2 -agonists, who participated in a 3-way cross-over knemometry study. The study comprised a run-in, two washout periods and three treatment periods (2 weeks each). Urine was collected at the end of each period. A normative range was derived using the 95% prediction interval for the geometric mean OUFCC, calculated from run-in and washout periods. Twenty-six children contributed 41 OUFCC values. The geometric mean OUFCC was 9.0 nmol/mmol (95% PI: 3.6, 22.7 nmol/mmol). The OUFCC preliminary normative range was 3.6 to 22.7 nmol/mmol in Tanner stage one children. A larger study in healthy children is warranted to confirm these findings and to assess potential differences in OUFCC across developmental stages and age groups, and by gender and race. 2013-004719-32, CLINICALTRIALS. NCT02063139.

Mood Changes After Indoor Tanning Among College Women: Associations with Psychiatric/Addictive Symptoms

PubMed Central

Heckman, Carolyn; Darlow, Susan; Cohen-Filipic, Jessye; Kloss, Jacqueline

2016-01-01

Indoor tanning (IT) has been linked with psychiatric and addictive symptoms, and frequent tanning may indicate tanning dependence (addiction). The current study evaluated the effects of an IT episode on mood states and the association of these effects with psychiatric and addictive symptoms among young adult female indoor tanners. One-hundred thirty-nine female university students aged 18-25 years who had indoor tanned completed an online survey including the Positive and Negative Affects Scales and a standardized psychiatric interview (the MINI International Neuropsychiatric Interview) via telephone. Psychiatric and addictive symptoms were relatively common among these young adult female indoor tanners. Overall, participants reported significant decreases in both negative (upset, scared, irritable, nervous, jittery, afraid) and positive (feeling interested) mood states after their most recent tanning episode. Multivariable linear regression analyses showed that more frequent indoor tanning in the past month and symptoms of illicit drug use disorders were associated with decreases in negative mood, and symptoms of generalized anxiety disorder were associated with a decrease in feeling interested. In summary, indoor tanners report relatively high rates of psychiatric and substance use symptoms, including symptoms of tanning dependence, and indoor tanning appears to alter mood. Women with certain substance use and psychiatric characteristics may be more vulnerable to such mood changes after tanning indoors. Further research is needed to clarify the relationships among these variables. PMID:27403462

Tanning accelerators: prevalence, predictors of use, and adverse effects.

PubMed

Herrmann, Jennifer L; Cunningham, Rachel; Cantor, Alan; Elewski, Boni E; Elmets, Craig A

2015-01-01

Tanning accelerators are topical products used by indoor tanners to augment and hasten the tanning process. These products contain tyrosine, psoralens, and/or other chemicals. We sought to better define the population using accelerators, identify predictors of their use, and describe any related adverse effects. This cross-sectional study surveyed 200 indoor tanners about their tanning practices and accelerator use. Primary analysis compared accelerator users with nonusers with respect to questionnaire variables. Descriptive statistics and χ(2) contingency tables were applied to identify statistically significant variables. Of respondents, 53% used accelerators; 97% were female and 3% were male with a median age of 22 years (range: 19-67). Users were more likely to spray tan, tan frequently, and be addicted to tanning. Acne and rashes were more common in accelerator users. Adverse reactions to accelerators prevented their further use 31% of the time. A limited adult population was evaluated; exact accelerator ingredients were not examined. Tanning accelerator users are high-risk indoor tanners who tan more frequently and who are more likely addicted to tanning. Acne and rashes are more common with these products and act as only mild deterrents to continued use. Additional research should investigate accelerators' longer-term health effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Mood Changes After Indoor Tanning Among College Women: Associations with Psychiatric/Addictive Symptoms.

PubMed

Heckman, Carolyn; Darlow, Susan; Cohen-Filipic, Jessye; Kloss, Jacqueline

2016-06-23

Indoor tanning (IT) has been linked with psychiatric and addictive symptoms, and frequent tanning may indicate tanning dependence (addiction). The current study evaluated the effects of an IT episode on mood states and the association of these effects with psychiatric and addictive symptoms among young adult female indoor tanners. One-hundred thirty-nine female university students aged 18-25 years who had indoor tanned completed an online survey including the Positive and Negative Affects Scales and a standardized psychiatric interview (the MINI International Neuropsychiatric Interview) via telephone. Psychiatric and addictive symptoms were relatively common among these young adult female indoor tanners. Overall, participants reported significant decreases in both negative (upset, scared, irritable, nervous, jittery, afraid) and positive (feeling interested) mood states after their most recent tanning episode. Multivariable linear regression analyses showed that more frequent indoor tanning in the past month and symptoms of illicit drug use disorders were associated with decreases in negative mood, and symptoms of generalized anxiety disorder were associated with a decrease in feeling interested. In summary, indoor tanners report relatively high rates of psychiatric and substance use symptoms, including symptoms of tanning dependence, and indoor tanning appears to alter mood. Women with certain substance use and psychiatric characteristics may be more vulnerable to such mood changes after tanning indoors. Further research is needed to clarify the relationships among these variables.

75 FR 54465 - Temporary Registration of Municipal Advisors

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

...-5615; Leigh W. Duffy, Attorney-Adviser, Office of Market Supervision, at (202) 551- 2938; or any of the... to the subsequent proposal. \\2\\ 17 CFR 240.15Ba2-6T. \\3\\ 15 U.S.C. 78a et seq. I. Introduction As... their municipal advisory services.\\7\\ \\4\\ 15 U.S.C. 78o-4(a). All references in this Release to the...

The criminalisation of HIV transmission

PubMed Central

Chalmers, J

2002-01-01

This paper, in addition to providing some background to the Kelly case, briefly explores the current possibilities for prosecution under English law. It then proceeds to outline and comment on the issues relevant to criminalisation, responding in part to points made by Bennett, Draper, and Frith and also by Bird and Leigh Brown in a recent article in the British Medical Journal. PMID:12042400

Enhancing Interoperability Among Enlisted Medical Personnel. A Case Study of Military Surgical Technologists

DTIC Science & Technology

2009-01-01

Thomas Manacapilli, Daniel Gershwin, Andrew Baxter, Roland J. Yardley Prepared for the Office of the Secretary of Defense Approved for public release...particularly thank Pete Altman, LTC Kathleen McArthur, CAPT Leigh Wickes, HMCS Douglas Glascoe, HMCM James Menke, Jerral Behnke, LTC Katrina Glavan-Heise, and...TIO Transformation Integration Office TNCC Thomas Nelson Community College TRADOC Training and Doctrine Command TS-C Tech in Surgery—Certified USD

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with

Emergence of Sex Differences in Insomnia Symptoms in Adolescents: A Large-Scale School-Based Study

PubMed Central

Zhang, Jihui; Chan, Ngan Yin; Lam, Siu Ping; Li, Shirley Xin; Liu, Yaping; Chan, Joey W.Y.; Kong, Alice Pik Shan; Ma, Ronald C.W.; Chan, Kate C.C.; Li, Albert Martin; Wing, Yun-Kwok

2016-01-01

Study Objectives: This study aimed to explore the moderation of pubertal status on the onset of sex differences in the prevalence of insomnia symptoms and their health correlates. Methods: A total of 7,507 children and adolescents (weighted percentage of female: 48.5%) aged between 6–17 y were recruited from thirty-one primary and secondary schools. Participants with difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and/or early morning awakening (EMA) ≥ 3 times/week in the past month were considered as having insomnia symptoms. The severity of insomnia was measured by the Insomnia Severity Index (ISI). Results: The prevalence of insomnia symptoms increased from 3.4% to 12.2% in girls (3.6-fold) and from 4.3% to 9.1% in boys (2.1-fold) from Tanner stage 1 to 5. There was a significant interaction between sex and Tanner stage in the prevalence of insomnia (P < 0.001) with an emergence of female preponderance at Tanner stage 4 even after controlling for age, family income, and school start time. Similar sex-Tanner stage interactions were found in DIS, DMS, and ISI total score but not EMA. Insomnia symptoms were strongly associated with behavioral problems, poor mental health, and poor general health in both sexes. Boys with insomnia would report more maladaptive lifestyles (smoking, alcohol, and energy drinks) whereas girls with insomnia were more susceptible to emotional and relationship difficulties. Conclusions: Pubertal maturation was associated with a progressive increase in the prevalence of insomnia symptoms with the emergence of female preponderance in both the prevalence and severity of insomnia symptoms at late puberty. Clinical Trials Registration: Chinese Clinical Trial Register, http://www.chictr.org.cn, ID: ChiCTR-TRC-12002798 Citation: Zhang J, Chan NY, Lam SP, Li SX, Liu Y, Chan JW, Kong AP, Ma RC, Chan KC, Li AM, Wing YK. Emergence of sex differences in insomnia symptoms in adolescents: a large-scale school-based study. SLEEP

Prepubertal Serum Concentrations of Organochlorine Pesticides and Age at Sexual Maturity in Russian Boys

PubMed Central

Lam, Thuy; Williams, Paige L.; Lee, Mary M.; Korrick, Susan A.; Birnbaum, Linda S.; Burns, Jane S.; Sergeyev, Oleg; Revich, Boris; Altshul, Larisa M.; Patterson, Donald G.

2015-01-01

Background Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. Objective We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys. Methods From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. Results In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: –1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: –3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: –1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of βHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6–9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), βHCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. Conclusions and relevance Higher prepubertal serum HCB and βHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation. Citation Lam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O

Bracing is an effective therapy for pectus carinatum: interim results.

PubMed

Lee, Richy T; Moorman, Scott; Schneider, Marc; Sigalet, David L

2013-01-01

Pectus Carinatum is a common congenital chest wall malformation. Until recently the mainstay of treatment was surgical remodeling of the deformed chest wall. Initial results suggest that non-operative bracing may be an effective therapy, but the optimal strategy for correction is not known. Herein we report the results of a self-adjustable low profile bracing system worn continuously until the defect is corrected (correction phase), then worn at night (8 h/day) until completion of axial growth (maintenance phase)-the Calgary Protocol. Patients referred to a pediatric surgery chest wall clinic were prospectively asked to join an IRB approved outcomes monitoring study. 124 patients were evaluated from 2007 to 2011, and 98 were prescribed a brace and counseled to follow the protocol. 98 patients consented to follow-up at starting bracing age: 14.4 ± 1.9 years, Tanner stage: 3.6 ± 0.5, protrusion: 2.1 ± 1.0 cm, self-rating of appearance: 2.9 ± 1.1, and exercise tolerance: 4.4 ± 1.1 (1-5 with 5 = normal). 10 patients are in correction phase, and 44 patients have completed correction after 7.0 ± 7.3 months: Tanner stage: 3.8 ± 0.1, protrusion: 0.5 ± 0.6 cm*, appearance: 4.3 ± 0.3* and exercise tolerance 4.6 ± 1.0. Correction occurred more quickly in patients prior to achieving Tanner stage IV (4.2 ± 0.9 months) vs. Tanner stage IV (8.0 ± 7.1 months) at the beginning of bracing. 21 patients completed maintenance bracing after 17.9 ± 19.0 months: Tanner stage: 3.9 ± 0.2, protrusion 0.5 ± 0.7 cm*, appearance: 4.3 ± 0.9*, and exercise tolerance: 4.8 ± 1.4. Average follow-up after bracing is 13.9 ± 16.0 months (mean ± S.D., *P < .05). There was one recurrence, likely due to early discontinuation of maintenance. This responded to an additional 6 months of bracing. 42 patients failed therapy secondary to non-compliance or were lost in follow up, while 2 patients did not respond to bracing and required open operation. If patients are compliant, a self

Cognitive Rationalizations for Tanning-Bed Use: A Preliminary Exploration

PubMed Central

Banerjee, Smita C.; Hay, Jennifer L.; Greene, Kathryn

2016-01-01

Objectives To examine construct and predictive utility of an adapted cognitive rationalization scale for tanning-bed use. Methods Current/former tanning-bed-using undergraduate students (N = 216; 87.6% females; 78.4% white) at a large northeastern university participated in a survey. A cognitive rationalization for tanning-bed use scale was adapted. Standardized self-report measures of past tanning-bed use, advantages of tanning, perceived vulnerability to photoaging, tanning-bed use dependence, and tanning- bed use intention were also administered. Results The cognitive rationalization scale exhibited strong construct and predictive validity. Current tanners and tanning-bed-use-dependent participants endorsed rationalizations more strongly than did former tanners and not-tanning-bed-use-dependent participants respectively. Conclusions Findings indicate that cognitive rationalizations help explain discrepancy between inconsistent cognitions. PMID:23985280

Instructional Storytelling: Application of the Clinical Judgment Model in Nursing.

PubMed

Timbrell, Jessica

2017-05-01

Little is known about the teaching and learning implications of instructional storytelling (IST) in nursing education or its potential connection to nursing theory. The literature establishes storytelling as a powerful teaching-learning method in the educational, business, humanities, and health sectors, but little exploration exists that is specific to nursing. An example of a story demonstrating application of the domains of Tanner's clinical judgment model links storytelling with learning outcomes appropriate for the novice nursing student. Application of Tanner's clinical judgment model offers consistency of learning experience while preserving the creativity inherent in IST. Further research into student learning outcomes achievement using IST is warranted as a step toward establishing best practices with IST in nursing education. [J Nurs Educ. 2017;56(5):305-308.]. Copyright 2017, SLACK Incorporated.

Design of Tactile Sensor Using Dynamic Wafer Technology Based on VLSI Technique

DTIC Science & Technology

2001-10-25

Charles Noback, Rober Carola," Human Anatomy and Physiology" third edition, 1995. [5] M.H. Raibert and John E. Tanner, "Design and Implementation of VLSI Tactile Sensing Computer" Robotics Research vol 1, 1983.

Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

ClinicalTrials.gov

2014-01-08

Precocious; Leuprolide Acetate; Luteinizing Hormone (LH); Gonadotrophin-releasing Hormone Agonist (GnRHa); Tanner Staging; Depot Formulation; Suppression of LH; Central Precocious Puberty (CPP); Gonadotrophin-releasing Hormone (GnRH); Lupron; GnRH Analog; Pediatrics Central Precocious Puberty

EVA 2 activity on Flight Day 5 to service the Hubble Space Telescope

NASA Image and Video Library

1997-02-15

S82-E-5429 (15 Feb. 1997) --- Astronauts Gregory J. Harbaugh (left) and Joseph R. Tanner (right) during Multi Layer Insulation (MLI) inspection in Bay 10. This view was taken with an Electronic Still Camera (ESC).

KSC00pp1070

NASA Image and Video Library

2000-07-28

KENNEDY SPACE CENTER, FLA. -- During a visit to KSC, NASCAR race driver Jeff Gordon (far right) and his wife (far left) pose with astronauts Michael Lopez-Alegria (second from left) and Joe Tanner (third from left)

KSC-00pp1070

NASA Image and Video Library

2000-07-28

KENNEDY SPACE CENTER, FLA. -- During a visit to KSC, NASCAR race driver Jeff Gordon (far right) and his wife (far left) pose with astronauts Michael Lopez-Alegria (second from left) and Joe Tanner (third from left)

The Brainstem Switch for Gaze Shifts in Humans

DTIC Science & Technology

2001-10-25

Page 1 of 4 THE BRAINSTEM SWITCH FOR GAZE SHIFTS IN HUMANS A. N. Kumar1, R. J. Leigh1,2, S. Ramat3 Department of 1Biomedical Engineering, Case...omnipause neurons during gaze shifts. Using the scleral search coil technique, eye movements were measured in seven normal subjects, as they made...voluntary, disjunctive gaze shifts comprising saccades and vergence movements. Conjugate oscillations of small amplitude and high frequency were identified

What does an innovative teaching assignment strategy mean to nursing students?

PubMed

Neuman, Lois H; Pardue, Karen T; Grady, Janet L; Gray, Mary Tod; Hobbins, Bonnie; Edelstein, Jan; Herrman, Judith W

2009-01-01

The concept of innovation in nursing education has been addressed in published literature on faculty-defined and faculty-created teaching strategies and instructional methods. In this project, innovation is defined as "using knowledge to create ways and services that are new (or perceived as new) in order to transform systems" (Pardue, Tagliareni, Valiga, Davison-Price, & Orchowsky, 2005). Studies on nursing student perceptions of innovation are limited, and it is unclear how undergraduate and graduate students conceptualize innovative learning experiences. This project explored students' perceptions of their experiences with instructor-defined, innovative teaching/learning strategies in four types of nursing education programs. Issues nurse educators should consider as they apply new techniques to their teaching are discussed.

Puberty, statural growth, and growth hormone release in children with cerebral palsy

PubMed Central

Kuperminc, Michelle N.; Gurka, Matthew J.; Houlihan, Christine M.; Henderson, Richard C.; Roemmich, James N.; Rogol, Alan D.

2010-01-01

Objective Children with cerebral palsy (CP) are smaller than normally growing children.. The association between the growth hormone (GH) axis and growth in children with CP during puberty is unknown. We compared growth and markers of the GH axis in pre-pubertal and pubertal children with moderate to severe CP and without CP over a three-year period. Study design Twenty children with CP, ages 6–18, Gross Motor Function Classification System levels III–V, were compared to a group of sixty-three normally growing children of similar age. Anthropometry, Tanner stage, bone age, and laboratory analyses were performed every six months for three years. Laboratory values included spontaneous overnight GH release, fasting IGF-1 and IGFBP-3. Repeated measures models were used to evaluate interactions among Tanner stage and group (children with CP vs. reference children), taking into account gender, age, and nutritional status. Results Children with CP grew more slowly than those without CP at all Tanner stages (p<0.01). Patterns of IGF-1 and GH secretion in children with CP were similar to those of the reference group; however, the concentrations of IGF-1 (p<0.01) and GH (p<0.01) were lower in girls with CP, with a similar trend for boys (p=0.10 and 0.14, respectively). Conclusions Diminished circulating IGF-1 and GH concentrations may explain the differences in growth between the two groups. PMID:20216931

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

PubMed

Koebnick, C; Kelly, L A; Lane, C J; Roberts, C K; Shaibi, G Q; Toledo-Corral, C M; Davis, J N; Weigensberg, M J; Goran, M I

2008-09-01

To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

The role of testosterone and estradiol in brain volume changes across adolescence: a longitudinal structural MRI study.

PubMed

Herting, Megan M; Gautam, Prapti; Spielberg, Jeffrey M; Kan, Eric; Dahl, Ronald E; Sowell, Elizabeth R

2014-11-01

It has been postulated that pubertal hormones may drive some neuroanatomical changes during adolescence, and may do so differently in girls and boys. Here, we use growth curve modeling to directly assess how sex hormones [testosterone (T) and estradiol (E₂)] relate to changes in subcortical brain volumes utilizing a longitudinal design. 126 adolescents (63 girls), ages 10 to 14, were imaged and restudied ∼2 years later. We show, for the first time, that best-fit growth models are distinctly different when using hormones as compared to a physical proxy of pubertal maturation (Tanner Stage) or age, to predict brain development. Like Tanner Stage, T and E₂ predicted white matter and right amygdala growth across adolescence in both sexes, independent of age. Tanner Stage also explained decreases in both gray matter and caudate volumes, whereas E₂ explained only gray matter decreases and T explained only caudate volume decreases. No pubertal measures were related to hippocampus development. Although specificity was seen, sex hormones had strikingly similar relationships with white matter, gray matter, right amygdala, and bilateral caudate volumes, with larger changes in brain volume seen at early pubertal maturation (as indexed by lower hormone levels), followed by less robust, or even reversals in growth, by late puberty. These novel longitudinal findings on the relationship between hormones and brain volume change represent crucial first steps toward understanding which aspects of puberty influence neurodevelopment. Copyright © 2014 Wiley Periodicals, Inc.

Bioengineering/Biophysicist Post-doctoral Fellow | Center for Cancer Research

Cancer.gov

A post-doctoral fellow position is available in the Tissue Morphodynamics Unit headed by Dr. Kandice Tanner at the National Cancer Institute. The Tanner lab combines biophysical and cell biological approaches to understand the interplay between tissue architecture and metastasis. We use a combination of imaging modalities, cell biology and animal models. It is expected that as a member of this lab, one will have an opportunity to be exposed to all these areas. We value a vibrant and collaborative environment where lab members share ideas, reagents and expertise and want to work on fundamental problems in the establishment of metastatic lesions. Our lab is located in the NIH main campus in Bethesda. The research facilities at NIH are outstanding and the lab has state-of-the-art equipment such as multi-photon and confocal microscopes, FACS facilities and animal vivarium.

EVA 2 activity on Flight Day 5 to service the Hubble Space Telescope

NASA Image and Video Library

1997-02-15

S82-E-5407 (15 Feb. 1997) --- Astronauts Gregory J. Harbaugh (left) and Joseph R. Tanner on Remote Manipulator System (RMS) during accessing Fine Guidance Sensor (FGS) in the F site. This view was taken with an Electronic Still Camera (ESC).

Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

DTIC Science & Technology

2012-01-01

antibody conjugation to HA The conjugation chemistry followed a method previously developed in our laboratory. Briefly, HA (12 mg) was modi - fied...Webster MW, McGill JB, Schwartz SL. Promotion and acceleration of diabetic ulcer healing by arginine-glycine-aspartic acid (RGD) peptide matrix. RGD...Study Group. Diabetes Care 1995; 18: 39–46. 32. Ho-Asjoe M, Chronnell CM, Frame JD, Leigh IM, Carver N. Immunohistochemical analysis of burn depth. J

A Study of Illinois Related Lost Time in Transport Aircraft Crewmembers.

DTIC Science & Technology

1992-05-01

pending. 14. Leigh JP: Employee and Job Attributes as Predictors of Absenteeism in a National Sample of Workers . Social Science in Medicine 1991; 33...Cincinnati College of Medicine Division of Occupational Medicine Department of Environmental Health May 27,1992 Copyright 1992 by David Louis. All Rights...or effect modifiers; and 3) to see if the pilots’ apparent "Healthy Worker Effect" is actually due to flying while ill or self-medication. Finally

U.S. Army Corps of Engineers Recreation Study. A Plan Prepared for the Assistant Secretary of the Army (Civil Works). Volume 2. Appendices

DTIC Science & Technology

1990-09-01

TELEPHONE (Include Area Code) 22c OFFICE SYMBOL WILLIAM J. HANSEN (703) 355-3089 CEWRC-IWR-R DD FORM 1473, 84 MAR 83 APR edition may be used until... William J. Hansen of the Institute for Water Resources was the Technical Study Manager. Mr. L. Leigh Skaggs of the Institute for Water Resources...Mr. William Thornton, Missouri River Division, Mr. Bruce Hardie, Southwestern Division and Mr. Allen Summers, North Pacific Division. U.S. ARMY

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (79th, Anaheim, CA, August 10-13, 1996). International Communications Division.

ERIC Educational Resources Information Center

Association for Education in Journalism and Mass Communication.

The international communications section of the Proceedings contains the following 14 papers: "Spinning Stories: Latin America and the World Wide Web" (Eliza Tanner); "Private-Enterprise Broadcasting and Accelerating Dependency: Case Studies from Nigeria and Uganda" (Folu Folarin Ogundimu); "The Transitional Media System…

78 FR 23243 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

...: EDF Trading North America, LLC, EDF Industrial Power Services (NY), LLC, EDF Industrial Power Services (IL), LLC, EDF Industrial Power Services (CA), LLC, Tanner Street Generation, LLC Description: Notice... England Power Pool Participants Committee, ISO New England Inc. Description: Regulation Market Opportunity...

STS-115 Crewmembers prepare for their return home on the Shuttle Atlantis

NASA Image and Video Library

2006-09-17

ISS013-E-82298 (17 Sept. 2006) --- Astronauts Christopher J. Ferguson (left), STS-115 pilot; Joseph R. Tanner and Heidemarie M. Stefanyshyn-Piper, both mission specialists, make preparations for their return home on the aft flight deck of the Space Shuttle Atlantis.

Proceedings of the American Journalism Historians' Association Conference (Roanoke, Virginia, October 6-8, 1994). Part II.

ERIC Educational Resources Information Center

American Journalism Historians' Association.

The second part of the proceedings of this conference of journalism historians contains the following 21 papers: "The First Information Revolution" (Irving Fang); "The 'Andromeda Strain' Phenomenon: Mutating Systems and International Communication Policy" (Eliza Tanner); "Guns or Butter?: Black Press Editorial Policy…

Predictors of weight loss in Mexican American adolescents

USDA-ARS?s Scientific Manuscript database

This study examined predictors of weight change in Mexican American adolescents. Eighty overweight Mexican American children were randomized to receive either the intensive intervention or self help program. Physiological (e.g. standardized BMI (zBMI), percent body fat, and tanner stage), psychologi...

The relationship between pubertal gynecomastia, prostate specific antigen, free androgen index, SHBG and sex steroids.

PubMed

Kilic, Mustafa; Kanbur, Nuray; Derman, Orhan; Akgül, Sinem; Kutluk, Tezer

2011-01-01

To investigate the relationships between pubertal gynecomastia, prostate-specific antigen (PSA), free androgen index (FAI), sex hormone-binding globulin (SHBG) and sex steroids. A total of 61 male adolescents (10-17 years old; mean: 13.67 +/- 1.08) with gynecomastia were enrolled into the study group. A total of 65 healthy age-matched adolescents were included in the control group. Body mass index (BMI), Tanner staging, testis volume, stretched penis length (SPL) and bone age were evaluated. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), testosterone, free testosterone, SHBG, PSA levels were determined and FAI was calculated. In the study group, free testosterone (p = 0.012) and FAI (p = 0.05) were significantly lower than the control group. In the control group, SHBG levels decreased (p < 0.05) and FAI increased (p < 0.05) significantly with increasing Tanner stages; however, no such difference was observed in the study group (p > 0.05). High FAI was found to decrease the risk of gynecomastia (odds ratio: 0.211, 95% confidence interval: 0.064-0.694, p = 0.01). PSA showed a positive correlation with FAI, free testosterone, Tanner staging, testosterone, E2 and LH levels. PSA is a good indicator of androgen activity during puberty. However, owing to FAI remaining as the single significant variable for pubertal gynecomastia, we suggest that it is still the best parameter to elucidate the etiopathogenesis of gynecomastia as well as other pubertal developmental abnormalities in male adolescents, and further longitudinal studies are needed to investigate the relationships between PSA and FAI in puberty.

Gonadal dysfunction in morbidly obese adolescent girls.

PubMed

Chin, Vivian; Censani, Marisa; Lerner, Shulamit; Conroy, Rushika; Oberfield, Sharon; McMahon, Donald; Zitsman, Jeffrey; Fennoy, Ilene

2014-04-01

To describe gonadal dysfunction and evaluate polycystic ovary syndrome (PCOS) and its association with metabolic syndrome (MeS) among girls in a morbidly obese adolescent population. In a cross-sectional study of 174 girls, height, weight, waist circumference, Tanner stage, reproductive hormones, carbohydrate and lipid markers, drug use, and menstrual history were obtained at baseline. Exclusion criteria were menarcheal age <2 years, hormonal contraceptive or metformin use, Tanner stage <4, and incomplete data on PCOS or MeS classification. University medical center outpatient clinic. Ninety-eight girls ages 13-19.6 years, Tanner 5, average body mass index of 46.6 kg/m(2), menarche at 11.4 years, and average menarcheal age of 5 years. None. Polycystic ovary syndrome and MeS. Ninety-eight girls were divided into four groups: PCOS by National Institutes of Health criteria (PCOSN, n = 24), irregular menses only (n = 25), elevated T (≥55 ng/dL) only (n = 6), and obese controls (n = 43). Metabolic syndrome by modified Cook criteria affected 32 girls or 33% overall: 6 of 24 PCOSN, 7 of 25 irregular menses only, 4 of 6 elevated T only, and 15 of 43 obese controls. Polycystic ovary syndrome by National Institutes of Health criteria and its individual components were not associated with MeS after adjusting for body mass index. Unlike obese adults, PCOSN and its individual components were not associated with MeS in the untreated morbidly obese adolescent population. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Use-of-time and health-related quality of life in 10- to 13-year-old children: not all screen time or physical activity minutes are the same.

PubMed

Tsiros, Margarita D; Samaras, Michelle G; Coates, Alison M; Olds, Timothy

2017-11-01

To investigate associations between aspects of time use and health-related quality of life (HRQoL) in youth. 239 obese and healthy-weight 10- to 13-year-old Australian children completed the Pediatric Quality of Life Inventory (PedsQL™) quantifying their health-related quality of life. Time use was evaluated over four days using the Multimedia Activity Recall for Children and Adolescents (MARCA), a validated 24 h recall tool. The average number of minutes/day spent in physical activity (divided into sport, active transport and play), screen time (divided into television, videogames and computer use), and sleep were calculated. Percent fat was measured using dual-energy X-ray absorptiometry, Tanner stage by self-report, and household income by parental report. Sex-stratified analysis was conducted using Partial Least Squares regression, with percent fat, Tanner stage, household income, and use-of-time as the independent variables, and PedsQL™ total, physical and psychosocial subscale scores as the dependent variables. For boys, the most important predictors of HRQoL were percent fat (negative), videogames (negative), sport (positive), and Tanner stage (negative). For girls, the significant predictors were percent fat (negative), television (negative), sport (positive), active transport (negative), and household income (positive). While body fat was the most significant correlate of HRQoL, sport was independently associated with better HRQoL, and television and videogames with poorer HRQoL. Thus, parents and clinicians should be mindful that not all physical activity and screen-based behaviours have equivocal relationships with children's HRQoL. Prospective research is needed to confirm causation and to inform current activity guidelines.

Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease.

PubMed

Martikainen, Mika H; Ng, Yi Shiau; Gorman, Gráinne S; Alston, Charlotte L; Blakely, Emma L; Schaefer, Andrew M; Chinnery, Patrick F; Burn, David J; Taylor, Robert W; McFarland, Robert; Turnbull, Doug M

2016-06-01

Extrapyramidal movement disorders associated with mitochondrial disease are difficult to treat and can lead to considerable disability. Moreover, potential new treatment trials on the horizon highlight the importance of genotype-phenotype associations and deep phenotyping of the movement disorders related to mitochondrial disease. To describe the phenotype, genetic etiology, and investigation of extrapyramidal movement disorders in a large and well-defined mitochondrial disease cohort. An observational cohort study at a single national referral center. Among 678 patients (87% adults) followed up at the Newcastle mitochondrial disease specialized referral center between January 1, 2000, and January 31, 2015, 42 patients (12 pediatric, 30 adult) with genetic or biochemical evidence of mitochondrial disease and with 1 or more predefined extrapyramidal movement disorders (parkinsonism, dystonia, tremor, chorea, and restless legs syndrome) were included. We investigated the prevalence and genetic causes of dystonia and parkinsonism as well as radiological findings in the context of movement disorders in mitochondrial disease. All patients were interviewed and examined. All available medical notes and clinical, radiological, and genetic investigations were reviewed. Forty-two patients (mean [SD] age, 37 [25] years; 38% female) with mitochondrial disease (12 pediatric [age range, 4-14 years], 30 adult [age range, 20-81 years]) with extrapyramidal movement disorders were identified. Dystonia manifested in 11 pediatric patients (92%), often in the context of Leigh syndrome; parkinsonism predominated in 13 adult patients (43%), among whom 5 (38%) harbored either dominant (n = 1) or recessive (n = 4) mutations in POLG. Eleven adult patients (37%) manifested with either generalized or multifocal dystonia related to mutations in mitochondrial DNA, among which the most common were the m.11778G>A mutation and mutations in MT-ATP6 (3 of 11 patients [27%] each). Bilateral

Altering Practices to Include Bimodal-bilingual (ASL-Spoken English) Programming at a Small School for the Deaf in Canada.

PubMed

Priestley, Karen; Enns, Charlotte; Arbuckle, Shauna

2018-01-01

Bimodal-bilingual programs are emerging as one way to meet broader needs and provide expanded language, educational and social-emotional opportunities for students who are deaf and hard of hearing (Marschark, M., Tang, G. & Knoors, H. (Eds). (2014). Bilingualism and bilingual Deaf education. New York, NY: Oxford University Press; Paludneviciene & Harris, R. (2011). Impact of cochlear implants on the deaf community. In Paludneviciene, R. & Leigh, I. (Eds.), Cochlear implants evolving perspectives (pp. 3-19). Washington, DC: Gallaudet University Press). However, there is limited research on students' spoken language development, signed language growth, academic outcomes or the social-emotional factors associated with these programs (Marschark, M., Tang, G. & Knoors, H. (Eds). (2014). Bilingualism and bilingual Deaf education. New York, NY: Oxford University Press; Nussbaum, D & Scott, S. (2011). The cochlear implant education center: Perspectives on effective educational practices. In Paludneviciene, R. & Leigh, I. (Eds.) Cochlear implants evolving perspectives (pp. 175-205). Washington, DC: Gallaudet University Press. The cochlear implant education center: Perspectives on effective educational practices. In Paludnevicience & Leigh (Eds). Cochlear implants evolving perspectives (pp. 175-205). Washington, DC: Gallaudet University Press; Spencer, P. & Marschark, M. (Eds.) (2010). Evidence-based practice in educating deaf and hard-of-hearing students. New York, NY: Oxford University Press). The purpose of this case study was to look at formal and informal student outcomes as well as staff and parent perceptions during the first 3 years of implementing a bimodal-bilingual (ASL and spoken English) program within an ASL milieu at a small school for the deaf. Speech and language assessment results for five students were analyzed over a 3-year period and indicated that the students made significant positive gains in all areas, although results were variable. Staff and parent

78 FR 36122 - Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands Crab...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... the harvesting and processing sectors'' and to monitor the ``economic stability for harvesters.... 120806311-3530-02] RIN 0648-BC25 Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and... Tanner Crabs (FMP). These regulations revise the annual economic data reports (EDRs) currently required...

Implications of the Equation of Transfer within the Visible and Infrared Spectrum

DTIC Science & Technology

1982-08-01

spectrum at twilight leigh or molecular scattering Rs Is highly wavelength and night but will not be dealt with herein. dependent being proportional to the...with wavelength, by atomic or molecular collision. The atmosphere is The path function due to scattering is the integral of assumed to be in local...speed of light, h is the Planck constant and band spectra are molecular and tend to be at the longer wavelengths. The continua are essentially part of

Joint Force Quarterly. Issue 66, 3rd Quarter 2012

DTIC Science & Technology

2012-07-01

reported that Soldier behavior gradually improved. One unit at Ft. Leonard Wood required 2 hours of training per week and witnessed a marked...Mark A. Stokes, Murray Scot Tanner, Joshua K. Wiseman, Xiaoming Zhang, and You Ji. Transatlantic Perspectives, No. 2 The United States, Russia, Europe

78 FR 39724 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... Trading North America, LLC, EDF Industrial Power Services (NY), LLC, EDF Industrial Power Services (IL), LLC, EDF Industrial Power Services (CA), LLC, Tanner Street Generation, LLC. Description: Notice of...: AP Holdings, LLC, AP Gas & Electric (PA), LLC, AP Gas & Electric (TX), LLC, AP Gas & Electric (MD...

Restructuring for an Interdisciplinary Curriculum.

ERIC Educational Resources Information Center

Jenkins, John M., Ed.; Tanner, Daniel, Ed.

Articles for developing an integrated secondary curriculum are presented in this book. The articles include: "Synthesis Versus Fragmentation: The Way Out of Curriculum Confusion," by Daniel Tanner; "The Interrelated Curriculum," by Steven S. Means; "Integrated Teaching and Learning in Essential Schools," by Richard Lear; "Interdisciplinary Teaming…

Physician Knowledge of Child Sexual Abuse.

ERIC Educational Resources Information Center

Socolar, Rebecca R. S.

1996-01-01

A survey of physicians (n=113) concerning their knowledge about child sexual abuse found several areas of inadequate knowledge, including assessment of chlamydia infection, Tanner staging, and documentation of historical and physical exam findings. Factors associated with better knowledge scores were physician participation in continuing medical…

"Burakugaku" ("Buraku" Study): A Paradigm Shift for Education

ERIC Educational Resources Information Center

Kawamoto, Yoshikazu; Shimizu, Hidetada

2004-01-01

Burakumin, Japan's largest minority group, have been discriminated against throughout Japanese history for engaging in jobs that were considered to be defiling, e.g., slaughterers, tanners, and undertakers. Specifically, burakumin played the social and occupational roles despised by the majority Japanese, but those without which the Japanese…

A Pilot Study: Attention Deficit Hyperactivity Disorder, Sensation Seeking, and Pubertal Changes

PubMed Central

Martin, Catherine A.; Guenthner, Greg; Bingcang, Christopher; Smith, W. Jackson; Curry, Thomas; Omar, Hatim A.; Raynes, Mary Kay; Kelly, Thomas H.

2006-01-01

This study was designed to examine the relationship of pubertal changes and sensation seeking (SS) in adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Patients with current or past histories of uncomplicated stimulant medication use for ADHD between the ages of 11 and 15 (13 ± 1.5) were recruited from a Child Psychiatry and a General Pediatric Clinic. SS was measured using the SS Scale for Children. Pubertal development was measured using Tanner staging, free testosterone, and DHEAS. Subjects and their parent were interviewed with the Diagnostic Interview Schedule for Children (DISC). SS total score was correlated with Tanner stage, free testosterone, and DHEAS (p ≤ 0.01). The combined parent and child reports of symptoms of Oppositional Defiant Disorder from the DISC were inversely related to age (p ≤ 0.05). Understanding SS in ADHD adolescents as they move through puberty will aid clinicians in monitoring ADHD adolescents and their trajectory into high-risk behaviors. PMID:16832566

Nanosilicon for nanomedicine: a step towards biodegradable electronic implants?

PubMed

Canham, Leigh

2013-10-01

Leigh Canham received his BSc degree in physics from University College London (London, UK) in 1979 and his PhD in solid state physics from King's College London (London, UK). He now has over 30 years of experience conducting research on widely differing aspects of silicon technology. Two key personal discoveries--that nanostructured silicon can emit visible light efficiently (1990) and can be rendered medically biodegradable (1995)--have had significant academic (>15,000 citations) and commercial (multiple companies created) impact. Professor Canham is a scientist who is devoted to finding novel properties and uses for semiconductors that already pervade our everyday lives. He has 13 years of experience of start up company management, right through from cofounding with seed venture capital finance to NASDAQ listing. He has served on the board of two companies based in England, UK, one in Singapore and one in Australia. Since 1999, he has held an Honorary Professorship at the School of Physics, University of Birmingham (Birmingham, UK) for his work on luminescent silicon. In 2011, Leigh was a shortlisted finalist for the European Inventor of the Year Award from the European Patent Office for his work on biodegradable silicon. In 2012, he became a Thomson Reuters Citation Laureate for his work on luminescent silicon. Professor Canham has authored over 150 peer-reviewed papers and has more than 100 granted patents worldwide.

Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

DTIC Science & Technology

2013-09-01

Jacobus J M van Der Hoeven, Elsken van Der Wall, Petra van Der Groep, Paul J van Diest, Emile F I Comans, Urvi Joshi, et al. 2002. “Biologic...Leigh G Seamon, William B Farrar, and Edward W Martin . 2008. “Novel perioperative imaging with 18F-FDG PET/CT and intraoperative 18F-FDG detection...www.springerlink.com/content/n752170246r84660/. Hall, Nathan C, Stephen P Povoski, Douglas A Murrey, Michael V Knopp, and Edward W Martin . 2007. “Combined

Changes to United States Navy Submarine Design and Construction during World War I, as Determined by the General Board.

DTIC Science & Technology

2017-06-09

informed the Board that 25 knots was unachievable with a diesel engine.98 The only way to achieve speeds that high was to use steam turbine propulsion...13 November 1917. Leigh described how that with the wind blowing at “5 or 6” and with the submarines periscope “just awash,” the Mason apparatus was...Anchor (deck) housed in hawse pipe. 44. Towing gear operable inside of boat. 45. Chart Board. 46. Clearing Lines and Jumping Wires – Sounding

Studies in Intelligence. Volume 56, Number 4

DTIC Science & Technology

2012-12-01

two hour walk in the nearby woods . It was drizzling, but neither of us noticed. He insisted at each subsequent meeting that he would terminate...Shambaugh, and Murray Scot Tanner. See, also, Michael Swaine, The Role of the Chinese Military in National Security Policymaking (Santa Monica, CA: RAND

Development of an alternative low salt bovine hide preservation using PEG and crude glycerol, part 1: evaluation of PEG molecular weight fractions

USDA-ARS?s Scientific Manuscript database

Brine curing using sodium chloride is widely used for the short-term preservation of cattle hides. Due to economics and efficiency, it has become the traditional method of hide preservation used by meat packers, hide processors, and tanners worldwide. But brine curing is known to cause serious efflu...

The AMATYC Review. Volume 13, 1991-1992.

ERIC Educational Resources Information Center

Cohen, Don, Ed.

1992-01-01

This document consists of the two numbers of "The AMATYC Review" issued during publication year 1991-1992. The following articles are featured: (1) "Educational Reflections" (D. A. Crocker); (2) "Mathematics: An International View" (I. Malyshev, J. R. Becker, editors); (3) "Pandora's Rectangular Parallelepiped" (L. R. Tanner, editor); (4) "The…

Tanning

MedlinePlus

... be dangerous and are not approved by the Food and Drug Administration (FDA). Sunless tanners have no known risk for skin cancer, but you do have to be careful. Most spray tans, lotions, and gels use DHA, a color additive that makes your skin look tan. DHA is ...

Challenging Cognitive Construals: A Dynamic Alternative to Stable Misconceptions

ERIC Educational Resources Information Center

Gouvea, Julia S.; Simon, Matt R.

2018-01-01

In biology education research, it has been common to model cognition in terms of relatively stable knowledge structures (e.g., mental models, alternative frameworks, deeply held misconceptions). For example, John D. Coley and Kimberley D. Tanner recently proposed that many student difficulties in biology stem from underlying cognitive frameworks…

Timing of Puberty in Overweight Versus Obese Boys.

PubMed

Lee, Joyce M; Wasserman, Richard; Kaciroti, Niko; Gebremariam, Achamyeleh; Steffes, Jennifer; Dowshen, Steven; Harris, Donna; Serwint, Janet; Abney, Dianna; Smitherman, Lynn; Reiter, Edward; Herman-Giddens, Marcia E

2016-02-01

Studies of the relationship of weight status with timing of puberty in boys have been mixed. This study examined whether overweight and obesity are associated with differences in the timing of puberty in US boys. We reanalyzed recent community-based pubertal data from the American Academy of Pediatrics' Pediatric Research in Office Settings study in which trained clinicians assessed boys 6 to 16 years for height, weight, Tanner stages, testicular volume (TV), and other pubertal variables. We classified children based on BMI as normal weight, overweight, or obese and compared median age at a given Tanner stage or greater by weight class using probit and ordinal probit models and a Bayesian approach. Half of boys (49.9%, n = 1931) were white, 25.8% (n = 1000) were African American, and 24.3% (n = 941) were Hispanic. For genital development in white and African American boys across a variety of Tanner stages, we found earlier puberty in overweight compared with normal weight boys, and later puberty in obese compared with overweight, but no significant differences for Hispanics. For TV (≥3 mL or ≥4 mL), our findings support earlier puberty for overweight compared with normal weight white boys. In a large, racially diverse, community-based sample of US boys, we found evidence of earlier puberty for overweight compared with normal or obese, and later puberty for obese boys compared with normal and overweight boys. Additional studies are needed to understand the possible relationships among race/ethnicity, gender, BMI, and the timing of pubertal development. Copyright © 2016 by the American Academy of Pediatrics.

The relationship between Insulin-like Growth Factor 1, sex steroids and timing of the pubertal growth spurt.

PubMed

Cole, T J; Ahmed, M L; Preece, M A; Hindmarsh, P; Dunger, D B

2015-06-01

Progress through puberty involves a complex hormonal cascade, but the individual contributions of hormones, particularly IGF-1, are unknown. We reanalysed Chard growth study data to explore the tempo of puberty based on changes in both height and hormone levels, using a novel method of growth curve analysis. Schoolboys (n = 54) and girls (n = 70) from Chard, Somerset, England, recruited in 1981 at age 8/9 and followed to age 16. Every 6 months, height and Tanner stages (genitalia, breast, pubic hair) were recorded, and in a subsample (24 boys, 27 girls), blood samples were taken. Serum IGF-1, testosterone (boys) and oestradiol (girls) were measured by radioimmunoassay. Individual growth curves for each outcome were analysed using variants of the super-imposition by translation and rotation (SITAR) method, which estimates a mean curve and subject-specific random effects corresponding to size, and age and magnitude of peak velocity. The SITAR models fitted the data well, explaining 99%, 65%, 86% and 47% of variance for height, IGF-1, testosterone and oestradiol, respectively, and 69-88% for the Tanner stages. During puberty, the variables all increased steeply in value in individuals, the ages at peak velocity for the different variables being highly correlated, particularly for IGF-1 vs height (r = 0·74 for girls, 0·92 for boys). IGF-1, like height, the sex steroids and Tanner stages, rises steeply in individuals during puberty, with the timings of the rises tightly synchronized within individuals. This suggests that IGF-1 may play an important role in determining the timing of puberty. © 2015 The Authors Clinical Endocrinology Published by John Wiley & Sons Ltd.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

PubMed

Tack, Lloyd J W; Craen, Margarita; Lapauw, Bruno; Goemaere, Stefan; Toye, Kaatje; Kaufman, Jean-Marc; Vandewalle, Sara; T'Sjoen, Guy; Zmierczak, Hans-Georg; Cools, Martine

2018-06-01

Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

75 FR 52511 - North Pacific Fishery Management Council; Notice of Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...; review Bristol Bay red king crab CIE report, review and recommend approaches for Tanner crab model, review and recommend approaches for Pribilof Islands blue king crab and red king crab models, receive an... Fishery Management Council's Crab Plan Team (CPT). SUMMARY: The CPT will meet September 13-16, 2010, at...

Auditory Pattern Memory: Mechanisms of Tonal Sequence Discrimination by Human Observers

DTIC Science & Technology

1988-10-30

and Creelman (1977) in a study of categorical perception. Tanner’s model included a short-term decaying memory for the acoustic input to the system plus...auditory pattern components, J. &Coust. Soc. 91 Am., 76, 1037- 1044. Macmillan, N. A., Kaplan H. L., & Creelman , C. D. (1977). The psychophysics of

50 CFR 680.3 - Relation to other laws.

Code of Federal Regulations, 2013 CFR

2013-10-01

....3 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... governing the conservation and management of king crab and Tanner crab in the BSAI area are contained in 50... requirements using the ADF&G “Intent to Operate” registration form and “Fish Tickets.” (b) Sport, personal use...

50 CFR 680.3 - Relation to other laws.

Code of Federal Regulations, 2011 CFR

2011-10-01

....3 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... governing the conservation and management of king crab and Tanner crab in the BSAI area are contained in 50... requirements using the ADF&G “Intent to Operate” registration form and “Fish Tickets.” (b) Sport, personal use...

50 CFR 680.3 - Relation to other laws.

Code of Federal Regulations, 2014 CFR

2014-10-01

....3 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... governing the conservation and management of king crab and Tanner crab in the BSAI area are contained in 50... requirements using the ADF&G “Intent to Operate” registration form and “Fish Tickets.” (b) Sport, personal use...

50 CFR 680.3 - Relation to other laws.

Code of Federal Regulations, 2010 CFR

2010-10-01

....3 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... governing the conservation and management of king crab and Tanner crab in the BSAI area are contained in 50... requirements using the ADF&G “Intent to Operate” registration form and “Fish Tickets.” (b) Sport, personal use...

50 CFR 680.3 - Relation to other laws.

Code of Federal Regulations, 2012 CFR

2012-10-01

....3 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... governing the conservation and management of king crab and Tanner crab in the BSAI area are contained in 50... requirements using the ADF&G “Intent to Operate” registration form and “Fish Tickets.” (b) Sport, personal use...

Measuring complexity in Brazilian economic crises.

PubMed

Mortoza, Letícia P D; Piqueira, José R C

2017-01-01

Capital flows are responsible for a strong influence on the foreign exchange rates and stock prices macroeconomic parameters. In volatile economies, capital flows can change due to several types of social, political and economic events, provoking oscillations on these parameters, which are recognized as economic crises. This work aims to investigate how these two macroeconomic variables are related with crisis events by using the traditional complex measures due to Lopez-Mancini-Calbet (LMC) and to Shiner-Davison-Landsberg (SDL), that can be applied to any temporal series. Here, Ibovespa (Bovespa Stock Exchange main Index) and the "dollar-real" parity are the background for calculating the LMC and SDL complexity measures. By analyzing the temporal evolution of these measures, it is shown that they might be related to important events that occurred in the Brazilian economy.

NATO Planning Guide for the Estimation of CBRN Casualties

DTIC Science & Technology

2014-11-01

for CBRN Defense ( J -8, JRO). The publication of this IDA document does not indicate endorsement by the Department of Defense, nor should the...Vehicle - Closed Windows 4.2 MTR, ACE, CHAPP, 36 M106 A2 4.2, M113 Stationary Vehicle - Open Windows, TruckNan 40 Fan on Fresh Air * Adapted from J ...5. CFHD= ECt50-severe(HD/PC/V) ED50-severe(HD/PC/L) , (4-5) where: 47 Gene E. McClellan, George H. Anno , and Leigh N. Matheson, Consequence

From School to Work via Military Service: an Improved Transition.

DTIC Science & Technology

1980-06-01

BIBLIOGRAPHY 1. Arrow, K. J., "Higher Education of a Filter," Journal of Public Economy. v. 2, p. 193-216, July 1973. 2. Averitt, R., The Dual Economy...Returns to Education ," Journal of Political Economy, v. 82, pp. 985-998, September/ October 1974. 42. Leigh, D. E., An Analysis of the Determinants of...SCCUPGeV’ CLASSIVICATIaM Off T*InS WAoo gk Date ateed REPORT DOCUMENTATION PAGE Bum R M. From School To Work Via Military Service: Master’s Thesis An

76 FR 68358 - Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands Crab...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

.... 0812081573-1645-03] RIN 0648-AX47 Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and.... SUPPLEMENTARY INFORMATION: The king and Tanner crab fisheries in the exclusive economic zone of the Bering Sea... (IFQ), which is a permit providing an exclusive harvesting privilege for a specific amount of raw crab...

50 CFR 600.1103 - Bering Sea and Aleutian Islands (BSAI) Crab species program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Bering Sea and Aleutian Islands (BSAI... PROVISIONS Specific Fishery or Program Fishing Capacity Reduction Regulations § 600.1103 Bering Sea and... Fishery Management Plan for the Bering Sea/Aleutian Islands King and Tanner Crabs pursuant to § 679.2 of...

50 CFR 600.1103 - Bering Sea and Aleutian Islands (BSAI) Crab species program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Bering Sea and Aleutian Islands (BSAI... PROVISIONS Specific Fishery or Program Fishing Capacity Reduction Regulations § 600.1103 Bering Sea and... Fishery Management Plan for the Bering Sea/Aleutian Islands King and Tanner Crabs pursuant to § 679.2 of...

Keys of Japanese Prosody and Didactical-Technical Analysis of OJAD (Online Japanese Accent Dictionary)

ERIC Educational Resources Information Center

Delgado Algarra, Emilio José

2016-01-01

Most of the studies focus on the teaching of foreign languages indicate that little attention is paid to the prosodic features both didactic materials and teaching-learning processes (Martinsen, Avord and Tanner, 2014). In this context and throughout this article, an analysis of the didactical and technical dimensions of OJAD (Japanese Accent…

YPAR, Critical Whiteness, and Generative Possibilities. A Response to "Sam and Cristina: A Critical Dialogue between a Teacher and Student about the Commoditization of People of Color by Schools"

ERIC Educational Resources Information Center

Corces-Zimmerman, Chris; Utt, Jamie; Cabrera, Nolan L.

2017-01-01

In this response to the article by Tanner and Corrie, the authors provide three critiques of the methodology and theoretical framing of the study with the hopes of informing future scholarship and practice. Specifically, the three critiques addressed in this paper include the integration of CWS frameworks and YPAR methodology, the application and…

78 FR 15677 - Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands Crab...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

...-BC25 Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands Crab... Amendment 42 to the Fishery Management Plan for Bering Sea/Aleutian Islands King and Tanner Crabs (FMP) for... economic zone of the Bering Sea and Aleutian Islands (BSAI) are managed under the FMP. The FMP was prepared...

50 CFR 600.1103 - Bering Sea and Aleutian Islands (BSAI) Crab species program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Bering Sea and Aleutian Islands (BSAI... PROVISIONS Specific Fishery or Program Fishing Capacity Reduction Regulations § 600.1103 Bering Sea and... Fishery Management Plan for the Bering Sea/Aleutian Islands King and Tanner Crabs pursuant to § 679.2 of...

50 CFR 600.1103 - Bering Sea and Aleutian Islands (BSAI) Crab species program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Bering Sea and Aleutian Islands (BSAI... PROVISIONS Specific Fishery or Program Fishing Capacity Reduction Regulations § 600.1103 Bering Sea and... Fishery Management Plan for the Bering Sea/Aleutian Islands King and Tanner Crabs pursuant to § 679.2 of...

78 FR 17341 - Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and Aleutian Islands Crab...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

.... 120806311-3213-01] RIN 0648-BC25 Fisheries of the Exclusive Economic Zone Off Alaska; Bering Sea and... Bering Sea/Aleutian Islands King and Tanner Crabs (FMP). If approved, these regulations would revise the... of the CR Program were analyzed in the Bering Sea/Aleutian Islands Crab Fisheries Final EIS. Due to...

Strategic Studies Quarterly. Volume 9, Number 1. Spring 2015

DTIC Science & Technology

2015-01-01

Cliff, and Phillip C. Saunders (Washington, DC: NDU Press, 2012), 78-79. 72. Murray Scot Tanner, "The Missions of the People’s Liberation Army Air...October 2013), http://issuu.com/ewipublications/docs /mcp_final_l 0_22_2013/4. 23. James Wood Forsyth Jr., "What Great Powers Make It: International

Using P-Stat, BMDP and SPSS for a cross-products factor analysis.

PubMed

Tanner, B A; Leiman, J M

1983-06-01

The major disadvantage of the Q factor analysis with Euclidean distances described by Tanner and Koning [Comput. Progr. Biomed. 12 (1980) 201-202] is the considerable editing required. An alternative procedure with commercially distributed software, and with cross-products in place of Euclidean distances is described. This procedure does not require any editing.

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (82nd, New Orleans, Louisiana, August 3-8, 1999). International Communication, Part 1.

ERIC Educational Resources Information Center

Association for Education in Journalism and Mass Communication.

The International Communication, Part 1 section of the Proceedings contains the following 9 papers: "Chilean Conversations: On-line Forum Participants Discuss the Detention of Augusto Pinochet" (Eliza Tanner); "Media of the World and World of the Media: A Crossnational Study of the Ranking of the 'Top 10 World Events' from 1988 to…

Lessons about Art in History and History in Art.

ERIC Educational Resources Information Center

Erickson, Mary, Ed.; Clark, Gilbert, Ed.

Written by teachers from the United States and Canada, these lesson plans focus on integrating the teaching of history and art history. Seventeen lesson plans cover the topics of (1) Slavery, Henry Ossawa Tanner, and His Family--Grades: Elementary; (2) Chinese Landscape Painting--Grades: Elementary; (3) Regionalism: American Art of the Great…

Health Instruction Packages: Consumer--Dental Hygiene.

ERIC Educational Resources Information Center

Tanner, Floyd R.; And Others

Text, illustrations, and exercises are utilized in this set of five learning modules to instruct dental patients and the general public in the fundamental principles of dental hygiene. The first module, "Identify the Responsibilities for Your Oral Health" by Floyd R. Tanner, discusses the respective roles of the dentist and the patient…

A complex stand on the white river national wildlife refuge: implications for bottomland hardwood old growth

Treesearch

Brian Roy Lockhart; Jamie E. Kellum

2006-01-01

With the possible re-discovery of the ivory-billed woodpecker (Campephilus principalis), interest has increased in the habitat requirements for the species and the current state of these habitats (Fitzpatrick et al. 2005). Tanner (1942) indicated that the ivory-billed woodpecker needs large, decadent trees for foraging. Trees in such decline provide...

Comparison of modern icing cloud instruments

NASA Technical Reports Server (NTRS)

Takeuchi, D. M.; Jahnsen, L. J.; Callander, S. M.; Humbert, M. C.

1983-01-01

Intercomparison tests with Particle Measuring Systems (PMS) were conducted. Cloud liquid water content (LWC) measurements were also taken with a Johnson and Williams (JW) hot-wire device and an icing rate device (Leigh IDS). Tests include varying cloud LWC (0.5 to 5 au gm), cloud median volume diameter (MVD) (15 to 26 microns), temperature (-29 to 20 C), and air speeds (50 to 285 mph). Comparisons were based upon evaluating probe estimates of cloud LWC and median volume diameter for given tunnel settings. Variations of plus or minus 10% and plus or minus 5% in LWC and MVD, respectively, were determined of spray clouds between test made at given tunnel settings (fixed LWC, MVD, and air speed) indicating cloud conditions were highly reproducible. Although LWC measurements from JW and Leigh devices were consistent with tunnel values, individual probe measurements either consistently over or underestimated tunnel values by factors ranging from about 0.2 to 2. Range amounted to a factor of 6 differences between LWC estimates of probes for given cloud conditions. For given cloud conditions, estimates of cloud MVD between probes were within plus or minus 3 microns and 93% of the test cases. Measurements overestimated tunnel values in the range between 10 to 20 microns. The need for improving currently used calibration procedures was indicated. Establishment of test facility (or facilities) such as an icing tunnel where instruments can be calibrated against known cloud standards would be a logical choice.

Children and adolescents with gender identity disorder referred to a pediatric medical center.

PubMed

Spack, Norman P; Edwards-Leeper, Laura; Feldman, Henry A; Leibowitz, Scott; Mandel, Francie; Diamond, David A; Vance, Stanley R

2012-03-01

To describe the patients with gender identity disorder referred to a pediatric medical center. We identify changes in patients after creation of the multidisciplinary Gender Management Service by expanding the Disorders of Sex Development clinic to include transgender patients. Data gathered on 97 consecutive patients <21 years, with initial visits between January 1998 and February 2010, who fulfilled the following criteria: long-standing cross-gender behaviors, provided letters from current mental health professional, and parental support. Main descriptive measures included gender, age, Tanner stage, history of gender identity development, and psychiatric comorbidity. Genotypic male:female ratio was 43:54 (0.8:1); there was a slight preponderance of female patients but not significant from 1:1. Age of presentation was 14.8 ± 3.4 years (mean ± SD) without sex difference (P = .11). Tanner stage at presentation was 4.1 ± 1.4 for genotypic female patients and 3.6 ± 1.5 for genotypic male patients (P = .02). Age at start of medical treatment was 15.6 ± 2.8 years. Forty-three patients (44.3%) presented with significant psychiatric history, including 20 reporting self-mutilation (20.6%) and suicide attempts (9.3%). After establishment of a multidisciplinary gender clinic, the gender identity disorder population increased fourfold. Complex clinical presentations required additional mental health support as the patient population grew. Mean age and Tanner Stage were too advanced for pubertal suppressive therapy to be an affordable option for most patients. Two-thirds of patients were started on cross-sex hormone therapy. Greater awareness of the benefit of early medical intervention is needed. Psychological and physical effects of pubertal suppression and/or cross-sex hormones in our patients require further investigation.

Eating attitudes and habitual calcium intake in peripubertal girls are associated with initial bone mineral content and its change over 2 years.

PubMed

Barr, S I; Petit, M A; Vigna, Y M; Prior, J C

2001-05-01

This 2-year prospective study examined associations among bone mineral acquisition and physical, maturational, and lifestyle variables during the pubertal transition in healthy girls. Forty-five girls, initially 10.5+/-0.6 years, participated. Body composition and bone mineral content (BMC) at the spine and total body (TB) were assessed at baseline and annually thereafter using dual-energy X-ray absorptiometry (DXA). Nutrient intakes were assessed using 3-day diet records and a calcium food frequency questionnaire (FFQ), physical activity by questionnaire, sexual maturation using Tanner's stages of breast and pubic hair maturation, growth by height and weight, and eating attitudes using the children's Eating Attitudes Test (Children's EAT). Mean children's EAT subscale scores (dieting, oral control [OC], and bulimia) were stable over time. Median split of OC subscale scores was used to form high and low OC groups. Groups had similar body composition, dietary intake, activity, and Tanner stage at baseline and 2 years. Using height, weight, and Tanner breast stage as covariates, girls with low OC scores had greater TB BMC at baseline (1452+/-221 g vs. 1387+/-197 g; p = 0.030) and 2 years (2003+/-323 g vs. 1909+/-299 g; p = 0.049) and greater lumbar spine (LS) BMC at 2 years (45.2+/-8.8 g vs. 41.2+/-9.6 g; p = 0.042). In multiple regression analysis, OC score predicted baseline, 2 years, and 2-year change in TB and spinal BMC, contributing 0.9-7.6% to explained variance. Calcium intake predicted baseline, 2 years, and 2-year change in TB BMC, explaining 1.6-5.3% of variance. We conclude that both OC and habitual calcium intake may influence bone mineral acquisition.

Comparison of fault-related folding algorithms to restore a fold-and-thrust-belt

NASA Astrophysics Data System (ADS)

Brandes, Christian; Tanner, David

2017-04-01

Fault-related folding means the contemporaneous evolution of folds as a consequence of fault movement. It is a common deformation process in the upper crust that occurs worldwide in accretionary wedges, fold-and-thrust belts, and intra-plate settings, in either strike-slip, compressional, or extensional regimes. Over the last 30 years different algorithms have been developed to simulate the kinematic evolution of fault-related folds. All these models of fault-related folding include similar simplifications and limitations and use the same kinematic behaviour throughout the model (Brandes & Tanner, 2014). We used a natural example of fault-related folding from the Limón fold-and-thrust belt in eastern Costa Rica to test two different algorithms and to compare the resulting geometries. A thrust fault and its hanging-wall anticline were restored using both the trishear method (Allmendinger, 1998; Zehnder & Allmendinger, 2000) and the fault-parallel flow approach (Ziesch et al. 2014); both methods are widely used in academia and industry. The resulting hanging-wall folds above the thrust fault are restored in substantially different fashions. This is largely a function of the propagation-to-slip ratio of the thrust, which controls the geometry of the related anticline. Understanding the controlling factors for anticline evolution is important for the evaluation of potential hydrocarbon reservoirs and the characterization of fault processes. References: Allmendinger, R.W., 1998. Inverse and forward numerical modeling of trishear fault propagation folds. Tectonics, 17, 640-656. Brandes, C., Tanner, D.C. 2014. Fault-related folding: a review of kinematic models and their application. Earth Science Reviews, 138, 352-370. Zehnder, A.T., Allmendinger, R.W., 2000. Velocity field for the trishear model. Journal of Structural Geology, 22, 1009-1014. Ziesch, J., Tanner, D.C., Krawczyk, C.M. 2014. Strain associated with the fault-parallel flow algorithm during kinematic fault

Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls.

PubMed

Windham, Gayle C; Pinney, Susan M; Voss, Robert W; Sjödin, Andreas; Biro, Frank M; Greenspan, Louise C; Stewart, Susan; Hiatt, Robert A; Kushi, Lawrence H

2015-10-01

Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program. Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset. Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1-4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling. Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs. This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.

Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide.

PubMed

Codner, Ethel; Mook-Kanamori, Dennis; Bazaes, Rodrigo A; Unanue, Nancy; Sovino, Hugo; Ugarte, Francisca; Avila, Alejandra; Iñiguez, German; Cassorla, Fernando

2005-07-01

An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate. We studied 56 adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged 11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 microg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography. We found five DM1 but no C girls with abnormally located terminal hair (Fisher's exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05). These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

Body Image Satisfaction, Eating Attitudes and Perceptions of Female Body Silhouettes in Rural South African Adolescents

PubMed Central

Micklesfield, Lisa K.; Kahn, Kathleen; Tollman, Stephen M.; Pettifor, John M.; Norris, Shane A.

2016-01-01

This study aims to examine the associations between BMI, disordered eating attitude, body dissatisfaction in female adolescents, and descriptive attributes assigned to silhouettes of varying sizes in male and female adolescents, aged 11 to 15, in rural South Africa. Height and weight were measured to determine BMI. Age and sex-specific cut-offs for underweight and overweight/obesity were determined using the International Obesity Task Force cut-offs. Body image satisfaction using Feel-Ideal Discrepancy (FID) scores, Eating Attitudes Test-26 (EAT-26), and perceptual female silhouettes were collected through self-administered questionnaires in 385 adolescents from the Agincourt Health and Socio-Demographic Surveillance System (HSDSS). Participants self-reported their Tanner pubertal stage and were classified as early pubertal (< = Tanner stage 2), and mid to post pubertal (Tanner stage > 2). Mid to post pubertal boys and girls were significantly heavier, taller, and had higher BMI values than their early pubertal counterparts (all p<0.001). The prevalence of overweight and obesity was higher in the girls than the boys in both pubertal stages. The majority (83.5%) of the girls demonstrated body dissatisfaction (a desire to be thinner or fatter). The girls who wanted to be fatter had a significantly higher BMI than the girls who wanted to be thinner (p<0.001). There were no differences in EAT-26 scores between pubertal groups, within the same sex, and between boys and girls within the two pubertal groups. The majority of the boys and the girls in both pubertal groups perceived the underweight silhouettes to be “unhappy” and “weak” and the majority of girls in both pubertal groups perceived the normal silhouettes to be the “best”. These findings suggest a need for policy intervention that will address a healthy body size among South African adolescents. PMID:27171420

The Effect of School Design on Student Performance

ERIC Educational Resources Information Center

Ariani, Mohsen Ghasemi; Mirdad, Fatemeh

2016-01-01

The present study aims at exploring the influence of school design on student performance. The participants consisted of 150 students who studied at two Iranian public school and private school in Mashhad City. School Design and Planning Laboratory (SDPL) model of Georgia University (and Tanner (2009)) was used as an appraisal indicator of school…

50 CFR 679.54 - Release of observer data to the public.

Code of Federal Regulations, 2013 CFR

2013-10-01

... round weight of incidentally caught halibut or Pacific herring to the total round weight of groundfish in sampled catch. (4) The ratio of number of king crab or C. bairdi Tanner crab to the total round... of Chinook salmon to the total round weight of groundfish. (vii) The ratio of the number of other...

50 CFR 679.54 - Release of observer data to the public.

Code of Federal Regulations, 2014 CFR

2014-10-01

... round weight of incidentally caught halibut or Pacific herring to the total round weight of groundfish in sampled catch. (4) The ratio of number of king crab or C. bairdi Tanner crab to the total round... of Chinook salmon to the total round weight of groundfish. (vii) The ratio of the number of other...

Meaningful Measurement: The Role of Assessments in Improving High School Education in the Twenty-First Century

ERIC Educational Resources Information Center

Pinkus, Lyndsay M., Ed.

2009-01-01

In the chapters presented in this volume, leading experts describe some of the assessment challenges in greater detail and provide federal recommendations on how to address them. In "College and Work Readiness as a Goal of High Schools: The Role of Standards, Assessments, and Accountability," John Tanner of the Center for Innovative Measures at…

KSC00pp1721

NASA Image and Video Library

2000-10-27

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, STS-97 Mission Specialist Carlos Noriega checks out the mission payload, the P6 integrated truss segment, while Mission Specialist Joe Tanner looks on. Mission STS-97 is the sixth construction flight to the International Space Station. The P6 comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. The mission includes two spacewalks by Noriega and Tanner to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST

KSC00pp1720

NASA Image and Video Library

2000-10-27

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, STS-97 Mission Specialists Carlos Noriega (far left) and Joe Tanner (right) check out the mission payload, the P6 integrated truss segment. Mission STS-97 is the sixth construction flight to the International Space Station. The P6 comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. The mission includes two spacewalks by Noriega and Tanner to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST

KSC-00pp1721

NASA Image and Video Library

2000-10-27

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, STS-97 Mission Specialist Carlos Noriega checks out the mission payload, the P6 integrated truss segment, while Mission Specialist Joe Tanner looks on. Mission STS-97 is the sixth construction flight to the International Space Station. The P6 comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. The mission includes two spacewalks by Noriega and Tanner to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST

KSC-00pp1723

NASA Image and Video Library

2000-10-27

In the Space Station Processing Facility, STS-97 Mission Specialists Carlos Noriega (left) and Joe Tanner check out the mission payload, the P6 integrated truss segment. Mission STS-97 is the sixth construction flight to the International Space Station. The P6 comprises Solar Array Wing-3 and the Integrated Electronic Assembly, to be installed on the International Space Station. The Station’s electrical power system will use eight photovoltaic solar arrays, each 112 feet long by 39 feet wide, to convert sunlight to electricity. The solar arrays are mounted on a “blanket” that can be folded like an accordion for delivery. Once in orbit, astronauts will deploy the blankets to their full size. Gimbals will be used to rotate the arrays so that they will face the Sun to provide maximum power to the Space Station. The mission includes two spacewalks by Noriega and Tanner to complete the solar array connections. STS-97 is scheduled to launch Nov. 30 at about 10:06 p.m. EST