Molecular and clinical studies of X-linked deafness among Pakistani families.

PubMed

Waryah, Ali M; Ahmed, Zubair M; Bhinder, Munir A; Binder, Munir A; Choo, Daniel I; Sisk, Robert A; Shahzad, Mohsin; Khan, Shaheen N; Friedman, Thomas B; Riazuddin, Sheikh; Riazuddin, Saima

2011-07-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis.

Molecular and Clinical Studies of X-linked Deafness Among Pakistani Families

PubMed Central

Waryah, Ali M.; Ahmed, Zubair M.; Choo, Daniel I.; Sisk, Robert A.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

2011-01-01

There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132, PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p.Q136X and p.W114X, respectively. Family PKDF740 is segregating congenital blindness, mild to profound progressive hearing loss that is characteristic of Norrie disease (MIM#310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c.49delG causing a frameshift and premature truncation (p.V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling, and molecular epidemiology of hearing loss among Pakistanis. PMID:21633365

Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

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

Beggs, A.H.; Neumann, P.E.; Anderson, M.S.

1992-01-15

Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative tomore » Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.« less

[No X-chromosome linked juvenile foveal retinoschisis].

PubMed

Pérez Alvarez, M J; Clement Fernández, F

2002-08-01

To describe the clinical characteristics of two cases of juvenile foveal retinoschisis in women with an atypical hereditary pattern, no X-chromosome linked. An autosomal recessive inheritance is proposed. Two generations of a family (5 members) in which only two sisters were evaluated. The complete examination of these two cases includes retinography, fluorescein angiography, automated perimetry, color vision testing, electroretinogram, electrooculogram and visually evoked potentials. Comparing our cases with the classic form of X-linked juvenile retinoschisis, they are less severely affected. The best visual acuity and the less disturbed or even normal electroretinogram confirm this fact. We emphasise the existence of isolated plaques of retinal pigment epithelium atrophy with perivascular pigment clumps without foveal schisis in one patient, which could represent an evolved form of this entity. The hereditary foveal juvenile retinoschisis in women suggests an autosomal inheritance (autosomal recessive in our cases) and presents less severe involvement (Arch Soc Esp Oftalmol 2002; 77: 443-448).

The X linked recessive form of XY gonadal dysgenesis with a high incidence of gonadal germ cell tumours: clinical and genetic studies.

PubMed

Mann, J R; Corkery, J J; Fisher, H J; Cameron, A H; Mayerová, A; Wolf, U; Kennaugh, A A; Woolley, V

1983-08-01

Five phenotypic females in one family had the genotype 46,XY and all had gonadal germ cell tumours. Studies of the family pedigree suggest that this form of XY gonadal dysgenesis is inherited in an X linked recessive manner. G banding of elongated metaphase chromosomes from two subjects with XY gonadal dysgenesis and a female carrier showed no aberrations of the X chromosome. The titres of H-Y antigen in three girls with XY gonadal dysgenesis were in the male control range. Thus it appears that, in the X linked form, XY gonadal dysgenesis may be caused by a point deletion or mutation of a gene on the X chromosome, which controls the gonad specific receptor for the H-Y antigen. Studies of Xg blood groups were uninformative about linkage of Xg with the X borne gene causing the XY gonadal dysgenesis. Dermatoglyphic studies in the girls with XY gonadal dysgenesis and female carriers revealed high a-b palmar ridge counts and a tendency for the A mainline to terminate in the thenar area. Both of these features have been described in patients with Turner's syndrome.

Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel

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

Scott, D.A.; Sheffield, V.C.; Stone, E.M.

1995-10-01

Nonsyndromic deafness accounts for {approximately}70% of all genetically determined deafness. Several types of nonsyndromic deafness, with a variety of inheritance patterns, have been genetically linked, including dominant, recessive and X-linked forms. Two of these forms - DFNA3, a dominant form causing moderate to severe hearing loss, predominantly in the high frequencies, and DFNB1, a recessive form causing profound, prelingual, neurosensory deafness affecting all frequencies - have been linked to the same pericentromeric region of chromosome 13. This finding is equally compatible with (1) the existence two closely linked deafness genes, (2) different mutations within a single deafness gene, and (3)more » a single mutation in a single gene that behaves differently in different genetic backgrounds. 12 refs., 2 figs., 1 tab.« less

X-linked dominant retinitis pigmentosa in an American family

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

McGuire, R.E.; Daiger, S.P.; Blanton, S.H.

1994-09-01

Retinitis pigmentosa is a genetically heterogeneous disease with autosomal dominant (adRP), autosomal recessive and X-linked forms. At least 3 forms of X-linked retinitis pigmentosa have been reported: RP2 which maps to Xp11.4-p 11.23, RP3 which maps to Xp21.1 and RP6, which maps to Xp21.3-p21.1. The X-linked forms of retinitis pigmentosa are generally considered to be recessive as female carriers are not affected or are much less affected than males. Here we report a five generation American family with X-linked retinitis pigmentosa in which both males and females are significantly affected. The disease locus in this family appears to be distinctmore » from RP2 and RP3. The American family (UTAD054) presents with early-onset retinitis pigmentosa. The family appeared to fit an autosomal dominant pattern; however, linkage testing excluded all known adRP loci. Absence of male-to-male transmission in the pedigree suggested the possibility of X-linked dominant inheritance. Thus we tested six microsatellite markers that map to Xp (DXS987, DXS989, DXS993, DXS999, DXS1003 and DXS1110). Of these, DXS989 showed tight linkage with one allele (199) showing a 100% concordance with disease status. The odds favoring an X-linked dominant mode of inheritance in this family, versus autosomal dominant, are 10{sup 5}:1. In addition, recombinations for DXS999, and dXS1110, the two markers flanking DXS989, were observed in affected individuals. These data map the disease locus in this family to a 9 mb region on the X chromosome between Xp22.11 and Xp21.41. In addition, the recombinant individuals exclude close linkage to RP2 and RP3. The observance of high penetrance in females indicates that this family has X-linked dominant retinitis pigmentosa. We suggest that this mode of inheritance should be considered in other families with dominant retinitis pigmentosa but an absence of male-to-male transmission.« less

Localization to Xq22 and clinical update of a family with X-linked recessive mental retardation with progression sensorineural deafness, progressive tapeto-retinal degeneration and dystonia

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

Tranebjaerg, L.; Schwartz, C.; Huggins, K.

1994-07-15

In a reinvestigation of a six-generation Norwegian family, originally reported with non-syndromic X-linked recessive deafness by Mohr and Mageroy, we have demonstrated several syndromic manifestations. The 10 clinically characterized affected males range in age from 14-61 years, and show progressive mental deterioration and visual disability. Ophthalmological and electrophysiological studies showed myopia, decreased visual acuity, combined cone-rod dystrophy as well as central areolar dystrophy by means of ERG. Brain CT-scans showed cortical and central atrophy without predilection to specific areas. Linkage analysis, using X-chromosomal RFLPs and CA-repeats, yielded a maximum LOD score of 4.37 with linkage to DXS17. DXS17 is localizedmore » to Xq22. One recombinant with COL4A5 (deficient in Alport syndrome) was observed. Results from the studies of this family will be important in reclassification of non-syndromic X-linked deafness since the family now represents syndromic deafness and XLMR with a specific phenotype.« less

Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs.

PubMed

Mack, David L; Poulard, Karine; Goddard, Melissa A; Latournerie, Virginie; Snyder, Jessica M; Grange, Robert W; Elverman, Matthew R; Denard, Jérôme; Veron, Philippe; Buscara, Laurine; Le Bec, Christine; Hogrel, Jean-Yves; Brezovec, Annie G; Meng, Hui; Yang, Lin; Liu, Fujun; O'Callaghan, Michael; Gopal, Nikhil; Kelly, Valerie E; Smith, Barbara K; Strande, Jennifer L; Mavilio, Fulvio; Beggs, Alan H; Mingozzi, Federico; Lawlor, Michael W; Buj-Bello, Ana; Childers, Martin K

2017-04-05

X-linked myotubular myopathy (XLMTM) results from MTM1 gene mutations and myotubularin deficiency. Most XLMTM patients develop severe muscle weakness leading to respiratory failure and death, typically within 2 years of age. Our objective was to evaluate the efficacy and safety of systemic gene therapy in the p.N155K canine model of XLMTM by performing a dose escalation study. A recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing canine myotubularin (cMTM1) under the muscle-specific desmin promoter (rAAV8-cMTM1) was administered by simple peripheral venous infusion in XLMTM dogs at 10 weeks of age, when signs of the disease are already present. A comprehensive analysis of survival, limb strength, gait, respiratory function, neurological assessment, histology, vector biodistribution, transgene expression, and immune response was performed over a 9-month study period. Results indicate that systemic gene therapy was well tolerated, prolonged lifespan, and corrected the skeletal musculature throughout the body in a dose-dependent manner, defining an efficacious dose in this large-animal model of the disease. These results support the development of gene therapy clinical trials for XLMTM. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Malformations among 289,365 Births Attributed to Mutations with Autosomal Dominant and Recessive and X-Linked Inheritance.

PubMed

Toufaily, M Hassan; Westgate, Marie-Noel; Nasri, Hanah; Holmes, Lewis B

2018-01-01

The number of malformations attributed to mutations with autosomal or X-linked patterns of inheritance has increased steadily since the cataloging began in the 1960s. These diagnoses have been based primarily on the pattern of phenotypic features among close relatives. A malformations surveillance program conducted in consecutive pregnancies can identify both known and "new" hereditary disorders. The Active Malformations Surveillance Program was carried out among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in Boston. The findings recorded by examining pediatricians and all consultants were reviewed by study clinicians to establish the most likely diagnoses. The findings in laboratory testing in the newborn period were reviewed, as well. One hundred ninety-six (0.06%) infants among 289,365 births had a malformation or malformation syndrome that was attributed to Mendelian inheritance. A total of 133 (68%) of the hereditary malformations were attributed to autosomal dominant inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty-six (23%) were attributed to mutations with autosomal recessive inheritance, 17 associated with consanguinity. Seventeen (9%) were attributed to X-linked inheritance. Fifteen novel familial phenotypes were identified. The family histories showed that most (53 to 71%) of the affected infants were born, as a surprise, to healthy, unaffected parents. It is important for clinicians to discuss with surprised healthy parents how they can have an infant with an hereditary condition. Future studies, using DNA samples from consecutive populations of infants with malformations and whole genome sequencing, will identify many more mutations in loci associated with mendelizing phenotypes. Birth Defects Research 110:92-97, 2018.© 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Language dominance, handedness and sex: recessive X-linkage theory and test.

PubMed

Jones, Gregory V; Martin, Maryanne

2010-06-01

The possibility is investigated that cerebral dominance for language and handedness share a common X-linkage and that the relation between the two is therefore a function of sex. In particular, an X-linked recessive account is shown to predict an overall configuration of language dominance, handedness and sex within which there is a sex effect in the pattern of language dominance among right-handed but not left-handed people. The recent accurate determination of cerebral dominance among relatively large samples of the general population by means of functional transcranial Doppler ultrasonography makes it possible to test this new theory rigorously, and its parameter-free pattern of predictions is found to be supported. Copyright (c) 2009 Elsevier Srl. All rights reserved.

INTERACTION OF X AND ULTRAVIOLET RADIATION IN PRODUCTION OF RECESSIVE LETHALS IN DROSOPHILA MELANOGASTER (in Italian)

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

Nicoletti, B.; Olivieri, G.

1962-01-01

The possibility that uv rays given to different biological systems before or after x rays could modify genetic or cytological effects is reviewed and discussed. Kaufmann and Hollaender's conclusions about the recovering effect of uv rays on chromosomal damage induced in Drosophila sperms by a pre-treatment of x rays are discussed and analyzed taking into accourt some general considerations. Preliminary results of similar experiments on the frequency of sex-linked recessive lethals induced after single and combined x + uv treatments in Drosophila sperms are reported. All our experiments indicate no effect of the uv treatment (at the given wave lengthsmore » and doses) in lowering the frequency of the x-ray-induced recessive lethals. On the contrary, there are some indications for a synergistic action between the two radiations. These results not in agreement with the generally accepted theory that uv rays do recover X-ray- induced chromosomal damages, could be expiained With the well established correlation between chromosomal rejoined breaks and genic mutations. (auth)« less

Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant).

PubMed

Bichet, Daniel G; Bockenhauer, Detlef

2016-03-01

Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. About 90% of patients with congenital NDI are males with X-linked NDI who have mutations in the vasopressin V2 receptor (AVPR2) gene encoding the vasopressin V2 receptor. In less than 10% of the families studied, congenital NDI has an autosomal recessive or autosomal dominant mode of inheritance with mutations in the aquaporin-2 (AQP2) gene. When studied in vitro, most AVPR2 and AQP2 mutations lead to proteins trapped in the endoplasmic reticulum and are unable to reach the plasma membrane. Prior knowledge of AVPR2 or AQP2 mutations in NDI families and perinatal mutation testing is of direct clinical value and can avert the physical and mental retardation associated with repeated episodes of dehydration. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes

PubMed Central

Krasovec, Marc; Filatov, Dmitry A.

2018-01-01

Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (πx = 0.016; πaut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex. PMID:29751495

A Comparison of Selective Pressures in Plant X-Linked and Autosomal Genes.

PubMed

Krasovec, Marc; Nevado, Bruno; Filatov, Dmitry A

2018-05-03

Selection is expected to work differently in autosomal and X-linked genes because of their ploidy difference and the exposure of recessive X-linked mutations to haploid selection in males. However, it is not clear whether these expectations apply to recently evolved sex chromosomes, where many genes retain functional X- and Y-linked gametologs. We took advantage of the recently evolved sex chromosomes in the plant Silene latifolia and its closely related species to compare the selective pressures between hemizygous and non-hemizygous X-linked genes as well as between X-linked genes and autosomal genes. Our analysis, based on over 1000 genes, demonstrated that, similar to animals, X-linked genes in Silene evolve significantly faster than autosomal genes—the so-called faster-X effect. Contrary to expectations, faster-X divergence was detectable only for non-hemizygous X-linked genes. Our phylogeny-based analyses of selection revealed no evidence for faster adaptation in X-linked genes compared to autosomal genes. On the other hand, partial relaxation of purifying selection was apparent on the X-chromosome compared to the autosomes, consistent with a smaller genetic diversity in S. latifolia X-linked genes (π x = 0.016; π aut = 0.023). Thus, the faster-X divergence in S. latifolia appears to be a consequence of the smaller effective population size rather than of a faster adaptive evolution on the X-chromosome. We argue that this may be a general feature of “young” sex chromosomes, where the majority of X-linked genes are not hemizygous, preventing haploid selection in heterogametic sex.

X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

PubMed

Hong, Che Ry; Kang, Hee Gyung; Choi, Hyun Jin; Cho, Min Hyun; Lee, Jung Won; Kang, Ju Hyung; Park, Hye Won; Koo, Ja Wook; Ha, Tae-Sun; Kim, Su-Yung; Il Cheong, Hae

2014-01-01

A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

X-linked adrenoleukodystrophy in heterozygous female patients: women are not just carriers.

PubMed

Lourenço, Charles Marques; Simão, Gustavo Novelino; Santos, Antonio Carlos; Marques, Wilson

2012-07-01

X-linked adrenoleukodystrophy (X-ALD) is a recessive X-linked disorder associated with marked phenotypic variability. Female carriers are commonly thought to be normal or only mildly affected, but their disease still needs to be better described and systematized. To review and systematize the clinical features of heterozygous women followed in a Neurogenetics Clinic. We reviewed the clinical, biochemical, and neuroradiological data of all women known to have X-ADL. The nine women identified were classified into three groups: with severe and aggressive diseases; with slowly progressive, spastic paraplegia; and with mildly decreased vibratory sensation, brisk reflexes, and no complaints. Many of these women did not have a known family history of X-ALD. Heterozygous women with X-ADL have a wide spectrum of clinical manifestations, ranging from mild to severe phenotypes.

X-linked recessive primary retinal dysplasia is linked to the Norrie disease locus.

PubMed

Ravia, Y; Braier-Goldstein, O; Bat-Miriam, K M; Erlich, S; Barkai, G; Goldman, B

1993-08-01

X-linked primary retinal dysplasia (PRD) refers to an abnormal proliferation of retinal tissue causing either its neural elements or its glial tissue to form folds, giving rise to gliosis. A Jewish family of oriental origin was previously reported by Godel and Goodman, in which a total of five males suffer from different degrees of blindness. The authors postulated that the described findings are distinguished from Norrie disease, since in this case no clinical findings, other than those associated with the eyes, were noticed in the affected males. In addition, two of the carrier females exhibit minimal eye changes. We have performed linkage analysis of the family using the L1.28, p58-1 and m27 beta probes, and DXS426 and MAOB associated microsatellites. Our results map the gene responsible for the disorder between the MAOB and DXS426, m27 beta and p58-1 loci, on the short arm of the X chromosome at Xp11.3, which suggest the possibility that the same gene is responsible for both primary retinal dysplasia and Norrie disease.

Molecular characterization of a novel X-linked syndrome involving developmental delay and deafness.

PubMed

Hildebrand, Michael S; de Silva, Michelle G; Tan, Tiong Yang; Rose, Elizabeth; Nishimura, Carla; Tolmachova, Tanya; Hulett, Joanne M; White, Susan M; Silver, Jeremy; Bahlo, Melanie; Smith, Richard J H; Dahl, Hans-Henrik M

2007-11-01

X-linked syndromes associated with developmental delay and sensorineural hearing loss (SNHL) have been characterized at the molecular level, including Mohr-Tranebjaerg syndrome and Norrie disease. In this study we report on a novel X-linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X-linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X-chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3-q21.32 and a deletion was identified in a regulatory region upstream of the POU3F4 gene in affected family members. Since mutations in POU3F4 cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (CHM) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP-1) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP-1 expression in the brain determined. However, subsequent analysis revealed that this change in CHM was polymorphic having no effect on REP-1 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. Copyright 2007 Wiley-Liss, Inc.

Use of topical dorzolamide for patients with X-linked juvenile retinoschisis: case report.

PubMed

Bastos, André Luís Carvalho de Moura; Freitas, Bruno de Paula; Villas Boas, Oscar; Ramiro, Alexandre Campelo

2008-01-01

X-linked juvenile retinoschisis (XLRS) is a recessively inherited vitreoretinal degeneration characterized by macular pathology and splitting of the neuroretinal layers that is associated with alterations in the XLRS1 gene. There have been no therapeutic interventions known to be effective for patients with X-linked juvenile retinoschisis, but some studies are trying to determine the importance of dorzolamide for the treatment of foveal lesions in this disease. The authors, using optical coherence tomography, describe findings in a patient with X-linked juvenile retinoschisis, before and after a topical use of dorzolamide. Besides the improvement in his visual acuity, further studies are required to elucidate the real prevalence of nonresponse to dorzolamide and the frequency with which there may be a recurrence of foveal cystic changes during continued treatment.

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

PubMed

Katz, Bradley J; Zhao, Yu; Warner, Judith E A; Tong, Zongzhong; Yang, Zhenglin; Zhang, Kang

2006-10-15

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such

The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2.

PubMed

Tiret, Laurent; Blot, Stéphane; Kessler, Jean-Louis; Gaillot, Hugues; Breen, Matthew; Panthier, Jean-Jacques

2003-09-01

Myotubular/centronuclear myopathies are a nosological group of hereditary disorders characterised by severe architectural and metabolic remodelling of skeletal muscle fibres. In most myofibres, nuclei are found at an abnormal central position within a halo devoid of myofibrillar proteins. The X-linked form (myotubular myopathy) is the most prevalent and severe form in human, leading to death during early postnatal life. Maturation of fibres is not completed and fibres resemble myotubes. Linkage analysis in human has helped to identify MTM1 as the morbid gene. MTM1 encodes myotubularin, a dual protein phosphatase. In families in which myotubular myopathy segregates, detected mutations in MTM1 abolish the specific phosphatase activity targeting the second messenger phosphatidylinositol 3-phosphate. Autosomal forms (centronuclear) have a later onset and are often compatible with life. At birth, fibres are normally constituted but progressively follow remodelling with a secondary centralisation of nuclei. Their prevalence is low; hence, no linkage data can be performed and no molecular aetiology is known. In the Labrador Retriever, a spontaneous disorder strikingly mimics the clinical evolution of the human centronuclear myopathy. We have established a canine pedigree and show that the disorder segregates as an autosomal recessive trait in that pedigree. We have further mapped the dog locus to a region on chromosome 2 that is orthologous to human chromosome 10p. To date, no human MTM1 gene member has been mapped to this genetic region. This report thus describes the first spontaneous mammalian model of centronuclear myopathy and defines a new locus for this group of diseases.

Editorial: X-chromosome-linked Kallmann's syndrome: Pathology at the molecular level

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

Prager, D.; Braunstein, G.D.

Kallmann's syndrome or olfactogenital dysplasia refers to a disorder characterized by hypogonadotropic hypogonadism and anosmia or hyposmia which can occur sporadically or in a familial setting. Originally described in 1856, the first familial cases were reported by Kallmann et al., in 1944. Based on segregation analysis of multiple families, three modes of transmission have been documented: X-linked, autosomal dominant with variable penetrance, and autosomal recessive. Kallmann's syndrome occurs in less than 1 in 10,000 male births, with a 5-fold excess of affected males to females, suggesting that the X-linked form is the most frequent. By genetic linkage analysis the X-linkedmore » form of Kallmann's syndrome was localized to Xp22.3. This was confirmed by the description of patients with contiguous gene syndromes due to deletions of various portions of the distal short arm of the X-chromosome. Such patients present with complex phenotypes characterized by a combination of Kallmann's syndrome with X-linked icthyosis due to steroid sulfatase deficiency, chondrodysplasia punctata, short stature, and mental retardation. DNA analysis has identified and mapped the genes responsible for these disorders. 10 refs., 1 fig., 1 tab.« less

Application of carrier testing to genetic counseling for X-linked agammaglobulinemia

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

Allen, R.C.; Nachtman, R.G.; Belmont, J.W.

Bruton X-linked agammaglobulinemia (XLA) is a phenotypically recessive genetic disorder of B lymphocyte development. Female carriers of XLA, although asymptomatic, have a characteristic B cell lineage-specific skewing of the pattern of X inactivation. Skewing apparently results from defective growth and maturation of B cell precursors bearing a mutant active X chromosome. In this study, carrier status was tested in 58 women from 22 families referred with a history of agammaglobulinemia. Primary carrier analysis to examine patterns of X inactivation in CD19[sup +] peripheral blood cells (B lymphocytes) was conducted using quantitative PCR at the androgen-receptor locus. Obligate carriers of XLAmore » demonstrated >95% skewing of X inactivation in peripheral blood CD19[sup +] cells but not in CD19[sup [minus

Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome?

PubMed Central

Jonsson, J J; Renieri, A; Gallagher, P G; Kashtan, C E; Cherniske, E M; Bruttini, M; Piccini, M; Vitelli, F; Ballabio, A; Pober, B R

1998-01-01

We describe a family with four members, a mother, two sons, and a daughter, who show clinical features consistent with X linked Alport syndrome. The two males presented with additional features including mental retardation, dysmorphic facies with marked midface hypoplasia, and elliptocytosis. The elliptocytosis was not associated with any detectable abnormalities in red cell membrane proteins; red cell membrane stability and rigidity was normal on ektacytometry. Molecular characterisation suggests a submicroscopic X chromosome deletion encompassing the entire COL4A5 gene. We propose that the additional abnormalities found in the affected males of this family are attributable to deletion or disruption of X linked recessive genes adjacent to the COL4A5 gene and that this constellation of findings may represent a new X linked contiguous gene deletion syndrome. Images PMID:9598718

Mutagenic Potential of Nitroguanidine in the Drosophila melanogaster Sex-Linked Recessive Lethal Test

DTIC Science & Technology

1988-07-01

Security Classification) Mtutagenic potential of nitroguan idine in the Drosophila melano- gaster sex-linked recessive lethal test 12. PERSONAL AUTHOR(S...Frederick, MD 21701-5012 Commander Commandant US Army Environmental Hygine Academy of Health Sciences. US Army Agency ATTN: AHS-CDM ATTN: Librarian, HSDH

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

Simultaneous Occurence of an Autosomal Dominant Inherited MSX1 Mutation and an X-linked Recessive Inherited EDA Mutation in One Chinese Family with Non-syndromic Oligodontia.

PubMed

Zhang, Xiao Xia; Wong, Sing Wai; Han, Dong; Feng, Hai Lan

2015-01-01

To describe the simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with nonsyndromic oligodontia. Clinical data of characteristics of tooth agenesis were collected. MSX1 and EDA gene mutations were detected in a Chinese family of non-syndromic oligodontia. Mild hypodontia in the parents and severe oligodontia in the son was recorded. A novel missense heterozygous mutation c.517C>A (p.Arg173Ser) was detected in the MSX1 gene in the boy and the father. A homozygous missense mutation c.1001G>A (p.Arg334His) was detected in the EDA gene in the boy and the same mutant occurred heterozygously in the mother. Simultaneous occurence of two different gene mutations with different inheritence patterns, which both caused oligodontia, which occurred in one subject and in one family, was reported.

X-linked juvenile retinoschisis in females and response to carbonic anhydrase inhibitors: case report and review of the literature.

PubMed

Ali, Syed; Seth, Rajeev

2013-01-01

A 63 year old woman was referred to the retina clinic after her vision failed to improve in her left eye after cataract surgery. X-linked retinoschisis was diagnosed in the patient after her retina exam revealed an area of retinoschisis and a foveal cyst. The OCT confirmed the macular cyst and the ERG showed loss of B waves. The florescein angiogram showed no significant perifoveal leakage. Her foveal cyst resolved after treatment with carbonic anhydrase inhibitors. The patient's son was examined and his ophthalmologic exam, ERG and imaging findings were consistent with X-linked retinoschisis. However, his bilateral foveal cysts did not respond to treatment with carbonic anhydrase inhibitors. X-linked retinoschisis is a very rare disease in women due to its X-linked recessive inheritance and the foveal cysts associated with it can respond to carbonic anhydrase inhibitors.

Vitreoretinal surgery without schisis cavity excision for the management of juvenile X linked retinoschisis.

PubMed

García-Arumí, J; Corcóstegui, I A; Navarro, R; Zapata, M A; Berrocal, M H

2008-11-01

Juvenile X linked retinoschisis (XLRS) is a congenital X linked recessive retinal disorder characterised by cystic maculopathy and peripheral schisis. This study presents the case of an 8-month-old boy with a documented positive family history of XLRS, with a large retinoschisis cavity affecting the macula, first in the left eye and 1 year later in the right eye. The patient underwent pars plana vitrectomy in both eyes using 23-G instruments, posterior hyaloid dissection, a small retinotomy, fluid drainage with a 42-G cannula, infrared diode laser and silicone oil as internal tamponade. The anatomical and functional outcomes at 3 years following the first surgery are described. To the authors' knowledge, there is no previously reported experience with this technique in patients with XLRS.

Transcription map of Xq27: candidates for several X-linked diseases.

PubMed

Zucchi, I; Jones, J; Affer, M; Montagna, C; Redolfi, E; Susani, L; Vezzoni, P; Parvari, R; Schlessinger, D; Whyte, M P; Mumm, S

1999-04-15

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found. Copyright 1999 Academic Press.

Faster-X evolution of gene expression is driven by recessive adaptive cis-regulatory variation in Drosophila.

PubMed

Llopart, Ana

2018-05-01

The hemizygosity of the X (Z) chromosome fully exposes the fitness effects of mutations on that chromosome and has evolutionary consequences on the relative rates of evolution of X and autosomes. Specifically, several population genetics models predict increased rates of evolution in X-linked loci relative to autosomal loci. This prediction of faster-X evolution has been evaluated and confirmed for both protein coding sequences and gene expression. In the case of faster-X evolution for gene expression divergence, it is often assumed that variation in 5' noncoding sequences is associated with variation in transcript abundance between species but a formal, genomewide test of this hypothesis is still missing. Here, I use whole genome sequence data in Drosophila yakuba and D. santomea to evaluate this hypothesis and report positive correlations between sequence divergence at 5' noncoding sequences and gene expression divergence. I also examine polymorphism and divergence in 9,279 noncoding sequences located at the 5' end of annotated genes and detected multiple signals of positive selection. Notably, I used the traditional synonymous sites as neutral reference to test for adaptive evolution, but I also used bases 8-30 of introns <65 bp, which have been proposed to be a better neutral choice. X-linked genes with high degree of male-biased expression show the most extreme adaptive pattern at 5' noncoding regions, in agreement with faster-X evolution for gene expression divergence and a higher incidence of positively selected recessive mutations. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Unilateral Autosomal Recessive Anophthalmia in a Patient with Cystic Craniopharyngioma

PubMed Central

Kumar, Amandeep; Bansal, Ankit; Garg, Ajay; Sharma, Bhawani S.

2014-01-01

Abstract Anophthalmia is a rare ocular malformation. It is a genetically determined disorder and is typically associated with syndromes. However, sporadic nonsyndromic familial as well as non-familial cases of anophthalmia have also been reported. Non-syndromic familial cases are usually bilateral and have been attributed to autosomal recessive, autosomal dominant, and X-linked inheritance patterns. The authors hereby report a rare case of autosomal recessive unilateral anophthalmia in a patient with no other associated congenital anomaly. Patient was operated for craniopharyngioma. The clinical, radiological and intraoperative findings are discussed. PMID:27928292

Suspected X-linked facial dysmorphia and growth retardation in related Labrador retriever puppies.

PubMed

Dierks, C; Hoffmann, H; Heinrich, F; Hellige, M; Hewicker-Trautwein, M; Distl, O

2017-02-01

Seven male Labrador retriever puppies from four different litters were identified with a brachycephalic-like face and skull, associated with low birth weight, severe growth retardation, and reduced abilities to crawl and suckle, which were not compatible with survival. Excessive doming of the cranium, brachygnathia superior and inferior, and an abnormally opened fontanelle were found in all affected puppies by computed tomography and at post-mortem examination. Pedigree analysis supported an X-linked recessive mode of inheritance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR.

PubMed

Riveiro-Alvarez, Rosa; Trujillo-Tiebas, Maria José; Gimenez-Pardo, Ascension; Garcia-Hoyos, Maria; Cantalapiedra, Diego; Lorda-Sanchez, Isabel; Rodriguez de Alba, Marta; Ramos, Carmen; Ayuso, Carmen

2005-09-02

Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.

Recession in the Regions

ERIC Educational Resources Information Center

Plant, Helen

2009-01-01

National policy stresses the key role of adult learning and skills in securing economic recovery. This close linking of adult learning policy to the recession agenda raises important questions. How has the recession impacted on the implementation of adult learning policy? What has it meant for service delivery? And what have been the consequences…

Convergence of Human Genetics and Animal Studies: Gene Therapy for X-Linked Retinoschisis

PubMed Central

Bush, Ronald A.; Wei, Lisa L.; Sieving, Paul A.

2015-01-01

Retinoschisis is an X-linked recessive genetic disease that leads to vision loss in males. X-linked retinoschisis (XLRS) typically affects young males; however, progressive vision loss continues throughout life. Although discovered in 1898 by Haas in two brothers, the underlying biology leading to blindness has become apparent only in the last 15 years with the advancement of human genetic analyses, generation of XLRS animal models, and the development of ocular monitoring methods such as the electroretinogram and optical coherence tomography. It is now recognized that retinoschisis results from cyst formations within the retinal layers that interrupt normal visual neurosignaling and compromise structural integrity. Mutations in the human retinoschisin gene have been correlated with disease severity of the human XLRS phenotype. Introduction of a normal human retinoschisin cDNA into retinoschisin knockout mice restores retinal structure and improves neural function, providing proof-of-concept that gene replacement therapy is a plausible treatment for XLRS. PMID:26101206

Faster-X evolution: Theory and evidence from Drosophila.

PubMed

Charlesworth, Brian; Campos, José L; Jackson, Benjamin C

2018-02-12

A faster rate of adaptive evolution of X-linked genes compared with autosomal genes can be caused by the fixation of recessive or partially recessive advantageous mutations, due to the full expression of X-linked mutations in hemizygous males. Other processes, including recombination rate and mutation rate differences between X chromosomes and autosomes, may also cause faster evolution of X-linked genes. We review population genetics theory concerning the expected relative values of variability and rates of evolution of X-linked and autosomal DNA sequences. The theoretical predictions are compared with data from population genomic studies of several species of Drosophila. We conclude that there is evidence for adaptive faster-X evolution of several classes of functionally significant nucleotides. We also find evidence for potential differences in mutation rates between X-linked and autosomal genes, due to differences in mutational bias towards GC to AT mutations. Many aspects of the data are consistent with the male hemizygosity model, although not all possible confounding factors can be excluded. © 2018 John Wiley & Sons Ltd.

A Mutation in the Rett Syndrome Gene, MECP2, Causes X-Linked Mental Retardation and Progressive Spasticity in Males

PubMed Central

Meloni, Ilaria; Bruttini, Mirella; Longo, Ilaria; Mari, Francesca; Rizzolio, Flavio; D’Adamo, Patrizia; Denvriendt, Koenraad; Fryns, Jean-Pierre; Toniolo, Daniela; Renieri, Alessandra

2000-01-01

Heterozygous mutations in the X-linked MECP2 gene cause Rett syndrome, a severe neurodevelopmental disorder of young females. Only one male presenting an MECP2 mutation has been reported; he survived only to age 1 year, suggesting that mutations in MECP2 are male lethal. Here we report a three-generation family in which two affected males showed severe mental retardation and progressive spasticity, previously mapped in Xq27.2-qter. Two obligate carrier females showed either normal or borderline intelligence, simulating an X-linked recessive trait. The two males and the two obligate carrier females presented a mutation in the MECP2 gene, demonstrating that, in males, MECP2 can be responsible for severe mental retardation associated with neurological disorders. PMID:10986043

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

PubMed Central

Bustamante, Jacinta; Arias, Andres A; Vogt, Guillaume; Picard, Capucine; Galicia, Lizbeth Blancas; Prando, Carolina; Grant, Audrey V; Marchal, Christophe C; Hubeau, Marjorie; Chapgier, Ariane; de Beaucoudrey, Ludovic; Puel, Anne; Feinberg, Jacqueline; Valinetz, Ethan; Jannière, Lucile; Besse, Céline; Boland, Anne; Brisseau, Jean-Marie; Blanche, Stéphane; Lortholary, Olivier; Fieschi, Claire; Emile, Jean-François; Boisson-Dupuis, Stéphanie; Al-Muhsen, Saleh; Woda, Bruce; Newburger, Peter E; Condino-Neto, Antonio; Dinauer, Mary C; Abel, Laurent; Casanova, Jean-Laurent

2011-01-01

Germline mutations in CYBB, the human gene encoding the gp91phox subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This ‘experiment of nature’ indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria. PMID:21278736

X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations

PubMed Central

Savige, Judith; Storey, Helen; Il Cheong, Hae; Gyung Kang, Hee; Park, Eujin; Hilbert, Pascale; Persikov, Anton; Torres-Fernandez, Carmen; Ars, Elisabet; Torra, Roser; Hertz, Jens Michael; Thomassen, Mads; Shagam, Lev; Wang, Dongmao; Wang, Yanyan; Flinter, Frances; Nagel, Mato

2016-01-01

Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all published COL4A5, COL4A3 and COL4A4 variants in the LOVD databases. It also determined genotype-phenotype correlations for variants where clinical data were available. Individuals were referred for genetic testing where Alport syndrome was suspected clinically or on biopsy (renal failure, hearing loss, retinopathy, lamellated glomerular basement membrane), variant pathogenicity was assessed using currently-accepted criteria, and variants were examined for gene location, and age at renal failure onset. Results were compared using Fisher’s exact test (DNA Stata). Altogether 754 new DNA variants were identified, an increase of 25%, predominantly in people of European background. Of the 1168 COL4A5 variants, 504 (43%) were missense mutations, 273 (23%) splicing variants, 73 (6%) nonsense mutations, 169 (14%) short deletions and 76 (7%) complex or large deletions. Only 135 of the 432 Gly residues in the collagenous sequence were substituted (31%), which means that fewer than 10% of all possible variants have been identified. Both missense and nonsense mutations in COL4A5 were not randomly distributed but more common at the 70 CpG sequences (p<10−41 and p<0.001 respectively). Gly>Ala substitutions were underrepresented in all three genes (p< 0.0001) probably because of an association with a milder phenotype. The average age at end-stage renal failure was the same for all mutations in COL4A5 (24.4 ±7.8 years), COL4A3 (23.3 ± 9.3) and COL4A4 (25.4 ± 10.3) (COL4A5 and COL4A3, p = 0.45; COL4A5 and COL4A4, p = 0.55; COL4A3 and COL4A4, p = 0.41). For COL4A5, renal failure occurred sooner with non-missense than missense variants (p<0.01). For the COL4A3 and COL4A4 genes, age at renal

X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations.

PubMed

Savige, Judith; Storey, Helen; Il Cheong, Hae; Gyung Kang, Hee; Park, Eujin; Hilbert, Pascale; Persikov, Anton; Torres-Fernandez, Carmen; Ars, Elisabet; Torra, Roser; Hertz, Jens Michael; Thomassen, Mads; Shagam, Lev; Wang, Dongmao; Wang, Yanyan; Flinter, Frances; Nagel, Mato

2016-01-01

Alport syndrome results from mutations in the COL4A5 (X-linked) or COL4A3/COL4A4 (recessive) genes. This study examined 754 previously- unpublished variants in these genes from individuals referred for genetic testing in 12 accredited diagnostic laboratories worldwide, in addition to all published COL4A5, COL4A3 and COL4A4 variants in the LOVD databases. It also determined genotype-phenotype correlations for variants where clinical data were available. Individuals were referred for genetic testing where Alport syndrome was suspected clinically or on biopsy (renal failure, hearing loss, retinopathy, lamellated glomerular basement membrane), variant pathogenicity was assessed using currently-accepted criteria, and variants were examined for gene location, and age at renal failure onset. Results were compared using Fisher's exact test (DNA Stata). Altogether 754 new DNA variants were identified, an increase of 25%, predominantly in people of European background. Of the 1168 COL4A5 variants, 504 (43%) were missense mutations, 273 (23%) splicing variants, 73 (6%) nonsense mutations, 169 (14%) short deletions and 76 (7%) complex or large deletions. Only 135 of the 432 Gly residues in the collagenous sequence were substituted (31%), which means that fewer than 10% of all possible variants have been identified. Both missense and nonsense mutations in COL4A5 were not randomly distributed but more common at the 70 CpG sequences (p<10-41 and p<0.001 respectively). Gly>Ala substitutions were underrepresented in all three genes (p< 0.0001) probably because of an association with a milder phenotype. The average age at end-stage renal failure was the same for all mutations in COL4A5 (24.4 ±7.8 years), COL4A3 (23.3 ± 9.3) and COL4A4 (25.4 ± 10.3) (COL4A5 and COL4A3, p = 0.45; COL4A5 and COL4A4, p = 0.55; COL4A3 and COL4A4, p = 0.41). For COL4A5, renal failure occurred sooner with non-missense than missense variants (p<0.01). For the COL4A3 and COL4A4 genes, age at renal failure

Time to Play: Recognizing the Benefits of Recess

ERIC Educational Resources Information Center

Ramstetter, Catherine; Murray, Robert

2017-01-01

Given the evidence of the value of recess for children and teachers, what can educators, schools, and districts do to promote this critical aspect of the education of the whole child? Daily decisions about who gets recess and when and where it will happen are often made by teachers; thus, teachers are a crucial link for recess. Policies that…

Genetics of recessive cognitive disorders.

PubMed

Musante, Luciana; Ropers, H Hilger

2014-01-01

Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitochondrial Hsp60 Chaperonopathy Causes an Autosomal-Recessive Neurodegenerative Disorder Linked to Brain Hypomyelination and Leukodystrophy

PubMed Central

Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna

2008-01-01

Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration. PMID:18571143

Maxillary distraction osteogenesis for treatment of cleft lip and palate in a patient with X-linked agammaglobulinemia.

PubMed

Sato, Yutaka; Mishimagi, Takashi; Katsuki, Yuko; Harada, Kiyoshi

2014-07-01

X-linked agammaglobulinemia (XLA) is a congenital immune deficiency disorder caused by abnormal antibody production. It is a rare disease with an estimated frequency of 1 in 379,000 that has X-linked recessive heredity and develops only in males. The clinical problems include bacterial infection such as otitis media, sinusitis, and bronchitis. In recent years it has become possible to diagnose XLA in the early stage and intravenous immunoglobulin replacement therapy has permitted survival to adulthood. However, there have been no reports of oral surgery in patients with XLA. Here, we describe a case in which immunoglobulin replacement therapy given pre- and postoperatively was used to control infection in oral surgery and maxillary distraction osteogenesis performed for improving occlusion and appearance of a cleft lip and palate in a patient with XLA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene

PubMed Central

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-01-01

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. PMID:20137772

[Importance of family examination in juvenile X-linked retinoschisis].

PubMed

Kłosowska-Zawadka, A; Bernardczyk-Meller, J; Gotz-Wieckowska, A; Krawczyński, M

2005-12-01

Congenital (juvenile) retinoschisis belongs to the group of hereditary vitreoretinopathies. This disorder is inherited in an X-linked recessive pattern and its onset usually occurs in 5- to 10-year-old boys. Presenting clinical signs include decreased visual acuity due to maculopathy. The authors present a case of a 17-year-old boy with decreased visual acuity, hypermetropia, and bilateral retinoschisis with maculopathy upon fundus examination. In view of a 50% risk of the disorder occurring in the brothers of the affected male, they underwent full ophthalmological and electrophysiological examinations (until then asymptomatic). In one of them decreased visual acuity, mixed astigmatism, and maculopathy were present, without any changes of the peripheral retina. In the youngest brother decreased visual acuity, hypermetropia, and maculopathy were diagnosed. Genetic counseling and ophthalmological examination of family members at risk facilitated early recognition of the pathological changes in the siblings. Genetic counseling with pedigree analysis and genetic analysis, if possible, should be offered to all affected patients and family members.

Genetics Home Reference: X-linked dilated cardiomyopathy

MedlinePlus

... Twitter Home Health Conditions X-linked dilated cardiomyopathy X-linked dilated cardiomyopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked dilated cardiomyopathy is a form of heart ...

Genetics Home Reference: X-linked sideroblastic anemia

MedlinePlus

... Twitter Home Health Conditions X-linked sideroblastic anemia X-linked sideroblastic anemia Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia is an inherited disorder that ...

Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

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

Shugart, Yin Y.; Banerjee, P.; Knowles, J.A.

1995-08-01

The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS.more » 26 refs., 2 figs., 1 tab.« less

Genetic Analysis of X-Chromosome Dosage Compensation in Caenorhabditis elegans

PubMed Central

Meneely, Philip M.; Wood, William B.

1987-01-01

We have shown that the phenotypes resulting from hypomorphic mutations (causing reduction but not complete loss of function) in two X-linked genes can be used as a genetic assay for X-chromosome dosage compensation in Caenorhabditis elegans between males ( XO) and hermaphrodites (XX). In addition we show that recessive mutations in two autosomal genes, dpy-21 V and dpy-26 IV, suppress the phenotypes resulting from the X-linked hypomorphic mutations, but not the phenotypes resulting from comparable autosomal hypomorphic mutations. This result strongly suggests that the dpy-21 and dpy-26 mutations cause increased X expression, implying that the normal function of these genes may be to lower the expression of X-linked genes. Recessive mutations in two other dpy genes, dpy-22 X and dpy-23 X, increase the severity of phenotypes resulting from some X-linked hypomorphic mutations, although dpy-23 may affect the phenotypes resulting from the autosomal hypomorphs as well. The mutations in all four of the dpy genes show their effects in both XO and XX animals, although to different degrees. Mutations in 18 other dpy genes do not show these effects. PMID:3666440

Geomorphological origin of recession curves

NASA Astrophysics Data System (ADS)

Biswal, Basudev; Marani, Marco

2010-12-01

We identify a previously undetected link between the river network morphology and key recession curves properties through a conceptual-physical model of the drainage process of the riparian unconfined aquifer. We show that the power-law exponent, α, of -dQ/dt vs. Q curves is related to the power-law exponent of N(l) vs. G(l) curves (which we show to be connected to Hack's law), where l is the downstream distance from the channel heads, N(l) is the number of channel reaches exactly located at a distance l from their channel head, and G(l) is the total length of the network located at a distance greater or equal to l from channel heads. Using Digital Terrain Models and daily discharge observations from 67 US basins we find that geomorphologic α estimates match well the values obtained from recession curves analyses. Finally, we argue that the link between recession flows and network morphology points to an important role of low-flow discharges in shaping the channel network.

Mapping the x-linked lymphoproliferative syndrome

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

Skare, J.C.; Milunsky, A.; Byron, K.S.

1987-04-01

The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predictmore » which members of a family with X-linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally.« less

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

PubMed

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

PubMed

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-02-12

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: X-linked severe combined immunodeficiency

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked SCID X-linked severe combined immunodeficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked severe combined immunodeficiency (SCID) is an inherited ...

Genetics Home Reference: X-linked adrenal hypoplasia congenita

MedlinePlus

... Home Health Conditions X-linked adrenal hypoplasia congenita X-linked adrenal hypoplasia congenita Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked adrenal hypoplasia congenita is a disorder that ...

Genetics Home Reference: X-linked chondrodysplasia punctata 1

MedlinePlus

... Home Health Conditions X-linked chondrodysplasia punctata 1 X-linked chondrodysplasia punctata 1 Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked chondrodysplasia punctata 1 is a disorder of ...

X-linked juvenile retinoschisis: mutations at the retinoschisis and Norrie disease gene loci?

PubMed

Hiraoka, M; Rossi, F; Trese, M T; Shastry, B S

2001-01-01

Juvenile retinoschisis (RS) and Norrie disease (ND) are X-linked recessive retinal disorders. Both disorders, in the majority of cases, are monogenic and are caused by mutations in the RS and ND genes, respectively. Here we report the identification of a family in which mutations in both the RS and ND genes are segregating with RS pathology. Although the mutations identified in this report were not functionally characterized with regard to their pathogenicity, it is likely that both of them are involved in RS pathology in the family analyzed. This suggests the complexity and digenic nature of monogenic human disorders in some cases. If this proves to be a widespread problem, it will complicate the strategies used to identify the genes involved in diseases and to develop methods for intervention.

Playing fair: the contribution of high-functioning recess to overall school climate in low-income elementary schools.

PubMed

London, Rebecca A; Westrich, Lisa; Stokes-Guinan, Katie; McLaughlin, Milbrey

2015-01-01

Recess is a part of the elementary school day with strong implications for school climate. Positive school climate has been linked to a host of favorable student outcomes, from attendance to achievement. We examine 6 low-income elementary schools' experiences implementing a recess-based program designed to provide safe, healthy, and inclusive play to study how improving recess functioning can affect school climate. Data from teacher, principal, and recess coach interviews; student focus groups; recess observations; and a teacher survey are triangulated to understand the ways that recess changed during implementation. Comparing schools that achieved higher- and lower-functioning recesses, we link recess functioning with school climate. Recess improved in all schools, but 4 of the 6 achieved a higher-functioning recess. In these schools, teachers and principals agreed that by the end of the year, recess offered opportunities for student engagement, conflict resolution, pro-social skill development, and emotional and physical safety. Respondents in these four schools linked these changes to improved overall school climate. Recess is an important part of the school day for contributing to school climate. Creating a positive recess climate helps students to be engaged in meaningful play and return to class ready to learn. © 2014, American School Health Association.

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.

Novel compound heterozygous mutations in SERPINH1 cause rare autosomal recessive osteogenesis imperfecta type X.

PubMed

Song, Y; Zhao, D; Xu, X; Lv, F; Li, L; Jiang, Y; Wang, O; Xia, W; Xing, X; Li, M

2018-03-09

We identified novel compound heterozygous mutations in SERPINH1 in a Chinese boy suffering from recurrent fractures, femoral deformities, and growth retardation, which resulted in extremely rare autosomal recessive OI type X. Long-term treatment of BPs was effective in increasing BMD Z-score, reducing fracture incidence and reshaping vertebrae compression. Osteogenesis imperfecta (OI) is a heritable bone disorder characterized by low bone mineral density, recurrent fractures, and progressive bone deformities. Mutation in serpin peptidase inhibitor clade H, member 1 (SERPINH1), which encodes heat shock protein 47 (HSP47), leads to rare autosomal recessive OI type X. We aimed to detect the phenotype and the pathogenic mutation of OI type X in a boy from a non-consanguineous Chinese family. We investigated the pathogenic mutations and analyzed their relationship with the phenotype in the patient using next-generation sequencing (NGS) and Sanger sequencing. Moreover, the efficacy of long-term bisphosphonate treatment in this patient was evaluated. The patient suffered from multiple fractures, low bone mass, and bone deformities in the femur, without dentinogenesis imperfecta or hearing loss. Compound heterozygous variants were found in SERPINH1 as follows: c.149 T>G in exon 2 and c.1214G>A in exon 5. His parents were heterozygous carriers of each of these mutations, respectively. Bisphosphonates could be helpful in increasing BMD Z-score, reducing bone fracture risk and reshaping the compressed vertebral bodies of this patient. We reported novel compound heterozygous mutations in SERPINH1 in a Chinese OI patient for the first time, which expanded the spectrum of phenotype and genotype of extremely rare OI type X.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

PubMed Central

Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

2016-01-01

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder

PubMed Central

Zong, Liang; Guan, Jing; Ealy, Megan; Zhang, Qiujing; Wang, Dayong; Wang, Hongyang; Zhao, Yali; Shen, Zhirong; Campbell, Colleen A; Wang, Fengchao; Yang, Ju; Sun, Wei; Lan, Lan; Ding, Dalian; Xie, Linyi; Qi, Yue; Lou, Xin; Huang, Xusheng; Shi, Qiang; Chang, Suhua; Xiong, Wenping; Yin, Zifang; Yu, Ning; Zhao, Hui; Wang, Jun; Wang, Jing; Salvi, Richard J; Petit, Christine; Smith, Richard J H; Wang, Qiuju

2015-01-01

Background Auditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified. Methods We performed whole-exome sequencing on DNA samples from the AUNX1 family and another small phenotypically similar but unrelated ANSD family. Results We identified two missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1 family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD identified 9 more missense mutations in AIFM1. Bioinformatics analysis and expression studies support this gene as being causative of ANSD. Conclusions Variants in AIFM1 gene are a common cause of familial and sporadic ANSD and provide insight into the expanded spectrum of AIFM1-associated diseases. The finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD implies that MRI may be of value in localising the site of lesion and suggests that cochlea implantation in these patients may have limited success. PMID:25986071

Economic recession and suicidal behaviour: Possible mechanisms and ameliorating factors.

PubMed

Haw, Camilla; Hawton, Keith; Gunnell, David; Platt, Stephen

2015-02-01

A growing body of research evidence from countries around the world indicates that economic recession is associated with increases in suicide, particularly in males of working age. To explore contributory and ameliorating factors associated with economic recession and suicide and thereby stimulate further research in this area and encourage policy makers to consider how best to reduce the impact of recession on mental health and suicidal behaviour. We conducted a selective review of the worldwide literature focusing on possible risk factors, mechanisms and preventative strategies for suicidal behaviour linked to economic recession. A model of how recession might affect suicide rates is presented. A major and often prolonged effect of recession is on unemployment and job insecurity. Other important effects include those exerted by financial loss, bankruptcy and home repossession. It is proposed these factors may lead directly or indirectly to mental health problems such as depression, anxiety and binge drinking and then to suicidal behaviour. Countries with active labour market programmes and sustained welfare spending during recessions have less marked increases in suicide rates than those that cut spending on welfare and job-search initiatives for the unemployed. Other measures likely to help include targeted interventions for unemployed people, membership of social organisations and responsible media reporting. Good primary care and mental health services are needed to cope with increased demand in times of economic recession but some governments have in fact reduced healthcare spending as an austerity measure. The research evidence linking recession, unemployment and suicide is substantial, but the evidence for the other mechanisms we have investigated is much more tentative. We describe the limitations of the existing body of research as well as make suggestions for future research into the effects of economic recession on suicidal behaviour. © The Author

Genetics Home Reference: X-linked congenital stationary night blindness

MedlinePlus

... Health Conditions X-linked congenital stationary night blindness X-linked congenital stationary night blindness Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked congenital stationary night blindness is a disorder ...

Genetics Home Reference: X-linked lissencephaly with abnormal genitalia

MedlinePlus

... Health Conditions X-linked lissencephaly with abnormal genitalia X-linked lissencephaly with abnormal genitalia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked lissencephaly with abnormal genitalia (XLAG) is a ...

Genetics Home Reference: X-linked sideroblastic anemia and ataxia

MedlinePlus

... Health Conditions X-linked sideroblastic anemia and ataxia X-linked sideroblastic anemia and ataxia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked sideroblastic anemia and ataxia is a rare ...

Genetics Home Reference: X-linked intellectual disability, Siderius type

MedlinePlus

... Health Conditions X-linked intellectual disability, Siderius type X-linked intellectual disability, Siderius type Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked intellectual disability, Siderius type is a condition ...

Genetics Home Reference: X-linked hyper IgM syndrome

MedlinePlus

... Home Health Conditions X-linked hyper IgM syndrome X-linked hyper IgM syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked hyper IgM syndrome is a condition that ...

Cytoskeleton and nuclear lamina affection in recessive osteogenesis imperfecta: A functional proteomics perspective.

PubMed

Gagliardi, Assunta; Besio, Roberta; Carnemolla, Chiara; Landi, Claudia; Armini, Alessandro; Aglan, Mona; Otaify, Ghada; Temtamy, Samia A; Forlino, Antonella; Bini, Luca; Bianchi, Laura

2017-09-07

Osteogenesis imperfecta (OI) is a collagen-related disorder associated to dominant, recessive or X-linked transmission, mainly caused by mutations in type I collagen genes or in genes involved in type I collagen metabolism. Among the recessive forms, OI types VII, VIII, and IX are due to mutations in CRTAP, P3H1, and PPIB genes, respectively. They code for the three components of the endoplasmic reticulum complex that catalyzes 3-hydroxylation of type I collagen α1Pro986. Under-hydroxylation of this residue leads to collagen structural abnormalities and results in moderate to lethal OI phenotype, despite the exact molecular mechanisms are still not completely clear. To shed light on these recessive forms, primary fibroblasts from OI patients with mutations in CRTAP (n=3), P3H1 (n=3), PPIB (n=1) genes and from controls (n=4) were investigated by a functional proteomic approach. Cytoskeleton and nucleoskeleton asset, protein fate, and metabolism were delineated as mainly affected. While western blot experiments confirmed altered expression of lamin A/C and cofilin-1, immunofluorescence analysis using antibody against lamin A/C and phalloidin showed an aberrant organization of nucleus and cytoskeleton. This is the first report describing an altered organization of intracellular structural proteins in recessive OI and pointing them as possible novel target for OI treatment. OI is a prototype for skeletal dysplasias. It is a highly heterogeneous collagen-related disorder with dominant, recessive and X-linked transmission. There is no definitive cure for this disease, thus a better understanding of the molecular basis of its pathophysiology is expected to contribute in identifying potential targets to develop new treatments. Based on this concept, we performed a functional proteomic study to delineate affected molecular pathways in primary fibroblasts from recessive OI patients, carrying mutations in CRTAP (OI type VII), P3H1 (OI type VIII), and PPIB (OI type IX) genes

Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype

PubMed Central

Pierson, Christopher R.; Dulin-Smith, Ashley N.; Durban, Ashley N.; Marshall, Morgan L.; Marshall, Jordan T.; Snyder, Andrew D.; Naiyer, Nada; Gladman, Jordan T.; Chandler, Dawn S.; Lawlor, Michael W.; Buj-Bello, Anna; Dowling, James J.; Beggs, Alan H.

2012-01-01

X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to use as a model in the testing of certain preclinical therapeutics. Many MTM patients succumb early in life, but some have a more favorable prognosis. We used human genotype–phenotype correlation data to develop a myotubularin-deficient mouse model with a less severe phenotype than is seen in Mtm1 KO mice. We modeled the human c.205C>T point mutation in Mtm1 exon 4, which is predicted to introduce the p.R69C missense change in myotubularin. Hemizygous male Mtm1 p.R69C mice develop early muscle atrophy prior to the onset of weakness at 2 months. The median survival period is 66 weeks. Histopathology shows small myofibers with centrally placed nuclei. Myotubularin protein is undetectably low because the introduced c.205C>T base change induced exon 4 skipping in most mRNAs, leading to premature termination of myotubularin translation. Some full-length Mtm1 mRNA bearing the mutation is present, which provides enough myotubularin activity to account for the relatively mild phenotype, as Mtm1 KO and Mtm1 p.R69C mice have similar muscle phosphatidylinositol 3-phosphate levels. These data explain the basis for phenotypic variability among human patients with MTM1 p.R69C mutations and establish the Mtm1 p.R69C mouse as a valuable model for the disease, as its less severe phenotype will expand the scope of testable preclinical therapies. PMID:22068590

Nephrogenic diabetes insipidus: an X chromosome-linked dominant inheritance pattern with a vasopressin type 2 receptor gene that is structurally normal.

PubMed Central

Friedman, E; Bale, A E; Carson, E; Boson, W L; Nordenskjöld, M; Ritzén, M; Ferreira, P C; Jammal, A; De Marco, L

1994-01-01

Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly transmitted in an X chromosome-linked recessive manner and characterized by the lack of renal response to the action of antidiuretic hormone [Arg8]vasopressin. The vasopressin type 2 receptor (V2R) has been suggested to be the gene that causes the disease, and its role in disease pathogenesis is supported by mutations within this gene in affected individuals. Using the PCR, denaturing gradient gel electrophoresis, and direct DNA sequencing, we examined the V2R gene in four unrelated kindreds. In addition, linkage analysis with chromosome Xq28 markers was done in one large Brazilian kindred with an apparent unusual X chromosome-linked dominant inheritance pattern. In one family, a mutation in codon 280, causing a Tyr-->Cys substitution in the sixth transmembrane domain of the receptor, was found. In the other three additional families with nephrogenic diabetes insipidus, the V2R-coding region was normal in sequence. In one large Brazilian kindred displaying an unusual X chromosome-linked dominant mode of inheritance, the disease-related gene was localized to the same region of the X chromosome as the V2R, but no mutations were found, thus raising the possibility that this disease is caused by a gene other than V2R. Images PMID:8078903

The population genetics of X-autosome synthetic lethals and steriles.

PubMed

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Genetics Home Reference: X-linked dystonia-parkinsonism

MedlinePlus

... X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic analysis. Brain Pathol. 1992 Oct;2(4):287-95. Review. Citation on PubMed Kaji R, Goto S, Tamiya G, Ando S, Makino S, Lee LV. Molecular dissection and anatomical basis of dystonia: X-linked ...

Obstruction of adaptation in diploids by recessive, strongly deleterious alleles.

PubMed

Assaf, Zoe June; Petrov, Dmitri A; Blundell, Jamie R

2015-05-19

Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.

Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

MedlinePlus

... thalassemia X-linked intellectual disability syndrome Alpha thalassemia X-linked intellectual disability syndrome Printable PDF Open All ... view the expand/collapse boxes. Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder ...

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

X-linked congenital panhypopituitarism.

PubMed

Schimke, R N; Spaulding, J J; Hollowell, J G

1971-05-01

Two half brothers with panhypopituitary dwarfism are reported who have the same mother and different, unrelated fathers. The subject of hereditary panhypopituitarism is reviewed briefly. It is concluded that there are at least two forms of hereditary panhypopituitary dwarfism, one of which may be X-linked.

Increase in viability due to the accumulation of X chromosome mutations in Drosophila melanogaster males.

PubMed

Woodruff, Ronny C; Balinski, Michael A

2018-05-09

To increase our understanding of the role of new X-chromosome mutations in adaptive evolution, single-X Drosophila melanogaster males were mated with attached-X chromosome females, allowing the male X chromosome to accumulate mutations over 28 generations. Contrary to our hypothesis that male viability would decrease over time, due to the accumulation and expression of X-linked recessive deleterious mutations in hemizygous males, viability significantly increased. This increase may be attributed to germinal selection and to new X-linked beneficial or compensatory mutations, possibly supporting the faster-X hypothesis.

Phenotype-genotype correlations in X linked retinitis pigmentosa.

PubMed Central

Kaplan, J; Pelet, A; Martin, C; Delrieu, O; Aymé, S; Bonneau, D; Briard, M L; Hanauer, A; Larget-Piet, L; Lefrançois, P

1992-01-01

Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal degenerations in which all modes of inheritance have been described. We have previously found two different clinical profiles in X linked RP as a function of age and mode of onset. The first clinical form has very early onset with severe myopia. The second form starts later with night blindness with mild myopia or none. At least two genes have been identified in X linked forms, namely RP2 (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the short arm of the X chromosome. In order to contribute to phenotype-genotype correlations in X linked RP, we tested the hypothesis that the two clinical profiles could be accounted for by the two different gene loci. The present study provides evidence for linkage of the clinical form with early myopia as the onset symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0), while the clinical form with later night blindness as the onset symptom is linked to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0). Images PMID:1357178

Sex-specific silencing of X-linked genes by Xist RNA

PubMed Central

Gayen, Srimonta; Maclary, Emily; Hinten, Michael; Kalantry, Sundeep

2016-01-01

X-inactive specific transcript (Xist) long noncoding RNA (lncRNA) is thought to catalyze silencing of X-linked genes in cis during X-chromosome inactivation, which equalizes X-linked gene dosage between male and female mammals. To test the impact of Xist RNA on X-linked gene silencing, we ectopically induced endogenous Xist by ablating the antisense repressor Tsix in mice. We find that ectopic Xist RNA induction and subsequent X-linked gene silencing is sex specific in embryos and in differentiating embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). A higher frequency of XΔTsixY male cells displayed ectopic Xist RNA coating compared with XΔTsixX female cells. This increase reflected the inability of XΔTsixY cells to efficiently silence X-linked genes compared with XΔTsixX cells, despite equivalent Xist RNA induction and coating. Silencing of genes on both Xs resulted in significantly reduced proliferation and increased cell death in XΔTsixX female cells relative to XΔTsixY male cells. Thus, whereas Xist RNA can inactivate the X chromosome in females it may not do so in males. We further found comparable silencing in differentiating XΔTsixY and 39,XΔTsix (XΔTsixO) ESCs, excluding the Y chromosome and instead implicating the X-chromosome dose as the source of the sex-specific differences. Because XΔTsixX female embryonic epiblast cells and EpiSCs harbor an inactivated X chromosome prior to ectopic inactivation of the active XΔTsix X chromosome, we propose that the increased expression of one or more X-inactivation escapees activates Xist and, separately, helps trigger X-linked gene silencing. PMID:26739568

The Great Recession, unemployment and suicide

PubMed Central

Norström, Thor; Grönqvist, Hans

2015-01-01

Background How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. Methods We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960–2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. Results The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Conclusions Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. PMID:25339416

Understanding Factors Associated with Children's Motivation to Engage in Recess-Time Physical Activity

ERIC Educational Resources Information Center

Efrat, Merav W.

2016-01-01

Physical activity is linked with health and academic benefits. While recess provides the greatest opportunity for children to accumulate physical activity, most children are not motivated to engage in sufficient amounts of physical activity during recess. Research demonstrates a strong relationship between self-efficacy and children's motivation…

Macular hole in juvenile X-linked retinoschisis.

PubMed

Al-Swaina, Nayef; Nowilaty, Sawsan R

2013-10-01

An 18 year-old male with no antecedent of trauma, systemic syndrome or myopia was referred for surgical treatment of a full thickness macular hole in the left eye. A more careful inspection revealed discrete foveal cystic changes in the fellow eye and subtle peripheral depigmented retinal pigment epithelial changes in both eyes. A spectral-domain optical coherence tomography (SD-OCT) scan confirmed, in addition to the full thickness macular hole in the left eye, microcystic spaces in the nuclear layers of both retinae. The diagnosis of X-linked retinoschisis was confirmed with a full field electroretinogram displaying the typical negative ERG. Macular holes are uncommon in the young and those complicating X-linked retinoschisis are rare. This report highlights the importance of investigating the presence of a macular hole in a young patient and illustrates the clinical and SD-OCT clues beyond the foveal center which led to the correct diagnosis of X-linked juvenile retinoschisis.

The Great Recession, unemployment and suicide.

PubMed

Norström, Thor; Grönqvist, Hans

2015-02-01

How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960-2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. 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.

Role of prostaglandins in the pathogenesis of X-linked hypophosphatemia.

PubMed

Baum, Michel; Syal, Ashu; Quigley, Raymond; Seikaly, Mouin

2006-08-01

X-linked hypophosphatemia is an X-linked dominant disorder resulting from a mutation in the PHEX gene. PHEX stands for phosphate-regulating gene with endopeptidase activity, which is located on the X chromosome. Patients with X-linked hypophosphatemia have hypophosphatemia due to renal phosphate wasting and low or inappropriately normal levels of 1,25-dihydroxyvitamin D. The renal phosphate wasting is not intrinsic to the kidney but likely due to an increase in serum levels of fibroblast growth factor-23 (FGF-23), and perhaps other phosphate-wasting peptides previously known as phosphatonins. Patients with X-linked hypophosphatemia have short stature, rickets, bone pain and dental abscesses. Current therapy is oral phosphate and vitamin D which effectively treats the rickets and bone pain but does not adequately improve short stature. In this review, we describe recent observations using Hyp mice; mice with the same mutation as patients with X-linked hypophosphatemia. We have recently found that Hyp mice have abnormal renal prostaglandin production, which may be an important factor in the pathogenesis of this disorder. Administration of FGF-23 in vivo results in phosphaturia and an increase in prostaglandin excretion, and FGF-23 increases proximal tubule prostaglandin production in vitro. In Hyp mice, indomethacin improves the phosphate transport defect in vitro and in vivo. Whether indomethacin has the same effect in patients with X-linked hypophosphatemia is unknown.

Contemporary Medical and Surgical Management of X-linked Hypophosphatemic Rickets.

PubMed

Sharkey, Melinda S; Grunseich, Karl; Carpenter, Thomas O

2015-07-01

X-linked hypophosphatemia is an inheritable disorder of renal phosphate wasting that clinically manifests with rachitic bone pathology. X-linked hypophosphatemia is frequently misdiagnosed and mismanaged. Optimized medical therapy is the cornerstone of treatment. Even with ideal medical management, progressive bony deformity may develop in some children and adults. Medical treatment is paramount to the success of orthopaedic surgical procedures in both children and adults with X-linked hypophosphatemia. Successful correction of complex, multiapical bone deformities found in patients with X-linked hypophosphatemia is possible with careful surgical planning and exacting surgical technique. Multiple methods of deformity correction are used, including acute and gradual correction. Treatment of some pediatric bony deformity with guided growth techniques may be possible. Copyright 2015 by the American Academy of Orthopaedic Surgeons.

Autosomal recessive PGM3 mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment

PubMed Central

Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie; Lyons, Jonathan J.; Datta, Shrimati; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; Biancalana, Matthew; Wolfe, Lynne A.; DiMaggio, Thomas; Matthews, Helen F.; Kranick, Sarah M.; Stone, Kelly D.; Holland, Steven M.; Reich, Daniel S.; Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua; Freeman, Alexandra F.; Freeze, Hudson H.; Su, Helen C.; Milner, Joshua D.

2014-01-01

Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective To define a genetic syndrome of severe atopy, elevated serum IgE, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from two families who had similar syndromic features were studied. Thorough clinical evaluations, including brain MRI and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T cell cytokine production were measured. Whole exome sequencing was performed to identify disease-causing mutations. Immunoblotting, qRT-PCR, enzymatic assays, nucleotide sugar and sugar phosphate analyses along with MALDI-TOF mass spectrometry of glycans were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH2 and TH17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T cell lymphopenia, particularly of CD8+ T cells, and reduced memory B cells. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurological abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced UDP-GlcNAc, along with decreased O- and N-linked protein glycosylation in patients’ cells. These results define a new Congenital Disorder of Glycosylation. Conclusions Autosomal recessive, hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability and hypomyelination. PMID:24589341

Genetics Home Reference: immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

MedlinePlus

... Health Conditions IPEX syndrome Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome Printable PDF Open All Close All ... expand/collapse boxes. Description Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is ...

X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.

PubMed

Christie, P T; Harding, B; Nesbit, M A; Whyte, M P; Thakker, R V

2001-08-01

X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.

The effects of sex-biased gene expression and X-linkage on rates of sequence evolution in Drosophila.

PubMed

Campos, José Luis; Johnston, Keira; Charlesworth, Brian

2017-12-08

A faster rate of adaptive evolution of X-linked genes compared with autosomal genes (the faster-X effect) can be caused by the fixation of recessive or partially recessive advantageous mutations. This effect should be largest for advantageous mutations that affect only male fitness, and least for mutations that affect only female fitness. We tested these predictions in Drosophila melanogaster by using coding and functionally significant non-coding sequences of genes with different levels of sex-biased expression. Consistent with theory, nonsynonymous substitutions in most male-biased and unbiased genes show faster adaptive evolution on the X. However, genes with very low recombination rates do not show such an effect, possibly as a consequence of Hill-Robertson interference. Contrary to expectation, there was a substantial faster-X effect for female-biased genes. After correcting for recombination rate differences, however, female-biased genes did not show a faster X-effect. Similar analyses of non-coding UTRs and long introns showed a faster-X effect for all groups of genes, other than introns of female-biased genes. Given the strong evidence that deleterious mutations are mostly recessive or partially recessive, we would expect a slower rate of evolution of X-linked genes for slightly deleterious mutations that become fixed by genetic drift. Surprisingly, we found little evidence for this after correcting for recombination rate, implying that weakly deleterious mutations are mostly close to being semidominant. This is consistent with evidence from polymorphism data, which we use to test how models of selection that assume semidominance with no sex-specific fitness effects may bias estimates of purifying selection. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Great Recession and the Risk for Child Maltreatment

PubMed Central

Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

2013-01-01

This study draws on the Fragile Families and Child Wellbeing Study (N = 2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services. PMID:24045057

Impaired plasticity of macrophages in X-linked adrenoleukodystrophy.

PubMed

Weinhofer, Isabelle; Zierfuss, Bettina; Hametner, Simon; Wagner, Magdalena; Popitsch, Niko; Machacek, Christian; Bartolini, Barbara; Zlabinger, Gerhard; Ohradanova-Repic, Anna; Stockinger, Hannes; Köhler, Wolfgang; Höftberger, Romana; Regelsberger, Günther; Forss-Petter, Sonja; Lassmann, Hans; Berger, Johannes

2018-05-30

X-linked adrenoleukodystrophy is caused by ATP-binding cassette transporter D1 (ABCD1) mutations and manifests by default as slowly progressive spinal cord axonopathy with associated demyelination (adrenomyloneuropathy). In 60% of male cases, however, X-linked adrenoleukodystrophy converts to devastating cerebral inflammation and demyelination (cerebral adrenoleukodystrophy) with infiltrating blood-derived monocytes and macrophages and cytotoxic T cells that can only be stopped by allogeneic haematopoietic stem cell transplantation or gene therapy at an early stage of the disease. Recently, we identified monocytes/macrophages but not T cells to be severely affected metabolically by ABCD1 deficiency. Here we found by whole transcriptome analysis that, although monocytes of patients with X-linked adrenoleukodystrophy have normal capacity for macrophage differentiation and phagocytosis, they are pro-inflammatory skewed also in patients with adrenomyloneuropathy in the absence of cerebral inflammation. Following lipopolysaccharide activation, the ingestion of myelin debris, normally triggering anti-inflammatory polarization, did not fully reverse the pro-inflammatory status of X-linked adrenoleukodystrophy macrophages. Immunohistochemistry on post-mortem cerebral adrenoleukodystrophy lesions reflected the activation pattern by prominent presence of enlarged lipid-laden macrophages strongly positive for the pro-inflammatory marker co-stimulatory molecule CD86. Comparative analyses of lesions with matching macrophage density in cases of cerebral adrenoleukodystrophy and acute multiple sclerosis showed a similar extent of pro-inflammatory activation but a striking reduction of anti-inflammatory mannose receptor (CD206) and haemoglobin-haptoglobin receptor (CD163) expression on cerebral adrenoleukodystrophy macrophages. Accordingly, ABCD1-deficiency leads to an impaired plasticity of macrophages that is reflected in incomplete establishment of anti-inflammatory responses

Genetics Home Reference: X-linked spondyloepiphyseal dysplasia tarda

MedlinePlus

... Educational Resources (6 links) Cincinnati Children's Hospital: Coxa Vera Disease InfoSearch: Spondyloepiphyseal dysplasia tarda X-linked Johns ... Free article on PubMed Central Savarirayan R, Thompson E, Gécz J. Spondyloepiphyseal dysplasia tarda (SEDL, MIM #313400). ...

In vivo imaging of skeletal muscle in mice highlights muscle defects in a model of myotubular myopathy

PubMed Central

Mercier, Luc; Böhm, Johann; Fekonja, Nina; Allio, Guillaume; Lutz, Yves; Koch, Marc; Goetz, Jacky G.; Laporte, Jocelyn

2016-01-01

ABSTRACT Skeletal muscle structure and function are altered in different myopathies. However, the understanding of the molecular and cellular mechanisms mainly rely on in vitro and ex vivo investigations in mammalian models. In order to monitor in vivo the intracellular structure of the neuromuscular system in its environment under normal and pathological conditions, we set-up and validated non-invasive imaging of ear and leg muscles in mice. This original approach allows simultaneous imaging of different cellular and intracellular structures such as neuromuscular junctions and sarcomeres, reconstruction of the 3D architecture of the neuromuscular system, and video recording of dynamic events such as spontaneous muscle fiber contraction. Second harmonic generation was combined with vital dyes and fluorescent-coupled molecules. Skin pigmentation, although limiting, did not prevent intravital imaging. Using this versatile toolbox on the Mtm1 knockout mouse, a model for myotubular myopathy which is a severe congenital myopathy in human, we identified several hallmarks of the disease such as defects in fiber size and neuromuscular junction shape. Intravital imaging of the neuromuscular system paves the way for the follow-up of disease progression or/and disease amelioration upon therapeutic tests. It has also the potential to reduce the number of animals needed to reach scientific conclusions. PMID:28243519

siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster.

PubMed

Menon, Debashish U; Coarfa, Cristian; Xiao, Weimin; Gunaratne, Preethi H; Meller, Victoria H

2014-11-18

Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.

The Great Recession and the risk for child maltreatment.

PubMed

Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

2013-10-01

This study draws on the Fragile Families and Child Wellbeing Study (N=2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetics Home Reference: X-linked agammaglobulinemia

MedlinePlus

... Sep;104(3):221-30. Citation on PubMed Smith CIE, Berglöf A. X-Linked Agammaglobulinemia. 2001 Apr ... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

Shaped Recess Flow Control

NASA Technical Reports Server (NTRS)

Shyam, Vikram (Inventor); Poinsatte, Philip (Inventor); Thurman, Douglas (Inventor)

2017-01-01

One or more embodiments of techniques or systems for shaped recess flow control are provided herein. A shaped recess or cavity can be formed on a surface associated with fluid flow. The shaped recess can be configured to create or induce fluid effects, temperature effects, or shedding effects that interact with a free stream or other structures. The shaped recess can be formed at an angle to a free stream flow and may be substantially "V" shaped. The shaped recess can be coupled with a cooling channel, for example. The shaped recess can be upstream or downstream from a cooling channel and aligned in a variety of manners. Due to the fluid effects, shedding effects, and temperature effects created by a shaped recess, lift-off or separation of cooling jets of cooling channels can be mitigated, thereby enhancing film cooling effectiveness.

Gingival recession in smokers and non-smokers with minimal periodontal disease.

PubMed

Müller, Hans-Peter; Stadermann, Sabine; Heinecke, Achim

2002-02-01

Smoking is a major risk factor for destructive periodontal disease. There is limited information with regard to effects of smoking in subjects with minimal periodontal destruction. The aim of the present investigation was to assess the development of gingival recession in young adult smokers and non-smokers. 61 systemically healthy young adults, 19 to 30 years of age completed the final examination. 30 volunteers smoked at least 20 cigarettes per day, whereas 31 subjects were non-smokers. Clinical periodontal conditions were assessed 4x within a time period of 6 months. Site-specific analyses considering the correlated structure of data were performed. At the outset, 50% of subjects presented with gingival recession at 1 or more sites. There was no significant difference in the prevalence of gingival recession between non-smokers and smokers. Severe recession in excess of 2 mm affected about 23% non-smokers but only 7% smokers. Some further gingival recession developed during the 6-month observation period. In a multivariate logistic regression analysis, the risk for recession development appeared not to be influenced by smoking status after adjusting for periodontal probing depth, recession at baseline, tooth brushing frequency, gender, jaw, tooth type and site. Present data did not support the hypothesis that smokers are at an increased risk for the development of gingival recession.

Severe manifestations in carrier females in X linked retinitis pigmentosa.

PubMed Central

Souied, E; Segues, B; Ghazi, I; Rozet, J M; Chatelin, S; Gerber, S; Perrault, I; Michel-Awad, A; Briard, M L; Plessis, G; Dufier, J L; Munnich, A; Kaplan, J

1997-01-01

Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP. Images PMID:9350809

The first de novo mutation of the connexin 32 gene associated with X linked Charcot-Marie-Tooth disease.

PubMed Central

Meggouh, F; Benomar, A; Rouger, H; Tardieu, S; Birouk, N; Tassin, J; Barhoumi, C; Yahyaoui, M; Chkili, T; Brice, A; LeGuern, E

1998-01-01

X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP technique and direct sequencing of PCR amplified genomic DNA fragments of the Cx32 gene from a Moroccan patient and her relatives, we identified the first de novo mutation of the Cx32 gene, consisting of a deletion of a G residue at position 499 in the Cx32 open reading frame. This previously unreported mutation produces a frameshift at position 147 in the protein and introduces a premature stop codon (TAG) at nucleotide 643, which results in the production of a truncated Cx32 molecule. This mutation illustrates the risk of an erroneous diagnosis of autosomal recessive CMT, especially in populations where consanguineous unions are frequent, and its consequences for genetic counselling, which can be avoided by molecular analysis. Images PMID:9541114

X linked mental retardation: a clinical guide.

PubMed

Raymond, F L

2006-03-01

Mental retardation is more common in males than females in the population, assumed to be due to mutations on the X chromosome. The prevalence of the 24 genes identified to date is low and less common than expansions in FMR1, which cause Fragile X syndrome. Systematic screening of all other X linked genes in X linked families with mental retardation is currently not feasible in a clinical setting. The phenotypes of genes causing syndromic and non-syndromic mental retardation (NLGN3, NLGN4, RPS6KA3(RSK2), OPHN1, ATRX, SLC6A8, ARX, SYN1, AGTR2, MECP2, PQBP1, SMCX, and SLC16A2) are first discussed, as these may be the focus of more targeted mutation analysis. Secondly, the relative prevalence of genes causing only non-syndromic mental retardation (IL1RAPL1, TM4SF2, ZNF41, FTSJ1, DLG3, FACL4, PAK3, ARHGEF6, FMR2, and GDI) is summarised. Thirdly, the problem of recurrence risk where a molecular genetics diagnosis has not been made and what proportion of the male excess of mental retardation is due to monogenic disorders of the X chromosome are discussed.

A Simulation of X-Linked Inheritance.

ERIC Educational Resources Information Center

Harrell, Pamela Esprivalo

1997-01-01

Describes how to lead students through a classroom-based simulation to teach a variety of concepts such as X-linked traits, sex determination, and sex anomalies. The simulation utilizes inexpensive materials such as plastic eggs that twist apart to represent human eggs and sperm. (AIM)

Escape of X-linked miRNA genes from meiotic sex chromosome inactivation

PubMed Central

Sosa, Enrique; Flores, Luis; Yan, Wei; McCarrey, John R.

2015-01-01

Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis. PMID:26395485

Differential Muscle Hypertrophy Is Associated with Satellite Cell Numbers and Akt Pathway Activation Following Activin Type IIB Receptor Inhibition in Mtm1 p.R69C Mice

PubMed Central

Lawlor, Michael W.; Viola, Marissa G.; Meng, Hui; Edelstein, Rachel V.; Liu, Fujun; Yan, Ke; Luna, Elizabeth J.; Lerch-Gaggl, Alexandra; Hoffmann, Raymond G.; Pierson, Christopher R.; Buj-Bello, Anna; Lachey, Jennifer L.; Pearsall, Scott; Yang, Lin; Hillard, Cecilia J.; Beggs, Alan H.

2015-01-01

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials. PMID:24726641

Causes of Charcot-Marie-Tooth Disease (CMT)

MedlinePlus

... t always easy to trace through a family tree: X-linked, autosomal dominant and autosomal recessive. X- ... can be easy to recognize in the family tree. In contrast, X-linked or autosomal recessive types ...

Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease.

PubMed

Horn, Morten A; Erichsen, Martina M; Wolff, Anette S B; Månsson, Jan-Eric; Husebye, Eystein S; Tallaksen, Chantal M E; Skjeldal, Ola H

2013-09-01

X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids. © 2013 John Wiley & Sons Ltd.

THE EFFECTS OF CHLORAMPHENICOL, STREPTOMYCIN, AND PENICILLIN ON THE INDUCTION OF MUTATIONS BY X-RAYS IN DROSOPHILA MELANOGASTER

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

Clark, A.M.

The injection of chloramphenicol, streptomycin, or penicillin into Drosophila males just before exposure to x irradiation caused a reduction in the yield of sex linked recessive lethal mutations. The effect appears to be primarily on spermatids and possibly spermatocytes. (auth)

The Great Recession and risk for child abuse and neglect

PubMed Central

Schneider, William; Waldfogel, Jane; Brooks-Gunn, Jeanne

2016-01-01

This paper examines the association between the Great Recession and four measures of the risk for maternal child abuse and neglect: (1) maternal physical aggression; (2) maternal psychological aggression; (3) physical neglect by mothers; and (4) supervisory/exposure neglect by mothers. It draws on rich longitudinal data from the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort study of families in 20 U.S. cities (N = 3,177; 50% African American, 25% Hispanic; 22% non-Hispanic white; 3% other). The study collected information for the 9-year follow-up survey before, during, and after the Great Recession (2007-2010). Interview dates were linked to two macroeconomic measures of the Great Recession: the national Consumer Sentiment Index and the local unemployment rate. Also included are a wide range of socio-demographic controls, as well as city fixed effects and controls for prior parenting. Results indicate that the Great Recession was associated with increased risk of child abuse but decreased risk of child neglect. Households with social fathers present may have been particularly adversely affected. Results also indicate that economic uncertainty during the Great Recession, as measured by the Consumer Sentiment Index and the unemployment rate, had direct effects on the risk of abuse or neglect, which were not mediated by individual-level measures of economic hardship or poor mental health. PMID:28461713

Socio-economic factors linked with mental health during the recession: a multilevel analysis.

PubMed

Ruiz-Pérez, Isabel; Bermúdez-Tamayo, Clara; Rodríguez-Barranco, Miguel

2017-03-06

Periods of financial crisis are associated with higher psychological stress among the population and greater use of mental health services. The objective is to analyse contextual factors associated with mental health among the Spanish population during the recession. Cross-sectional, descriptive study of two periods: before the recession (2006) and after therecession (2011-2012). The study population comprised individuals aged 16+ years old, polled for the National Health Survey. There were 25,234 subjects (2006) and 20,754 subjects (2012). The dependent variable was psychic morbidity. 1) socio-demographic (age, socio-professional class, level of education, nationality, employment situation, marital status), 2) psycho-social (social support) and 3) financial (GDP per capita, risk of poverty, income per capita per household), public welfare services (health spending per capita), labour market (employment and unemployment rates, percentage of temporary workers). Multilevel logistic regression models with mixed effects were constructed to determine change in psychic morbidity according to the variables studied. The macroeconomic variables associated with worse mental health for both males and females were lower health spending per capita and percentage of temporary workers. Among women, the risk of poor mental health increased 6% for each 100€ decrease in healthcare spending per capita. Among men, the risk of poor mental health decreased 8% for each 5-percentage point increase in temporary workers. Higher rates of precarious employment in a region have a negative effect on people's mental health; likewise lower health spending per capita. Policies during periods of recession should focus on support and improved conditions for vulnerable groups such as temporary workers. Healthcare cutbacks should be avoided in order to prevent increased prevalence of poor mental health.

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract.

PubMed

Zhang, D D; Du, J Z; Topolewski, J; Wang, X M

2016-07-29

Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the X or Y chromosome. Congenital cataract is a symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome. On the other hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract. This could help identify novel approaches for the prevention, early diagnosis, and comprehensive disease treatment.

Genetics Home Reference: X-linked lymphoproliferative disease

MedlinePlus

... infects most humans. In some people it causes infectious mononucleosis (commonly known as "mono"). Normally, after initial infection, ... severe susceptibility to EBV infection severe susceptibility to infectious mononucleosis X-linked lymphoproliferative syndrome XLP Related Information How ...

Playing Fair: The Contribution of High-Functioning Recess to Overall School Climate in Low-Income Elementary Schools

ERIC Educational Resources Information Center

London, Rebecca A.; Westrich, Lisa; Stokes-Guinan, Katie; McLaughlin, Milbrey

2015-01-01

Background: Recess is a part of the elementary school day with strong implications for school climate. Positive school climate has been linked to a host of favorable student outcomes, from attendance to achievement. We examine 6 low-income elementary schools' experiences implementing a recess-based program designed to provide safe, healthy,…

COL4A6 is dispensable for autosomal recessive Alport syndrome.

PubMed

Murata, Tomohiro; Katayama, Kan; Oohashi, Toshitaka; Jahnukainen, Timo; Yonezawa, Tomoko; Sado, Yoshikazu; Ishikawa, Eiji; Nomura, Shinsuke; Tryggvason, Karl; Ito, Masaaki

2016-07-05

Alport syndrome is caused by mutations in the genes encoding α3, α4, or α5 (IV) chains. Unlike X-linked Alport mice, α5 and α6 (IV) chains are detected in the glomerular basement membrane of autosomal recessive Alport mice, however, the significance of this finding remains to be investigated. We therefore generated mice lacking both α3 and α6 (IV) chains and compared their renal function and survival with Col4a3 knockout mice of 129 × 1/Sv background. No significant difference was observed in the renal function or survival of the two groups, or when the mice were backcrossed once to C57BL/6 background. However, the survival of backcrossed double knockout mice was significantly longer than that of the mice of 129 × 1/Sv background, which suggests that other modifier genes were involved in this phenomenon. In further studies we identified two Alport patients who had a homozygous mutation in intron 46 of COL4A4. The α5 and α6 (IV) chains were focally detected in the glomerular basement membrane of these patients. These findings indicate that although α5 and α6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role.

COL4A6 is dispensable for autosomal recessive Alport syndrome

PubMed Central

Murata, Tomohiro; Katayama, Kan; Oohashi, Toshitaka; Jahnukainen, Timo; Yonezawa, Tomoko; Sado, Yoshikazu; Ishikawa, Eiji; Nomura, Shinsuke; Tryggvason, Karl; Ito, Masaaki

2016-01-01

Alport syndrome is caused by mutations in the genes encoding α3, α4, or α5 (IV) chains. Unlike X-linked Alport mice, α5 and α6 (IV) chains are detected in the glomerular basement membrane of autosomal recessive Alport mice, however, the significance of this finding remains to be investigated. We therefore generated mice lacking both α3 and α6 (IV) chains and compared their renal function and survival with Col4a3 knockout mice of 129 × 1/Sv background. No significant difference was observed in the renal function or survival of the two groups, or when the mice were backcrossed once to C57BL/6 background. However, the survival of backcrossed double knockout mice was significantly longer than that of the mice of 129 × 1/Sv background, which suggests that other modifier genes were involved in this phenomenon. In further studies we identified two Alport patients who had a homozygous mutation in intron 46 of COL4A4. The α5 and α6 (IV) chains were focally detected in the glomerular basement membrane of these patients. These findings indicate that although α5 and α6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role. PMID:27377778

[Sex-linked juvenile retinoschisis].

PubMed

François, P; Turut, P; Soltysik, C; Hache, J C

1976-02-01

About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria

PubMed Central

Brancaleoni, V.; Balwani, M.; Granata, F.; Graziadei, G.; Missineo, P.; Fiorentino, V.; Fustinoni, S.; Cappellini, M.D.; Naik, H.; Desnick, R.J.; Di Pierro, E.

2015-01-01

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

Linkage localization of X-linked Charcot-Marie-Tooth disease

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

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

X-inactivation patterns in female Leber`s hereditary optic neuropathy patients do not support a strong X-linked determinant

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

Pegoraro, E.; Hoffman, E.P.; Carelli, V.

1996-02-02

Leber`s hereditary optic neuropathy (LHON) accounts for about 3% of the cases of blindness in young adult males. The underlying mitochondrial pathogenesis of LHON has been well studied, with specific mitochondrial DNA (mtDNA) mutations of structural genes described and well characterized. However, enigmatic aspects of the disease are not explained by mutation data, such as the higher proportion of affected males, the later onset of the disease in females, and the presence of unaffected individuals with a high proportion of mutant mtDNA. A hypothesis which has been put forward to explain the unusual disease expression is a dual model ofmore » mtDNA and X-linked nuclear gene inheritance. If a nuclear X-linked modifier gene influences the expression of the mitochondrial-linked mutant gene then the affected females should be either homozygous for the nuclear determinant, or if heterozygous, lyonization should favor the mutant X. In order to determine if an X-linked gene predisposes to LHON phenotype we studied X-inactivation patterns in 35 females with known mtDNA mutations from 10 LHON pedigrees. Our results do not support a strong X-linked determinant in LHON cause: 2 of the 10 (20%) manifesting carriers showed skewing of X-inactivation, as did 3 of the 25 (12%) nonmanifesting carriers. 39 refs., 2 figs., 1 tab.« less

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility.

PubMed

Lu, Xuemei; Shapiro, Joshua A; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-08-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice.

PubMed

Lawlor, Michael W; Viola, Marissa G; Meng, Hui; Edelstein, Rachel V; Liu, Fujun; Yan, Ke; Luna, Elizabeth J; Lerch-Gaggl, Alexandra; Hoffmann, Raymond G; Pierson, Christopher R; Buj-Bello, Anna; Lachey, Jennifer L; Pearsall, Scott; Yang, Lin; Hillard, Cecilia J; Beggs, Alan H

2014-06-01

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Bibi, Nosheen; Ahmad, Saeed; Ahmad, Wasim; Naeem, Muhammad

2011-02-01

Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Submicroscopic interstitial deletion of the X chromosome explains a complex genetic syndrome dominated by Norrie disease.

PubMed

Gal, A; Wieringa, B; Smeets, D F; Bleeker-Wagemakers, L; Ropers, H H

1986-01-01

Norrie disease (ND), an X-linked recessive disorder, is characterized by congenital blindness followed by bulbar atrophy. We have examined a three-generation family in which ND is part of a complex X-linked syndrome with severe mental retardation, hypogonadism, growth disturbances, and increased susceptibility to infections as additional features. This syndrome is apparently due to an interstitial deletion, as evidenced by the failure of the L1.28 DNA probe (DXS7 locus, Xp11.3) to detect complementary DNA sequences on the defective X chromosome of an affected male and of several obligatory heterozygotes. Attempts to further define this deletion with other DNA probes from the proximal short arm of the X chromosome or by prometaphase chromosome analysis were unsuccessful.

Genome-wide misexpression of X-linked versus autosomal genes associated with hybrid male sterility

PubMed Central

Lu, Xuemei; Shapiro, Joshua A.; Ting, Chau-Ti; Li, Yan; Li, Chunyan; Xu, Jin; Huang, Huanwei; Cheng, Ya-Jen; Greenberg, Anthony J.; Li, Shou-Hsien; Wu, Mao-Lien; Shen, Yang; Wu, Chung-I

2010-01-01

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible. PMID:20511493

Genetics Home Reference: X-linked cardiac valvular dysplasia

MedlinePlus

... inflammation of the inner lining of the heart (endocarditis), abnormal blood clots, or sudden death. X-linked ... Johns Hopkins Medicine: Mitral Valve Prolapse MedlinePlus Encyclopedia: Endocarditis MedlinePlus Encyclopedia: Mitral Valve Prolapse General Information from ...

Starving for Recess

ERIC Educational Resources Information Center

Patt, Mary Johnson

2011-01-01

Every weekday, millions of American schoolchildren throw away their half-eaten cafeteria lunches so that they can run outside to play. The traditional placement of lunch before recess, coupled with the recent decline in overall recess time to meet academic time constraints, forces children to choose between two essential needs: (1) food; and (2)…

X-linked mental retardation associated with macro-orchidism.

PubMed Central

Turner, G; Eastman, C; Casey, J; McLeay, A; Procopis, P; Turner, B

1975-01-01

Two families are described with an X-linked form of mental retardation in whom the affected males were found to have bilateral enlargement of the testes. No conclusive evidence of any endocrinological disturbance was found. Images PMID:1240971

The Great Recession and Behavior Problems in 9-Year Old Children

PubMed Central

Schneider, William; Waldfogel, Jane; Brooks-Gunn, Jeanne

2015-01-01

This paper examines associations between the Great Recession and four aspects of 9-year olds’ behavior—aggression (externalizing), anxiety/depression (internalizing), alcohol and drug use, and vandalism—using the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort drawn from twenty U.S. cities (21%, White, 50% African-American, 26% Hispanic, and 3% other race/ethnicity). The study was in the field for the 9-year follow-up right before and during the Great Recession (2007-2010) (N = 3,311). Interview dates (month) were linked to the national Consumer Sentiment Index (CSI), calculated from a national probability sample drawn monthly to assess consumer confidence and uncertainty about the economy, as well as to data on local unemployment rates. Controlling for city-fixed effects and extensive controls (including prior child behavior at age 5), we find that greater uncertainty as measured by the CSI was associated with higher rates of all four behavior problems for boys (in both maternal and child reports). Such associations were not found for girls (all gender differences were significant). Links between the CSI and boys’ behavior problems were concentrated in single-parent families and were partially explained by parenting behaviors. Local unemployment rates, in contrast, had fewer associations with children's behavior, suggesting that in the Great Recession, what was most meaningful for child behavior problems was the uncertainty about the national economy, rather than local labor markets. PMID:26347985

The great recession and behavior problems in 9-year old children.

PubMed

Schneider, William; Waldfogel, Jane; Brooks-Gunn, Jeanne

2015-11-01

This article examines associations between the Great Recession and 4 aspects of 9-year olds' behavior-aggression (externalizing), anxiety/depression (internalizing), alcohol and drug use, and vandalism-using the Fragile Families and Child Wellbeing Study, a longitudinal birth cohort drawn from 20 U.S. cities (21%, White, 50% Black, 26% Hispanic, and 3% other race/ethnicity). The study was in the field for the 9-year follow-up right before and during the Great Recession (2007-2010; N = 3,311). Interview dates (month) were linked to the national Consumer Sentiment Index (CSI), calculated from a national probability sample drawn monthly to assess consumer confidence and uncertainty about the economy, as well as to data on local unemployment rates. Controlling for city-fixed effects and extensive controls (including prior child behavior at age 5), we find that greater uncertainty as measured by the CSI was associated with higher rates of all 4 behavior problems for boys (in both maternal and child reports). Such associations were not found for girls (all gender differences were significant). Links between the CSI and boys' behavior problems were concentrated in single-parent families and were partially explained by parenting behaviors. Local unemployment rates, in contrast, had fewer associations with children's behavior, suggesting that in the Great Recession, what was most meaningful for child behavior problems was the uncertainty about the national economy, rather than local labor markets. (c) 2015 APA, all rights reserved).

Recess--It's Indispensable!

ERIC Educational Resources Information Center

Jarrett, Olga; Waite-Stupiansky, Sandra

2009-01-01

The demise of recess in many elementary schools--and of outdoor play in general--is an issue of great concern to many members of the Play, Policy, and Practice Interest Forum. Most people remember recess as an important part of the school day. It was a time to be outdoors; to organize games; to play on the swings, slides, and other playground…

The multifocal electroretinogram in X-linked juvenile retinoschisis.

PubMed

Huang, Shizhou; Wu, Dezheng; Jiang, Futian; Luo, Guangwei; Liang, Jiongji; Wen, Feng; Yu, Minzhong; Long, Shixian; Wu, Lezheng

2003-05-01

To measure and compare the multifocal electroretinography in normal control and X-linked juvenile retinoschisis, 13 cases (13 right eyes) of normal control and nine cases (17 eyes) of X-linked juvenile retinoschisis were measured with VERIS Science 4.0. Four cases (eight eyes) out of the nine retinoschisis cases were tested with Ganzfeld ERG at the same day. The results showed statistically significant difference of average response densities and latencies in six ring retinal regions between the normal control and retinoschisis. The trace array and 3-D topography of multifocal ERG showed multi-area amplitude decrease with absence or reduction of central peak amplitude in patients with retinoschisis. The P1/N1 ratio of multifocal ERG average response densities in six ring retinal regions was different from the b/a ratio of Ganzfeld ERG. The multifocal ERG and Ganzfeld ERG each had its advantage in the diagnosis of retinoschisis.

X-Linked Retinoschisis: Phenotypic Variability in a Chinese Family

PubMed Central

Xiao, Yangyan; Liu, Xiao; Tang, Luosheng; Wang, Xia; Coursy, Terry; Guo, Xiaojian; Li, Zhuo

2016-01-01

X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. Our study is to describe the clinical characteristics of a four generations of this family (a total of 18 members)with X-linked retinoschisis (XLRS) and detected a novel mutations of c.3G > A (p.M1?) in the initiation codon of the RS1 gene. by direct sequencing.Identification of this mutation in this family provides evidence about potential genetic or environmental factors on its phenotypic variance, as patients presented with different phenotypes regardless of having the same mutation. Importantly, OCT has proven vital for XLRS diagnosis in children. PMID:26823236

X-Linked Retinoschisis: Phenotypic Variability in a Chinese Family.

PubMed

Xiao, Yangyan; Liu, Xiao; Tang, Luosheng; Wang, Xia; Coursey, Terry G; Coursy, Terry; Guo, Xiaojian; Li, Zhuo

2016-01-29

X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spoke-wheel pattern in the macular region of the retina and splitting of the neurosensory retina. Our study is to describe the clinical characteristics of a four generations of this family (a total of 18 members)with X-linked retinoschisis (XLRS) and detected a novel mutations of c.3G > A (p.M1?) in the initiation codon of the RS1 gene. by direct sequencing.Identification of this mutation in this family provides evidence about potential genetic or environmental factors on its phenotypic variance, as patients presented with different phenotypes regardless of having the same mutation. Importantly, OCT has proven vital for XLRS diagnosis in children.

The crucial role of recess in schools.

PubMed

Ramstetter, Catherine L; Murray, Robert; Garner, Andrew S

2010-11-01

Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose of this review was to examine the value of recess as an integral component of the school day. A comprehensive review of recess-specific literature was conducted, beginning with a Google Scholar search, to cull definitions, position statements, and policy recommendations from national/international associations and organizations. A multi-database search followed. Additional articles were selected from reference lists. The search yielded a range of articles, from those focused on specific aspects of recess to those that examined multiple factors, including how to structure and conduct recess. Several themes emerged supporting recess as beneficial for children's cognitive, social, emotional, and physical functioning. Optimal recess was well-supervised and safe. Crucial components were well-maintained playground equipment and well-trained supervisors. Recess serves a critical role in school as a necessary break from the rigors of academic challenges. Recess is a complement to, not a replacement for, physical education. Both promote activity and a healthy lifestyle; however, recess--particularly unstructured recess and free play--provides a unique contribution to a child's creative, social, and emotional development. From the perspective of children's health and well-being, recess time should be considered a child's personal time and should not be withheld for academic or punitive reasons. © 2010, American School Health Association.

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

PubMed Central

Olcese, Chiara; Patel, Mitali P.; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J.; Vaughan, Cara K.; Hayward, Jane; Goldenberg, Alice; Emes, Richard D.; Munye, Mustafa M.; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean- François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R.; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M. K.; Antonarakis, Stylianos E.; Loebinger, Michael R.; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Beales, Philip L.; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Allan, Daly; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; McCarthy, Shane; Muddyman, Dawn; Muntoni, Francesco; Parker, Victoria; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter J.; Schmidts, Miriam; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M.

2017-01-01

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins. PMID:28176794

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

PubMed

Olcese, Chiara; Patel, Mitali P; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J; Vaughan, Cara K; Hayward, Jane; Goldenberg, Alice; Emes, Richard D; Munye, Mustafa M; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean-François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M K; Antonarakis, Stylianos E; Loebinger, Michael R; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M

2017-02-08

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2-DNAAF4-HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.

A candidate gene for X-linked Ocular Albinism (OA1)

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

Bassi, M.T.; Schiaffino, V.; Rugarli, E.

1994-09-01

Ocular Albinism of the Nettleship-Fall type 1 (OA1) is the most common form of ocular albinism. It is transmitted as an X-linked recessive trait with affected males showing severe reduction of visual acuity, nystagmus, strabismus, photophobia. Ophthalmologic examination reveals foveal hypoplasia, hypopigmentation of the retina and iris translucency. Microscopic examination of melanocytes suggests that the underlying defect in OA1 is an abnormality in melanosome formation. Recently we assembled a 350 kb cosmid contig spanning the entire critical region on Xp22.3, which measures approximately 110 kb. A minimum set of cosmids was used to identify transcribed sequences using both cDNA selectionmore » and exon amplification. Two putative exons recovered by exon amplification strategy were found to be highly conserved throughout evolution and, therefore, they were used as probes for the screening of fetal and adult retina cDNA libraries. This led to the isolation of clones spanning a full-length cDNA which measures 7.6 kb. Sequence analysis revealed that the predicted protein product shows homology with syntrophines and a Xenopus laevis apical protein. The gene covers approximately 170 kb of DNA and spans the entire critical region for OA1, being deleted in two patients with contiguous gene deletion including OA1 and in one patient with isolated OA1. Therefore, this new gene represents a very strong candidate for involvement in OA1 (an alternative, but unlikely possibility to be considered is that the true OA1 gene lies within an intron of the former). Northern analysis revealed very high level of expression in retina and melanoma. Unlike most Xp22.3 genes, this gene is conserved in the mouse. We are currently performing SSCP analysis and direct sequencing of exons on DNAs from approximately 60 unrelated patients with OA1 for mutation detection.« less

Does gingival recession require surgical treatment?

PubMed Central

Chan, Hsun-Liang; Chun, Yong-Hee Patricia; MacEachern, Mark

2016-01-01

Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. It is estimated that 23% of adults in the US have one or more tooth surfaces with ≥ 3 mm gingival recession. Clinicians often time face dilemmas of whether or not to treat such a condition surgically. Therefore, we were charged by the editorial board to answer this critical question: “Does gingival recession require surgical treatment?” An initial condensed literature search was performed using a combination of gingival recession and surgery controlled terms and keywords. An analysis of the search results highlights our limited understanding of the factors that often guide the treatment of gingival recession. Understanding the etiology, prognosis and treatment of gingival recession continues to offer many unanswered questions and challenges in the field of periodontics as we strive to provide the best care possible for our patients. PMID:26427577

Paternal inheritance of classic X-linked bilateral periventricular nodular heterotopia.

PubMed

Kasper, Burkhard S; Kurzbuch, Katrin; Chang, Bernard S; Pauli, Elisabeth; Hamer, Hajo M; Winkler, Jürgen; Hehr, Ute

2013-06-01

Periventricular nodular heterotopia (PNH) is a developmental disorder of the central nervous system, characterized by heterotopic nodules of gray matter resulting from disturbed neuronal migration. The most common form of bilateral PNH is X-linked dominant inherited, caused by mutations in the Filamin A gene (FLNA) and associated with a wide variety of other clinical findings including congenital heart disease. The typical patient with FLNA-associated PNH is female and presents with difficult to treat seizures. In contrast, hemizygous FLNA loss of function mutations in males are reported to be perinatally lethal. In X-linked dominant traits like FLNA-associated PNH the causal mutation is commonly inherited from the mother. Here, we present an exceptional family with paternal transmission of classic bilateral FLNA-associated PNH from a mildly affected father with somatic and germline mosaicism for a c.5686G>A FLNA splice mutation to both daughters with strikingly variable clinical manifestation and PNH extent in cerebral MR imaging. Our observations emphasize the importance to consider in genetic counseling and risk assessment the rare genetic constellation of paternal transmission for families with X-linked dominant inherited FLNA-associated PNH. Copyright © 2013 Wiley Periodicals, Inc.

Novel compound heterozygous mutations in CNGA1in a Chinese family affected with autosomal recessive retinitis pigmentosa by targeted sequencing.

PubMed

Wang, Min; Gan, Dekang; Huang, Xin; Xu, Gezhi

2016-07-08

About 37 genes have been reported to be involved in autosomal recessive retinitis pigmentosa, a hereditary retinal disease. However, causative genes remain unclear in a lot of cases. Two sibs of a Chinese family with ocular disease were diagnosed in Eye and ENT Hospital of Fudan University. Targeted sequencing performed on proband to screen pathogenic mutations. PCR combined Sanger sequencing then performed on eight family members including two affected and six unaffected individuals to determine whether mutations cosegregate with disease. Two affected members exhibited clinical features that fit the criteria of autosomal recessive retinitis pigmentosa. Two heterozygous mutations (NM000087, p.Y82X and p.L89fs) in CNGA1 were revealed on proband. Affected members were compound heterozygotes for the two mutations whereas unaffected members either had no mutation or were heterozygote carriers for only one of the two mutations. That is, these mutations cosegregate with autosomal recessive retinitis pigmentosa. Compound heterozygous mutations (NM000087, p.Y82X and p.L89fs) in exon 6 of CNGA1are pathogenic mutations in this Chinese family. Of which, p.Y82X is firstly reported in patient with autosomal recessive retinitis pigmentosa.

Neovascular glaucoma in a patient with X-linked juvenile retinoschisis.

PubMed

Zuo, Chengguo; Chen, Changzheng; Xing, Yiqiao; Du, Lei

2005-09-01

To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS.

Genotypic analysis of X-linked retinoschisis in Western Australia.

PubMed

Lamey, Tina; Laurin, Sarina; Chelva, Enid; De Roach, John

2010-01-01

X-linked Retinoschisis is a leading cause of juvenile macular degeneration. Four Western Australian families affected by X-Linked Retinoschisis were analysed using DNA and clinical information from the Australian Inherited Retinal Disease (IRD) Register and DNA Bank. By direct sequencing of the RS1 gene, three genetic variants were identified; 52+1G > T, 289T > G and 416delA. 289T > G has not been previously reported and is likely to cause a substitution of a membrane binding residue (W92G) in the functional discoidin domain. All clinically diagnosed individuals showed typical electronegative ERGs. The 52+1G > T obligate carrier also recorded a bilaterally abnormal rod ERG and mildly abnormal photopic responses. mfERG trace arrays showed reduced response densities in the paramacular region extending futher temporally for each eye.

Do economic recessions during early and mid-adulthood influence cognitive function in older age?

PubMed

Leist, Anja K; Hessel, Philipp; Avendano, Mauricio

2014-02-01

Fluctuations in the national economy shape labour market opportunities and outcomes, which in turn may influence the accumulation of cognitive reserve. This study examines whether economic recessions experienced in early and mid-adulthood are associated with later-life cognitive function. Data came from 12,020 respondents in 11 countries participating in the Survey of Health, Ageing and Retirement in Europe (SHARE). Cognitive assessments in 2004/2005 and 2006/2007 were linked to complete work histories retrospectively collected in 2008/2009 and to historical annual data on fluctuations in Gross Domestic Product per capita for each country. Controlling for confounders, we assessed whether recessions experienced at ages 25-34, 35-44 and 45-49 were associated with cognitive function at ages 50-74. Among men, each additional recession at ages 45-49 was associated with worse cognitive function at ages 50-74 (b=-0.06, CI -0.11 to -0.01). Among women, each additional recession at ages 25-44 was associated with worse cognitive function at ages 50-74 (b25-34=-0.03, CI -0.04 to -0.01; b35-44=-0.02, CI -0.04 to -0.00). Among men, recessions at ages 45-49 influenced risk of being laid-off, whereas among women, recessions at ages 25-44 led to working part-time and higher likelihood of downward occupational mobility, which were all predictors of worse later-life cognitive function. Recessions at ages 45-49 among men and 25-44 among women are associated with later-life cognitive function, possibly through more unfavourable labour market trajectories. If replicated in future studies, findings indicate that policies that ameliorate the impact of recessions on labour market outcomes may promote later-life cognitive function.

Do Economic Recessions During Early and Mid-Adulthood Influence Cognitive Function in Older Age?

PubMed Central

Leist, Anja K.; Hessel, Philipp; Avendano, Mauricio

2014-01-01

Background Fluctuations in the national economy shape labour market opportunities and outcomes, which in turn may influence the accumulation of cognitive reserve. This study examines whether economic recessions experienced in early and mid-adulthood are associated with later-life cognitive function. Method Data came from 12,020 respondents in 11 countries participating in the Survey of Health, Ageing and Retirement in Europe (SHARE). Cognitive assessments in 2004/5 and 2006/7 were linked to complete work histories retrospectively collected in 2008/9, and to historical annual data on fluctuations in Gross Domestic Product (GDP) per capita for each country. Controlling for confounders, we assessed whether recessions experienced at ages 25-34, 35-44 and 45-49 were associated with cognitive function at ages 50-74. Results Among men, each additional recession at ages 45-49 was associated with worse cognitive function at ages 50-74 (b = -0.06, Confidence Interval [CI] -0.11, -0.01). Among women, each additional recession at ages 25-44 was associated with worse cognitive function at ages 50-74 (b25-34 = -0.03, CI -0.04, -0.01; b35-44= -0.02, CI -0.04, -0.00). Among men, recessions at ages 45-49 influenced risk of being laid-off, whereas among women, recessions at ages 25-44 led to working part-time and higher likelihood of downward occupational mobility, which were all predictors of worse later-life cognitive function. Conclusions Recessions at ages 45-49 among men and 25-44 among women are associated with later-life cognitive function, possibly via more unfavourable labour market trajectories. If replicated in future studies, findings may indicate that policies that ameliorate the impact of recessions on labour market outcomes may promote later-life cognitive function. PMID:24258197

Pyoderma Gangrenosum–Like Ulcer in a Patient With X-Linked Agammaglobulinemia

PubMed Central

Murray, Patrick R.; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B.; Ecker, David J.; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L.

2011-01-01

Background Pyoderma gangrenosum–like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient’s culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. Observation An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when sub-cultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. Conclusions This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum–like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum–like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy. PMID:20479300

Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.

PubMed

Jonsson, Kenneth B; Zahradnik, Richard; Larsson, Tobias; White, Kenneth E; Sugimoto, Toshitsugu; Imanishi, Yasuo; Yamamoto, Takehisa; Hampson, Geeta; Koshiyama, Hiroyuki; Ljunggren, Osten; Oba, Koichi; Yang, In Myung; Miyauchi, Akimitsu; Econs, Michael J; Lavigne, Jeffrey; Jüppner, Harald

2003-04-24

Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied. Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic

Unusual phenotypic expression of an XLRS1 mutation in X-linked juvenile retinoschisis.

PubMed

Dodds, Jodi A; Srivastava, Anand K; Holden, Kenton R

2006-04-01

X-linked juvenile retinoschisis is a rare progressive vitreoretinal degenerative process that appears in early childhood, results in decreased visual acuity and blindness (if severe), and is caused by various mutations within the XLRS1 gene at Xp22.2. We report an affected family of Western European ancestry with X-linked juvenile retinoschisis. The family was found to carry a 304C-->T substitution in exon 4 of the XLRS1 gene, resulting in an Arg102Trp amino acid substitution. Two of the four available clinical cases in this family were found to carry the mutation. All available mothers of affected males were found to be unaffected carriers of the mutation, a typical feature of X-linked diseases. Two new female carriers, sisters of affected males, were identified and counseled accordingly. Questionnaires on visual functioning were given to the affected family members to examine the psychologic and sociologic impact of X-linked juvenile retinoschisis, which documented an associated stigma even when affected with a "mild" phenotype.

X-linked Charcot-Marie-Tooth (CMT) neuropathies (CMTX1, CMTX2, CMTX3) show different clinical phenotype and molecular genetics

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

Ionasescu, V.V.; Searby, C.C.; Ionasescu, R.

1994-09-01

The purpose of this study was to compare the X-linked dominant type CMTX1 (20 families) with X-linked recessive types CMTX2 and CMTX3 (2 families). The clinical phenotype was consistent with CMT peripheral neuropathy in all cases including distal weakness, atrophy and sensory loss, pes cavus and areflexia. Additional clinicial involvement of the central nervous system was present in one family with CMTX2 (mental retardation) and one family with CMTX3 (spastic paraparesis). Tight genetic linkage to Xq13.1 was present in 20 families with CMTX1 (Z=34.07 at {theta}=0) for the marker DXS453. Fifteen of the CMTX1 families showed point mutations of themore » connexin 32 coding region (5 nonsense mutations, 8 missense mutations, 2 deletions). Five CMTX1 neuropathy families showed no evidence of point mutations of the CX32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype in these families may be the result of promoter mutations, 3{prime}-untranslated region mutations or exon/intron splice site mutations or a mutation with a different type of connexin but which has close structural similarities to CX32. No mutations of the CX32 coding region were found in the CMTX2 or CMTX3 families. Linkage to Xq13.1 was excluded in both families. Genetic linkage to Xp22.2 was present in the CMTX2 family (Z=3.54 at {theta}=0) for the markers DXS987 and DXS999. Suggestion of linkage to Xq26 (Z=1.81 at {theta}=0) for the marker DXS86 was present in the CMTX3 family.« less

Expression pattern of X-linked genes in sex chromosome aneuploid bovine cells.

PubMed

Basrur, Parvathi K; Farazmand, Ali; Stranzinger, Gerald; Graphodatskaya, Daria; Reyes, Ed R; King, W Allan

2004-01-01

Expression of the X-inactive specific transcript (XIST) gene is a prerequisite step for dosage compensation in mammals, accomplished by silencing one of the two X chromosomes in normal female diploid cells or all X chromosomes in excess of one in sex chromosome aneuploids. Our previous studies showing that XIST expression does not eventuate the inactivation of X-linked genes in fetal bovine testis had suggested that XIST expression may not be an indicator of X inactivation in this species. In this study, we used a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) approach on cultures of bovine cells with varying sex chromosome constitution (XY, XX, XXY and XXX) to test whether the levels of XIST expressed conform to the number of late replicating (inactive) X chromosomes displayed by proliferating cells in these cultures. Expression patterns of four X-linked genes, including hypoxanthine phosphorybosyl transferase (HPRT), glucose-6-phosphate dehydrogenase (G6PD), zinc finger protein locus on the X (ZFX). and 'selected mouse cDNA on the X' (SMCX), in all these cells were also tested. Results showed that XIST expression was significantly higher (p < 0.05) in XXX cells compared to XX and XXY cells and that G6PD. HPRT, and SMCX loci are subject to X inactivation. The significantly higher levels of ZFX expressed in XXX cells compared to XX and XXY cells (p < 0.05) confirmed that this bovine locus, as human ZFX, escapes X inactivation. However, the levels of XIST and ZFX expressed were not proportional to the X chromosome load in these cells suggesting that X-linked loci escaping inactivation may be regulated at transcription (or post-transcription) level by mechanisms that prevent gene-specific product accumulation beyond certain levels in sex chromosome aneuploids.

Fastener Recess Evaluation

DTIC Science & Technology

1978-04-01

lbs respectively. The Torx recess suffered most under the test methods adopted (as would any similar recess such as the internal hex). Zero values ...Administrationi, National Tool Center Apex Machine and Tool Co. r~. Phillips International Co.] Hi-Shear Corp. General Dynamics Corp. Defense Logistics Agency...29 6. Undersized Bits 30 7. Worn Bit Test 31 8. Stock Bit and Screw Comparison 32 9. Ribbed Bits 36 V FIELD DATA OBSERVATIONS 38 1. Torque Values 38 2

X-linked cardiomyopathy is heterogeneous

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

Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of amore » large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.« less

X-Linked Intellectual Disability: Unique Vulnerability of the Male Genome

ERIC Educational Resources Information Center

Stevenson, Roger E.; Schwartz, Charles E.

2009-01-01

X-linked intellectual disability (XLID) accounts for approximately 16% of males with intellectual disability (ID). This is, in part, related to the fact that males have a single X chromosome. Progress in the clinical and molecular characterization of XLID has outpaced progress in the delineation of ID due to genes on the other 22 chromosomes.…

Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation

PubMed Central

Royo, Hélène; Seitz, Hervé; ElInati, Elias; Peters, Antoine H. F. M.; Stadler, Michael B.; Turner, James M. A.

2015-01-01

During the pachytene stage of meiosis in male mammals, the X and Y chromosomes are transcriptionally silenced by Meiotic Sex Chromosome Inactivation (MSCI). MSCI is conserved in therian mammals and is essential for normal male fertility. Transcriptomics approaches have demonstrated that in mice, most or all protein-coding genes on the X chromosome are subject to MSCI. However, it is unclear whether X-linked non-coding RNAs behave in a similar manner. The X chromosome is enriched in microRNA (miRNA) genes, with many exhibiting testis-biased expression. Importantly, high expression levels of X-linked miRNAs (X-miRNAs) have been reported in pachytene spermatocytes, indicating that these genes may escape MSCI, and perhaps play a role in the XY-silencing process. Here we use RNA FISH to examine X-miRNA expression in the male germ line. We find that, like protein-coding X-genes, X-miRNAs are expressed prior to prophase I and are thereafter silenced during pachynema. X-miRNA silencing does not occur in mouse models with defective MSCI. Furthermore, X-miRNAs are expressed at pachynema when present as autosomally integrated transgenes. Thus, we conclude that silencing of X-miRNAs during pachynema in wild type males is MSCI-dependent. Importantly, misexpression of X-miRNAs during pachynema causes spermatogenic defects. We propose that MSCI represents a chromosomal mechanism by which X-miRNAs, and other potential X-encoded repressors, can be silenced, thereby regulating genes with critical late spermatogenic functions. PMID:26509798

Keeping Recess in Schools

ERIC Educational Resources Information Center

Zavacky, Francesca; Michael, Shannon L.

2017-01-01

Recess is an important part of a comprehensive school physical activity program by providing physical activity to students during the school day, in addition to physical education and classroom physical activity. Unfortunately, recess in the United States is not an expected part of the school day, especially in middle and high schools. High-stakes…

Mutational studies in X-linked Charcot-Marie-Tooth disease (CMTX)

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

Cherryson, A.K.; Yeung, L.; Kennerson, M.L.

1994-09-01

Charcot-Marie-Tooth disease, also known as hereditary motor and sensory neuropathy (HMSN), is a heterogeneous group of slowly progressive disorders of the peripheral nerve. X-linked CMT (CMTX) is characterized by slow motor nerve conduction velocities in affected males and the presence of mildly affected or normal carrier females with intermediate or normal nerve conduction velocities. CMTX, which has an incidence of 3.1 per 100,000 and accounts for approximately 10% of CMT cases, has been mapped to Xq13. One of the genes lying in this region, connexin 32, has been found to contain alterations in individuals affected with X-linked CMT. We havemore » identified our X-linked families from dominant type 1 CMT families using the clinical criteria given above. These families were screened for point mutations in connexin 32. We have identified three missense mutations, a G{r_arrow}A transition at amino acid 35 (valine to methionine), a C{r_arrow}G transition at amino acid 158 (proline to alanine) and a T{r_arrow}A transition at amino acid 182 (serine to threonine). Another family showed a 18 bp deletion, which removed the amino acid 111 to 116 inclusive (histidine, glycine, aspartic acid, proline, leucine, histidine).« less

More Recess Time, Please!

ERIC Educational Resources Information Center

Chang, Rong; Coward, Fanni Liu

2015-01-01

Students in Shanghai, China, get much more recess time than their U.S. counterparts throughout their education. As U.S. education reform efforts seek ways of raising achievement, they have begun replacing recess with academic time. The lesson from Shanghai is that this may not be the best strategy. But whether the Shanghai system of more and…

Recess Makes Kids Smarter

ERIC Educational Resources Information Center

Adams, Caralee

2011-01-01

Recess has been scaled back or cut altogether in a number of schools around the country. The trend can be traced back to the late eighties and was accelerated under No Child Left Behind. Districts under pressure to show academic progress began to squeeze as much instruction into the day as possible. Others eliminated recess because of concerns…

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

PubMed

Lefebvre, Mathilde; Dufernez, Fabienne; Bruel, Ange-Line; Gonzales, Marie; Aral, Bernard; Saint-Onge, Judith; Gigot, Nadège; Desir, Julie; Daelemans, Caroline; Jossic, Frédérique; Schmitt, Sébastien; Mangione, Raphaele; Pelluard, Fanny; Vincent-Delorme, Catherine; Labaune, Jean-Marc; Bigi, Nicole; D'Olne, Dominique; Delezoide, Anne-Lise; Toutain, Annick; Blesson, Sophie; Cormier-Daire, Valérie; Thevenon, Julien; El Chehadeh, Salima; Masurel-Paulet, Alice; Joyé, Nicole; Vibert-Guigue, Claude; Rigonnot, Luc; Rousseau, Thierry; Vabres, Pierre; Hervé, Philippe; Lamazière, Antonin; Rivière, Jean-Baptiste; Faivre, Laurence; Laurent, Nicole; Thauvin-Robinet, Christel

2015-07-01

Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations. © 2015 John Wiley & Sons, Ltd.

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

MedlinePlus

... Share: Email Facebook Twitter Home Health Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ... Javascript to view the expand/collapse boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus ...

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

PubMed Central

Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

2016-01-01

Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

X-linked intellectual disability update 2017.

PubMed

Neri, Giovanni; Schwartz, Charles E; Lubs, Herbert A; Stevenson, Roger E

2018-04-25

The X-chromosome comprises only about 5% of the human genome but accounts for about 15% of the genes currently known to be associated with intellectual disability. The early progress in identifying the X-linked intellectual disability (XLID)-associated genes through linkage analysis and candidate gene sequencing has been accelerated with the use of high-throughput technologies. In the 10 years since the last update, the number of genes associated with XLID has increased by 96% from 72 to 141 and duplications of all 141 XLID genes have been described, primarily through the application of high-resolution microarrays and next generation sequencing. The progress in identifying genetic and genomic alterations associated with XLID has not been matched with insights that improve the clinician's ability to form differential diagnoses, that bring into view the possibility of curative therapies for patients, or that inform scientists of the impact of the genetic alterations on cell organization and function. © 2018 Wiley Periodicals, Inc.

A family study of congenital X linked sideroblastic anaemia.

PubMed Central

Holmes, J; May, A; Geddes, D; Jacobs, A

1990-01-01

We report on the cytogenetic findings in a family study of pyridoxine responsive, X linked sideroblastic anaemia. An increase in the number of X chromosomes was observed in a small proportion of metaphases prepared from five female members, but these findings did not strictly correlate with the carrier status of the condition. No consistent cytogenetic abnormality could be identified or associated with this rare familial condition. The diagnosis and counselling of carriers of this condition is discussed. Images PMID:2308152

Absence of FKBP10 in Recessive Type XI Osteogenesis Imperfecta Leads to Diminished Collagen Cross-Linking and Reduced Collagen Deposition in Extracellular Matrix

PubMed Central

Barnes, Aileen M.; Cabral, Wayne A.; Weis, MaryAnn; Makareeva, Elena; Mertz, Edward L.; Leikin, Sergey; Eyre, David; Trujillo, Carlos; Marini, Joan C.

2012-01-01

Recessive osteogenesis imperfecta (OI) is caused by defects in genes whose products interact with type I collagen for modification and/or folding. We identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in FKBP10 or PPIB, which encode endoplasmic reticulum resident chaperone/isomerases FKBP65 and CyPB, respectively. In one pedigree branch, both parents carry a deletion in PPIB (c.563_566delACAG), causing lethal type IX OI in their two children. In another branch, a child with moderate type XI OI has a homozygous FKBP10 mutation (c.1271_1272delCCinsA). Proband FKBP10 transcripts are 4% of control and FKBP65 protein is absent from proband cells. Proband collagen electrophoresis reveals slight band broadening, compatible with ≈10% overmodification. Normal chain incorporation, helix folding, and collagen Tm support a minimal general collagen chaperone role for FKBP65. However, there is a dramatic decrease in collagen deposited in culture despite normal collagen secretion. Mass spectrometry reveals absence of hydroxylation of the collagen telopeptide lysine involved in cross-linking, suggesting that FKBP65 is required for lysyl hydroxylase activity or access to type I collagen telopeptide lysines, perhaps through its function as a peptidylprolyl isomerase. Proband collagen to organics ratio in matrix is approximately 30% of normal in Raman spectra. Immunofluorescence shows sparse, disorganized collagen fibrils in proband matrix. PMID:22718341

Lamellar macular hole in X linked retinoschisis

PubMed Central

Kumar, Vinod; Goel, Neha

2016-01-01

X linked retinoschisis (XLRS) is the most common juvenile onset retinal degeneration. The disorder leads to poor vision in old age. Complications, however, can lead to earlier loss of vision in this condition. This report describes two patients of XLRS, who had presented with poor vision because of having had a lamellar macular hole at a young age. Lamellar macular holes are rare and have never been reported to cause early onset poor vision in XLRS. PMID:27170611

Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis.

PubMed

Eriksson, Urban; Larsson, Eva; Holmström, Gerd

2004-04-01

To describe the value of optical coherence tomography (OCT) as a diagnostic tool in the diagnosis of X-linked retinoschisis. We report three boys aged between 8 and 17 years, diagnosed with X-linked retinoschisis. During investigations they were examined with OCT (Zeiss Humphrey OCT 1, upgraded version). Single scans of the central posterior pole and the region around the vascular arcades were obtained. Two of the boys underwent full-field ERG according to ISCEV standards. Genetic analysis was performed in all three boys, with sequencing of the XLRS gene. The OCT results revealed a pattern with a cleavage of the retina in two distinct planes, one deep (outer retina) and one superficial. This was very obvious in one patient and a similar but not as pronounced pattern was seen in the other two cases. The two layers were superficially connected with thin-walled, vertical palisades, separated by low reflective, cystoid spaces, confluent and most prominent in the foveal region. Full-field ERG and/or DNA analysis are well known methods used for diagnosis of X-linked juvenile retinoschisis. In this paper, we suggest that OCT can also be a helpful diagnostic tool.

X-linked cataract and Nance-Horan syndrome are allelic disorders.

PubMed

Coccia, Margherita; Brooks, Simon P; Webb, Tom R; Christodoulou, Katja; Wozniak, Izabella O; Murday, Victoria; Balicki, Martha; Yee, Harris A; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J; Maher, Eamonn R; Moore, Anthony T; Russell-Eggitt, Isabelle M; Hardcastle, Alison J

2009-07-15

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication-triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved.

X-linked cataract and Nance-Horan syndrome are allelic disorders

PubMed Central

Coccia, Margherita; Brooks, Simon P.; Webb, Tom R.; Christodoulou, Katja; Wozniak, Izabella O.; Murday, Victoria; Balicki, Martha; Yee, Harris A.; Wangensteen, Teresia; Riise, Ruth; Saggar, Anand K.; Park, Soo-Mi; Kanuga, Naheed; Francis, Peter J.; Maher, Eamonn R.; Moore, Anthony T.; Russell-Eggitt, Isabelle M.; Hardcastle, Alison J.

2009-01-01

Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Protein truncation mutations in a novel gene (NHS) have been identified in patients with this syndrome. We previously mapped X-linked congenital cataract (CXN) in one family to an interval on chromosome Xp22.13 which encompasses the NHS locus; however, no mutations were identified in the NHS gene. In this study, we show that NHS and X-linked cataract are allelic diseases. Two CXN families, which were negative for mutations in the NHS gene, were further analysed using array comparative genomic hybridization. CXN was found to be caused by novel copy number variations: a complex duplication–triplication re-arrangement and an intragenic deletion, predicted to result in altered transcriptional regulation of the NHS gene. Furthermore, we also describe the clinical and molecular analysis of seven families diagnosed with NHS, identifying four novel protein truncation mutations and a novel large deletion encompassing the majority of the NHS gene, all leading to no functional protein. We therefore show that different mechanisms, aberrant transcription of the NHS gene or no functional NHS protein, lead to different diseases. Our data highlight the importance of copy number variation and non-recurrent re-arrangements leading to different severity of disease and describe the potential mechanisms involved. PMID:19414485

HLA-linked rheumatoid arthritis

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

Hasstedt, S.J.; Clegg, D.O.; Ingles, L.

Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. Inmore » addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically. 79 refs., 9 tabs.« less

Genetic localization and phenotypic expression of X-linked cataract (Xcat) in Mus musculus.

PubMed

Favor, J; Pretsch, W

1990-01-01

Linkage data relative to the markers tabby and glucose-6-phosphate dehydrogenase are presented to locate X-linked cataract (Xcat) in the distal portion of the mouse X-chromosome between jimpy and hypophosphatemia. The human X-linked cataract-dental syndrome, Nance-Horan Syndrome, also maps closely to human hypophosphatemia and would suggest homology between mouse Xcat and human Nance-Horan Syndrome genes. In hemizygous males and homozygous females penetrance is complete with only slight variation in the degree of expression. Phenotypic expression in Xcat heterozygous females ranges from totally clear to totally opaque lenses. The phenotypic expression between the two lenses of a heterozygous individual could also vary between totally clear and totally opaque lenses. However, a correlation in the degree of expression between the eyes of an individual was observed. A variegated pattern of lens opacity was evident in female heterozygotes. Based on these observations, the site of gene action for the Xcat locus is suggested to be endogenous to the lens cells and the precursor cell population of the lens is concluded to be small. The identification of an X-linked cataract locus is an important contribution to the estimate of the number of mutable loci resulting in cataract, an estimate required so that dominant cataract mutagenesis results may be expressed on a per locus basis. The Xcat mutation may be a useful marker for a distal region of the mouse X-chromosome which is relatively sparsely marked and the X-linked cataract mutation may be employed in gene expression and lens development studies.

The faster-X effect: integrating theory and data.

PubMed

Meisel, Richard P; Connallon, Tim

2013-09-01

Population genetics theory predicts that X (or Z) chromosomes could play disproportionate roles in speciation and evolutionary divergence, and recent genome-wide analyses have identified situations in which X or Z-linked divergence exceeds that on the autosomes (the so-called 'faster-X effect'). Here, we summarize the current state of both the theory and data surrounding the study of faster-X evolution. Our survey indicates that the faster-X effect is pervasive across a taxonomically diverse array of evolutionary lineages. These patterns could be informative of the dominance or recessivity of beneficial mutations and the nature of genetic variation acted upon by natural selection. We also identify several aspects of disagreement between these empirical results and the population genetic models used to interpret them. However, there are clearly delineated aspects of the problem for which additional modeling and collection of genomic data will address these discrepancies and provide novel insights into the population genetics of adaptation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids.

PubMed Central

Shows, T B; Brown, J A

1975-01-01

Human genes coding for hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase), glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49; D-glucose-6-phosphate:NADP+ 1-oxidoreductase), and phosphoglycerate kinase (PGK, EC 2.7.2.3; ATP:3-phospho-D-glycerate 1-phosphotransferase) have been assigned to specific regions on the long arm of the X chromosome by somatic cell gentic techniques. Gene assignment and linear order were determined by employing human somatic cells possessing an X/9 translocation or an X/22 translocation in man-mouse cell hybridization studies. The X/9 translocation involved the majority of the X long arm translocated to chromosome 9 and the X/22 translocation involved the distal half of the X long arm translocated to 22. In each case these rearrangements appeared to be reciprocal. Concordant segregation of X-linked enzymes and segments of the X chromosome generated by the translocations indicated assignment of the PGK gene to a proximal long arm region (q12-q22) and the HPRT and G6PD genes to the distal half (q22-qter) of the X long arm. Further evidence suggests a gene order on the X long arm of centromere-PGK-HPRT-G6PD. Images PMID:1056018

Lamellar macular hole in X linked retinoschisis.

PubMed

Kumar, Vinod; Goel, Neha

2016-05-11

X linked retinoschisis (XLRS) is the most common juvenile onset retinal degeneration. The disorder leads to poor vision in old age. Complications, however, can lead to earlier loss of vision in this condition. This report describes two patients of XLRS, who had presented with poor vision because of having had a lamellar macular hole at a young age. Lamellar macular holes are rare and have never been reported to cause early onset poor vision in XLRS. 2016 BMJ Publishing Group Ltd.

A case report of recessive myotonia congenita and early onset cognitive impairment: Is it a causal or casual link?

PubMed

Portaro, Simona; Cacciola, Alberto; Naro, Antonino; Milardi, Demetrio; Morabito, Rosa; Corallo, Francesco; Marino, Silvia; Bramanti, Alessia; Mazzon, Emanuela; Calabrò, Rocco Salvatore

2018-06-01

Myotonia congenita (MC) is a non-dystrophic myotonia inherited either in dominant (Thomsen) or recessive (Becker) form. MC is due to an abnormal functioning of skeletal muscle voltage-gated chloride channel (CLCN1), but the genotype/phenotype correlation remains unclear. A 48-year-old man, from consanguineous parents, presented with a fixed muscle weakness, muscle atrophy, and a cognitive impairment. Notably, his brother presented the same mutation but with a different phenotype, mainly involving cognitive function. The patient was submitted to cognitive assessment, needle electromyography, brain and muscle MRI, and genetic analysis. The Milan Overall Dementia Assessment showed short-term memory, verbal fluency and verbal intelligence impairment. His genetic analysis showed a recessive splice-site mutation in the CLCN1 gene (IVS19+2T>A). Muscle MRI revealed a symmetric and bilateral fat infiltration of the tensor of fascia lata, gluteus medius, and gluteus maximus muscles, associated to mild atrophy. Recessive myotonia congenita was diagnosed. Further studies should establish if and to which extent the CLCN1 mutation is responsible for this c MC phenotype, taking into account a gene-gene and /or a gene-environment.

Two sisters with clinical diagnosis of Wiskott-Aldrich Syndrome: Is the condition in the family autosomal recessive?

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

Kondoh, T.; Hayashi, K.; Matsumoto, T.

1995-10-09

We report two sisters in a family representing manifestations of Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disorder. An elder sister had suffered from recurrent infections, small thrombocytopenic petechiae, purpura, and eczema for 7 years. The younger sister had the same manifestations as the elder sister`s for a 2-year period, and died of intracranial bleeding at age 2 years. All the laboratory data of the two patients were compatible with WAS, although they were females. Sialophorin analysis with the selective radioactive labeling method of this protein revealed that in the elder sister a 115-KD band that should be specific for sialophorinmore » was reduced in quantity, and instead an additional 135-KD fragment was present as a main band. Polymerase chain reaction (PCR) analysis of the sialophorin gene and single-strand conformation polymorphism (SSCP) analysis of the PCR product demonstrated that there were no detectable size-change nor electrophoretic mobility change in the DNA from both patients. The results indicated that their sialophorin gene structure might be normal. Studies on the mother-daughter transmission of X chromosome using a pERT84-MaeIII polymorphic marker mapped at Xp21 and HPRT gene polymorphism at Xq26 suggested that each sister had inherited a different X chromosome from the mother. Two explanations are plausible for the occurrence of the WAS in our patients: the WAS in the patients is attributable to an autosomal gene mutation which may regulate the sialophorin gene expression through the WAS gene, or, alternatively, the condition in this family is an autosomal recessive disorder separated etiologically from the X-linked WAS. 17 refs., 6 figs., 1 tab.« less

A major X-linked locus affects kidney function in mice

PubMed Central

Leduc, Magalie S.; Savage, Holly S.; Stearns, Timothy M.; Cario, Clinton L.; Walsh, Kenneth A.; Paigen, Beverly; Berndt, Annerose

2012-01-01

Chronic kidney disease is a common disease with increasing prevalence in the western population. One common reason for chronic kidney failure is diabetic nephropathy. Diabetic nephropathy and hyperglycemia are characteristics of the mouse inbred strain KK/HlJ, which is predominantly used as a model for metabolic syndrome due to its inherited glucose intolerance and insulin resistance. We used KK/HlJ, an albuminuria-sensitive strain, and C57BL/6J, an albuminuria-resistant strain, to perform a quantitative trait locus (QTL) cross to identify the genetic basis for chronic kidney failure. Albumin-creatinine-ratio (ACR) was measured in 130 F2 male offspring. One significant QTL was identified on chromosome (Chr) X and four suggestive QTLs were found on Chrs 6, 7, 12, and 13. Narrowing of the QTL region was focused on the X-linked QTL and performed by incorporating genotype and expression analyses for genes located in the region. From the 485 genes identified in the X-linked QTL region, a few candidate genes were identified using a combination of bioinformatic evidence based on genomic comparison of the parental strains and known function in urine homeostasis. Finally, this study demonstrates the significance of the X chromosome in the genetic determination of albuminuria. PMID:23011808

Differences in Physical Activity during School Recess

ERIC Educational Resources Information Center

Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

2011-01-01

Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

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

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

The Physiological Impacts of Wealth Shocks in Late Life: Evidence from the Great Recession

PubMed Central

Boen, Courtney; Yang, Y. Claire

2016-01-01

Given documented links between individual socioeconomic status (SES) and health, it is likely that—in addition to its impacts on individuals’ wallets and bank accounts—the Great Recession also took a toll on individuals’ disease and mortality risk. Exploiting a quasi-natural experiment design, this study utilizes nationally representative, longitudinal data from the National Social Life, Health, and Aging Project (NSHAP) (2005-2011) (N=930) and individual fixed effects models to examine how household-level wealth shocks experienced during the Great Recession relate to changes in biophysiological functioning in older adults. Results indicate that wealth shocks significantly predicted changes in physiological functioning, such that losses in net worth from the pre- to the post-Recession period were associated with increases in systolic blood pressure and C-reactive protein over the six year period. Further, while the association between wealth shocks and changes in blood pressure was unattenuated with the inclusion of other indicators of SES, psychosocial well-being, and health behaviors in analytic models, we document some evidence of mediation in the association between changes in wealth and changes in C-reactive protein, which suggests specificity in the social and biophysiological mechanisms relating wealth shocks and health at older ages. Linking macro-level conditions, meso-level household environments, and micro-level biological processes, this study provides new insights into the mechanisms through which economic inequality contributes to disease and mortality risk in late life. PMID:26773705

The physiological impacts of wealth shocks in late life: Evidence from the Great Recession.

PubMed

Boen, Courtney; Yang, Y Claire

2016-02-01

Given documented links between individual socioeconomic status (SES) and health, it is likely that-in addition to its impacts on individuals' wallets and bank accounts-the Great Recession also took a toll on individuals' disease and mortality risk. Exploiting a quasi-natural experiment design, this study utilizes nationally representative, longitudinal data from the National Social Life, Health, and Aging Project (NSHAP) (2005-2011) (N = 930) and individual fixed effects models to examine how household-level wealth shocks experienced during the Great Recession relate to changes in biophysiological functioning in older adults. Results indicate that wealth shocks significantly predicted changes in physiological functioning, such that losses in net worth from the pre-to the post-Recession period were associated with increases in systolic blood pressure and C-reactive protein over the six year period. Further, while the association between wealth shocks and changes in blood pressure was unattenuated with the inclusion of other indicators of SES, psychosocial well-being, and health behaviors in analytic models, we document some evidence of mediation in the association between changes in wealth and changes in C-reactive protein, which suggests specificity in the social and biophysiological mechanisms relating wealth shocks and health at older ages. Linking macro-level conditions, meso-level household environments, and micro-level biological processes, this study provides new insights into the mechanisms through which economic inequality contributes to disease and mortality risk in late life. Copyright © 2015 Elsevier Ltd. All rights reserved.

X-linked Alport syndrome caused by splicing mutations in COL4A5.

PubMed

Nozu, Kandai; Vorechovsky, Igor; Kaito, Hiroshi; Fu, Xue Jun; Nakanishi, Koichi; Hashimura, Yuya; Hashimoto, Fusako; Kamei, Koichi; Ito, Shuichi; Kaku, Yoshitsugu; Imasawa, Toshiyuki; Ushijima, Katsumi; Shimizu, Junya; Makita, Yoshio; Konomoto, Takao; Yoshikawa, Norishige; Iijima, Kazumoto

2014-11-07

X-linked Alport syndrome is caused by mutations in the COL4A5 gene. Although many COL4A5 mutations have been detected, the mutation detection rate has been unsatisfactory. Some men with X-linked Alport syndrome show a relatively mild phenotype, but molecular basis investigations have rarely been conducted to clarify the underlying mechanism. In total, 152 patients with X-linked Alport syndrome who were suspected of having Alport syndrome through clinical and pathologic investigations and referred to the hospital for mutational analysis between January of 2006 and January of 2013 were genetically diagnosed. Among those patients, 22 patients had suspected splice site mutations. Transcripts are routinely examined when suspected splice site mutations for abnormal transcripts are detected; 11 of them showed expected exon skipping, but others showed aberrant splicing patterns. The mutation detection strategy had two steps: (1) genomic DNA analysis using PCR and direct sequencing and (2) mRNA analysis using RT-PCR to detect RNA processing abnormalities. Six splicing consensus site mutations resulting in aberrant splicing patterns, one exonic mutation leading to exon skipping, and four deep intronic mutations producing cryptic splice site activation were identified. Interestingly, one case produced a cryptic splice site with a single nucleotide substitution in the deep intron that led to intronic exonization containing a stop codon; however, the patient showed a clearly milder phenotype for X-linked Alport syndrome in men with a truncating mutation. mRNA extracted from the kidney showed both normal and abnormal transcripts, with the normal transcript resulting in the milder phenotype. This novel mechanism leads to mild clinical characteristics. This report highlights the importance of analyzing transcripts to enhance the mutation detection rate and provides insight into genotype-phenotype correlations. This approach can clarify the cause of atypically mild phenotypes in X-linked

X linked exudative vitreoretinopathy: clinical features and genetic linkage analysis.

PubMed

Fullwood, P; Jones, J; Bundey, S; Dudgeon, J; Fielder, A R; Kilpatrick, M W

1993-03-01

A four generation family in which familial exudative vitreoretinopathy is inherited as an X linked condition is described. Essentially the condition is one of abnormal vascularisation and signs at birth are those of a retinopathy superficially resembling retinopathy of prematurity, retinal folds, or, in advanced cases, enophthalmos or even phthisis. Prognosis depends on the progression of the retinal changes. The family members, including seven affected males and five obligate carrier females, have been types for 20 DNA markers, and linkage analysis suggests a gene locus either at Xq21.3 or at Xp11. As the latter region includes the locus for the gene for Norrie disease, it is possible that this and X linked vitreoretinopathy are allelic. We can further speculate that the differences in severity of the clinical manifestations are dependent only upon the timing of the insult.

A family with X-linked anophthalmia: exclusion of SOX3 as a candidate gene.

PubMed

Slavotinek, Anne; Lee, Stephen S; Hamilton, Steven P

2005-10-01

We report on a four-generation family with X-linked anophthalmia in four affected males and show that this family has LOD scores consistent with linkage to Xq27, the third family reported to be linked to the ANOP1 locus. We sequenced the SOX3 gene at Xq27 as a candidate gene for the X-linked anophthalmia based on the high homology of this gene to SOX2, a gene previously mutated in bilateral anophthlamia. However, no amino acid sequence alterations were identified in SOX3. We have improved the definition of the phenotype in males with anophthalmia linked to the ANOP1 locus, as microcephaly, ocular colobomas, and severe renal malformations have not been described in families linked to ANOP1. (c) 2005 Wiley-Liss, Inc.

CAPILLARY NETWORK ALTERATIONS IN X-LINKED RETINOSCHISIS IMAGED ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

Romano, Francesco; Arrigo, Alessandro; Chʼng, Soon Wai; Battaglia Parodi, Maurizio; Manitto, Maria Pia; Martina, Elisabetta; Bandello, Francesco; Stanga, Paulo E

2018-06-05

To assess foveal and parafoveal vasculature at the superficial capillary plexus, deep capillary plexus, and choriocapillaris of patients with X-linked retinoschisis by means of optical coherence tomography angiography. Six patients with X-linked retinoschisis (12 eyes) and seven healthy controls (14 eyes) were recruited and underwent complete ophthalmologic examination, including best-corrected visual acuity, dilated fundoscopy, and 3 × 3-mm optical coherence tomography angiography macular scans (DRI OCT Triton; Topcon Corp). After segmentation and quality review, optical coherence tomography angiography slabs were imported into ImageJ 1.50 (NIH; Bethesda) and digitally binarized. Quantification of vessel density was performed after foveal avascular zone area measurement and exclusion. Patients were additionally divided into "responders" and "nonresponders" to dorzolamide therapy. Foveal avascular zone area resulted markedly enlarged at the deep capillary plexus (P < 0.001), particularly in nonresponders. Moreover, patients disclosed a significant deep capillary plexus rarefaction, when compared with controls (P: 0.04); however, a subanalysis revealed that this damage was limited to the fovea (P: 0.006). Finally, the enlargement of foveal avascular zone area positively correlated with a decline in best-corrected visual acuity (P: 0.01). Prominent foveal vascular impairment is detectable in the deep capillary plexus of patients with X-linked retinoschisis. Our results correlate with functional outcomes, suggesting a possible vascular role in X-linked retinoschisis clinical manifestations.

Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix.

PubMed

Barnes, Aileen M; Cabral, Wayne A; Weis, MaryAnn; Makareeva, Elena; Mertz, Edward L; Leikin, Sergey; Eyre, David; Trujillo, Carlos; Marini, Joan C

2012-11-01

Recessive osteogenesis imperfecta (OI) is caused by defects in genes whose products interact with type I collagen for modification and/or folding. We identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in FKBP10 or PPIB, which encode endoplasmic reticulum resident chaperone/isomerases FKBP65 and CyPB, respectively. In one pedigree branch, both parents carry a deletion in PPIB (c.563_566delACAG), causing lethal type IX OI in their two children. In another branch, a child with moderate type XI OI has a homozygous FKBP10 mutation (c.1271_1272delCCinsA). Proband FKBP10 transcripts are 4% of control and FKBP65 protein is absent from proband cells. Proband collagen electrophoresis reveals slight band broadening, compatible with ≈10% over-modification. Normal chain incorporation, helix folding, and collagen T(m) support a minimal general collagen chaperone role for FKBP65. However, there is a dramatic decrease in collagen deposited in culture despite normal collagen secretion. Mass spectrometry reveals absence of hydroxylation of the collagen telopeptide lysine involved in cross-linking, suggesting that FKBP65 is required for lysyl hydroxylase activity or access to type I collagen telopeptide lysines, perhaps through its function as a peptidylprolyl isomerase. Proband collagen to organics ratio in matrix is approximately 30% of normal in Raman spectra. Immunofluorescence shows sparse, disorganized collagen fibrils in proband matrix. Published 2012 Wiley Periodicals, Inc.*This article is a US Government work and, as such, is in the public domain of the United States of America.

Fort Play Children Recreate Recess

ERIC Educational Resources Information Center

Powell, Mark

2007-01-01

Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

Gingival recession: a cross-sectional clinical investigation.

PubMed

Goutoudi, P; Koidis, P T; Konstantinidis, A

1997-06-01

In this cross-sectional study, risk and potentially causative factors of gingival recession were examined and their relationship to apical migration of the gingival margin evaluated. Thirty eight patients (18-60 years), displaying one or more sites with gingival recession but without any significant periodontal disease participated. A total of 28 parameters were evaluated in both 'test' teeth (50 teeth with gingival recession) and 'control' teeth (50 contralateral teeth). The results revealed that gingival margin recession was associated with both high inflammatory and plaque scores, with decreased widths of keratinized and attached gingiva and with the subjects' toothbrush bristle hardness.

Early RAAS Blockade Exerts Renoprotective Effects in Autosomal Recessive Alport Syndrome.

PubMed

Uchida, Nao; Kumagai, Naonori; Nozu, Kandai; Fu, Xue Jun; Iijima, Kazumoto; Kondo, Yoshiaki; Kure, Shigeo

2016-11-01

Alport syndrome is a progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes that encode collagen type IV alpha 3, alpha 4, and alpha 5 chains, respectively. Because of abnormal collagen chain, glomerular basement membrane becomes fragile and most of the patients progress to end-stage renal disease in early adulthood. COL4A5 mutation causes X-linked form of Alport syndrome, and two mutations in either COL4A3 or COL4A4 causes an autosomal recessive Alport syndrome. Recently, renin-angiotensin-aldosterone system (RAAS) blockade has been shown to attenuate effectively disease progression in Alport syndrome. Here we present three Japanese siblings and their father all diagnosed with autosomal recessive Alport syndrome and with different clinical courses, suggesting the importance of the early initiation of RAAS blockade. The father was diagnosed with Alport syndrome. His consanguineous parents and his wife were healthy. All three siblings showed hematuria since infancy. Genetic analysis revealed that they shared the same gene mutations in COL4A3 in a compound heterozygous state: c.2330G>A (p.Gly777Ala) from the mother and c.4354A>T (p.Ser1452Cys) from the father. Although RAAS blockade was initiated for the older sister and brother when their renal function was already impaired, it did not attenuate disease progression. In the youngest brother, RAAS blockade was initiated during normal renal function stage. After the initiation, his renal function has been normal with the very mild proteinuria to date at the age of 17 years. We propose that in Alport syndrome, RAAS blockade should be initiated earlier than renal function is impaired.

A novel pathogenic variant in the MARVELD2 gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

PubMed

Taghipour-Sheshdeh, Afsaneh; Nemati-Zargaran, Fatemeh; Zarepour, Narges; Tahmasebi, Parisa; Saki, Nader; Tabatabaiefar, Mohammad Amin; Mohammadi-Asl, Javad; Hashemzadeh-Chaleshtori, Morteza

2018-05-09

Hearing loss (HL) is the most common sensorineural disorder and one of the most common human defects. HL can be classified according to main criteria, including: the site (conductive, sensorineural and mixed), onset (pre-lingual and post-lingual), accompanying signs and symptoms (syndromic and non-syndromic), severity (mild, moderate, severe and profound) and mode of inheritance (Autosomal recessive, autosomal dominant, X-linked and mitochondrial). Autosomal recessive non-syndromic HL (ARNSHL) forms constitute a major share of the HL cases. In the present study, next-generation sequencing (NGS) was applied to investigate the underlying etiology of HL in a multiplex ARNSHL family from Khuzestan province, southwest Iran. In this descriptive study, 20 multiplex ARNSHL families from Khuzestan province, southwest of Iran were recruited. After DNA extraction, genetic linkage analysis (GLA) was applied to screen for a panel of more prevalent loci. One family, which was not linked to these loci, was subjected to Otogenetics deafness Next Generation Sequencing (NGS) panel. NGS results showed a novel deletion-insertion variant (c.1555delinsAA) in the MARVELD2 gene. The variant which is a frameshift in the seventh exon of the MARVELD2 gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guideline. NGS is very promising to identify the molecular etiology of highly heterogeneous diseases such as HL. MARVELD2 might be important in the etiology of HL in this region of Iran. Copyright © 2017. Published by Elsevier Inc.

X-linked Acrogigantism (X-LAG) Syndrome: Clinical Profile and Therapeutic Responses

PubMed Central

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J.; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H.; Bours, Vincent; Liu, Pengfei; De Herder, Wouter; Pellegata, Natalia; Lupski, James R.; Daly, Adrian F.; Stratakis, Constantine A.

2015-01-01

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. PMID:25712922

Event-scale power law recession analysis: quantifying methodological uncertainty

NASA Astrophysics Data System (ADS)

Dralle, David N.; Karst, Nathaniel J.; Charalampous, Kyriakos; Veenstra, Andrew; Thompson, Sally E.

2017-01-01

The study of single streamflow recession events is receiving increasing attention following the presentation of novel theoretical explanations for the emergence of power law forms of the recession relationship, and drivers of its variability. Individually characterizing streamflow recessions often involves describing the similarities and differences between model parameters fitted to each recession time series. Significant methodological sensitivity has been identified in the fitting and parameterization of models that describe populations of many recessions, but the dependence of estimated model parameters on methodological choices has not been evaluated for event-by-event forms of analysis. Here, we use daily streamflow data from 16 catchments in northern California and southern Oregon to investigate how combinations of commonly used streamflow recession definitions and fitting techniques impact parameter estimates of a widely used power law recession model. Results are relevant to watersheds that are relatively steep, forested, and rain-dominated. The highly seasonal mediterranean climate of northern California and southern Oregon ensures study catchments explore a wide range of recession behaviors and wetness states, ideal for a sensitivity analysis. In such catchments, we show the following: (i) methodological decisions, including ones that have received little attention in the literature, can impact parameter value estimates and model goodness of fit; (ii) the central tendencies of event-scale recession parameter probability distributions are largely robust to methodological choices, in the sense that differing methods rank catchments similarly according to the medians of these distributions; (iii) recession parameter distributions are method-dependent, but roughly catchment-independent, such that changing the choices made about a particular method affects a given parameter in similar ways across most catchments; and (iv) the observed correlative relationship

HYDRORECESSION: A toolbox for streamflow recession analysis

NASA Astrophysics Data System (ADS)

Arciniega, S.

2015-12-01

Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

Genetic Analysis of a Kindred With X-linked Mental Handicap and Retinitis Pigmentosa

PubMed Central

Aldred, M. A.; Dry, K. L.; Knight-Jones, E. B.; Hardwick, L. J.; Teague, P. W.; Lester, D. H.; Brown, J.; Spowart, G.; Carothers, A. D.; Raeburn, J. A.; Bird, A. C.; Fielder, A. R.; Wright, A. F.

1994-01-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538 and 5'-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. PMID:7977353

A heterozygous mutation in RPGR associated with X-linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX).

PubMed

Zhou, Qi; Yao, Fengxia; Wang, Feng; Li, Hui; Chen, Rui; Sui, Ruifang

2018-01-01

Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4-year follow-up and molecular findings in a 28-year-old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X-linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Ophthalmologic examination, optical coherent tomographic imaging, and visual electrophysiology tests showed classic manifestations of RP. The karyotype of peripheral blood showed mosaicism (45,X [72%]/46,XX[28%]). A novel heterozygous frameshift mutation (c.2403_2406delAGAG, p.T801fsX812) in the RP GTPase regulator (RPGR) gene was detected using next generation sequencing and validated by Sanger sequencing. We believe that this is the first report of X-linked RP in a patient with Turner syndrome associated with mosaicism, and an RPGR heterozygous mutation. We hypothesize that X-linked RP in this woman is not related to Turner syndrome, but may be a manifestation of the lack of a normal paternal X chromosome with intact but mutated RPGR. © 2017 Wiley Periodicals, Inc.

Foveomacular schisis in juvenile X-linked retinoschisis: an optical coherence tomography study.

PubMed

Yu, Jia; Ni, Yingqin; Keane, Pearse A; Jiang, Chunhui; Wang, Wenji; Xu, Gezhi

2010-06-01

To explore the structural features of juvenile X-linked retinoschisis using spectral-domain optical coherence tomography (OCT). Retrospective, observational cross-sectional study. Eighteen male patients (34 eyes) who were diagnosed with juvenile X-linked retinoschisis at the Eye & ENT Hospital of Fudan University over an 18-month period were included. Their OCT images, which were obtained using spectral-domain OCT (Cirrus HD-OCT; Carl Zeiss Meditec), were analyzed. The anatomic location of the schisis cavity in juvenile X-linked retinoschisis was characterized by direct inspection of OCT images. On OCT, the schisis cavity was visible at the fovea in all 34 eyes, and it was associated with increased retinal thickness. Schisis was present at the retinal nerve fiber layer in 4 eyes, at the inner nuclear layer in 29 eyes, and at the outer nuclear layer/outer plexiform layer in 22 eyes. In most cases, widespread foveomacular schisis was detected using OCT; however, in 9 eyes (6 patients), the schisis was confined to the fovea. Schisis of the inner nuclear layer and outer nuclear layer/outer plexiform layer almost always involved the foveal center, but retinal nerve fiber layer schisis was seen only in the parafoveal area. Despite conventional wisdom, in patients with X-linked retinoschisis, the schisis cavity can occur in a number of different layers of the neurosensory retina (retinal nerve fiber layer, inner nuclear layer, and outer nuclear layer/outer plexiform layer). In addition, different forms of schisis may affect different locations in the macula (foveal vs parafoveal), and, in most eyes, the schisis involves the entire foveomacular region. Copyright 2010 Elsevier Inc. All rights reserved.

A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis

PubMed Central

Jwa, Nam Soo; Kim, Sung Soo; Lee, Sung Chul; Kwon, Oh Woong

2006-01-01

Purpose To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. Methods Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. Results A novel Leu103Phe missense mutation was identified. Conclusions A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis. PMID:16768192

X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.

PubMed Central

Bichet, D G; Arthus, M F; Lonergan, M; Hendy, G N; Paradis, A J; Fujiwara, T M; Morgan, K; Gregory, M C; Rosenthal, W; Didwania, A

1993-01-01

In X-linked nephrogenic diabetes insipidus (NDI) the urine of male patients is not concentrated after the administration of the antidiuretic hormone arginine-vasopressin. This disease is due to mutations in the V2 receptor gene that maps to chromosome region Xq28. In 1969, Bode and Crawford suggested that most NDI patients in North America shared common ancestors of Ulster Scot immigrants who arrived in Halifax in 1761 on the ship Hopewell. A link between this family and a large Utah kindred was also suggested. DNA was obtained from 17 affected male patients from the "Hopewell" kindred and from four additional families from Nova Scotia and New Brunswick who shared the same Xq28 NDI haplotype. The Utah kindred and two families (Q2, Q3) from Quebec were also studied. The "Hopewell" mutation, W71X, is a single base substitution (G-->A) that changes codon 71 from TGG (tryptophan) to TGA (stop). The W71X mutation was found in affected members of the Hopewell and of the four satellite families. The W71X mutation is the cause of X-linked NDI for the largest number of related male patients living in North America. Other families (Utah, Q2 and Q3) that are historically and ethnically unrelated bear other mutations in the V2 receptor gene. Images PMID:8104196

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both

What's Physical Activity Got to Do With It? Social Trends in Less Active Students at Recess.

PubMed

Woods, Amelia Mays; McLoughlin, Gabriella M; Kern, Ben D; Graber, Kim C

2018-07-01

Public health concerns regarding childhood obesity and sedentary behavior make investigations of children's physical activity (PA) promotion crucial. School recess, a highly discretional time, plays a central role in shaping children's activity preferences. Participants included 40 children (30 girls, 10 boys) from fourth and fifth grades, categorized as low active during recess (<26% moderate-to-vigorous PA [MVPA]). PA was measured via accelerometer (Actigraph wGT3X+) and activity choice gauged through a self-report measure over a 3-day period. To assess attitudes and perceptions of recess, individual interviews were conducted. Accelerometer data were analyzed into minutes and percentage of MVPA; interviews were transcribed verbatim and analyzed utilizing open and axial coding. Participants were active for 18% of recess, choosing activities that were primarily individual-based. Interview data showed low active children attribute recess enjoyment to social interaction and time away from schoolwork as well as an intention to avoid other children who were unkind and/or caused social conflict. This study supports the importance of gaining a child's perspective of their own behavior, particularly those children classified as less active. Findings add a unique contribution to school health research through an innovative, child-centered approach to explore perceptions of PA. © 2018, American School Health Association.

The forensic value of X-linked markers in mixed-male DNA analysis.

PubMed

He, HaiJun; Zha, Lagabaiyila; Cai, JinHong; Huang, Jian

2018-05-04

Autosomal genetic markers and Y chromosome markers have been widely applied in analysis of mixed stains at crime scenes by forensic scientists. However, true genotype combinations are often difficult to distinguish using autosomal markers when similar amounts of DNA are contributed by multiple donors. In addition, specific individuals cannot be determined by Y chromosomal markers because male relatives share the same Y chromosome. X-linked markers, possessing characteristics somewhere intermediate between autosomes and the Y chromosome, are less universally applied in criminal casework. In this paper, X markers are proposed to apply to male mixtures because their true genes can be more easily and accurately recognized than the decision of the genotypes of AS markers. In this study, an actual two-man mixed stain from a forensic case file and simulated male-mixed DNA were examined simultaneously with the X markers and autosomal markers. Finally, the actual mixture was separated successfully by the X markers, although it was unresolved by AS-STRs, and the separation ratio of the simulated mixture was much higher using Chr X tools than with AS methods. We believe X-linked markers provide significant advantages in individual discrimination of male mixtures that should be further applied to forensic work.

Variation in the X-Linked EFHC2 Gene Is Associated with Social Cognitive Abilities in Males

PubMed Central

Startin, Carla M.; Fiorentini, Chiara; de Haan, Michelle; Skuse, David H.

2015-01-01

Females outperform males on many social cognitive tasks. X-linked genes may contribute to this sex difference. Males possess one X chromosome, while females possess two X chromosomes. Functional variations in X-linked genes are therefore likely to impact more on males than females. Previous studies of X-monosomic women with Turner syndrome suggest a genetic association with facial fear recognition abilities at Xp11.3, specifically at a single nucleotide polymorphism (SNP rs7055196) within the EFHC2 gene. Based on a strong hypothesis, we investigated an association between variation at SNP rs7055196 and facial fear recognition and theory of mind abilities in males. As predicted, males possessing the G allele had significantly poorer facial fear detection accuracy and theory of mind abilities than males possessing the A allele (with SNP variant accounting for up to 4.6% of variance). Variation in the X-linked EFHC2 gene at SNP rs7055196 is therefore associated with social cognitive abilities in males. PMID:26107779

Systematic review of suicide in economic recession

PubMed Central

Oyesanya, Mayowa; Lopez-Morinigo, Javier; Dutta, Rina

2015-01-01

AIM: To provide a systematic update of the evidence concerning the relationship between economic recession and suicide. METHODS: A keyword search of Ovid Medline, Embase, Embase Classic, PsycINFO and PsycARTICLES was performed to identify studies that had investigated the association between economic recession and suicide. RESULTS: Thirty-eight studies met predetermined selection criteria and 31 of them found a positive association between economic recession and increased suicide rates. Two studies reported a negative association, two articles failed to find such an association, and three studies were inconclusive. CONCLUSION: Economic recession periods appear to increase overall suicide rates, although further research is warranted in this area, particularly in low income countries. PMID:26110126

Genetics Home Reference: Menkes syndrome

MedlinePlus

... males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In about one-third of cases, Menkes syndrome is caused by new ...

Recessive Dystrophic Epidermolysis Bullosa and Pregnancy.

PubMed

Boria, F; Maseda, R; Martín-Cameán, M; De la Calle, M; de Lucas, R

2017-12-01

Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis bullosa) is characterized by the absence or considerably reduced expression of type VII collagen, which leads to marked fragility of the skin and mucous membranes and subsequent blister formation, whether spontaneously or following minimal injury. There have been very few reports of this disease in pregnant women. We present 2 cases of pregnant women with recessive dystrophic epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean delivery, with no further complications for mother or child. Although recessive dystrophic epidermolysis bullosa increases the risk of maternal complications, a patient is not advised against pregnancy. With adequate monitoring, these patients can fulfil their desire to become mothers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Meiotic drive impacts expression and evolution of x-linked genes in stalk-eyed flies.

PubMed

Reinhardt, Josephine A; Brand, Cara L; Paczolt, Kimberly A; Johns, Philip M; Baker, Richard H; Wilkinson, Gerald S

2014-01-01

Although sex chromosome meiotic drive has been observed in a variety of species for over 50 years, the genes causing drive are only known in a few cases, and none of these cases cause distorted sex-ratios in nature. In stalk-eyed flies (Teleopsis dalmanni), driving X chromosomes are commonly found at frequencies approaching 30% in the wild, but the genetic basis of drive has remained elusive due to reduced recombination between driving and non-driving X chromosomes. Here, we used RNAseq to identify transcripts that are differentially expressed between males carrying either a driving X (XSR) or a standard X chromosome (XST), and found hundreds of these, the majority of which are X-linked. Drive-associated transcripts show increased levels of sequence divergence (dN/dS) compared to a control set, and are predominantly expressed either in testes or in the gonads of both sexes. Finally, we confirmed that XSR and XST are highly divergent by estimating sequence differentiation between the RNAseq pools. We found that X-linked transcripts were often strongly differentiated (whereas most autosomal transcripts were not), supporting the presence of a relatively large region of recombination suppression on XSR presumably caused by one or more inversions. We have identified a group of genes that are good candidates for further study into the causes and consequences of sex-chromosome drive, and demonstrated that meiotic drive has had a profound effect on sequence evolution and gene expression of X-linked genes in this species.

The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21)

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

Saugier-Veber, P.; Abadie, V.; Turleau, C.

Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here the authors report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at [theta] = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes thatmore » have hypogonadism and hypogenitalism and that have been localized previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women. 25 refs., 2 figs., 3 tabs.« less

Abnormal protein in the cerebrospinal fluid of patients with a submicroscopic X-chromosomal deletion associated with Norrie disease: preliminary report.

PubMed

Joy, J E; Poglod, R; Murphy, D L; Sims, K B; de la Chapelle, A; Sankila, E M; Norio, R; Merril, C R

1991-01-01

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and, in many cases, mental retardation. Some Norrie disease cases have been shown to be associated with a submicroscopic deletion in chromosomal region Xp11.3. Cerebrospinal fluid (CSF) was collected from four male patients with an X-chromosomal deletion associated with Norrie disease. CSF proteins were resolved using two-dimensional gel electrophoresis and then analyzed by computer using the Elsie V program. Our analysis revealed a protein that appears to be altered in patients with Norrie disease deletion.

Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X-linked inheritance.

PubMed

Russell-Eggitt, I M

2000-12-01

When an X-linked pedigree of posterior lenticonus with cataract was identified further evidence for X-linked inheritance of this condition was sought. Forty-three cases of posterior lenticonus were identified from a database of 354 children with cataract. Two children with the X-linked syndromes of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded from further analysis. None of the children was deaf. None of the non-syndromic cases had microcornea. There were 38 cases of non-syndromic posterior lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23 apparently sporadic cases. Of the 106 cases on the database with unilateral cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees were compatible with X-linked inheritance or autosomal dominant inheritance with variable expression. However, in 2 pedigrees there was father to son transmission. Posterior lenticonus is a common cause of unilateral infantile cataract, but is thought to be a rare cause of bilateral cataracts. This study suggests that posterior lenticonus is responsible for a significant proportion of childhood cataracts (approximately 14% of unilateral and approximately 9% of bilateral cases). Posterior lenticonus is generally thought to occur as a sporadic condition. This study demonstrates that there is a family history of early-onset cataract in a significant number of bilateral cases (approximately 58%).

Study of Basin Recession Characteristics and Groundwater Storage Properties

NASA Astrophysics Data System (ADS)

Yen-Bo, Chen; Cheng-Haw, Lee

2017-04-01

Stream flow and groundwater storage are freshwater resources that human live on.In this study, we discuss southern area basin recession characteristics and Kao-Ping River basin groundwater storage, and hope to supply reference to Taiwan water resource management. The first part of this study is about recession characteristics. We apply Brutsaert (2008) low flow analysis model to establish two recession data pieces sifting models, including low flow steady period model and normal condition model. Within individual event analysis, group event analysis and southern area basin recession assessment, stream flow and base flow recession characteristics are parameterized. The second part of this study is about groundwater storage. Among main basin in southern Taiwan, there are sufficient stream flow and precipitation gaging station data about Kao-Ping River basin and extensive drainage data, and data about different hydrological characteristics between upstream and downstream area. Therefore, this study focuses on Kao-Ping River basin and accesses groundwater storage properties. Taking residue of groundwater volume in dry season into consideration, we use base flow hydrograph to access periodical property of groundwater storage, in order to establish hydrological period conceptual model. With groundwater storage and precipitation accumulative linearity quantified by hydrological period conceptual model, their periodical changing and alternation trend properties in each drainage areas of Kao-Ping River basin have been estimated. Results of this study showed that the recession time of stream flow is related to initial flow rate of the recession events. The recession time index is lower when the flow is stream flow, not base flow, and the recession time index is higher in low flow steady flow period than in normal recession condition. By applying hydrological period conceptual model, groundwater storage could explicitly be analyzed and compared with precipitation, by only

Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa

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

Aldred, M.A.; Dry, K.L.; Hardwick, L.J.

1994-11-01

A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538more » and 5{prime}-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. 33 refs., 2 figs., 2 tabs.« less

[Prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia with X-chromosome inversion].

PubMed

Shi, Hui-juan; Fang, Qun; Wang, Lian-tang

2005-07-13

To investigate the possibility of prenatal diagnosis of the fetal suspected to be affected by anhidrotic ectodermal dysplasia (EDA) in a family with X-linked EDA so as to provide a basis for prenatal diagnosis and genetic counseling of this disorder. Pedigree analysis and genetic counseling were performed in a family after a proband was diagnosed with EDA. The peripheral blood samples were collected from the proband, a 12-year-old boy, his mother, and his 2 aunts, one being pregnant, to undergo chromosome karyotype analysis. The fetus Puncture of umbilical vein was performed to collect the blood of fetus for chromosome examination. Induced abortion was conducted due to the diagnosis of the fetus with EDA. Autopsy, immunohistochemistry of the skin tissues of face, breast, epigastrium, and thigh, and X-ray photography of the lower jawbone were made. Pericentric inversion occurring at one of the X-chromosome [inv (x) (p22q13)] was found in the proband and his nephew (the fetus), both patients, and his mother and his second aunt (the pregnant woman), both carriers. Autopsy of the fetus showed epidermis dysplasia and deficiency of hair follicle and sebaceous gland. Immunohistochemistry showed that epithelial membrane antigen and cytokeratin were negatively expressed in the fetal skin tissues. Pedigree analysis and genetic counseling for the family members of EDA patients and prenatal and postpartum examination for the fetus help diagnose EDA.

A Complex Genetic Basis to X-Linked Hybrid Male Sterility Between Two Species of House Mice

PubMed Central

Good, Jeffrey M.; Dean, Matthew D.; Nachman, Michael W.

2008-01-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome. PMID:18689897

A complex genetic basis to X-linked hybrid male sterility between two species of house mice.

PubMed

Good, Jeffrey M; Dean, Matthew D; Nachman, Michael W

2008-08-01

The X chromosome plays a central role in the evolution of reproductive isolation, but few studies have examined the genetic basis of X-linked incompatibilities during the early stages of speciation. We report the results of a large experiment focused on the reciprocal introgression of the X chromosome between two species of house mice, Mus musculus and M. domesticus. Introgression of the M. musculus X chromosome into a wild-derived M. domesticus genetic background produced male-limited sterility, qualitatively consistent with previous experiments using classic inbred strains to represent M. domesticus. The genetic basis of sterility involved a minimum of four X-linked factors. The phenotypic effects of major sterility QTL were largely additive and resulted in complete sterility when combined. No sterility factors were uncovered on the M. domesticus X chromosome. Overall, these results revealed a complex and asymmetric genetic basis to X-linked hybrid male sterility during the early stages of speciation in mice. Combined with data from previous studies, we identify one relatively narrow interval on the M. musculus X chromosome involved in hybrid male sterility. Only a handful of spermatogenic genes are within this region, including one of the most rapidly evolving genes on the mouse X chromosome.

Localisation of the gene for X-linked reticulate pigmentary disorder with systemic manifestations (PDR), previously known as X-linked cutaneous amyloidosis

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

Gedeon, A.K.; Mulley, J.C.; Kozman, H.

1994-08-01

X-linked reticulate pigmentary disorder (PDR), previously reported as X-linked cutaneous amyloidosis (MIM No. 301220), is characterized by brown pigmentation of the skin which follows the lines of Blaschko in females but appears as reticulate sheets in males. Males may suffer severe gastrointestinal disorders in infancy with failure to thrive and early death. Nowadays symptomatic treatment allows survival and other manifestations may appear such as corneal dystrophy with severe photophobia or chronic respiratory disease. Amyloid deposition in the skin may be no more than an age-dependent secondary manifestation. The PDR gene was localized by linkage analysis to Xp21-p22. The background geneticmore » map is Xpter-DXS996-22.5-DXS207-3.3-DXS999-3.3-DXS365-14.2-DXS989-4.1-3`DMD-3.5-DXS997-1.0-STR44-9.3-DYSI-2.3-DXS1068-11.0-DXS228 with distances between markers given in cM. Recombinants detected with DXS999 distally and DXS228 proximally, define the limits to the localization. Linkage was found with several markers within this interval. Peak lod scores of 3.21 at {theta} = 0.0 were obtained between PDR and DXS989 and between PDR and 5`DYSI within the dystrophin locus. 29 refs., 2 figs., 2 tabs.« less

Remote Recession Sensing of Ablative Heat Shield Materials

NASA Technical Reports Server (NTRS)

Winter, Michael W.; Stackpoole, Margaret; Nawaz, Anuscheh; Gonzales, Gregory Lewis; Ho, Thanh

2014-01-01

Material recession and charring are two major processes determining the performance of ablative heat shield materials. Even in ground testing, the characterization of these two mechanisms relies on measurements of material thickness before and after testing, thus providing only information integrated over the test time. For recession measurements, optical methods such as imaging the sample surface during testing are under investigation but require high alignment and instrument effort, therefore being not established as a standard measurement method. For char depth measurements, the most common method so far consists in investigation of sectioned samples after testing or in the case of Stardust where core extractions were performed to determine char information. In flight, no reliable recession measurements are available, except total recession after recovering the heat shield on ground. Developments of mechanical recession sensors have been started but require substantial on board instrumentation adding mass and complexity. In this work, preliminary experiments to evaluate the feasibility of remote sensing of material recession and possibly char depth through optically observing the emission signatures of seeding materials in the post shock plasma is investigated. It is shown that this method can provide time resolved recession measurements without the necessity of accurate alignment procedures of the optical set-up and without any instrumentation on board of a spacecraft. Furthermore, recession data can be obtained without recovering flight hardware which would be a huge benefit for inexpensive heat shield material testing on board of small re-entry probes, e.g. on new micro-satellite re-entry probes as a possible future application of Cubesats or RBR

MicroRNAs and intellectual disability (ID) in Down syndrome, X-linked ID, and Fragile X syndrome

PubMed Central

Siew, Wei-Hong; Tan, Kai-Leng; Babaei, Maryam Abbaspour; Cheah, Pike-See; Ling, King-Hwa

2013-01-01

Intellectual disability (ID) is one of the many features manifested in various genetic syndromes leading to deficits in cognitive function among affected individuals. ID is a feature affected by polygenes and multiple environmental factors. It leads to a broad spectrum of affected clinical and behavioral characteristics among patients. Until now, the causative mechanism of ID is unknown and the progression of the condition is poorly understood. Advancement in technology and research had identified various genetic abnormalities and defects as the potential cause of ID. However, the link between these abnormalities with ID is remained inconclusive and the roles of many newly discovered genetic components such as non-coding RNAs have not been thoroughly investigated. In this review, we aim to consolidate and assimilate the latest development and findings on a class of small non-coding RNAs known as microRNAs (miRNAs) involvement in ID development and progression with special focus on Down syndrome (DS) and X-linked ID (XLID) [including Fragile X syndrome (FXS)]. PMID:23596395

American undergraduate students' value development during the Great Recession.

PubMed

Park, Heejung; Twenge, Jean M; Greenfield, Patricia M

2017-02-01

The Great Recession's influence on American undergraduate students' values was examined, testing Greenfield's and Kasser's theories concerning value development during economic downturns. Study 1 utilised aggregate-level data to investigate (a) population-level value changes between the pre-recession (2004-2006: n = 824,603) and recession freshman cohort (2008-2010: n = 662,262) and (b) overall associations of population-level values with national economic climates over long-term periods by correlating unemployment rates and concurrent aggregate-level values across 1966-2015 (n = 10 million). Study 2 examined individual-level longitudinal value development from freshman to senior year, and whether the developmental trajectories differed between those who completed undergraduate education before the Great Recession (freshmen in 2002, n = 12,792) versus those who encountered the Great Recession during undergraduate years (freshmen in 2006, n = 13,358). Results suggest American undergraduate students' increased communitarianism (supporting Greenfield) and materialism (supporting Kasser) during the Great Recession. The recession also appears to have slowed university students' development of positive self-views. Results contribute to the limited literature on the Great Recession's influence on young people's values. They also offer theoretical and practical implications, as values of this privileged group of young adults are important shapers of societal values, decisions, and policies. © 2016 International Union of Psychological Science.

SiC and Si3N4 Recession Due to SiO2 Scale Volatility Under Combustor Conditions

NASA Technical Reports Server (NTRS)

Smialek, James L.; Robinson, R. Craig; Opila, Elizabeth J.; Fox, Dennis S.; Jacobson, Nathan S.

1999-01-01

SiC and Si3N4 materials were tested under various turbine engine combustion environments, chosen to represent either conventional fuel-lean or fuel-rich mixtures proposed for high speed aircraft. Representative CVD, sintered, and composite materials were evaluated in both furnace and high pressure burner rig exposure. While protective SiO2 scales form in all cases, evidence is presented to support paralinear growth kinetics, i.e. parabolic growth moderated simultaneously by linear volatilization. The volatility rate is dependent on temperature, moisture content, system pressure, and gas velocity. The burner tests were used to map SiO2 volatility (and SiC recession) over a range of temperature, pressure, and velocity. The functional dependency of material recession (volatility) that emerged followed the form: exp(-QIRT) * P(exp x) * v(exp y). These empirical relations were compared to rates predicted from the thermodynamics of volatile SiO and SiO(sub x)H(sub Y) reaction products and a kinetic model of diffusion through a moving, boundary layer. For typical combustion conditions, recession of 0.2 to 2 micron/h is predicted at 1200- 1400C, far in excess of acceptable long term limits.

An Autosomal Gene That Affects X Chromosome Expression and Sex Determination in CAENORHABDITIS ELEGANS

PubMed Central

Meneely, Philip M.; Wood, William B.

1984-01-01

Recessive mutant alleles at the autosomal dpy-21 locus of C. elegans cause a dumpy phenotype in XX animals but not in XO animals. This dumpy phenotype is characteristic of X chromosome aneuploids with higher than normal X to autosome ratios and is proposed to result from overexpression of X-linked genes. We have isolated a new dpy-21 allele that also causes partial hermaphroditization of XO males, without causing the dumpy phenotype. All dpy-21 alleles show hermaphroditization effects in XO males that carry a duplication of part of the X chromosome and also partially suppress a transformer (tra-1) mutation that converts XX animals into males. Experiments with a set of X chromosome duplications show that the defects of dpy-21 mutants can result from interaction with several different regions of the X chromosome. We propose that dpy-21 regulates X chromosome expression and may be involved in interpreting X chromosome dose for the developmental decisions of both sex determination and dosage compensation. PMID:6537930

Probable autosomal recessive Marfan syndrome.

PubMed Central

Fried, K; Krakowsky, D

1977-01-01

A probable autosomal recessive mode of inheritance is described in a family with two affected sisters. The sisters showed the typical picture of Marfan syndrome and were of normal intelligence. Both parents and all four grandparents were personally examined and found to be normal. Homocystinuria was ruled out on repeated examinations. This family suggests genetic heterogeneity in Marfan syndrome and that in some rare families the mode of inheritance may be autosomal recessive. Images PMID:592353

The Great Recession and Workers' Health Benefits.

PubMed

Koh, Kanghyock

2018-03-01

During a recession, cost-sharing of employer-sponsored health benefits could increase to reduce labor costs in the U.S. Using a variation in the severity of recession shocks across industries, I find evidence that the enrollment rate of high deductible health plans (HDHPs) among workers covered by employer-sponsored health benefits increased more among firms in industries that experienced severe recession shocks. As potential mechanisms, I study employer-side and worker-side mechanisms. I find that employers changed health benefit offerings to force or incentivize workers to enroll in HDHPs. But I find little evidence of an increase in workers' demand for HDHPs due to a reduction in income. These results suggest that the HDHP enrollment rate increased during the Great Recession, as employers tried to save costs of offering health benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost inefficiency under financial strain: a stochastic frontier analysis of hospitals in Washington State through the Great Recession.

PubMed

Izón, Germán M; Pardini, Chelsea A

2017-06-01

The importance of increasing cost efficiency for community hospitals in the United States has been underscored by the Great Recession and the ever-changing health care reimbursement environment. Previous studies have shown mixed evidence with regards to the relationship between linking hospitals' reimbursement to quality of care and cost efficiency. Moreover, current evidence suggests that not only inherently financially disadvantaged hospitals (e.g., safety-net providers), but also more financially stable providers, experienced declines to their financial viability throughout the recession. However, little is known about how hospital cost efficiency fared throughout the Great Recession. This study contributes to the literature by using stochastic frontier analysis to analyze cost inefficiency of Washington State hospitals between 2005 and 2012, with controls for patient burden of illness, hospital process of care quality, and hospital outcome quality. The quality measures included in this study function as central measures for the determination of recently implemented pay-for-performance programs. The average estimated level of hospital cost inefficiency before the Great Recession (10.4 %) was lower than it was during the Great Recession (13.5 %) and in its aftermath (14.1 %). Further, the estimated coefficients for summary process of care quality indexes for three health conditions (acute myocardial infarction, pneumonia, and heart failure) suggest that higher quality scores are associated with increased cost inefficiency.

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

Recessed floating pier caps for highway bridges.

DOT National Transportation Integrated Search

1973-01-01

Presented are alternate designs for two existing bridges in Virginia - one with steel beams and the other with prestressed concrete beams - whereby the pier caps are recessed within the depth of the longitudinal beams. The purpose of this recession i...

Bone Collagen: New Clues to its Mineralization Mechanism From Recessive Osteogenesis Imperfecta

PubMed Central

Eyre, David R.; Ann Weis, Mary

2013-01-01

Until 2006 the only mutations known to cause osteogenesis imperfecta (OI) were in the two genes coding for type I collagen chains. These dominant mutations affecting the expression or primary sequence of collagen α1(I) and α2(I) chains account for over 90% of OI cases. Since then a growing list of mutant genes causing the 5–10% of recessive cases has rapidly emerged. They include CRTAP, LEPRE1 and PPIB, which encode three proteins forming the prolyl 3-hydroxylase complex; PLOD2 and FKBP10, which encode respectively lysyl hydroxylase 2 and a foldase required for its activity in forming mature cross-links in bone collagen; SERPIN H1, which encodes the collagen chaperone HSP47; SERPIN F1, which encodes pigment epithelium-derived factor required for osteoid mineralization; and BMP1, which encodes the type I procollagen C-propeptidase. All cause fragile bone in infancy, which can include over-mineralization or under-mineralization defects as well as abnormal collagen post-translational modifications. Consistently both dominant and recessive variants lead to abnormal cross-linking chemistry in bone collagen. These recent discoveries strengthen the potential for a common pathogenic mechanism of misassembled collagen fibrils. Of the new genes identified, eight encode proteins required for collagen post-translational modification, chaperoning of newly synthesized collagen chains into native molecules or transport through the endoplasmic reticulum and Golgi for polymerization, cross-linking and mineralization. In reviewing these findings, we conclude that a common theme is emerging in the pathogenesis of brittle bone disease of mishandled collagen assembly with important insights on post-translational features of bone collagen that have evolved to optimize it as a biomineral template. PMID:23508630

Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome.

PubMed

Stambolian, D; Favor, J; Silvers, W; Avner, P; Chapman, V; Zhou, E

1994-07-15

The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized by the congenital onset of cataracts. The cataracts have morphologies similar to those of cataracts found in the human Nance Horan (X-linked cataract dental) syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the localization of the Xcat mutation with respect to known molecular markers on the mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained from an interspecific cross. Genomic DNA from each mouse was subjected to Southern and PCR analysis to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Xcat to a 2-cM region, eliminate several genes from consideration as the Xcat mutation, identify molecular probes tightly linked with Xcat, and suggest candidate genes responsible for the Xcat phenotype.

Superior Recess Access of the Lumbar Facet Joint.

PubMed

Demir-Deviren, Sibel; Singh, Sukhminder; Hanelin, Joshua

2017-04-01

Descriptive approach to accessing the lumbar facet joint by superior recess. This study is aimed to describe an approach to accessing the lumbar facet joint through targeting the superior recess during lumbar facet joint injections. Lumbar facet joint injections are routinely performed for both the diagnosis and treatment of chronic low back pain. Previous studies either did not specify which part of the joint to target, or recommended targeting the inferior aspect of the joint to access the inferior recess. One study did mention the superior recess as an alternative to injecting the inferior recess, but none has focused on description of the technique. This is the first time this technique has been described. The records and fluoroscopic images were reviewed for all patients over a period of 9 months (January-September 2012) using the proposed technique. This resulted in a total of 48 patients; 15 men, 29 women, and a total of 117 facet joint intra-articular injections. Among these 48 patients, injections were repeated in total of 4 cases. The average time of injections among 4 repeat cases was 121 days. The success of the procedure was confirmed with an arthrogram demonstrating contrast flowing from the superior recess inferiorly through the joint space. Successful access of the lumbar facet joint through puncture of the superior recess was seen in 114 cases, with 3 unsuccessful attempts to enter facet joints due to osteophytes at involved levels. There were no complications observed during the procedure. We find this approach to be highly successful, safe, and well tolerated by the patient and recommend it as a technique for access of the lumbar facet joint in those patients in whom direct puncture of the inferior recess is difficult.

Assessing interethnic admixture using an X-linked insertion-deletion multiplex.

PubMed

Ribeiro-Rodrigues, Elzemar Martins; dos Santos, Ney Pereira Carneiro; dos Santos, Andrea Kely Campos Ribeiro; Pereira, Rui; Amorim, António; Gusmão, Leonor; Zago, Marco Antonio; dos Santos, Sidney Emanuel Batista

2009-01-01

In this study, a PCR multiplex was optimized, allowing the simultaneous analysis of 13 X-chromosome Insertion/deletion polymorphisms (INDELs). Genetic variation observed in Africans, Europeans, and Native Americans reveals high inter-population variability. The estimated proportions of X-chromosomes in an admixed population from the Brazilian Amazon region show a predominant Amerindian contribution (approximately 41%), followed by European (approximately 32%) and African (approximately 27%) contributions. The proportion of Amerindian contribution based on X-linked data is similar to the expected value based on mtDNA and Y-chromosome information. The accuracy for assessing interethnic admixture, and the high differentiation between African, European, and Native American populations, demonstrates the suitability of this INDEL set to measure ancestry proportions in three-hybrid populations, as it is the case of Latin American populations.

Chemical-mechanical polishing of recessed microelectromechanical devices

DOEpatents

Barron, Carole C.; Hetherington, Dale L.; Montague, Stephen

1999-01-01

A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g. CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate.

Chemical-mechanical polishing of recessed microelectromechanical devices

DOEpatents

Barron, C.C.; Hetherington, D.L.; Montague, S.

1999-07-06

A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g., CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate. 23 figs.

The rapid evolution of X-linked male-biased gene expression and the large-X effect in Drosophila yakuba, D. santomea, and their hybrids.

PubMed

Llopart, Ana

2012-12-01

The X chromosome has a large effect on hybrid dysfunction, particularly on hybrid male sterility. Although the evidence for this so-called large-X effect is clear, its molecular causes are not yet fully understood. One possibility is that, under certain conditions, evolution proceeds faster in X-linked than in autosomal loci (i.e., faster-X effect) due to both natural selection and their hemizygosity in males, an effect that is expected to be greatest in genes with male-biased expression. Here, I study genome-wide variation in transcript abundance between Drosophila yakuba and D. santomea, within these species and in their hybrid males to evaluate both the faster-X and large-X effects at the level of expression. I find that in X-linked male-biased genes (MBGs) expression evolves faster than in their autosomal counterparts, an effect that is accompanied by a unique reduction in expression polymorphism. This suggests that Darwinian selection is driving expression differences between species, likely enhanced by the hemizygosity of the X chromosome in males. Despite the recent split of the two sister species under study, abundant changes in both cis- and trans-regulatory elements underlie expression divergence in the majority of the genes analyzed, with significant differences in allelic ratios of transcript abundance between the two reciprocal F(1) hybrid males. Cis-trans coevolution at molecular level, evolved shortly after populations become isolated, may therefore contribute to explain the breakdown of the regulation of gene expression in hybrid males. Additionally, the X chromosome plays a large role in this hybrid male misexpression, which affects not only MBG but also, to a lesser degree, nonsex-biased genes. Interestingly, hybrid male misexpression is concentrated mostly in autosomal genes, likely facilitated by the rapid evolution of sex-linked trans-acting factors. I suggest that the faster evolution of X-linked MBGs, at both protein and expression levels

Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype.

PubMed

Gurgel-Giannetti, Juliana; Senkevics, Adriano S; Zilbersztajn-Gotlieb, Dinorah; Yamamoto, Lydia U; Muniz, Viviane P; Pavanello, Rita C M; Oliveira, Acary B; Zatz, Mayana; Vainzof, Mariz

2012-02-01

We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia. Copyright © 2011 Wiley Periodicals, Inc.

Economic recession and headache-related hospital admissions.

PubMed

Chinta, Ravi; Rao, M B; Narendran, Vivek; Malla, Ganesh; Joshi, Hem

2013-01-01

Incidence of headaches across different regions and its relationship to unemployment rates in the United States before and during an economic recession was evaluated. Years 2008 and 2009 were determined as recessionary period. Headache-related admissions, particularly the uncomplicated headaches, increased significantly during recession. Proportion of women with headaches has increased and the age group of 25-54 years was the most affected during the recession. The hospital charges have increased even though the average length and charge of stay decreased. These findings are consistent with our understanding of effects of stress and unemployment on psychological and physical health.

X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene.

PubMed

Lagresle-Peyrou, Chantal; Luce, Sonia; Ouchani, Farid; Soheili, Tayebeh Shabi; Sadek, Hanem; Chouteau, Myriam; Durand, Amandine; Pic, Isabelle; Majewski, Jacek; Brouzes, Chantal; Lambert, Nathalie; Bohineust, Armelle; Verhoeyen, Els; Cosset, François-Loïc; Magerus-Chatinet, Aude; Rieux-Laucat, Frédéric; Gandemer, Virginie; Monnier, Delphine; Heijmans, Catherine; van Gijn, Marielle; Dalm, Virgil A; Mahlaoui, Nizar; Stephan, Jean-Louis; Picard, Capucine; Durandy, Anne; Kracker, Sven; Hivroz, Claire; Jabado, Nada; de Saint Basile, Geneviève; Fischer, Alain; Cavazzana, Marina; André-Schmutz, Isabelle

2016-12-01

We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8 + T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Recessions, Job Loss, and Mortality Among Older US Adults

PubMed Central

Beckfield, Jason

2014-01-01

Objectives. We analyzed how recessions and job loss jointly shape mortality risks among older US adults. Methods. We used data for 50 states from the Health and Retirement Study and selected individuals who were employed at ages 45 to 66 years during 1992 to 2011. We assessed whether job loss affects mortality risks, whether recessions moderate the effect of job loss on mortality, and whether individuals who do and do not experience job loss are differentially affected by recessions. Results. Compared with individuals not experiencing job loss, mortality risks among individuals losing their job in a recession were strongly elevated (hazard ratio = 1.6; 95% confidence interval = 1.1, 2.3). Job loss during normal times or booms is not associated with mortality. For employed workers, we found a reduction in mortality risks if local labor market conditions were depressed, but this result was not consistent across different model specifications. Conclusions. Recessions increase mortality risks among older US adults who experience job loss. Health professionals and policymakers should target resources to this group during recessions. Future research should clarify which health conditions are affected by job loss during recessions and whether access to health care following job loss moderates this relation. PMID:25211731

Cloning and characterization of an alternatively spliced gene in proximal Xq28 deleted in two patients with intersexual genitalia and myotubular myopathy

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

Laporte, J.; Hu, Ling-Jia; Kretz, C.

1997-05-01

We have identified a novel human gene that is entirely deleted in two boys with abnormal genital development and myotubular myopathy (MTM1). The gene, F18, is located in proximal Xq28, approximately 80 kb centromeric to the recently isolated MTM1 gene. Northern analysis of mRNA showed a ubiquitous pattern and suggested high levels of expression in skeletal muscle, brain, and heart. A transcript of 4.6 kb was detected in a range of tissues, and additional alternate forms of 3.8 and 2.6 kb were present in placenta and pancreas, respectively. The gene extends over 100 kb and is composed of at leastmore » seven exons, of which two are non-coding. Sequence analysis of a 4.6-kb cDNA contig revealed two overlapping open reading frames (ORFs) that encode putative proteins of 701 and 424 amino acids, respectively. Two alternative spliced transcripts affecting the large open reading frame were identified that, together with the Northern blot results, suggest that distinct proteins are derived from the gene. No significant homology to other known proteins was detected, but segments of the first ORF encode polyglutamine tracts and proline-rich domains, which are frequently observed in DNA-binding proteins. The F18 gene is a strong candidate for being implicated in the intersexual genitalia present in the two MTM1-deleted patients. The gene also serves as a candidate for other disorders that map to proximal Xq28. 15 refs., 3 figs., 1 tab.« less

Hospital Capital Investment During the Great Recession.

PubMed

Choi, Sung

2017-01-01

Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

Hospital Capital Investment During the Great Recession

PubMed Central

Choi, Sung

2017-01-01

Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal. PMID:28617202

Comparison of results of medial rectus muscle recession using augmentation, Faden procedure, and slanted recession in the treatment of high accommodative convergence/accommodation ratio esotropia.

PubMed

Gharabaghi, Davoud; Zanjani, Leila Kazemi

2006-01-01

According to the literature, accommodative esotropia has an unpredictable course when nonsurgical treatment is considered, especially in cases with a high accommodative convergence/accommodation ratio (AC/A). The aim of this study was to compare the results of augmented recession, slanted recession, and recession with posterior fixation suture of the medial rectus muscles in the treatment of high AC/A esotropia. Twenty-eight children (4 to 14 years old) with high AC/A esotropia with a near-distance disparity greater than 10 PD were included in a prospective, randomized, blinded clinical trial. Nine children underwent recession of both medial rectus muscles and posterior fixation suture (Faden procedure), 9 children underwent augmented recession of the medial rectus muscles, and 10 children underwent slanted recession of both medial rectus muscles. The amount of esodeviation was measured before strabismus surgery and at least 6 months postoperatively. In the augmented recession group, the mean near-distance disparity was reduced from 16.33 +/- 2.17 PD preoperatively to 7.55 +/- 3.87 PD postoperatively (54.21%; P = .056). In the Faden procedure group, it was reduced from 15.22 +/- 4.08 PD to 2.55 +/- 4.03 PD (80.7%; P = .056). In the slanted recession group, it was reduced from 15.50 +/- 4.30 PD to 4.10 +/- 4.80 PD (67.55%; P = .056). The Faden procedure had the best outcome, but slanted recession also was successful. Because of our good results and an easy, non-invasive approach without any additional complications, we recommend slanted recession to treat high AC/A esotropia.

Novel XLRS1 gene mutations cause X-linked juvenile retinoschisis in Chinese families.

PubMed

Ma, Xiang; Li, Xiaoxin; Wang, Lihua

2008-01-01

To investigate various XLRS1 (RS1) gene mutations in Chinese families with X-linked juvenile retinoschisis (XLRS or RS). Genomic DNA was isolated from leukocytes of 29 male patients with X-linked juvenile retinoschisis, 38 female carriers, and 100 normal controls. All 6 exons of the RS1 gene were amplified by polymerase chain reaction, and the RS1 gene mutations were determined by direct sequencing. Eleven different RS1 mutations in 12 families were identified in the 29 male patients. The mutations comprised eight missense, two frameshift, and one splice donor site mutation. Four of these mutations, one frameshift mutation (26 del T) in exon 1, one frameshift mutation (488 del G) in exon 5, Asp145His and Arg156Gly in exon 5, have not been previously described. One novel non-disease-related polymorphism, 576C to T (Pro192Pro) in exon 6, was also found. Six recurrent mutations, Ser73Pro and Arg102Gln mutations in exon 4 and Arg200Cys, Arg209His, Arg213Gln, and Cys223Arg mutations in exon 6, were also identified in this study. RS1 gene mutations caused X-linked juvenile retinoschisis in these Chinese families.

Revision of Ernst Antevs' New England Varve Chronology: A Record of Meltwater Production and Southeastern LIS Recession: 18.2-12.5 kyr BP (Invited)

NASA Astrophysics Data System (ADS)

Ridge, J. C.

2013-12-01

New varve cores and 54 radiocarbon ages, have allowed the correction, closure of a gap, calibration, and expansion of Ernst Antevs' (1922) New England Varve Chronology from sediments of glacial Lake Hitchcock and it's successors in the Connecticut Valley of western New England (northeastern U.S.A.). The continuous 5659-yr chronology (18.2-12.5 kyr BP) has been renumbered as the North American Varve Chronology. Glacial varve thickness (18.2-13.7 kyr BP) documents abrupt changes in meltwater production related to varying ablation rate (summer climate) that is linked to ice sheet recession rates and advances, i.e. cold intervals are times of thin varves and slower ice recession or glacial readvances. To take advantage of the varve-climate relationship it is necessary to identify non-climatic events that can cause varve thickness to change. This includes sudden changes in lake level and flood events triggered by the abrupt drainage of tributary glacial lakes. A chronology of ice recession for intervals terminated by four stillstands and readvances of 1-2 century durations have been determined for the Connecticut Valley (from S to N): 50-100 m/yr in northern Connecticut to southern Massachusetts; Chicopee Readvance; 30-40 m/yr in central Mass.; Hatfield event; 80-90 m/yr from northern Mass. to central New Hampshire; North Charlestown end moraines; 300 m/yr to northern N.H.; Littleton Readvance; >300 m/yr to Quebec. Meltwater produced by ice recession of 300 m/yr modeled as a receding 1-bar ice sheet profile (from 100 km up ice near ELA to margin, valley width of 80 km, glacier flow rate of 200 m/yr at ELA) would be a minimum glacial meltwater discharge in the Connecticut Valley of ~90 x 109 m3/yr. This is ~10X the modern Conn. River discharge at Walpole, NH compressed almost entirely to the melt season. Non-glacial varves deposited after ice receded from the basin (13.7-12.5 kyr BP) also document climate change as a result of varve thickness varying with changes in

Short-term effects of the 2008 Great Recession on the health of the Italian population: an ecological study.

PubMed

Mattei, Giorgio; Ferrari, Silvia; Pingani, Luca; Rigatelli, Marco

2014-06-01

To report on the effects on health that the 2008 Great Recession is producing in Italy, by comparing the consistency of Italian data with general observations reported in the scientific literature, and by pointing out consequences on the rates of all-cause mortality, cardiovascular mortality, male suicidal behaviours, daytime alcohol drinking and traffic fatalities. This is an ecological study in which MEDLINE, PsycINFO and PubMed were searched for the literature with combinations of the following keywords: economic recession, financial crisis, unemployment, health, suicide and mental health. Data from two Italian government agencies (Italian Institute of Statistics, ISTAT, and Italian Agency of Drugs, AIFA) in the years from 2000 to 2010 were obtained and analysed, by producing models of multiple linear regressions. After the recession onset, all-cause mortality remained stable, and was not associated with the economic fluctuations. Differently, cardiovascular mortality was associated with the rate of unemployment, and showed a significant increase in 2010. Alcohol consumption increased in 2009, the year with the worst real GDP decrease (-5.1 %). Though the total rate of suicide was not associated with the economic situation, male completed and attempted suicides due to financial crisis were significantly associated with the rate of unemployment and the real GDP. The increasing diffusion of antidepressants was not associated with a lowering of the rate of suicide. The data on the Italian situation here discussed are sufficiently reliable to conclude that a link exists between the ongoing economic recession and health and mental health of Italians. Further research is needed to understand more in detail and with stronger reliability such link, to support primary and secondary preventive interventions and orient the development of effective sociopolitical interventions.

Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model.

PubMed

Muers, Mary R; Sharpe, Jacqueline A; Garrick, David; Sloane-Stanley, Jacqueline; Nolan, Patrick M; Hacker, Terry; Wood, William G; Higgs, Douglas R; Gibbons, Richard J

2007-06-01

Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate.

New method for calculating a mathematical expression for streamflow recession

USGS Publications Warehouse

Rutledge, Albert T.

1991-01-01

An empirical method has been devised to calculate the master recession curve, which is a mathematical expression for streamflow recession during times of negligible direct runoff. The method is based on the assumption that the storage-delay factor, which is the time per log cycle of streamflow recession, varies linearly with the logarithm of streamflow. The resulting master recession curve can be nonlinear. The method can be executed by a computer program that reads a data file of daily mean streamflow, then allows the user to select several near-linear segments of streamflow recession. The storage-delay factor for each segment is one of the coefficients of the equation that results from linear least-squares regression. Using results for each recession segment, a mathematical expression of the storage-delay factor as a function of the log of streamflow is determined by linear least-squares regression. The master recession curve, which is a second-order polynomial expression for time as a function of log of streamflow, is then derived using the coefficients of this function.

Alport Syndrome in Women and Girls.

PubMed

Savige, Judy; Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

2016-09-07

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%-30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The "Expert guidelines for the diagnosis and management of Alport syndrome" recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling

Alport Syndrome in Women and Girls

PubMed Central

Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

2016-01-01

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic

The Great Recession, Adolescent Smoking, and Smoking Inequalities: What Role Does Youth Unemployment Play in 24 European Countries?

PubMed

Rathmann, Katharina; Pförtner, Timo-Kolja; Elgar, Frank J; Hurrelmann, Klaus; Richter, Matthias

2017-11-01

Conflicting evidence has been reported on smoking behavior among adults during times of economic downturn. No study has yet investigated young people's smoking and inequalities in smoking during economic recessions. This study examines the association between country-level youth unemployment due to the economic recession and adolescent smoking and smoking inequalities in Europe. The WHO collaborative "Health Behaviour in School-aged Children" study in 2009/2010 included 15-year-old adolescents from 24 European countries (N = 43 093). Socioeconomic position (SEP) was measured by the Family Affluence Scale. Logistic multilevel models were conducted. The absolute rate of youth unemployment in 2010 (during the recession) and the relative change rate in youth unemployment (2005/2006-2009/2010) were regressed on smoking and SEP inequalities in smoking in 2010, respectively. Youth unemployment rates were not significantly associated with overall smoking in adolescents. A higher absolute youth unemployment rate in 2010 related to lower likelihoods of smoking among middle (OR: 0.99; 95% CI: 0.98-0.99) and low affluent adolescents (OR: 0.99; 95% CI: 0.98-0.99) compared to high affluent adolescents. In contrast, an increase in youth unemployment (2005/2006-2009/2010) was not associated with overall likelihoods of smoking and inequalities in smoking. Our findings indicate that an increase in youth unemployment was not related to smoking and smoking inequalities. However, higher absolute levels of youth unemployment are related to lower likelihoods of smoking in lower SEP adolescents. Thus, smoking among vulnerable groups is more linked to the overall insecure circumstances and the affordability of cigarettes rather than to the economic recession itself. Economic recessions have often led to increases in adult and youth unemployment rates. Conflicting evidence has been reported on smoking behavior among adults during times of economic downturn. This study examines for the first

Recession Rebound

ERIC Educational Resources Information Center

Weinstein, Margery

2011-01-01

A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

Congenital cataracts and other abnormalities in a female with 46.X, del(X)(q26q28)mat: A new locus for X-linked congenital cataract?

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

Babul, R.; Chitayat, D.; Teshima, I.

1994-09-01

Three forms of X-linked congenital cataracts have been delineated: congenital cataract with posterior Y-sutural opacities in heterozygotes, congenital cataract and microcornea or microphthalmia and congenital cataract-dental syndrome (Nance-Horan syndrome). Of these, only the Nance-Horan syndrome has been mapped to Xp22.3-p21.1. However, Warburg has suggested that these different forms of X-linked congenital cataracts are due to deletions of varying sizes, placing them in the vicinity of the Nance-Horan syndrome region. We report on a female patient born to a 29-year-old primigravida woman who at birth was found to have hypotonia, dysmorphic facial features, hydrocephalus and dense white congenital bilateral cataracts. Othermore » ophthalmological findings included bilateral nystagmus and shallow orbits. Chromosome analysis revealed 46,X,del(X)(q26q28)mat. The mother, however, is phenotypically normal. Brain CT scan on the female infant revealed communicating hydrocephalus and a muscle biopsy showed congenital muscle fiber disproportion. An EMG and NCV were normal. At 4 years of age, her height and weight were below -3SD and her OFC was +2SD. Molecular studies using DNA markers located in Xq26-qter have revealed that the proximal breakpoint in the patient and her mother is defined by the HPRT locus while the distal breakpoint is defined by the locus DXS1108. This indicates that the deletion is not terminal but rather interstitial, retaining sequences proximal to the telomeric region. Other molecular studies are in progress to determine the X-inactivation status of the deleted chromosome in our patient and her mother as a possible explanation for the variation in the phenotype. These clinical and molecular findings suggest that another locus for X-linked congenital cataract exists at Xq26-28.« less

Students with Juvenile Arthritis Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.

2009-01-01

The participation of a student with juvenile arthritis in recess can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with juvenile arthritis and present basic solutions to improve the education of these students in the recess setting. Initially the…

[X-linked adrenoleukodystrophy: a report of three cases. The importance of early diagnosis].

PubMed

López Úbeda, Marta; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José I; García Jiménez, María C

2017-10-01

X-linked adrenoleukodystrophy is the most common peroxisomal disorder. This disease is caused by a defect in the ABCD1 gen. Saturated very long chain fatty acids are accumulated in serum, adrenal cortex and central nervous system white matter. The clinical spectrum is characterized by progressive neurological dysfunction and adrenal insufficiency with a devastating prognosis. We report a first case of X-linked adrenoleukodystrophy with fatal evolution which identified two asymptomatic family members and established a preventive treatment. Although there is no definitive cure, we stress the importance of family study and evaluation of the individual in situation of risk to establish an early preventive treatment and to give in each particular situation suitable professional advice. Sociedad Argentina de Pediatría.

Patulous Subarachnoid Space of the Optic Nerve Associated with X-Linked Hypophosphatemic Rickets.

PubMed

Galvez-Ruiz, Alberto; Chaudhry, Imtiaz

2013-01-01

Although the deficiency forms are the most common manifestations of rickets, there are other forms of rickets that are resistant to vitamin D. Of these, the most common is X-linked hypophosphatemic rickets. Rickets represents a group of multiple cranial bone disorders-craniosynostosis and the presence of Chari I malformation being the most notable-that explain the increase in intracranial pressure. We present a 4-year-old patient with an unusual association of X-linked hypophosphataemic rickets, bilateral proptosis, and prominent bilateral widening of the optic nerve sheaths. Although the association between intracranial hypertension and rickets is known, to the best of our knowledge, such a prominent distention of the subarachnoid space of the optic nerve without papilloedema has not been previously described.

The Great Recession and America’s Geography of Unemployment

PubMed Central

Thiede, Brian C.; Monnat, Shannon M.

2017-01-01

Background The Great Recession of 2007–2009 was the most severe and lengthy economic crisis in the U.S. since the Great Depression. The impacts on the population were multi-dimensional, but operated largely through local labor markets. Objective To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. Methods We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. Results The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. Conclusions The local consequences of macroeconomic trends are associated with county population characteristics, as well as the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state inequality between local labor market conditions. Contribution To present new estimates of the recession’s impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately large recession

Retinal detachment 7 years after prophylactic schisis cavity excision in juvenile X-linked retinoschisis.

PubMed

Sobrin, Lucia; Berrocal, Audina M; Murray, Timothy G

2003-01-01

A 7-year-old boy with X-linked juvenile retinoschisis developed a retinal detachment at the site of previous prophylactic excision of a schisis cavity. The patient underwent a scleral buckle procedure, pars plana vitrectomy, membrane peel, and silicone oil injection with successful reattachment. At last follow-up, the visual acuity was 20/400 and the retina was attached. Prophylactic excision of a schisis cavity may be complicated by retinal detachment several years after the surgery. Given the favorable natural history of schisis cavities in X-linked juvenile retinoschisis, the decision to perform prophylactic excision should be undertaken cautiously after full consideration of the potential complications.

How does forest disturbance and succession affect summer streamflow recession?

NASA Astrophysics Data System (ADS)

Brena, A.; Stahl, K.; Weiler, M.

2011-12-01

Streamflow recession is a main signature of catchment behavior during dry conditions. The storage-discharge relationship of every catchment reflects the aquifer properties and land surface processes including evapotranspiration rates. Commonly, the storage-discharge relationship in watersheds is analyzed through the recession limb of the hydrograph, which generally follows a nonlinear pattern. It is, however, unknown how forest disturbance and succession may modify the degree of nonlinearity of baseflow recession and the magnitude of baseflow. The presented study analyzes and characterizes streamflow recession during summer before and after forest disturbance using data from six experimental paired-watersheds with controlled forest disturbances across different climatic regions and ecozones of the USA. Characteristic non-linear recession parameters were fitted by a Monte Carlo resampling method. No systematic relationship was found between annual precipitation, drainage area, mean elevation, and recession characteristics. However, higher storage rates and low flows across the sites were detected following forest disturbance. Exceptions are the snow-dominated watersheds and changes appear to be stronger in watersheds with deciduous forests. The results are however dependent on the method of recession limb selection, including start level and time. Further research is needed over a wide range of forest sites and according to the type of disturbance (e.g. fire, disease), which may ultimately define the dynamics of forest succession and therefore the streamflow recession behavior.

Students with Multiple Sclerosis Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.; Brentlinger, Jamie

2012-01-01

The participation of a student with Multiple Sclerosis (MS) in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with MS and present basic solutions to improve the experience of these students in the recess setting. Initially, the definition and prevalence of…

Women and Jobs in Recessions: 1969-92.

ERIC Educational Resources Information Center

Goodman, William; And Others

1993-01-01

The probability of losing one's job because of a recession is very different for women and men, but, in the last two recessions, gender differences were reduced. The major cause is the relative performance of industries that heavily employ women (such as services) versus those that heavily employ men (such as goods-producing). (JOW)

Strategies for Supporting Recess in Elementary Schools

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2014

2014-01-01

Recess provides students with a needed break from their structured school day. It can improve children's physical, social, and emotional well-being, and enhance learning. Recess helps children meet the goal of 60 minutes of physical activity (PA) each day, as recommended by the US Department of Health and Human Services. National…

The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice

PubMed Central

van Huet, Ramon A. C.; Pierrache, Laurence H.M.; Meester-Smoor, Magda A.; Klaver, Caroline C.W.; van den Born, L. Ingeborgh; Hoyng, Carel B.; de Wijs, Ilse J.; Collin, Rob W. J.; Hoefsloot, Lies H.

2015-01-01

Purpose To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). Methods We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon–intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. Results The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). Conclusions The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis. PMID:25999674

Dropped-head in recessive oculopharyngeal muscular dystrophy.

PubMed

Garibaldi, Matteo; Pennisi, Elena Maria; Bruttini, Mirella; Bizzarri, Veronica; Bucci, Elisabetta; Morino, Stefania; Talerico, Caterina; Stoppacciaro, Antonella; Renieri, Alessandra; Antonini, Giovanni

2015-11-01

A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD. Copyright © 2015 Elsevier B.V. All rights reserved.

Computational Analysis of End-of-Injection Transients and Combustion Recession

NASA Astrophysics Data System (ADS)

Jarrahbashi, Dorrin; Kim, Sayop; Knox, Benjamin W.; Genzale, Caroline L.; Georgia Institute of Technology Team

2016-11-01

Mixing and combustion of ECN Spray A after end of injection are modeled with different chemical kinetics models to evaluate the impact of mechanism formulation and low-temperature chemistry on predictions of combustion recession. Simulations qualitatively agreed with the past experimental observations of combustion recession. Simulations with the Cai mechanism show second-stage ignition in distinct regions near the nozzle, initially spatially separated from the lifted diffusion flame, but then rapidly merge with flame. By contrast, the Yao mechanism fails to predict sufficient low-temperature chemistry in mixtures upstream of the diffusion flame and combustion recession. The effects of the shape and duration of the EOI transient on the entrainment wave near the nozzle, the likelihood of combustion recession, and the spatiotemporal development of mixing and chemistry in near-nozzle mixtures are also investigated. With a more rapid ramp-down injection profile, a weaker combustion recession occurs. For extremely fast ramp-down, the entrainment flux varies rapidly near the nozzle and over-leaning of the mixture completely suppresses combustion recession. For a slower ramp-down profile complete combustion recession back toward the nozzle is observed.

Autosomal Genes of Autosomal/X-Linked Duplicated Gene Pairs and Germ-Line Proliferation in Caenorhabditis elegans

PubMed Central

Maciejowski, John; Ahn, James Hyungsoo; Cipriani, Patricia Giselle; Killian, Darrell J.; Chaudhary, Aisha L.; Lee, Ji Inn; Voutev, Roumen; Johnsen, Robert C.; Baillie, David L.; Gunsalus, Kristin C.; Fitch, David H. A.; Hubbard, E. Jane Albert

2005-01-01

We report molecular genetic studies of three genes involved in early germ-line proliferation in Caenorhabditis elegans that lend unexpected insight into a germ-line/soma functional separation of autosomal/X-linked duplicated gene pairs. In a genetic screen for germ-line proliferation-defective mutants, we identified mutations in rpl-11.1 (L11 protein of the large ribosomal subunit), pab-1 [a poly(A)-binding protein], and glp-3/eft-3 (an elongation factor 1-α homolog). All three are members of autosome/X gene pairs. Consistent with a germ-line-restricted function of rpl-11.1 and pab-1, mutations in these genes extend life span and cause gigantism. We further examined the RNAi phenotypes of the three sets of rpl genes (rpl-11, rpl-24, and rpl-25) and found that for the two rpl genes with autosomal/X-linked pairs (rpl-11 and rpl-25), zygotic germ-line function is carried by the autosomal copy. Available RNAi results for highly conserved autosomal/X-linked gene pairs suggest that other duplicated genes may follow a similar trend. The three rpl and the pab-1/2 duplications predate the divergence between C. elegans and C. briggsae, while the eft-3/4 duplication appears to have occurred in the lineage to C. elegans after it diverged from C. briggsae. The duplicated C. briggsae orthologs of the three C. elegans autosomal/X-linked gene pairs also display functional differences between paralogs. We present hypotheses for evolutionary mechanisms that may underlie germ-line/soma subfunctionalization of duplicated genes, taking into account the role of X chromosome silencing in the germ line and analogous mammalian phenomena. PMID:15687263

The Crucial Role of Recess in Schools

ERIC Educational Resources Information Center

Ramstetter, Catherine L.; Murray, Robert; Garner, Andrew S.

2010-01-01

Background: Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose…

A novel mutation in FRMD7 causing X-linked idiopathic congenital nystagmus in a large family

PubMed Central

He, Xiang; Gu, Feng; Wang, Yujing; Yan, Jinting; Zhang, Meng; Huang, Shangzhi

2008-01-01

Purpose To identify the gene responsible for causing an X-linked idiopathic congenital nystagmus (XLICN) in a six-generation Chinese family. Methods Forty-nine members of an XLICN family were recruited and examined after obtaining informed consent. Affected male individuals were genotyped with microsatellite markers around the FRMD7 locus. Mutations were comprehensively screened by direct sequencing using gene specific primers. An X-inactivation pattern was investigated by X chromosome methylation analysis. Results The patients showed phenotypes consistent with XLICN. Genotype analysis showed that male affected individuals in the family shared a common haplotype with the selected markers. Sequencing FRMD7 revealed a G>T transversion (c.812G>T) in exon 9, which caused a conservative substitution of Cys to Phe at codon 271 (p.C271F). This mutation co-segregated with all affected individuals and was present in the obligate, non-penetrant female carriers. However, the mutation was not observed in unaffected familial males or 400 control males. Females with the mutant gene could be affected or carrier and they shared the same inactivated X chromosome harboring the mutation in blood cells, which showed there is no clear causal link between X-inactivation pattern and phenotype. Conclusions We identified a novel mutation in FRMD7 and confirmed the role of this mutation in the pathogenesis of X-linked congenital nystagmus. PMID:18246032

The Recession Squeezes Training.

ERIC Educational Resources Information Center

Geber, Beverly

1991-01-01

Recession is having an impact on training departments. Besides a slowdown, it provides managers with a chance to reevaluate programs to ensure they are attuned to the specific goals of the company. (JOW)

Microsatellites within the feline androgen receptor are suitable for X chromosome-linked clonality testing in archival material.

PubMed

Farwick, Nadine M; Klopfleisch, Robert; Gruber, Achim D; Weiss, Alexander Th A

2017-04-01

Objectives A hallmark of neoplasms is their origin from a single cell; that is, clonality. Many techniques have been developed in human medicine to utilise this feature of tumours for diagnostic purposes. One approach is X chromosome-linked clonality testing using polymorphisms of genes encoded by genes on the X chromosome. The aim of this study was to determine if the feline androgen receptor gene was suitable for X chromosome-linked clonality testing. Methods The feline androgen receptor gene was characterised and used to test clonality of feline lymphomas by PCR and polyacrylamide gel electrophoresis, using archival formalin-fixed, paraffin-embedded material. Results Clonality of the feline lymphomas under study was confirmed and the gene locus was shown to represent a suitable target in clonality testing. Conclusions and relevance Because there are some pitfalls of using X chromosome-linked clonality testing, further studies are necessary to establish this technique in the cat.

Familial exudative vitreoretinopathy and related retinopathies

PubMed Central

Gilmour, D F

2015-01-01

Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR patients have an avascular peripheral retina which, depending on the degree of ischaemia, causes the secondary complications of the disease. Expressivity may be asymmetric and is highly variable. Five genes have been identified that when mutated, cause FEVR; NDP (X-linked), FZD4 (autosomal dominant and recessive), LRP5 (autosomal dominant and recessive), TSPAN12 (autosomal dominant and recessive), and ZNF408 (autosomal dominant). Four of these genes have been shown to have a central role in Norrin/Frizzled4 signalling, suggesting a critical role for this pathway in retinal angiogenesis. In addition to the ocular features, LRP5 mutations can cause osteopenia and osteoporosis. All FEVR patients in whom molecular testing is not easily accessible should have dual energy X-ray absorptiometry (DEXA) scans to assess bone mineral density, as treatment can be initiated to reduce the risk of bone fractures. PMID:25323851

X-linked agammaglobulinemia in northern Thailand.

PubMed

Trakultivakorn, Muthita; Ochs, Hans D

2006-03-01

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by a failure to generate immunoglobulins of all isotypes due to the absence of mature B cells and plasma cells, secondary to mutations in the Bruton's tyrosine kinase (Btk) gene. We report six patients with XLA, confirmed by mutation analysis, from northern Thailand. The mean age of onset was 2.5 years and the mean age at diagnosis was 7.3 years. All patients had a history of otitis media, pneumonia and arthritis at the time of diagnosis, five patients had developed bronchiectasis and 3 patients septicemia. Other infections reported included sinusitis (5/6), pericarditis (1/6), meningitis (1/6) and pyoderma (1/6). Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus were isolated on multiple occasions. One patient died of sepsis at the age of 16 years. These observations demonstrate that early diagnosis and treatment can improve prognosis and quality of life.

Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

PubMed

Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

2014-11-01

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

Aeroacoustical Study of the Tgv Pantograph Recess

NASA Astrophysics Data System (ADS)

NOGER, C.; PATRAT, J. C.; PEUBE, J.; PEUBE, J. L.

2000-03-01

The general focus of this aerodynamic noise research, induced by turbulent incompressible flow, is to improve our knowledge of acoustic production mechanisms in the TGV pantograph recess in order to be able to reduce the radiated noise. This work is performed under contract with SNCF as a part of the German-French Cooperation DEUFRAKO K2, and is supported by French Ministries for Transport and Research. Previous studies on TGV noise source locations (DEUFRAKO K) have identified the pantograph recess as one of the important aerodynamic noise sources, for speeds higher than 300 km/h, due to flow separation. The pantograph recess is a very complex rectangular cavity, located both on the power car and the first coach roofs of the TGV, and has not been studied before due to the complex shapes. Its aeroacoustic features are investigated experimentally in a low-subsonic wind tunnel, on a realistic 1/7th scale mock-up both with and without pantographs. Flow velocities, estimated with hot-wire anemometry, and parietal visualizations show the flow to reattach on the recess bottom wall and to separate again at the downstream face. Wall pressure fluctuations and “acoustic” measurements using 14 and 12 in microphones respectively are also measured to qualify the flow: no aerodynamic or acoustic oscillations are observed. The study indicates that the pantograph recess has a different behaviour compared to the usual cavity grazing flows.

Non-Overweight and Overweight Children's Physical Activity during School Recess

ERIC Educational Resources Information Center

Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer L.

2014-01-01

Objective: Little research has investigated children's physical activity levels during school recess and the contribution of recess to school day physical activity levels by weight status. The aims of this study were to examine non-overweight and overweight children's physical activity levels during school recess, and examine the contribution of…

A CLINICIAN'S GUIDE TO X-LINKED HYPOPHOSPHATEMIA

PubMed Central

Carpenter, Thomas O.; Imel, Erik A.; Holm, Ingrid A.; Jan de Beur, Suzanne M.; Insogna, Karl L.

2011-01-01

X-linked hypophosphatemia (XLH) is the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets. Physicians, patients, and XLH support groups have all expressed concerns about the dearth of information about this disease and the lack of treatment guidelines which frequently lead to missed diagnoses or mismanagement. This perspective addresses the recommendation by conferees for the dissemination of concise and accessible treatment guidelines for clinicians arising from the “Advances in Rare Bone Diseases Scientific Conference,” held at the National Institutes of Health in October 2008. We briefly review the clinical and pathophysiologic features of the disorder, and offer this guide in response to the conference recommendation, base on our collective accumulated experience in the management of this complex disorder. PMID:21538511

Sin1, a Mutation Affecting Female Fertility in Arabidopsis, Interacts with Mod1, Its Recessive Modifier

PubMed Central

Lang, J. D.; Ray, S.; Ray, A.

1994-01-01

In Arabidopsis thaliana, a mutation in the SIN1 gene causes aberrant ovule development and female-specific sterility. The effect of the sin1 mutation is polymorphic and pleiotropic in different genetic backgrounds. The polymorphism concerns morphology of the mutant ovules. The pleiotropism involves internodal distance and inflorescence initiation time. The particular ovule phenotype and the length of internodes are dependent on an interaction of sin1 with a second recessive gene, which we term mod1. The recessive mod1 allele in a homozygous sin1 mutant plant reduces internode length and ovule integument size. The mutation sin1, but not mod1, has a demonstrable effect on ovule morphology when acting idependently. In our crosses mod1 was inseparably linked to the well known mutation erecta that is known to cause a reduction in internode and pedicel lengths. PMID:7982564

Surgical management of gingival recession: A clinical update

PubMed Central

Alghamdi, Hamdan; Babay, Nadir; Sukumaran, Anil

2009-01-01

Gingival recession is defined as the apical migration of the junctional epithelium with exposure of root surfaces. It is a common condition seen in both dentally aware populations and those with limited access to dental care. The etiology of the condition is multifactorial but is commonly associated with underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal disease. Given the high rate of gingival recession defects among the general population, it is imperative that dental practitioners have an understanding of the etiology, complications and the management of the condition. The following review describes the surgical techniques to treat gingival recession. PMID:23960465

X-linked ocular albinism in Blacks. Ocular albinism cum pigmento.

PubMed

O'Donnell, F E; Green, W R; Fleischman, J A; Hambrick, G W

1978-07-01

X-linked ocular albinism can be an unsuspected cause of congenital nystagmus in blacks. In this study, eight of ten black ocular albinos from two kindreds had nonalbinotic, moderately pigmented fundi and no transillumination of the iris. We refer to this paradoxical condition as "ocular albinism cum pigmento." The only constant ophthalmoscopic feature was a foveal hypoplasia. Biopsy of clinically normal skin to demonstrate giant pigment granules is the most accurate means of diagnosis.

X-linked juvenile retinoschisis in a consanguineous family: phenotypic variability and report of a homozygous female patient.

PubMed

Gliem, Martin; Holz, Frank G; Stöhr, Heidi; Weber, Bernhard H F; Charbel Issa, Peter

2014-12-01

To describe the phenotypic variability in a consanguineous family with genetically confirmed X-linked retinoschisis. Five patients, including one homozygous female, were characterized by clinical examination, optical coherence tomography, fundus autofluorescence, mapping of macular pigment optical density, electroretinography, and DNA testing. The 36-year-old male index patient showed a ring of enhanced autofluorescence and outer retinal atrophy on optical coherence tomography. Electroretinography testing revealed a reduced a/b ratio. His mother presented with a central atrophic retina with markedly reduced autofluorescence signal and a surrounding ring of enhanced autofluorescence. The 40-year-old brother of the index patient and his 2 sons showed characteristic signs for X-linked retinoschisis, including retinal schisis and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1 gene in all affected family members while the mother of the index patient was homozygous for this mutation. X-linked retinoschisis can present with a wide phenotypic variability. Here, detailed family history and genetic testing established the diagnosis of X-linked retinoschisis despite striking differences in phenotypic presentation in affected subjects, homozygosity of one affected female, and seemingly dominant inheritance in three subsequent generations because of multiple consanguinity.

A fetus with an X;1 balanced reciprocal translocation and eye disease.

PubMed Central

Seller, M J; Pal, K; Horsley, S; Davies, A F; Berry, A C; Meredith, R; McCartney, A C

1995-01-01

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis. Images PMID:7562972

New perspectives in the diagnostic of gingival recession.

PubMed

Dominiak, Marzena; Gedrange, Tomasz

2014-01-01

Gingival recession (GR) is a common clinical situation observed in patient populations regardless of their age and ethnicity. It has been estimated that over 60% of the human population has gingival recession. It is the final effect of the interaction of multiple etiological factors. Identification and definition of the range of influence is often not possible, with the result that new methods for testing and elimination of potential etiological factors are still being sought. The aim of this study is to present the etiopathogenesis of gingival recessions with regard to the analysis of morphological and functional factors. For the assessment of the bone factors, we will describe the new cephalometric method for measuring sagital width of the bone in the central incisors area, places when GR are most commonly observed. Also, a review will be presented of modern methods of treatment; in particular classes recessions; usage substitute of autogenous tissue will be emphasized--collagen matrix, and primary culture fibroblasts on collagen net.

Housing instability and alcohol problems during the 2007-2009 US recession: the moderating role of perceived family support.

PubMed

Murphy, Ryan D; Zemore, Sarah E; Mulia, Nina

2014-02-01

The 2007-2009 US economic recession was marked by unprecedented rates of housing instability and relatively little is known about how this instability impacted alcohol problems. While previous studies have linked homelessness to increased rates of alcohol use and abuse, housing instability during a recession impacts a much larger segment of the population and usually does not result in homelessness. Using a nationally representative sample of US adults, this study examines the association between housing instability during the recession and alcohol outcomes. Additionally, we assess whether this association is moderated by perceived family support. In multivariate negative binomial regressions, both trouble paying the rent/mortgage (vs. stable housing) and lost (vs. stable) housing were associated with experiencing more negative drinking consequences and alcohol dependence symptoms. However, these associations were moderated by perceived family support. In contrast to those with low perceived family support, participants with high perceived family support reported relatively few alcohol problems, irrespective of housing instability. Furthermore, while job loss was strongly associated with alcohol problems in univariate models, no significant associations between job loss and alcohol outcomes were observed in multivariate models that included indicators of housing instability. Findings point to the importance of the informal safety net and suggest that alcohol screening and abuse prevention efforts should be intensified during periods of recession, particularly among those who experience housing instability.

X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

PubMed

Beckers, Albert; Lodish, Maya Beth; Trivellin, Giampaolo; Rostomyan, Liliya; Lee, Misu; Faucz, Fabio R; Yuan, Bo; Choong, Catherine S; Caberg, Jean-Hubert; Verrua, Elisa; Naves, Luciana Ansaneli; Cheetham, Tim D; Young, Jacques; Lysy, Philippe A; Petrossians, Patrick; Cotterill, Andrew; Shah, Nalini Samir; Metzger, Daniel; Castermans, Emilie; Ambrosio, Maria Rosaria; Villa, Chiara; Strebkova, Natalia; Mazerkina, Nadia; Gaillard, Stéphan; Barra, Gustavo Barcelos; Casulari, Luis Augusto; Neggers, Sebastian J; Salvatori, Roberto; Jaffrain-Rea, Marie-Lise; Zacharin, Margaret; Santamaria, Beatriz Lecumberri; Zacharieva, Sabina; Lim, Ee Mun; Mantovani, Giovanna; Zatelli, Maria Chaira; Collins, Michael T; Bonneville, Jean-François; Quezado, Martha; Chittiboina, Prashant; Oldfield, Edward H; Bours, Vincent; Liu, Pengfei; W de Herder, Wouter; Pellegata, Natalia; Lupski, James R; Daly, Adrian F; Stratakis, Constantine A

2015-06-01

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management. © 2015 Society for Endocrinology.

The Recess Renaissance

ERIC Educational Resources Information Center

Keeler, Rusty

2015-01-01

The author tells of his work around the country and world on transforming how schools do recess, free play, and outside time by transforming their outdoor spaces to match. Instead of a playground of fixed structures like traditional school grounds, newer spaces are filled with loose materials that children can use to build forts, dens, and tree…

Comparison of surgically induced astigmatism in patients with horizontal rectus muscle recession

PubMed Central

Çakmak, Harun; Kocatürk, Tolga; Dündar, Sema Oruç

2014-01-01

AIM To compare surgically induced astigmatism (SIA) following horizontal rectus muscle recession surgery between suspension recession with both the “hang-back” technique and conventional recession technique. METHODS Totally, 48 eyes of 24 patients who had undergone horizontal rectus muscle recession surgery were reviewed retrospectively. The patients were divided into two groups. Twelve patients were operated on by the hang-back technique (Group 1), and 12 by the conventional recession technique (Group 2). SIA was calculated on the 1st wk, 1st and in the 3rd mo after surgery using the SIA calculator. RESULTS SIA was statistically higher in the Group 1 all postoperative follow-up. SIA was the highest in the 1st wk, and decreased gradually in both groups. CONCLUSION The suspension recession technique induced much more SIA than the conventional recession technique. This difference also continued in the following visits. Therefore, the refractive power should be checked postoperatively in order to avoid refractive amblyopia. Conventional recession surgery should be the preferred method so as to minimize the postoperative refractive changes in patients with amblyopia. PMID:25161948

Aerodynamic Analysis of Simulated Heat Shield Recession for the Orion Command Module

NASA Technical Reports Server (NTRS)

Bibb, Karen L.; Alter, Stephen J.; Mcdaniel, Ryan D.

2008-01-01

The aerodynamic effects of the recession of the ablative thermal protection system for the Orion Command Module of the Crew Exploration Vehicle are important for the vehicle guidance. At the present time, the aerodynamic effects of recession being handled within the Orion aerodynamic database indirectly with an additional safety factor placed on the uncertainty bounds. This study is an initial attempt to quantify the effects for a particular set of recessed geometry shapes, in order to provide more rigorous analysis for managing recession effects within the aerodynamic database. The aerodynamic forces and moments for the baseline and recessed geometries were computed at several trajectory points using multiple CFD codes, both viscous and inviscid. The resulting aerodynamics for the baseline and recessed geometries were compared. The forces (lift, drag) show negligible differences between baseline and recessed geometries. Generally, the moments show a difference between baseline and recessed geometries that correlates with the maximum amount of recession of the geometry. The difference between the pitching moments for the baseline and recessed geometries increases as Mach number decreases (and the recession is greater), and reach a value of -0.0026 for the lowest Mach number. The change in trim angle of attack increases from approx. 0.5deg at M = 28.7 to approx. 1.3deg at M = 6, and is consistent with a previous analysis with a lower fidelity engineering tool. This correlation of the present results with the engineering tool results supports the continued use of the engineering tool for future work. The present analysis suggests there does not need to be an uncertainty due to recession in the Orion aerodynamic database for the force quantities. The magnitude of the change in pitching moment due to recession is large enough to warrant inclusion in the aerodynamic database. An increment in the uncertainty for pitching moment could be calculated from these results and

Fragile X syndrome in incestuous families

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

Seemanova, E.

1996-11-11

Reed suggested the investigation of children 219 from incestuous unions as a method for calculation of the detrimental heterozygosity of man. Some studies of latent genetics load in man have been based on the comparison of health status of incestuous children with their half-sibs born to the same mothers in matings with nonconsanguineous partners. These studies were limited to the detection of autosomal-recessive genes leading to abnormal phenotypes or mental deficiency in homozygotes. The highest coefficient of inbreeding in human beings is 1/4 in offspring of incestuous matings: hence, the high proportion of affected homozygotes and low incidence of affectedmore » individuals among their maternal half-sibs. Mental deficiency in incestuous children represents not only cases of simple recessive inheritance. Recently, we observed three incestuous families in which fragile X syndrome was detected. The fra(X) children were born to carriers from incestuous unions as well as to unrelated partners. Therefore, we recommend use of incestuous children and their maternal half-sibs as a control group for studies estimating latent genetic load after investigation for fra(X). The incidence of fra(X) syndrome is high, and mental retardation in heterozygotes is uncommon. Both of these factors can play a role in the occurrence of incest, and in pregnancy at young age, as well as in multiple partnerships. Families of heterozygotes for fragile X should be excluded from the material for the calculation of human latent detrimental (autosomal-recessive) genetic load. 3 refs., 3 figs.« less

Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy.

PubMed

Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

1995-05-20

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient.

Gingival recession: prevalence and risk indicators among young greek adults.

PubMed

Chrysanthakopoulos, Nikolaos A

2014-07-01

The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults.

Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1.

PubMed

Li, Jiali; Gao, Bei; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun; Zhang, Qingjiong

2015-06-01

MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1. The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls. The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at θ = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia. Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.

X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships.

PubMed

Kim, David Y; Mukai, Shizuo

2013-01-01

X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype.

Students with Fetal Alcohol Syndrome Participating in Recess

ERIC Educational Resources Information Center

Scheel, Rebecca; Lucas, Matthew D.

2011-01-01

For the student with Fetal Alcohol Syndrome (FAS), participation in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with FAS and present basic solutions to improve the experience of these students in the recess setting. Initially, the definition and…

Prevention, Recognition and Treatment of Common Recess Injuries

ERIC Educational Resources Information Center

Linker, Jenny M.; David, Shannon L.

2017-01-01

When examining recess within a school's comprehensive school physical activity program (CSPAP), stakeholders should consider that 30% to 70% of school injuries occur during this part of the school day (Posner, 2000). Thus, existing frameworks to prevent and manage recess injuries may require a thorough review. The purpose of this article is to…

Pattern of Glacier Recession in Indian Himalaya

NASA Astrophysics Data System (ADS)

Singh, Ajay; Patwardhan, Anand

All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate — for example, on the frequency of heat waves — this increase in surface temperatures has important consequences for the cryosphere subsequently hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. The Indian Himalayan region occupies a special place in the mountain ecosystems of the world. These geodynamically young mountains are not only important from the standpoint of climate and as a provider of life, giving water to a large part of the Indian subcontinent, but they also harbor a rich variety of flora, fauna, human communities and cultural diversity. Glaciers in this region are changing in area as well as in volume like those in other parts of the world. Studies have been carried out for recession in some of these glaciers using remote sensing as well as field observation techniques. Spatiotemporal pattern in the recession rate of the studied glaciers has been presented in this paper. Plausible causes for the recession have been also discussed. Finally, future scopes for observation and analysis in glaciers recession have been suggested.

Does the effect of a school recess intervention on physical activity vary by gender or race? Results from the Ready for Recess pilot study.

PubMed

Siahpush, Mohammad; Huberty, Jennifer L; Beighle, Aaron

2012-01-01

The recess environment in schools has been identified as an integral part of school-based programs to enhance physical activity (PA). The purpose of this study was to report pilot findings on the extent to which the Ready for Recess intervention was associated with a different amount of increase in moderate to vigorous PA (MPVA) during recess and the rest of the school day between girls and boys, and between nonwhites and whites. The Ready for Recess intervention modified the recess environment of schools by providing staff training and recreational equipment. The MPVA levels of 3rd, 4th, and 5th grade students (n = 93) at 2 schools were measured pre- and post-intervention using ActiGraph accelerometers. Multiple regression models with robust variance were utilized to test for the interaction of intervention with gender and race/ethnicity. The intervention was associated with an adjusted increase of 4.7 minutes (P <.001) in moderate/vigorous PA during recess. There was no evidence that this effect varied by gender (P = .944) or race (P = .731). The intervention was also associated with an adjusted increase of 29.6 minutes (P < .001) in moderate/vigorous PA during rest of the school day. While this effect did not vary by gender, there was some evidence (P = .034) that nonwhites benefited more from the intervention than whites. Simple strategies such as staff training and recreational equipment may be an effective way to increase PA in children (despite gender or ethnicity) during recess time as well as during the rest of the school day.

Mineralocorticoid Receptor Mutations and a Severe Recessive Pseudohypoaldosteronism Type 1

PubMed Central

Hubert, Edwige-Ludiwyne; Teissier, Raphaël; Fernandes-Rosa, Fábio L.; Fay, Michel; Rafestin-Oblin, Marie-Edith; Jeunemaitre, Xavier; Metz, Chantal; Escoubet, Brigitte

2011-01-01

Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease of mineralocorticoid resistance characterized by salt wasting and failure to thrive in infancy. Here we describe the first case of a newborn with severe recessive PHA1 caused by two heterozygous mutations in NR3C2, gene coding for the mineralocorticoid receptor (MR). Independent segregation of the mutations occurred in the family, with p.Ser166X being transmitted from the affected father and p.Trp806X from the asymptomatic mother Whereas the truncated MR166X protein was degraded, MR806X was expressed both at the mRNA and protein level. Functional studies demonstrated that despite its inability to bind aldosterone, MR806X had partial ligand-independent transcriptional activity. Partial nuclear localization of MR806X in the absence of hormone was identified as a prerequisite to initiate transcription. This exceptional case broadens the spectrum of clinical phenotypes of PHA1 and demonstrates that minimal residual activity of MR is compatible with life. It also suggests that rare hypomorphic NR3C2 alleles may be more common than expected from the prevalence of detected PHA1 cases. This might prove relevant for patient's care in neonatal salt losing disorders and may affect renal salt handling and blood pressure in the general population. PMID:21903996

Children's Recess Physical Activity: Movement Patterns and Preferences

ERIC Educational Resources Information Center

Woods, Amelia Mays; Graber, Kim C.; Daum, David Newman

2012-01-01

The benefits of recess can be reaped by all students regardless of socioeconomic status, race, or gender and at relatively little cost. The purpose of this study was to examine physical activity (PA) variables related to the recess PA patterns of third and fourth grade children and the social preferences and individuals influencing their PA…

Students with Sickle Cell Anemia Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.; Devlin, Katharine M.

2011-01-01

The participation of a student with Sickle Cell Anemia in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with Sickle Cell Anemia and present basic solutions to improve the experience of these students in the recess setting. Initially the definition,…

Computed tomography of the azygo-oesophageal recess. Normal appearances.

PubMed

Lund, G; Lien, H H

1982-01-01

Computed tomography of the azygo--oesophageal recess was performed in 85 normal subjects. The recess was convex towards the left or had an approximately straight left wall. Convexity towards the right did not occur. Localized bulges caused by the azygos vein, oesophagus and aorta were frequent. The recess became gradually deeper caudally in patients below 50 years of age. Above that age a marked posterior extension of the heart and a prevertebral position of the aorta often caused a localized shallowing at the level of the inferior pulmonary veins or the ventricles.

Recess environment and curriculum intervention on children's physical activity: IPLAY.

PubMed

Nigg, Claudio R; Kutchman, Eve; Amato, Katie; Schaefer, Christine A; Zhang, Guangxiang; Anwar, Md Mahabub Ul; Anthamatten, Peter; Browning, Raymond C; Brink, Lois; Hill, James

2018-04-10

Understanding the impacts of the built environment on physical activity (PA) is essential to promoting children's PA. The purpose of this study was to investigate the effects of schoolyard renovations and a PA recess curriculum alone and in combination on children's PA. This was a 2 (learning landscape [LL] vs. non-LL) × 2 (curriculum intervention vs. no curriculum intervention) factorial design with random assignment to the curriculum intervention, and six elementary schools per condition. PA outcomes were assessed preprogram, mid-program, immediate postprogram, and one year postprogram. No meaningful intervention effects were found. Lack of an effect may be due to the brief dose of recess, the curriculum not being integrated within the schoolyard, the LL implementation occurring prior to the study, or the already high levels of PA. Potential avenues to promote PA include making recess longer, integrating recess into the school curricula, and developing recess PA curricula integrating schoolyards.

Mitochondrial recessive ataxia syndrome mimicking dominant spinocerebellar ataxia.

PubMed

Palin, Eino J H; Hakonen, Anna H; Korpela, Mari; Paetau, Anders; Suomalainen, Anu

2012-04-15

We studied the genetic background of a family with SCA, showing dominant inheritance and anticipation. Muscle histology, POLG1 gene sequence, neuropathology and mitochondrial DNA analyses in a mother and a son showed typical findings for a mitochondrial disorder, and both were shown to be homozygous for a recessive POLG1 mutation, underlying mitochondrial recessive ataxia syndrome, MIRAS. The healthy father was a heterozygous carrier for the same mutation. Recessively inherited MIRAS mutations should be tested in dominantly inherited SCAs cases of unknown cause, as the high carrier frequency of MIRAS may result in two independent introductions of the mutant allele in the family and thereby mimic dominant inheritance. Copyright © 2011 Elsevier B.V. All rights reserved.

Gingival recession: prevalence and risk indicators among young greek adults

PubMed Central

2014-01-01

Objectives: The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. Material and Methods: A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. Results: The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. Conclusions: The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults. PMID:25136424

A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome

PubMed Central

Rakhimova, Saule E.; Nigmatullina, Nazym B.; Momynaliev, Kuvat T.; Ramanculov, Yerlan M.

2015-01-01

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome. PMID:26168235

A Novel Mutation in a Kazakh Family with X-Linked Alport Syndrome.

PubMed

Baikara, Barshagul T; Zholdybayeva, Elena V; Rakhimova, Saule E; Nigmatullina, Nazym B; Momynaliev, Kuvat T; Ramanculov, Yerlan M

2015-01-01

Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome.

Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q

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

Russell, L.J.; Compton, J.G.; Bale, S.J.

The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of themore » enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.« less

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

PubMed

Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W; Schneider, Pascal

2018-04-26

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Understanding Subsurface Flow Mechanisms by Studying Recession Flow Curves

NASA Astrophysics Data System (ADS)

patnaik, S.; Biswal, B.; D, N.

2013-12-01

The recession flows offer valuable information on the subsurface systems of the drainage which cannot be observed due to technological limitations. Many analytical frameworks have been proposed in the past to analyze recession flow curves assess. Among them the most widely used one is Brutsaert-Neiber method of expressing negative time derivative of Q (discharge at the basin outlet at time t), -dQ/dt, as a function of Q itself, which eliminates the need of finding a reference time. Typically, basins across geographical regions display a power law relationship of the type: -dQ/dt = kQ^α. For a particular basin, the exponent α remains fairly constant recession events while the coefficient k varies greatly from one recession event to another, indicating the dynamic nature -dQ/dt-Q relationship. Recent observations show that subsurface storage in a basin mainly controls the dynamic parameter k. As subsurface water takes long time to fully drain, k of a recession event can also be influenced by the storage that occurred during the past rainfall events. We indirectly analyze the effect of past storage on recession flow by considering past streamflow as a proxy of past storage. A stronger relationship implies that the basin is able to store water for longer duration, and vice versa. In this study, we used streamflow data from 388 USGS basins that are relatively unaffected by human activities to find out the factors that affect the relationship between the power law correlation (R^2_PN) between past discharge and k, where the subscript N is the number of days of past streamflow observations considered for the recession event. For most of the basins R^2_PN decreases with N. We then selected 18 physical and climatological parameters for each study basin and investigated how they influence the value of R^2_PN for each N. We followed multiple linear regression method and found that R^2_PN is strongly influenced by the selected parameters (R^2 = 0.58) for N =30 days. We also

Recess and Reading Achievement of Early Childhood Students in Public Schools

ERIC Educational Resources Information Center

Yesil Dagli, Ummuhan

2012-01-01

In recent years, schools have tended to eliminate recess period and to devote more time to instruction in order to increase academic achievement. Using a nationally representative sample, this study examined reading scores of students who experienced different numbers of recess days in a week, and different number of times and length of recess in…

Health in financial crises: economic recession and tuberculosis in Central and Eastern Europe.

PubMed

Arinaminpathy, Nimalan; Dye, Christopher

2010-11-06

The ongoing global financial crisis, which began in 2007, has drawn attention to the effect of declining economic conditions on public health. A quantitative analysis of previous events can offer insights into the potential health effects of economic decline. In the early 1990s, widespread recession across Central and Eastern Europe accompanied the collapse of the Soviet Union. At the same time, despite previously falling tuberculosis (TB) incidence in most countries, there was an upsurge of TB cases and deaths throughout the region. Here, we study the quantitative relationship between the lost economic productivity and excess TB cases and mortality. We use the data of the World Health Organization for TB notifications and deaths from 1980 to 2006, and World Bank data for gross domestic product. Comparing 15 countries for which sufficient data exist, we find strong linear associations between the lost economic productivity over the period of recession for each country and excess numbers of TB cases (r(2) = 0.94, p < 0.001) and deaths (r(2) = 0.94, p < 0.001) over the same period. If TB epidemiology and control are linked to economies in 2009 as they were in 1991 then the Baltic states, particularly Latvia, are now vulnerable to another upturn in TB cases and deaths. These projections are in accordance with emerging data on drug consumption, which indicate that these countries have undergone the greatest reductions since the beginning of 2008. We recommend close surveillance and monitoring during the current recession, especially in the Baltic states.

Health in financial crises: economic recession and tuberculosis in Central and Eastern Europe

PubMed Central

Arinaminpathy, Nimalan; Dye, Christopher

2010-01-01

The ongoing global financial crisis, which began in 2007, has drawn attention to the effect of declining economic conditions on public health. A quantitative analysis of previous events can offer insights into the potential health effects of economic decline. In the early 1990s, widespread recession across Central and Eastern Europe accompanied the collapse of the Soviet Union. At the same time, despite previously falling tuberculosis (TB) incidence in most countries, there was an upsurge of TB cases and deaths throughout the region. Here, we study the quantitative relationship between the lost economic productivity and excess TB cases and mortality. We use the data of the World Health Organization for TB notifications and deaths from 1980 to 2006, and World Bank data for gross domestic product. Comparing 15 countries for which sufficient data exist, we find strong linear associations between the lost economic productivity over the period of recession for each country and excess numbers of TB cases (r2 = 0.94, p < 0.001) and deaths (r2 = 0.94, p < 0.001) over the same period. If TB epidemiology and control are linked to economies in 2009 as they were in 1991 then the Baltic states, particularly Latvia, are now vulnerable to another upturn in TB cases and deaths. These projections are in accordance with emerging data on drug consumption, which indicate that these countries have undergone the greatest reductions since the beginning of 2008. We recommend close surveillance and monitoring during the current recession, especially in the Baltic states. PMID:20427332

Laminar flow in a recess of a hydrostatic bearing

NASA Technical Reports Server (NTRS)

San Andres, Luis A.; Velthuis, Johannes F. M.

1992-01-01

The flow in a recess of a hydrostatic journal bearing is studied in detail. The Navier-Stokes equations for the laminar flow of an incompressible liquid are solved numerically in a two-dimensional plane of a typical bearing recess. Pressure- and shear-induced flows, as well as a combination of these two flow conditions, are analyzed. Recess friction, pressure-ram effects at discontinuities in the flow region, and film entrance pressure loss effects are calculated. Entrance pressure loss coefficients over a forward-facing step are presented as functions of the mean flow Reynolds number for pure-pressure and shear-induced laminar flows.

Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

PubMed

Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

2014-08-01

Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

Ecologically unequal exchange, recessions, and climate change: A longitudinal study.

PubMed

Huang, Xiaorui

2018-07-01

This study investigates how the ecologically unequal exchange of carbon dioxide emissions varies with economic recessions. I propose a country-specific approach to examine (1) the relationship between carbon dioxide emissions in developing countries and the "vertical flow" of exports to the United States; and (2) the variations of the relationship before, during, and after two recent economic recessions in 2001 and 2008. Using data on 69 developing nations between 2000 and 2010, I estimate time-series cross-sectional regression models with two-way fixed effects. Results suggest that the vertical flow of exports to the United States is positively associated with carbon dioxide emissions in developing countries. The magnitude of this relationship increased in 2001, 2009, and 2010, and decreased in 2008, but remained stable in non-recession periods, suggesting that economic recessions in the United States are associated with variations of ecologically unequal exchange. Results highlight the impacts of U.S. recessions on carbon emissions in developing countries through the structure of international trade. Copyright © 2018 Elsevier Inc. All rights reserved.

Autosomal recessive cerebellar ataxias

PubMed Central

Palau, Francesc; Espinós, Carmen

2006-01-01

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

Gender Differences in Mental Health Outcomes before, during, and after the Great Recession.

PubMed

Dagher, Rada K; Chen, Jie; Thomas, Stephen B

2015-01-01

We examined gender differences in mental health outcomes during and post-recession versus pre-recession. We utilized 2005-2006, 2008-2009, and 2010-2011 data from the Medical Expenditure Panel Survey. Females had lower odds of depression diagnoses during and post-recession and better mental health during the recession, but higher odds of anxiety diagnoses post-recession. Males had lower odds of depression diagnoses and better mental health during and post-recession and lower Kessler 6 scores post-recession. We conducted stratified analyses, which confirmed that the aforementioned findings were consistent across the four different regions of the U.S., by employment status, income and health care utilization. Importantly, we found that the higher odds of anxiety diagnoses among females after the recession were mainly prominent among specific subgroups of females: those who lived in the Northeast or the Midwest, the unemployed, and those with low household income. Gender differences in mental health in association with the economic recession highlight the importance of policymakers taking these differences into consideration when designing economic and social policies to address economic downturns. Future research should examine the reasons behind the decreased depression diagnoses among both genders, and whether they signify decreased mental healthcare utilization or increased social support and more time for exercise and leisure activities.

Health Impacts of the Great Recession: A Critical Review

PubMed Central

Goldman-Mellor, Sidra; Falconi, April; Downing, Janelle

2016-01-01

The severity, sudden onset, and multipronged nature of the Great Recession (2007–2009) provided a unique opportunity to examine the health impacts of macroeconomic downturn. We comprehensively review empirical literature examining the relationship between the Recession and mental and physical health outcomes in developed nations. Overall, studies reported detrimental impacts of the Recession on health, particularly mental health. Macro- and individual-level employment- and housing-related sequelae of the Recession were associated with declining fertility and self-rated health, and increasing morbidity, psychological distress, and suicide, although traffic fatalities and population-level alcohol consumption declined. Health impacts were stronger among men and racial/ethnic minorities. Importantly, strong social safety nets in some European countries appear to have buffered those populations from negative health effects. This literature, however, still faces multiple methodological challenges, and more time may be needed to observe the Recession’s full health impact. We conclude with suggestions for future work in this field. PMID:27239427

Glacier recession in Iceland and Austria

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

Hall, D.K.; Williams, R.S. Jr.; Bayr, K.J.

1992-03-01

It has been possible to measure glacier recession on the basis of Landsat data, in conjunction with comparisons of the magnitude of recession of a glacier margin with in situ measurements at fixed points along the same margin. Attention is presently given to the cases of Vatnajokull ice cap, in Iceland, and the Pasterze Glacier, in Austria, on the basis of satellite data from 1973-1987 and 1984-1990, respectively. Indications of a trend toward negative mass balance are noted. Nevertheless, while most of the world's small glaciers have been receding, some are advancing either due to local climate or the tidewatermore » glacier cycle. 21 refs.« less

Gastrointestinal Manifestations in X-linked Agammaglobulinemia

PubMed Central

Barmettler, Sara; Otani, Iris M.; Minhas, Jasmit; Abraham, Roshini S.; Chang, Yenhui; Dorsey, Morna J.; Ballas, Zuhair K.; Bonilla, Francisco A.; Ochs, Hans D.; Walter, Jolan E.

2017-01-01

Purpose X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in XLA, the spectrum of gastrointestinal manifestations has not previously been fully explored. Methods We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the USIDNet, a national registry of primary immunodeficiencies. Results In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide-ranging, and management strategies were diverse and mainly experimental. Conclusions Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients. PMID:28236219

Surgical treatment of single gingival recessions: clinical guidelines.

PubMed

Pini-Prato, Giovanpaolo; Nieri, Michele; Pagliaro, Umberto; Giorgi, Teresa Schifter; La Marca, Michele; Franceschi, Debora; Buti, Jacopo; Giani, Monica; Weiss, Julia Hanne; Padeletti, Luigi; Cortellini, Pierpaolo; Chambrone, Leandro; Barzagli, Luca; Defraia, Efisio; Rotundo, Roberto

2014-01-01

The purpose of this clinical guidelines project was to determine the most appropriate surgical techniques, in terms of efficacy, complications, and patient opinions, for the treatment of buccal single gingival recessions without loss of interproximal soft and hard tissues. Literature searches were performed (electronically and manually) for entries up to 28 February, 2013 concerning the surgical approaches for the treatment of gingival recessions. Systematic reviews (SRs) of randomised controlled trials (RCTs) and individual RCTs that reported at least 6 months of follow-up of surgical treatment of single gingival recessions were included. The full texts of the selected SRs and RCTs were analysed using checklists for qualitative evaluation according to the Scottish Intercollegiate Guidelines Network (SIGN) method. The following variables were evaluated: Complete Root Coverage (CRC); Recession Reduction (RecRed); complications; functional and aesthetic satisfaction of the patients; and costs of therapies. Out of 30 systematic reviews, 3 SRs and 16 out of 313 RCTs were judged to have a low risk for bias (SIGN code: 1+). At a short-term evaluation, the coronally advanced flap plus connective tissue graft method (CAF+CTG) resulted in the best treatment in terms of CRC and/or RecRed; in case of cervical abrasion and presence of root sensitivity CAF + CTG + Restoration caused less sensitivity than CAF+CTG. CAF produced less postoperative discomfort for patients. Limited information is available regarding postoperative dental hypersensitivity and aesthetic satisfaction of the patients. In presence of aesthetic demands or tooth hypersensitivity, the best way to surgically treat single gingival recessions without loss of interproximal tissues is achieved using the CAF procedure associated with CTG. Considering postoperative discomfort, the CAF procedure is the less painful surgical approach, while the level of aesthetic satisfaction resulted higher after CAF either alone or

Recession curve analysis for groundwater levels: case study in Latvia

NASA Astrophysics Data System (ADS)

Gailuma, A.; VÄ«tola, I.; Abramenko, K.; Lauva, D.; Vircavs, V.; Veinbergs, A.; Dimanta, Z.

2012-04-01

Recession curve analysis is powerful and effective analysis technique in many research areas related with hydrogeology where observations have to be made, such as water filtration and absorption of moisture, irrigation and drainage, planning of hydroelectric power production and chemical leaching (elution of chemical substances) as well as in other areas. The analysis of the surface runoff hydrograph`s recession curves, which is performed to conceive the after-effects of interaction of precipitation and surface runoff, has approved in practice. The same method for analysis of hydrograph`s recession curves can be applied for the observations of the groundwater levels. There are manually prepared hydrograph for analysis of recession curves for observation wells (MG2, BG2 and AG1) in agricultural monitoring sites in Latvia. Within this study from the available monitoring data of groundwater levels were extracted data of declining periods, splitted by month. The drop-down curves were manually (by changing the date) moved together, until to find the best match, thereby obtaining monthly drop-down curves, representing each month separately. Monthly curves were combined and manually joined, for obtaining characterizing drop-down curves of the year for each well. Within the process of decreased recession curve analysis, from the initial curve was cut out upward areas, leaving only the drops of the curve, consequently, the curve is transformed more closely to the groundwater flow, trying to take out the impact of rain or drought periods from the curve. Respectively, the drop-down curve is part of the data, collected with hydrograph, where data with the discharge dominates, without considering impact of precipitation. Using the recession curve analysis theory, ready tool "A Visual Basic Spreadsheet Macro for Recession Curve Analysis" was used for selection of data and logarithmic functions matching (K. Posavec et.al., GROUND WATER 44, no. 5: 764-767, 2006), as well as

Management of gingival recession associated with orthodontic treatment: a case report.

PubMed

Rana, Tarun Kumar; Phogat, Megha; Sharma, Tarun; Prasad, Narayana; Singh, Shailendra

2014-07-01

Many patients undergo orthodontic treatment for aesthetic improvement. It is well established that the patients who undergo orthodontic treatment have a high susceptibility to present plaque accumulation on their teeth because of the presence of brackets, wires and/or other orthodontic elements on the teeth surfaces with which the oral hygiene procedures might be more difficult. The orthodontic treatment is a double-action procedure regarding the periodontal tissues which may be very meaningful in increasing the periodontal health status and may be a harmful procedure which can be followed by several types of periodontal complications. There is a strong correlation between the severity and extent of gingival recessions and the orthodontic treatment suggesting that orthodontic tooth movement may lead to gingival recession. The principal objective in the treatment of gingival recession is to cover the exposed root surfaces to improve aesthetics and to reduce hypersensitivity. Different soft tissue grafting procedures have been proposed in the treatment of gingival recessions. Subepithelial connective tissue graft is a reliable method for treatment of gingival recession. The purpose of this case report was to illustrate the relationship between orthodontic therapy and gingival recession and to describe the management of this case.

Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

PubMed Central

Kingsmore, Stephen

2012-01-01

Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder.

PubMed

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered.

Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder

PubMed Central

Yanagi, Kumiko; Kaname, Tadashi; Wakui, Keiko; Hashimoto, Ohiko; Fukushima, Yoshimitsu; Naritomi, Kenji

2012-01-01

Mutations in the X-linked genes neuroligin 3 (NLGN3) and neuroligin 4X (NLGN4X) were first implicated in the pathogenesis of X-linked autism in Swedish families. However, reports of mutations in these genes in autism spectrum disorder (ASD) patients from various ethnic backgrounds present conflicting results regarding the etiology of ASD, possibly because of genetic heterogeneity and/or differences in their ethnic background. Additional mutation screening study on another ethnic background could help to clarify the relevance of the genes to ASD. We scanned the entire coding regions of NLGN3 and NLGN4X in 62 Japanese patients with ASD by polymerase chain reaction-high-resolution melting curve and direct sequencing analyses. Four synonymous substitutions, one in NLGN3 and three in NLGN4X, were identified in four of the 62 patients. These substitutions were not present in 278 control X-chromosomes from unrelated Japanese individuals and were not registered in the database of Single Nucleotide Polymorphisms build 132 or in the Japanese Single Nucleotide Polymorphisms database, indicating that they were novel and specific to ASD. Though further analysis is necessary to determine the physiological and clinical importance of such substitutions, the possibility of the relevance of both synonymous and nonsynonymous substitutions with the etiology of ASD should be considered. PMID:22934180

Hardships of the Great Recession and health: Understanding varieties of vulnerability

PubMed Central

Kirsch, Julie A; Ryff, Carol D

2016-01-01

The Great Recession of 2007–2009 is regarded as the most severe economic downturn since World War II. This study examined relationships between reported recession hardships and physical health in a national survey of American adults (N = 1275). Furthermore, education and psychological resources (perceived control, purpose in life, and conscientiousness) were tested as moderators of the health impacts of the recession. A greater number of hardships predicted poorer health, especially among the less educated. Psychological resources interacted with education and hardships to predict health outcomes. Although typically viewed as protective factors, such resources became vulnerabilities among educationally disadvantaged adults experiencing greater recession hardships. PMID:28070407

Gingival recession: its causes and types, and the importance of orthodontic treatment

PubMed Central

Jati, Ana Suzy; Furquim, Laurindo Zanco; Consolaro, Alberto

2016-01-01

abstract Gingival recession has direct causes and predisposing factors. Orthodontic treatment is able to prevent recession and even contribute to its treatment, with or without periodontal approach, depending on the type and severity of gingival tissue damage. There is no evidence on the fact that orthodontic treatment alone might induce gingival recession, although it might lead the affected teeth (usually mandibular incisors or maxillary canines) to be involved in situations that act as predisposing factors, allowing direct causes to act and, therefore, trigger recession, especially when the buccal bone plate is very thin or presents with dehiscence. Several aspects regarding the relationship between orthodontic treatment and gingival recession have been addressed, and so has the importance of the periosteum to the mechanism of gingival recession formation. Clinical as well as experimental trials on the subject would help to clarify this matter, of which understanding is not very deep in the related literature. PMID:27409650

Predictable root recession coverage.

PubMed

Hoexter, David L

2006-01-01

Gingival recession, exposure of the tooth's root, is undesirable and, in many situations, contrary to normal physiology. Today's root coverage is predictable. With the use of an acellular dermal matrix membrane (Fasciablast), we can achieve a new blood supply and predictable coverage, with no second surgical procedure. Youth, esthetics and physiology are restored.

Classroom Benefits of Recess

ERIC Educational Resources Information Center

Brez, Caitlin; Sheets, Virgil

2017-01-01

Despite research demonstrating the importance of recess and free play for children, schools have been reducing free play time for more academic pursuits (Ramstetter et al. in "J Sch Health" 80:517-526, 2010; Waite-Stupiansky and Findlay in "Educ Forum" 66:16-25, 2001). Recently, there has been renewed interest in understanding…

Children's Physical Activity Levels during Indoor Recess Dance Videos

ERIC Educational Resources Information Center

Erwin, Heather; Koufoudakis, Ryann; Beighle, Aaron

2013-01-01

Background: Children's physical activity (PA) levels remain low, and schools are being asked to assume a leadership role in PA promotion. Research suggests outdoor recess contributes to children's overall PA levels. However, similar research is not available for indoor recess, which occurs frequently due to a variety of factors. The purpose of…

Addressing Problem Behavior at Recess Using Peer Praise Notes

ERIC Educational Resources Information Center

Teerlink, Elise; Caldarella, Paul; Anderson, Darlene H.; Richardson, Michael J.; Guzman, E. Geovanni

2017-01-01

School recess, though beneficial to students in many ways, can be a problematic setting due to inadequate supervision, structure, and safety. A peer praise note (PPN) intervention was implemented on the recess playground to address these concerns at a Title I elementary school. Researchers used a single-subject reversal design across all students…

Students with Attention Deficit Hyperactivity Disorder Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.; Justice, Michael J.; Rosko, Kelly M.

2014-01-01

The participation of a student with Attention Deficit Hyperactivity Disorder (ADHD) in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of children with ADHD and present basic solutions to improve the experience of these children in the recess setting. Initially, the…

MHC class 2 deficiency and X-linked agammaglobulinaemia in a consanguineous extended family.

PubMed

Broides, A; Shubinsky, G; Parvari, R; Grimbacher, B; Somech, R; Garty, B Z; Levy, J

2009-08-01

Manifestations of immunodeficiency within the same family are presumed to be the same disease. We report a consanguineous extended family where four patients have immunodeficiency, three have X-linked agammaglobulinaemia and one has major histocompatibility complex class 2 deficiency. Within one family, two rare genetic diseases with similar clinical manifestations can occur.

Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.

PubMed

Vawter, Marquis P; Harvey, Philip D; DeLisi, Lynn E

2007-09-05

Klinefelter's Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini-Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression-cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = -0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. Copyright 2007 Wiley-Liss, Inc.

An Ethyl-Nitrosourea-Induced Point Mutation in Phex Causes Exon Skipping, X-Linked Hypophosphatemia, and Rickets

PubMed Central

Carpinelli, Marina R.; Wicks, Ian P.; Sims, Natalie A.; O’Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J.; Bahlo, Melanie; Alexander, Warren S.; Hilton, Douglas J.

2002-01-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G1) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease. PMID:12414538

An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets.

PubMed

Carpinelli, Marina R; Wicks, Ian P; Sims, Natalie A; O'Donnell, Kristy; Hanzinikolas, Katherine; Burt, Rachel; Foote, Simon J; Bahlo, Melanie; Alexander, Warren S; Hilton, Douglas J

2002-11-01

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G(1)) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease.

Economic recession and fertility in the developed world.

PubMed

Sobotka, Tomáš; Skirbekk, Vegard; Philipov, Dimiter

2011-01-01

This article reviews research on the effects of economic recessions on fertility in the developed world. We study how economic downturns, as measured by various indicators, especially by declining GDP levels, falling consumer confidence, and rising unemployment, were found to affect fertility. We also discuss particular mechanisms through which the recession may have influenced fertility behavior, including the effects of economic uncertainty, falling income, changes in the housing market, and rising enrollment in higher education, and also factors that influence fertility indirectly such as declining marriage rates. Most studies find that fertility tends to be pro-cyclical and often rises and declines with the ups and downs of the business cycle. Usually, these aggregate effects are relatively small (typically, a few percentage points) and of short durations; in addition they often influence especially the timing of childbearing and in most cases do not leave an imprint on cohort fertility levels. Therefore, major long-term fertility shifts often continue seemingly uninterrupted during the recession—including the fertility declines before and during the Great Depression of the 1930s and before and during the oil shock crises of the 1970s. Changes in the opportunity costs of childbearing and fertility behavior during economic downturn vary by sex, age, social status, and number of children; childless young adults are usually most affected. Furthermore, various policies and institutions may modify or even reverse the relationship between recessions and fertility. The first evidence pertaining to the recent recession falls in line with these findings. In most countries, the recession has brought a decline in the number of births and fertility rates, often marking a sharp halt to the previous decade of rising fertility rates.

Using quantile regression to examine health care expenditures during the Great Recession.

PubMed

Chen, Jie; Vargas-Bustamante, Arturo; Mortensen, Karoline; Thomas, Stephen B

2014-04-01

To examine the association between the Great Recession of 2007-2009 and health care expenditures along the health care spending distribution, with a focus on racial/ethnic disparities. Secondary data analyses of the Medical Expenditure Panel Survey (2005-2006 and 2008-2009). Quantile multivariate regressions are employed to measure the different associations between the economic recession of 2007-2009 and health care spending. Race/ethnicity and interaction terms between race/ethnicity and a recession indicator are controlled to examine whether minorities encountered disproportionately lower health spending during the economic recession. The Great Recession was significantly associated with reductions in health care expenditures at the 10th-50th percentiles of the distribution, but not at the 75th-90th percentiles. Racial and ethnic disparities were more substantial at the lower end of the health expenditure distribution; however, on average the reduction in expenditures was similar for all race/ethnic groups. The Great Recession was also positively associated with spending on emergency department visits. This study shows that the relationship between the Great Recession and health care spending varied along the health expenditure distribution. More variability was observed in the lower end of the health spending distribution compared to the higher end. © Health Research and Educational Trust.

Treatment of gingival recession with coronally advanced flap procedures: a systematic review.

PubMed

Cairo, Francesco; Pagliaro, Umberto; Nieri, Michele

2008-09-01

The treatment of buccal gingival recessions is a common requirement due to aesthetic concern or root sensitivity. The aim of this manuscript was to systematically review the literature on coronally advanced flap (CAF) alone or in combination with tissue grafts, barrier membranes (BM), enamel matrix derivative (EMD) or other material for treating gingival recession. Randomized clinical trials on treatment of Miller Class I and II gingival recessions with at least 6 months of follow-up were identified. Data sources included electronic databases and hand-searched journals. The primary outcome variable was complete root coverage (CRC). The secondary outcome variables were recession reduction, clinical attachment gain, keratinized tissue gain, aesthetic satisfaction, root sensitivity, post-operative patient pain and complications. A total of 794 Miller Class I and II gingival recessions in 530 patients from 25 RCTs were evaluated in this systematic review. CAF was associated with mean recession reduction and CRC. The addition of connective tissue graft (CTG) or EMD enhanced the clinical outcomes of CAF in terms of CRC, while BM did not. The results with respect to the adjunctive use of acellular dermal matrix were controversial. CTG or EMD in conjunction with CAF enhances the probability of obtaining CRC in Miller Class I and II single gingival recessions.

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.

PubMed

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta; Wissinger, Bernd

2014-01-01

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family

PubMed Central

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta

2014-01-01

Purpose: Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. Methods: We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. Results: The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. Conclusion: We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease

Four-Year Placebo-Controlled Trial of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa (DHAX Trial)

PubMed Central

Hoffman, Dennis R.; Hughbanks-Wheaton, Dianna K.; Pearson, N. Shirlene; Fish, Gary E.; Spencer, Rand; Takacs, Alison; Klein, Martin; Locke, Kirsten G.; Birch, David G.

2016-01-01

IMPORTANCE X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100 000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non–X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Quantitative measures of gingival recession and the influence of gender, race, and attrition.

PubMed

Handelman, Chester S; Eltink, Anthony P; BeGole, Ellen

2018-01-29

Gingival recession in dentitions with otherwise healthy periodontium is a common occurrence in adults. Recession is clinically measured using a periodontal probe to the nearest millimeter. The aim of this study is to establish quantitative measures of recession, the clinical crown height, and a new measure the gingival margin-papillae measurement. The latter is seen as the shortest apico-coronal distance measured from the depth of the gingival margin to a line connecting the tips of the two adjacent papillae. Measurements on all teeth up to and including the first molar were performed on pretreatment study models of 120 adult Caucasian and African-American subjects divided into four groups of 30 by gender and race. Both the clinical crown height and the gingival margin-papillae measurements gave a true positive result for changes associated with gingival recession. Tooth wear shortens the clinical crown, and therefore, the measure of clinical crown height can give a false negative result when gingival recession is present. However, the gingival margin-papillae measurement was not affected by tooth wear and gave a true positive result for gingival recession. Tooth wear (attrition) was not associated with an increase in gingival recession. These measures are also useful in detecting recession prior to cemental exposure. Measures for recession and tooth wear were different for the four demographic groups studied. These measures can be used as quantitative standards in both clinical dentistry, research, and epidemiological studies.

A recoding scheme for X-linked and pseudoautosomal loci to be used with computer programs for autosomal LOD-score analysis.

PubMed

Strauch, Konstantin; Baur, Max P; Wienker, Thomas F

2004-01-01

We present a recoding scheme that allows for a parametric multipoint X-chromosomal linkage analysis of dichotomous traits in the context of a computer program for autosomes that can use trait models with imprinting. Furthermore, with this scheme, it is possible to perform a joint multipoint analysis of X-linked and pseudoautosomal loci. It is required that (1) the marker genotypes of all female nonfounders are available and that (2) there are no male nonfounders who have daughters in the pedigree. The second requirement does not apply if the trait locus is pseudoautosomal. The X-linked marker loci are recorded by adding a dummy allele to the males' hemizygous genotypes. For modelling an X-linked trait locus, five different liability classes are defined, in conjunction with a paternal imprinting model for male nonfounders. The formulation aims at the mapping of a diallelic trait locus relative to an arbitrary number of codominant markers with known genetic distances, in cases where a program for a genuine X-chromosomal analysis is not available. 2004 S. Karger AG, Basel.

Gage Measures Recessed Gaps

NASA Technical Reports Server (NTRS)

Zepeda, J. L.

1983-01-01

New tool measures separation between recessed parallel surfaces. Tiles have overhanging edges, tool designed to slip into gap from end so it extends through 0.040-inch crack. Measure gaps between 0.200 and 0.400 inch so gap fillers of proper thickness can be selected. Useful in numerous industrial situation involving gap measurements in inaccessable places.

Who Suffers during Recessions? NBER Working Paper No. 17951

ERIC Educational Resources Information Center

Hoynes, Hilary W.; Miller, Douglas L.; Schaller, Jessamyn

2012-01-01

In this paper we examine how business cycles affect labor market outcomes in the United States. We conduct a detailed analysis of how cycles affect outcomes differentially across persons of differing age, education, race, and gender, and we compare the cyclical sensitivity during the Great Recession to that in the early 1980s recession. We present…

Indocyanine green angiography of juvenile X-linked retinoschisis.

PubMed

Souied, Eric H; Goritsa, Anna; Querques, Giuseppe; Coscas, Gabriel; Soubrane, Gisele

2005-09-01

In juvenile X-linked retinoschisis (XLRS), fluorescein angiography is usually unremarkable and contributes poorly to the diagnosis. However, indocyanine green (ICG) angiography features in eyes that are affected with XLRS were not yet described. Retrospective observational case series. A complete ophthalmologic examination that included ICG angiography was performed on three unrelated male patients (six eyes) who were 15, 22, and 48 years old. A distinct hyperfluorescent stellate pattern in the macular area that was associated with radial lines of hypofluorescence that were centered on the foveola was observed on the early phase of ICG examination (six of six eyes). This feature disappeared on the late phase of ICG examination. On these six XLRS eyes, early phases of ICG examination revealed an unusual radial aspect on the macula. This finding suggests that ICG angiography may be useful for the diagnosis of XLRS.

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.

Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy.

PubMed

Jiang, Hua; Jiang, Min-Yan; Liu, Sha; Cai, Yan-Na; Liang, Cui-Li; Liu, Li

2015-08-01

Childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30% of patients who might benefit from a hematopoietic stem cell transplant will have a full human leukocyte antigen-matched donor, which is considered to be the best choice. We present a 5-year-old boy with cerebral X-linked adrenoleukodystrophy whose brain magnetic resonance imaging severity score was 7 and who needed an immediate transplantation without an available full human leukocyte antigen-matched donor. We combined haploidentical and umbilical cord blood sources for transplantation and saw encouraging results. After transplantation, the patient showed neurological stability for 6 months and the level of very long chain fatty acids had decreased. By 1 year, the patient appeared to gradually develop cognition, motor, and visual disturbances resulting from possible mix chimerism. Transplantation of haploidentical stem cells combined with the infusion of umbilical cord blood is a novel approach for treating cerebral X-linked adrenoleukodystrophy. It is critical to monitor posttransplant chimerism and carry out antirejection therapy timely for a beneficial clinical outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of a self-constructed material on children's physical activity during recess.

PubMed

Méndez-Giménez, Antonio; Cecchini, José-Antonio; Fernández-Río, Javier

2017-06-26

To analyze whether an intervention supported by free play with a self-constructed material increases the level of physical activity of students during recess. The participants were 166 children of third to sixth grade, between nine and 12 years old (average = 10.64; SS = 1.13). An experimental project was conducted with pre-test and post-test measurement, and a control group. Experimental group participants built cardboard paddles (third and fourth) and flying rings (fifth and sixth), a material they used freely for one week during recess. ActiGraph-GT3X accelerometers were used to measure physical activity. An ANOVA of repeated measures was used to find differences between groups and genders. Significant intervention effects were found in the analyzed variables: sedentary activity (F = 38.19; p < 0.01), light (F = 76.56; p < 0.01), moderate (F = 27.44; p < 0.01), vigorous (F = 61.55; p < 0.01), and moderate and vigorous (F = 68.76; p < 0.01). Significant gender differences were shown (time × group × gender) for moderate (F = 6.58; p < 0.05) and vigorous (F = 5.51; p < 0.05) activity. The self-constructed material is effective to increase the physical activity levels of children during recess; it decreases sedentary activity and light physical activity and increases the time devoted to moderate physical activity and vigorous physical activity, both in boys and in girls. The boys had an increase in vigorous physical activity and the girls in moderate physical activity. Due to its low cost, this strategy is recommended for administrators and teachers to increase the physical activity of children during recess. Analizar si una intervención basada en el juego libre con material autoconstruido aumenta el nivel de actividad física de los escolares durante el recreo. Participaron 166 niños de tercero a sexto de educación primaria, de entre nueve y 12 años de edad (media = 10,64; DE = 1,13). Se realizó un diseño experimental con medidas pretest y postest, y un

Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response.

PubMed

Spolarics, Zoltan; Peña, Geber; Qin, Yong; Donnelly, Robert J; Livingston, David H

2017-01-01

Females have a longer lifespan and better general health than males. Considerable number of studies also demonstrated that, after trauma and sepsis, females present better outcomes as compared to males indicating sex-related differences in the innate immune response. The current notion is that differences in the immuno-modulatory effects of sex hormones are the underlying causative mechanism. However, the field remains controversial and the exclusive role of sex hormones has been challenged. Here, we propose that polymorphic X-linked immune competent genes, which are abundant in the population are important players in sex-based immuno-modulation and play a key role in causing sex-related outcome differences following trauma or sepsis. We describe the differences in X chromosome (ChrX) regulation between males and females and its consequences in the context of common X-linked polymorphisms at the individual as well as population level. We also discuss the potential pathophysiological and immune-modulatory aspects of ChrX cellular mosaicism, which is unique to females and how this may contribute to sex-biased immune-modulation. The potential confounding effects of ChrX skewing of cell progenitors at the bone marrow is also presented together with aspects of acute trauma-induced de novo ChrX skewing at the periphery. In support of the hypothesis, novel observations indicating ChrX skewing in a female trauma cohort as well as case studies depicting the temporal relationship between trauma-induced cellular skewing and the clinical course are also described. Finally, we list and discuss a selected set of polymorphic X-linked genes, which are frequent in the population and have key regulatory or metabolic functions in the innate immune response and, therefore, are primary candidates for mediating sex-biased immune responses. We conclude that sex-related differences in a variety of disease processes including the innate inflammatory response to injury and infection may be

The dorso-lateral recess of the hypothalamic ventricle in neonatal rats.

PubMed

Menéndez, A; Alvarez-Uría, M

1987-10-01

Light and electron microscopy of the hypothalamic ventricle in neonatal rats demonstrate morphological specializations of the ventricular wall at the level of the premammillary region of the third ventricle. The morphological features are: (1) A ventricular recess that we have called the "hypothalamic dorso-lateral recess" (HDR). (2) The presence of intraventricular capillaries near the dorso-lateral recess. (3) The HDR possessing a specialized ependymal lining; this consists of non-ciliated cells with short microvilli and bleb-like processes. (4) The existence of cerebrospinal fluid-contacting neurons within the HDR. (5) The presence of numerous phagocytic supraependymal cells. The HDR is not found in adult rats. This indicates that the dorso-lateral recess may play a physiological role during development.

Factors Associated with School Lunch Consumption: Reverse Recess and School "Brunch".

PubMed

Chapman, Leah Elizabeth; Cohen, Juliana; Canterberry, Melanie; Carton, Thomas W

2017-09-01

While school foods have become healthier under the Healthy, Hunger Free Kids Act, research suggests there is still substantial food waste in cafeterias. It is therefore necessary to study factors that can impact food consumption, including holding recess before lunch ("reverse recess") and starting lunch periods very early or very late. This study examined the association between the timing of recess (pre-lunch vs post-lunch recess), the timing of the lunch period, and food consumed by students at lunch. We conducted a secondary data analysis from a repeated cross-sectional design. An 8-week plate waste study examining 20,183 trays of food was conducted in New Orleans, LA, in 2014. The study involved 1,036 fourth- and fifth-grade students from eight public schools. We measured percent of entrées, fruit, vegetables, and milk consumed by students at lunch. We used mixed-model analyses, controlling for student sex, grade, and the timing of the lunch period, and examined the association between reverse recess and student lunch consumption. Mixed-model analyses controlling for student sex, grade, and recess status examined whether the timing of the lunch period was associated with student lunch consumption. On average, students with reverse recess consumed 5.1% more of their fruit than students with post-lunch recess (P=0.009), but there were no significant differences in entrées, vegetables, or milk intake. Compared to students with "midday" lunch periods, on average students with "early" lunch periods consumed 5.8% less of their entrées (P<0.001) and 4.5% less of their milk (P=0.047). Students with "late" lunch periods consumed 13.8% less of their entrées (P<0.001) and 15.9% less of their fruit (P<0.001). Reverse recess was associated with increased fruit consumption. "Early" lunch periods were associated with decreased entrée and milk consumption, and "late" lunch periods were associated with decreased entrée and fruit consumption. Additional research is

Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia.

PubMed

Wang, L; Du, L; Ecarot, B

1999-04-01

Mutations in the PHEX gene (phosphate-regulating gene with homology to endopeptidases on the X-chromosome) are responsible for X-linked hypophosphatemia (HYP). We previously reported the full-length coding sequence of murine Phex cDNA and provided evidence of Phex expression in bone and tooth. Here, we report the cloning of the entire 3.5-kb 3'UTR of the Phex gene, yielding a total of 6248 bp for the Phex transcript. Southern blot and RT-PCR analyses revealed that the 3' end of the coding sequence and the 3'UTR of the Phex gene, spanning exons 16 to 22, are deleted in Hyp, the mouse model for HYP. Northern blot analysis of bone revealed lack of expression of stable Phex mRNA from the mutant allele and expression of Phex transcripts from the wild-type allele in Hyp heterozygous females. Expression of the Phex protein in heterozygotes was confirmed by Western analysis with antibodies raised against a COOH-terminal peptide of the mouse Phex protein. Taken together, these results indicate that the dominant pattern of Hyp inheritance in mice is due to Phex haploinsufficiency.

Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

PubMed Central

Hashimoto, Masayoshi; Neriya, Yutaro; Yamaji, Yasuyuki; Namba, Shigetou

2016-01-01

The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF) 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species. PMID:27833593

Using Quantile Regression to Examine Health Care Expenditures during the Great Recession

PubMed Central

Chen, Jie; Vargas-Bustamante, Arturo; Mortensen, Karoline; Thomas, Stephen B

2014-01-01

Objective To examine the association between the Great Recession of 2007–2009 and health care expenditures along the health care spending distribution, with a focus on racial/ethnic disparities. Data Sources/Study Setting Secondary data analyses of the Medical Expenditure Panel Survey (2005–2006 and 2008–2009). Study Design Quantile multivariate regressions are employed to measure the different associations between the economic recession of 2007–2009 and health care spending. Race/ethnicity and interaction terms between race/ethnicity and a recession indicator are controlled to examine whether minorities encountered disproportionately lower health spending during the economic recession. Principal Findings The Great Recession was significantly associated with reductions in health care expenditures at the 10th–50th percentiles of the distribution, but not at the 75th–90th percentiles. Racial and ethnic disparities were more substantial at the lower end of the health expenditure distribution; however, on average the reduction in expenditures was similar for all race/ethnic groups. The Great Recession was also positively associated with spending on emergency department visits. Conclusion This study shows that the relationship between the Great Recession and health care spending varied along the health expenditure distribution. More variability was observed in the lower end of the health spending distribution compared to the higher end. PMID:24134797

Inflammatory profile in X-linked adrenoleukodystrophy patients: Understanding disease progression.

PubMed

Marchetti, Desirèe Padilha; Donida, Bruna; Jacques, Carlos Eduardo; Deon, Marion; Hauschild, Tatiane Cristina; Koehler-Santos, Patricia; de Moura Coelho, Daniella; Coitinho, Adriana Simon; Jardim, Laura Bannach; Vargas, Carmen Regla

2018-01-01

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease characterized by progressive inflammatory demyelization in the brain, adrenal insufficiency, and an abnormal accumulation of very long chain fatty acids (VLCFA) in tissue and body fluids. Considering that inflammation might be involved in pathophysiology of X-ALD, we aimed to investigate pro- and anti-inflammatory cytokines in plasma from three different male phenotypes (CCER, AMN, and asymptomatic individuals). Our results showed that asymptomatic patients presented increased levels of pro-inflammatory cytokines IL-1β, IL-2, IL-8, and TNF-α and the last one was also higher in AMN phenotype. Besides, asymptomatic patients presented higher levels of anti-inflammatory cytokines IL-4 and IL-10. AMN patients presented higher levels of IL-2, IL-5, and IL-4. We might hypothesize that inflammation in X-ALD is related to plasmatic VLCFA concentration, since there were positive correlations between C26:0 plasmatic levels and pro-inflammatory cytokines in asymptomatic and AMN patients and negative correlation between anti-inflammatory cytokine and C24:0/C22:0 ratio in AMN patients. The present work yields experimental evidence that there is an inflammatory imbalance associated Th1, (IL-2, IL-6, and IFN-γ), Th2 (IL-4 and IL-10), and macrophages response (TNF-α and IL-1β) in the periphery of asymptomatic and AMN patients, and there is correlation between VLCFA plasmatic levels and inflammatory mediators in X-ALD. Furthermore, we might also speculate that the increase of plasmatic cytokines in asymptomatic patients could be considered an early biomarker of brain damage and maybe also a predictor of disease progression. © 2017 Wiley Periodicals, Inc.

Imprinted and X-linked non-coding RNAs as potential regulators of human placental function

PubMed Central

Buckberry, Sam; Bianco-Miotto, Tina; Roberts, Claire T

2014-01-01

Pregnancy outcome is inextricably linked to placental development, which is strictly controlled temporally and spatially through mechanisms that are only partially understood. However, increasing evidence suggests non-coding RNAs (ncRNAs) direct and regulate a considerable number of biological processes and therefore may constitute a previously hidden layer of regulatory information in the placenta. Many ncRNAs, including both microRNAs and long non-coding transcripts, show almost exclusive or predominant expression in the placenta compared with other somatic tissues and display altered expression patterns in placentas from complicated pregnancies. In this review, we explore the results of recent genome-scale and single gene expression studies using human placental tissue, but include studies in the mouse where human data are lacking. Our review focuses on the ncRNAs epigenetically regulated through genomic imprinting or X-chromosome inactivation and includes recent evidence surrounding the H19 lincRNA, the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with pregnancy complications. PMID:24081302

Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia.

PubMed

Gofshteyn, Jacqueline; Cárdenas, Ana María; Bearden, David

2016-11-01

Enterovirus may result in a devastating chronic encephalitis in immunocompromised patients, particularly in patients with X-linked agammaglobulinemia. Prognosis for patients with chronic enterovirus encephalitis is poor, almost invariably resulting in mortality without specific treatment. There are currently no approved antiviral agents for enterovirus, but the antidepressant drug fluoxetine has been identified through library-based compound screening as a potential anti-enteroviral agent in vitro. However, use of fluoxetine has not previously been studied in humans with enteroviral disease. A five year old boy with X-linked agammaglobulinemia presented with progressive neurological deterioration and was found to have chronic enterovirus encephalitis by brain biopsy. He failed to respond to standard treatment with high dose intravenous immunoglobulin, but showed stabilization and improvement following treatment with fluoxetine. This is the first report to describe the use of fluoxetine as a potential therapy for chronic enterovirus infection. Further investigation of fluoxetine as a treatment option for chronic enterovirus encephalitis is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy.

PubMed

Cartier, Nathalie; Hacein-Bey-Abina, Salima; Bartholomae, Cynthia C; Bougnères, Pierre; Schmidt, Manfred; Kalle, Christof Von; Fischer, Alain; Cavazzana-Calvo, Marina; Aubourg, Patrick

2012-01-01

X-linked adrenoleukodystrophy (X-ALD) is a severe genetic demyelinating disease caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. When performed at an early stage of the disease, allogeneic hematopoietic stem cell transplantation (HCT) can arrest the progression of cerebral demyelinating lesions. To overcome the limitations of allogeneic HCT, hematopoietic stem cell (HSC) gene therapy strategy aiming to perform autologous transplantation of lentivirally corrected cells was developed. We demonstrated the preclinical feasibility of HSC gene therapy for ALD based on the correction of CD34+ cells from X-ALD patients using an HIV1-derived lentiviral vector. These results prompted us to initiate an HSC gene therapy trial in two X-ALD patients who had developed progressive cerebral demyelination, were candidates for allogeneic HCT, but had no HLA-matched donors or cord blood. Autologous CD34+ cells were purified from the peripheral blood after G-CSF stimulation, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1 cDNA, and then reinfused into the patients after they had received full myeloablative conditioning. Over 3 years of follow-up, the hematopoiesis remained polyclonal in the two patients treated with 7-14% of granulocytes, monocytes, and T and B lymphocytes expressing the lentivirally encoded ALD protein. There was no evidence of clonal dominance or skewing based on the retrieval of lentiviral insertion repertoire in different hematopoietic lineages by deep sequencing. Cerebral demyelination was arrested 14 and 16months, respectively, in the two treated patients, without further progression up to the last follow-up, a clinical outcome that is comparable to that observed after allogeneic HCT. Longer follow-up of these two treated patients and HSC gene therapy performed in additional ALD patients are however needed to evaluate the safety and efficacy of lentiviral HSC

Association of Trauma from Occlusion with Localized Gingival Recession in Mandibular Anterior Teeth

PubMed Central

Kundapur, Pratibha Panduranga; Bhat, Khandige Mahalinga; Bhat, Giliyar Subraya

2009-01-01

Background: There have been passing references in history that excessive occlusal forces might be a causative factor in gingival recession. The purpose of the present cross-sectional study was to explore the role of trauma from occlusion on the development of gingival recession. Methods: Three hundred patients reporting to the department of Periodontics were screened for the presence of gingival recession in the lower incisors. A single trained examiner carried out clinical examination for signs of trauma from occlusion, such as fremitus test, presence of wear facets and mobility. The data were analyzed by chi square test. Results: No statistically significant relationship was observed between the presence of a positive fremitus and wear facets with gingival recession. However, a significant association was observed between patients who experienced mobility and gingival recession. Conclusion: There does appear to be a relationship between fremitus and tooth wear with gingival recession based on the results of the present study, though not conclusive. However, the sign of tooth mobility, which is a feature of trauma from occlusion, appeared to be a predictor of positive association with gingival recession. PMID:21528034

Genetics Home Reference: Emery-Dreifuss muscular dystrophy

MedlinePlus

... the two sex chromosomes in each cell. In males (who have only one X chromosome ), one altered ... each cell is sufficient to cause the condition. Males are affected by X-linked recessive disorders much ...

Genetics Home Reference: osteopetrosis

MedlinePlus

... is one of the two sex chromosomes . In males (who have only one X chromosome ), one altered ... will have two altered copies of this gene, males are affected by X-linked recessive disorders much ...

Genetics Home Reference: hypohidrotic ectodermal dysplasia

MedlinePlus

... chromosome , one of the two sex chromosomes . In males (who have only one X chromosome ), one altered ... copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much ...

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

PubMed Central

Madrigal, I; Rodríguez-Revenga, L; Armengol, L; González, E; Rodriguez, B; Badenas, C; Sánchez, A; Martínez, F; Guitart, M; Fernández, I; Arranz, JA; Tejada, MI; Pérez-Jurado, LA; Estivill, X; Milà, M

2007-01-01

Background Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients. PMID:18047645

Simpson-Golabi-Behmel syndrome: an X-linked encephalo-tropho-schisis syndrome. 1988.

PubMed

Neri, G; Marini, R; Cappa, M; Borrelli, P; Opitz, J M

2013-11-01

The following paper by Professor GiovanniNeri and colleagues was originally published in 1988, American Journal of Medical Genetics 30:287–299. This paper represented a seminal work at the time of publication as it not only reported a new family with a disorder that had been called the “gigantism-dysplasia syndrome”, but also suggested naming the condition the Simpson-Golabi-Behmel syndrome. This eponym has clearly stood “the test of time”, and that designation is now widely accepted. This paper is graciously republished by Wiley-Blackwell in the Special Festschrift issue honoring Professor Neri. We report on another family with the so-called "gigantism-dysplasia syndrome", an X-linked condition characterized by pre-and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi-Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al. in 1975 and by Behmel et al. in 1984. Therefore, we suggest that this entity be designated the Simpson-Golabi-Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X-linked encephalo-tropho-schisis syndrome. © 2013 Wiley Periodicals, Inc.

Soil thaw effects on river discharge recessions of a subarctic catchment

NASA Astrophysics Data System (ADS)

Ploum, Stefan; Lyon, Steve; Teuling, Ryan; van der Velde, Ype

2017-04-01

Thawing permafrost in circumpolar regions is likely to change subsurface hydrology. In high latitude areas continuous permafrost is expected to partially thaw leading to sporadic permafrost with deeper groundwater flow paths. Moreover, freeze-thaw cycles of the shallow subsurface are likely to increase. River discharge recession analysis can be particularly useful to understand the hydrological effects of a thawing Arctic. Here we examine river discharge recessions of the Abiskojokka, a 560 km2 watershed with sporadic permafrost, using a river discharge record of 30 years (1985 - 2015). Snow observation records were used to separate river recessions in snowmelt and snowfree periods. We found significant differences between recessions during the snowmelt and snowfree seasons. During the snowmelt, recessions were close to linear (b=1.11), while during the snowfree period, recessions were more non-linear (b=1.54). Typically, non-linearity has been found to increase with discharge magnitude, while we observed the opposite (snowfree periods tend to have lower discharges than the snowmelt periods). We explain these contrasting results by hypothesizing that increased connectivity (increasing magnitude and number of water flow paths) between groundwater and stream leads to higher non-linearity. In temperate catchments without frozen soils, connectivity tends to increase with increasing discharge. In contrast, in Arctic systems, where soils are frozen, connectivity between groundwater and stream is limited. Therefore, thawing of frozen soils is expected to increase connectivity and thus non-linearity of river discharges. We tested this hypothesis with a detailed analysis of all spring flood recessions. Years with cold soil temperatures (b=1.08) and years with a below median snowpack depth were found to have progressively linear slopes (b=1.08 and 1.01 respectively). On the other hand, years with warm soil conditions show increasingly non-linear recessions (b=1.67). Although

Connexin mutations in X-linked Charcot-Marie-Tooth disease

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

Bergoffen, J.; Scherer, S.S.; Wang, S.

1993-12-24

X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry techniques, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32more » plays an important role in peripheral nerve.« less

Autofluorescence Imaging and Spectral-Domain Optical Coherence Tomography in Incomplete Congenital Stationary Night Blindness and Comparison with Retinitis Pigmentosa

PubMed Central

CHEN, ROYCE W. S.; GREENBERG, JONATHAN P.; LAZOW, MARGOT A.; RAMACHANDRAN, RITHU; LIMA, LUIZ H.; HWANG, JOHN C.; SCHUBERT, CARL; BRAUNSTEIN, ALEXANDRA; ALLIKMETS, RANDO; TSANG, STEPHEN H.

2015-01-01

PURPOSE To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. DESIGN Prospective cross-sectional study. METHODS Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. RESULTS Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive

Molecular population genetics of X-linked genes in Drosophila pseudoobscura.

PubMed Central

Kovacevic, M; Schaeffer, S W

2000-01-01

This article presents a nucleotide sequence analysis of 500 bp determined in each of five X-linked genes, runt, sisterlessA, period, esterase 5, and Heat-shock protein 83, in 40 Drosophila pseudoobscura strains collected from two populations. Estimates of the neutral migration parameter for the five loci show that gene flow among D. pseudoobscura populations is sufficient to homogenize inversion frequencies across the range of the species. Nucleotide diversity at each locus fails to reject a neutral model of molecular evolution. The sample of 40 chromosomes included six Sex-ratio inversions, a series of three nonoverlapping inversions that are associated with a strong meiotic drive phenotype. The selection driven by the Sex-ratio meiotic drive element has not fixed variation across the X chromosome of D. pseudoobscura because, while significant linkage disequilibrium was observed within the sisterlessA, period, and esterase 5 genes, we did not find evidence for nonrandom association among loci. The Sex-ratio chromosome was estimated to be 25,000 years old based on the decomposition of linkage disequilibrium between esterase 5 and Heat-shock protein 83 or 1 million years old based on the net divergence of esterase 5 between Standard and Sex-ratio chromosomes. Genetic diversity was depressed within esterase 5 within Sex-ratio chromosomes, while the four other genes failed to show a reduction in heterozygosity in the Sex-ratio background. The reduced heterogeneity in esterase 5 is due either to its location near one of the Sex-ratio inversion breakpoints or that it is closely linked to a gene or genes responsible for the Sex-ratio meiotic drive system. PMID:10978282

Aetiology and Severity of Gingival Recession in an Adult Population Sample in Greece

PubMed Central

Chrysanthakopoulos, Nikolaos Andreas

2011-01-01

Background: Gingival recession is the most common and undesirable condition of the gingiva. The aim of study was to investigate the aetiology and severity of gingival recession in a Greek adult population sample. Methods: The study was performed on 165 males and 179 females, 18-68 years old who sought dental treatment in a private dental practice and showed gingival recession. All subjects were clinically examined and answered questions regarding their oral hygiene habits such as the type of toothbrush, frequency of brushing and method of brushing. The association between gingival recession and the following parameters was assessed: plaque score, gingival score and tooth position. Statistical analysis of the results was accomplished using chi-square test (α = 0.05). Results: The majority (79.4%) of the patients showed grade I gingival recession and 15.3% showed grade II gingival recession. The maxillary 1st and 2nd molars (35.3%) and the mandibular 1st and 2nd molars (28.7%) were the teeth most frequently affected by root surface exposure. Patients with sub-gingival calculus, bacterial plaque and gingival inflammation (P <60; 0.05), malpositioned teeth (P <60; 0.001), horizontal brushing method, medium type of toothbrush (P <60; 0.001) and brushing once daily (P <60; 0.001) appeared to be the most common precipitating aetiological factor for gingival recession. Conclusion: According to the results of the present study, gingival recession was the result of more than one factor acting together. Horizontal brushing method, usage of medium type toothbrush and tooth brushing once daily were found to be more associated with gingival recession. PMID:22013465

1 Tb/s x km multimode fiber link combining WDM transmission and low-linewidth lasers.

PubMed

Gasulla, I; Capmany, J

2008-05-26

We have successfully demonstrated an error-free transmission of 10 x 20 Gb/s 200 GHz-spaced ITU channels through a 5 km link of 62.5-microm core-diameter graded-index multimode silica fiber. The overall figure corresponds to an aggregate bit rate per length product of 1 Tb/s x km, the highest value ever reported to our knowledge. Successful transmission is achieved by a combination of low-linewidth DFB lasers and the central launch technique.

Giving Children a Voice: Exploring Qualitative Perspectives on Factors Influencing Recess Physical Activity

ERIC Educational Resources Information Center

Pawlowski, Charlotte Skau; Schipperijn, Jasper; Tjørnhøj-Thomsen, Tine; Troelsen, Jens

2018-01-01

Facilitators and barriers to recess physical activity are not well understood. To date, research on recess physical activity has predominantly focused on quantitative measures typically focusing on a narrow set of predefined factors, often constructed by adults. To really understand the factors affecting recess physical activity it is crucial to…

Sex-linked dominant

MedlinePlus

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

Space, body, time and relationship experiences of recess physical activity: a qualitative case study among the least physical active schoolchildren.

PubMed

Pawlowski, Charlotte Skau; Andersen, Henriette Bondo; Tjørnhøj-Thomsen, Tine; Troelsen, Jens; Schipperijn, Jasper

2016-01-06

Increasing recess physical activity has been the aim of several interventions, as this setting can provide numerous physical activity opportunities. However, it is unclear if these interventions are equally effective for all children, or if they only appeal to children who are already physically active. This study was conducted to explore the least physically active children's "lived experiences" within four existential lifeworlds linked to physical activity during recess: space, body, time, and relations. The study builds on ethnographic fieldwork in a public school in Denmark using a combination of participatory photo interviews and participant observation. Thirty-seven grade five children (11-12 years old) were grouped in quartiles based on their objectively measured daily physical activity levels. Eight children in the lowest activity quartile (six girls) were selected to participate in the study. To avoid stigmatising and to make generalisations more reliable we further recruited eight children from the two highest activity quartiles (four girls) to participate. An analysis of the least physically active children's "lived experiences" of space, body, time and relations revealed several key factors influencing their recess physical activity: perceived classroom safety, indoor cosiness, lack of attractive outdoor facilities, bodily dissatisfaction, bodily complaints, tiredness, feeling bored, and peer influence. We found that the four existential lifeworlds provided an in-depth understanding of the least physically active children's "lived experiences" of recess physical activity. Our findings imply that specific intervention strategies might be needed to increase the least physically active children's physical activity level. For example, rethinking the classroom as a space for physical activity, designing schoolyards with smaller secluded spaces and varied facilities, improving children's self-esteem and body image, e.g., during physical education, and

Real-Time X-ray Radiography Diagnostics of Components in Solid Rocket Motors

NASA Technical Reports Server (NTRS)

Cortopassi, A. C.; Martin, H. T.; Boyer, E.; Kuo, K. K.

2012-01-01

the recession of the solid propellant grain can drastically alter the flow-field and effect the recession of internal insulation and nozzle materials. Simultaneous measurement of the overall erosion rate, the development of the char layer, and the recession of the char-virgin interface during the motor operation can be rather difficult. While invasive techniques have been used with limited success, they have serious drawbacks. Break wires or make wire sensors can be installed into a sufficient number of locations in the charring material from which a time history of the charring surface can be deduced. These sensors fundamentally alter the local structure of the material in which they are imbedded. Also, the location of these sensors within the material is not known precisely without the use of an X-ray. To determine instantaneous recession rates, real-time X-ray radiography (X-ray RTR) has been utilized in several SRM experiments at PSU. The X-ray RTR system discussed in this paper consists of an X-ray source, X-ray image intensifier, and CCD camera connected to a capture computer. The system has been used to examine the ablation process of internal insulation as well as nozzle material erosion in a subscale SRM. The X-ray source is rated to 320 kV at 10 mA and has both a large (5.5 mm) and small (3.0 mm) focal spot. The lead-lined cesium iodide X-ray image intensifier produces an image which is captured by a CCD camera with a 1,000 x 1,000 pixel resolution. To produce accurate imagery of the object of interest, the alignment of the X-ray source to the X-ray image intensifier is crucial. The image sequences captured during the operation of an SRM are then processed to enhance the quality of the images. This procedure allows for computer software to extract data on the total erosion rate and the char layer thickness. Figure 1 Error! Reference source not found.shows a sequence of images captured during the operation the subscale SRM with the X-ray RTR system. The X

Reliability and validity of a school recess physical activity recall in Spanish youth.

PubMed

Martínez-Gómez, David; Calabro, M Andres; Welk, Gregory J; Marcos, Ascension; Veiga, Oscar L

2010-05-01

Recess is a frequent target in school-based physical activity (PA) promotion research but there are challenges in assessing PA during this time period. The purpose of this study was to evaluate the reliability and validity of a recess PA recall (RPAR) instrument designed to assess total PA and time spent in moderate to vigorous PA (MVPA) during recess. One hundred twenty-five 7th and 8th-grade students (59 females), age 12-14 years, participated in the study. Activity levels were objectively monitored on Mondays using different activity monitors (Yamax Digiwalker, Biotrainer and ActiGraph). On Tuesdays, 2 RPAR self-reports were administered within 1-hr. Test-retest reliability showed ICC = 0.87 and 0.88 for total PA and time spent in MVPA, respectively. The RPAR was correlated against Yamax (r = .35), Biotrainer (r = .40 and 0.54) and ActiGraph (r = .42) to assess total PA during recess. The RPAR was also correlated against ActiGraph (r = .54) to assess time spent in MVPA during recess. Mean difference between the RPAR and ActiGraph to assess time spent in MVPA during recess was no significant (2.15 +/- 3.67 min, p = .313). The RPAR showed an adequate reliability and a reasonable validity for assessing PA during the school recess in youth.

Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation.

PubMed Central

Stevenson, R E; Häne, B; Arena, J F; May, M; Lawrence, L; Lubs, H A; Schwartz, C E

1997-01-01

A syndrome with distinctive facies, poor muscle tone, absent deep tendon reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild-moderate mental retardation has occurred in four males in two generations of a white family of European ancestry. The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi. At birth and at maturity, growth (head circumference, height, weight) of affected males is comparable to or greater than unaffected male sibs. Moderate impairment of cognitive function was documented (IQ scores between 40-51). Carriers show no heterozygote manifestations. This X linked condition appears to be different from other syndromes with mental retardation, although there are certain similarities with the alpha thalassaemia-mental retardation syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in Xq13 and Xq21 respectively. Images PMID:9192265

Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation.

PubMed

Stevenson, R E; Häne, B; Arena, J F; May, M; Lawrence, L; Lubs, H A; Schwartz, C E

1997-06-01

A syndrome with distinctive facies, poor muscle tone, absent deep tendon reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild-moderate mental retardation has occurred in four males in two generations of a white family of European ancestry. The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi. At birth and at maturity, growth (head circumference, height, weight) of affected males is comparable to or greater than unaffected male sibs. Moderate impairment of cognitive function was documented (IQ scores between 40-51). Carriers show no heterozygote manifestations. This X linked condition appears to be different from other syndromes with mental retardation, although there are certain similarities with the alpha thalassaemia-mental retardation syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in Xq13 and Xq21 respectively.

Systematic review of autosomal recessive ataxias and proposal for a classification.

PubMed

Beaudin, Marie; Klein, Christopher J; Rouleau, Guy A; Dupré, Nicolas

2017-01-01

The classification of autosomal recessive ataxias represents a significant challenge because of high genetic heterogeneity and complex phenotypes. We conducted a comprehensive systematic review of the literature to examine all recessive ataxias in order to propose a new classification and properly circumscribe this field as new technologies are emerging for comprehensive targeted gene testing. We searched Pubmed and Embase to identify original articles on recessive forms of ataxia in humans for which a causative gene had been identified. Reference lists and public databases, including OMIM and GeneReviews, were also reviewed. We evaluated the clinical descriptions to determine if ataxia was a core feature of the phenotype and assessed the available evidence on the genotype-phenotype association. Included disorders were classified as primary recessive ataxias, as other complex movement or multisystem disorders with prominent ataxia, or as disorders that may occasionally present with ataxia. After removal of duplicates, 2354 references were reviewed and assessed for inclusion. A total of 130 articles were completely reviewed and included in this qualitative analysis. The proposed new list of autosomal recessive ataxias includes 45 gene-defined disorders for which ataxia is a core presenting feature. We propose a clinical algorithm based on the associated symptoms. We present a new classification for autosomal recessive ataxias that brings awareness to their complex phenotypes while providing a unified categorization of this group of disorders. This review should assist in the development of a consensus nomenclature useful in both clinical and research applications.

Dysregulation of X-Linked Gene Expression in Klinefelter’s Syndrome and Association With Verbal Cognition

PubMed Central

Vawter, Marquis P.; Harvey, Philip D.; DeLisi, Lynn E.

2007-01-01

Klinefelter’s Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini–Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression–cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = −0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition–gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. PMID:17347996

X-linked hypophosphataemia: a homologous disorder in humans and mice.

PubMed

Tenenhouse, H S

1999-02-01

X-linked hypophosphatemia is an inherited disorder of phosphate (Pi) homeostasis characterized by growth retardation, rickets and osteomalacia, hypophosphataemia, and aberrant renal Pi reabsorption and vitamin D metabolism. Studies in murine Hyp and Gy homologues have identified a specific defect in Na+-Pi cotransport at the brush border membrane, abnormal regulation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) synthesis and degradation, and an intrinsic defect in bone mineralization. The mutant gene has been identified in XLH patients, by positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to signify a PHosphate-regulating gene with homology to Endopeptidases on the X chromosome. PHEX/Phex is expressed in bones and teeth but not in kidney and efforts are under way to elucidate how loss of PHEX/Phex function elicits the mutant phenotype. Based on its homology to endopeptidases, it is postulated that PHEX/Phex is involved in the activation or inactivation of a peptide hormone(s) which plays a key role in the regulation of bone mineralization, renal Pi handling and vitamin D metabolism.

Role of ALDP (ABCD1) and Mitochondria in X-Linked Adrenoleukodystrophy

PubMed Central

McGuinness, M. C.; Lu, J.-F.; Zhang, H.-P.; Dong, G.-X.; Heinzer, A. K.; Watkins, P. A.; Powers, J.; Smith, K. D.

2003-01-01

Peroxisomal disorders have been associated with malfunction of peroxisomal metabolic pathways, but the pathogenesis of these disorders is largely unknown. X-linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very-long-chain fatty acids (VLCFA; C>22:0) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity. Previously, our laboratory and others have reported elevated VLCFA levels and reduced peroxisomal VLCFA β-oxidation in human and mouse X-ALD fibroblasts. In this study, we found normal levels of peroxisomal VLCFA β-oxidation in tissues from ALD mice with elevated VLCFA levels. Treatment of ALD mice with pharmacological agents resulted in decreased VLCFA levels without a change in VLCFA β-oxidation activity. These data indicate that ALDP does not determine the rate of VLCFA β-oxidation and that VLCFA levels are not determined by the rate of VLCFA β-oxidation. The rate of peroxisomal VLCFA β-oxidation in human and mouse fibroblasts in vitro is affected by the rate of mitochondrial long-chain fatty acid β-oxidation. We hypothesize that ALDP facilitates the interaction between peroxisomes and mitochondria, resulting, when ALDP is deficient in X-ALD, in increased VLCFA accumulation despite normal peroxisomal VLCFA β-oxidation in ALD mouse tissues. In support of this hypothesis, mitochondrial structural abnormalities were observed in adrenal cortical cells of ALD mice. PMID:12509471

Rocky coast processes: with special reference to the recession of soft rock cliffs

PubMed Central

SUNAMURA, Tsuguo

2015-01-01

Substantial progress in research on the recession of coastal cliffs composed of soft materials has been made in recent years and data with higher accuracy have been accumulated. This paper provides the state of the art review in the recession studies and highlights two new findings obtained from the reanalysis of existing data. The review topics are: episodic and localized nature of cliff recession; the development of cliffline; the relationship between cliff height and recession rate; mechanisms of cliff toe erosion by waves; a fundamental equation for wave-induced toe erosion; factors controlling toe erosion; and slope instabilities and mass movements. The findings are presented on (1) the temporal change in cliffline recession mode and (2) the effect of beach sediment at the cliff base on the cliff erosion. PMID:26568322

Rocky coast processes: with special reference to the recession of soft rock cliffs.

PubMed

Sunamura, Tsuguo

2015-01-01

Substantial progress in research on the recession of coastal cliffs composed of soft materials has been made in recent years and data with higher accuracy have been accumulated. This paper provides the state of the art review in the recession studies and highlights two new findings obtained from the reanalysis of existing data. The review topics are: episodic and localized nature of cliff recession; the development of cliffline; the relationship between cliff height and recession rate; mechanisms of cliff toe erosion by waves; a fundamental equation for wave-induced toe erosion; factors controlling toe erosion; and slope instabilities and mass movements. The findings are presented on (1) the temporal change in cliffline recession mode and (2) the effect of beach sediment at the cliff base on the cliff erosion.

Precarious Slopes? The Great Recession, Federal Stimulus, and New Jersey Schools. Working Paper #02-12

ERIC Educational Resources Information Center

Chakrabarti, Rajashri; Sutherland, Sarah

2012-01-01

While sparse literature exists investigating the impact of the Great Recession on various sectors of the economy, there is virtually no research that studies the effect of the Great Recession, or past recessions, on schools. This paper starts to fill the void. Studying school funding during the recession is of paramount importance because schools…

Pyoderma gangrenosum-like ulcer in a patient with X-linked agammaglobulinemia: identification of Helicobacter bilis by mass spectrometry analysis.

PubMed

Murray, Patrick R; Jain, Ashish; Uzel, Gulbu; Ranken, Raymond; Ivy, Cristina; Blyn, Lawrence B; Ecker, David J; Sampath, Rangarajan; Lee, Chyi-Chia Richard; Turner, Maria L

2010-05-01

Pyoderma gangrenosum-like ulcers and cellulitis of the lower extremities associated with recurrent fevers in patients with X-linked (Bruton) agammaglobulinemia have been reported to be caused by Helicobacter bilis (formerly classified as Flexispira rappini and then Helicobacter strain flexispira taxon 8). Consistent themes in these reports are the difficulty in recovering this organism in blood and wound cultures and in maintaining isolates in vitro. We confirmed the presence of this organism in a patient's culture by using a novel application of gene amplification polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry. An adolescent boy with X-linked agammaglobulinemia presented with indurated plaques and a chronic leg ulcer whose origin was strongly suspected to be an H bilis organism. Histologic analysis demonstrated positive Warthin-Starry staining of curvilinear rods, which grew in culture but failed to grow when subcultured. They could not be identified by conventional techniques. A combination of gene amplification by polymerase chain reaction and electrospray ionization time-of-flight mass spectrometry confirmed the identity of this organism. This novel technology was useful in the identification of a difficult-to-grow Helicobacter organism, the cause of pyoderma gangrenosum-like leg ulcers in patients with X-linked agammaglobulinemia. Correct identification of this organism as the cause of pyoderma gangrenosum-like ulcers in patients with X-linked agammaglobulinemia is of great importance for the early initiation of appropriate and curative antibiotic therapy.

Recess Physical Activity Packs in Elementary Schools: A Qualitative Investigation

ERIC Educational Resources Information Center

Elliott, Steven; Combs, Sue; Boyce, Robert

2011-01-01

To supplement the present weekly allotment of 30 minutes of physical education, a school district in southeastern North Carolina identified recess time as part of the state mandated (HSP-S-000) 150 minutes of physical activity (PA) per week and have purchased fitness equipment (recess packs) for the children to use. Twelve participants were…

Genetics Home Reference: autosomal recessive hypotrichosis

MedlinePlus

... Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair ( hypotrichosis ) ... erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular ...

Algebra, Home Mortgages, and Recessions

ERIC Educational Resources Information Center

Mariner, Jean A. Miller; Miller, Richard A.

2009-01-01

The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

BTKbase, mutation database for X-linked agammaglobulinemia (XLA).

PubMed Central

Vihinen, M; Brandau, O; Brandén, L J; Kwan, S P; Lappalainen, I; Lester, T; Noordzij, J G; Ochs, H D; Ollila, J; Pienaar, S M; Riikonen, P; Saha, B K; Smith, C I

1998-01-01

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 463 mutation entries from 406 unrelated families showing 303 unique molecular events. In addition to mutations, the database also lists variants or polymorphisms. Each patient is given a unique patient identity number (PIN). Information is included regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites that code for arginine residues. The putative structural implications of all the missense mutations are given in the database. The improved version of the registry having a number of new features is available at http://www. helsinki.fi/science/signal/btkbase.html PMID:9399844

Evidence against an X-linked visual loss susceptibility locus in Leber hereditary optic neuropathy

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

Chalmers, R.M.; Davis, M.B.; Sweeney, M.G.

1996-07-01

Pedigree analysis of British families with Leber hereditary optic neuropathy (LHON) closely fits a model in which a pathogenic mtDNA mutation interacts with an X-linked visual loss susceptibility locus (VLSL). This model predicts that 60% of affected females will show marked skewing of X inactivation. Linkage analysis in British and Italian families with genetically proven LHON has excluded the presence of such a VLSL over 169 cM of the X chromosome both when all families were analyzed together and when only families with the bp 11778 mutation were studied. Further, there was no excess skewing of X inactivation in affectedmore » females. There was no evidence for close linkage to three markers in the pseudoautosomal region of the sex chromosomes. The mechanism of incomplete penetrance and male predominance in LHON remains unclear. 27 refs., 1 fig., 3 tabs.« less

X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients.

PubMed

Shahrizaila, Nortina; Samulong, Sarimah; Tey, Shelisa; Suan, Liaw Chiew; Meng, Lao Kah; Goh, Khean Jin; Ahmad-Annuar, Azlina

2014-02-01

Data regarding Charcot-Marie-Tooth disease is lacking in Southeast Asian populations. We investigated the frequency of the common genetic mutations in a multiethnic Malaysian cohort. Patients with features of Charcot-Marie-Tooth disease or hereditary liability to pressure palsies were investigated for PMP22 duplication, deletion, and point mutations and GJB1, MPZ, and MFN2 point mutations. Over a period of 3 years, we identified 25 index patients. A genetic diagnosis was reached in 60%. The most common were point mutations in GJB1, accounting for X-linked Charcot-Marie-Tooth disease (24% of the total patient population), followed by PMP22 duplication causing Charcot-Marie-Tooth disease type 1A (20%). We also discovered 2 novel GJB1 mutations, c.521C>T (Proline174Leucine) and c.220G>A (Valine74Methionine). X-linked Charcot-Marie-Tooth disease was found to predominate in our patient cohort. We also found a better phenotype/genotype correlation when applying a more recently recommended genetic approach to Charcot-Marie-Tooth disease. Copyright © 2013 Wiley Periodicals, Inc.

Physical Education and Recess Contributions to Sixth Graders' Physical Activity

ERIC Educational Resources Information Center

Gutierrez, Ashley A.; Williams, Skip M.; Coleman, Margaret M.; Garrahy, Deborah A.; Laurson, Kelly R.

2016-01-01

Background: The purpose of this study was twofold: (a) to examine the percentage of the daily threshold (12,000 steps) that physical education (PE) class and recess contribute to 6th grade students' overall daily physical activity (PA) and (b) to examine the relationships between gender, PA outside of school, BMI, and steps during both recess and…

High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

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

Zonana, J.; Jones, M.; Litt, M.

1992-11-01

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci couldmore » be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.« less

A Recess Evaluation with the Players: Taking Steps Toward Participatory Action Research

PubMed Central

Ren, Julie Yunyi

2010-01-01

This playground study conceptualizes recess as a time and space that belongs to students; their inclusion in this evaluation is a notable difference from other recess/playground research. The goal was to help elementary school students make the changes they felt were needed on their playground. After conducting structured observations and student and recess aide focus groups, a report was presented to all stakeholders, and recess changes were made. We seek to show how the process of being inclusive during the evaluation was not only valuable for determining problem definition and potential interventions, but was also necessary to determine the best methods for solutions, move toward second-order change, and to create a space to facilitate children’s participation and empowerment. PMID:20544270

Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course.

PubMed

Wanjin, Xing; Morigen, Morigen

2015-01-01

In Mendellian genetics, the dominance and recessiveness are used to describe the functional relationship between two alleles of one gene in a heterozygote. The allele which constitutes a phenotypical character over the other is named dominant and the one functionally masked is called recessive. The definitions thereby led to the creation of Mendel's laws on segregation and independent assortment and subsequent classic genetics. The discrimination of dominance and recessiveness originally is a requirement for Mendel's logical reasoning, but now it should be explained by cellular and molecular principles in the modern genetics. To answer the question raised by students of how the dominance and recessiveness are controlled, we reviewed the recent articles and tried to summarize the cellular and molecular basis of dominant and recessive inheritance. Clearly, understanding the essences of dominant and recessive inheritance requires us to know the dissimilarity of the alleles and their products (RNA and/or proteins), and the way of their function in cells. The alleles spatio-temporally play different roles on offering cells, tissues or organs with discernible phenotypes, namely dominant or recessive. Here, we discuss the changes of allele dominance and recessiveness at the cellular and molecular levels based on the variation of gene structure, gene regulation, function and types of gene products, in order to make students understand gene mutation and function more comprehensively and concretely.

SiC and Si3N4 Recession Due to SiO2 Scale Volatility Under Combustor Conditions

NASA Technical Reports Server (NTRS)

Smialek, James L.; Robinson, Raymond C.; Opila, Elizabeth J.; Fox, Dennis S.; Jacobson, Nathan S.

1999-01-01

Silicon carbide (SiC) and Si3N4 materials were tested in various turbine engine combustion environments chosen to represent either conventional fuel-lean or fuel-rich mixtures proposed for high-speed aircraft. Representative chemical vapor-deposited (CVD), sintered, and composite materials were evaluated by furnace and high-pressure burner rig exposures. Although protective SiO2 scales formed in all cases, the evidence presented supports a model based on paralinear growth kinetics (i.e., parabolic growth moderated simultaneously by linear volatilization). The volatility rate is dependent on temperature, moisture content, system pressure, and gas velocity. The burner tests were thus used to map SiO2 volatility (and SiC recession) over a range of temperatures, pressures, and velocities. The functional dependency of material recession (volatility) that emerged followed the form A[exp(-Q / RT)](P(sup x)v(sup y). These empirical relations were compared with rates predicted from the thermodynamics of volatile SiO and SiOxHy reaction products and a kinetic model of diffusion through a moving boundary layer. For typical combustion conditions, recession of 0.2 to 2 micrometers/hr is predicted at 1200 to 1400 C, far in excess of acceptable long-term limits.

Financial Strain and Mental Health Among Older Adults During the Great Recession.

PubMed

Wilkinson, Lindsay R

2016-07-01

The economic recession has garnered the interest of many scholars, with much attention being drawn to how the recession has affected labor force participation, household wealth, and even retirement decisions. Certainly, the Great Recession has influenced the financial well-being of older adults, but has it had discernible effects on mental health? This study draws on 5,366 respondents from the Health and Retirement Study (2006-2010) to examine objective and subjective measures of financial well-being in the period surrounding the Great Recession. Guided by cumulative inequality theory, this research investigates whether the economic downturn contributed to worsening anxiety and depressive symptoms over a 4-year period. Results from linear fixed effects models reveal that decreases in objective financial resources were associated with increased financial strain during the Great Recession. Unlike the objective indicators, however, financial strain was a strong and robust predictor of worsening mental health between 2006 and 2010. Building on prior research, this study elucidates the factors that shape financial strain and provides evidence that the Great Recession not only affected the financial well-being of older adults but also had adverse effects on mental health. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Periosteoplasty for covering gingival recessions: Clinical results

PubMed Central

Virnik, Sascha; Chiari, Friedrich Michael; Gaggl, Alexander

2009-01-01

This is a case series in which a new technique for the surgical treatment of periodontal recessions is presented along with the results of the first clinical trial. A new technique of periodontal flap surgery was performed on 30 patients with severe periodontal recessions of the upper or lower front teeth. Root and soft tissue scaling was carried out with an open approach, then the periosteum was incised and mobilized at the apical part of the mucoperiosteum flap to cover the defect before the mucoperiosteum was reattached and fixed by sutures. Sulcus bleeding, periodontal probing depths, attachment loss and the length of the attached gingiva of the affected teeth were recorded preoperatively and at 3, 6, and 12 months postoperatively. Every clinical parameter was improved by surgery. No sulcus bleeding was observed at any time during the postoperative follow-up. A mean reattachment of 5.5 mm was noticed 12 months postoperatively at a mean probing depth of 0.3 mm. The mean height of the attached gingiva was 0 mm before surgery, 2.3 mm at three and six months postoperatively, and 2.2 mm at 12 months. The periosteum eversion technique is suitable for the treatment of gingival recessions resulting in good gingival function and a clear improvement in aesthetics. PMID:23674900

Surgical Responses of Medial Rectus Muscle Recession in Thyroid Eye Disease-Related Esotropia

PubMed Central

Lyu, In Jeong; Lee, Ju-Yeun; Kong, Mingui; Park, Kyung-Ah; Oh, Sei Yeul

2016-01-01

We evaluate the surgical outcomes and surgical responses of medial rectus muscle (MR) recession patients with thyroid eye disease (TED)-related esotropia (ET). The surgical dose-response curves 1 week postoperatively and at the final visit were analyzed. Univariable and multivariable linear regression analyses were applied to investigate factors influencing surgical dose-response. A total of 43 patients with TED-related ET that underwent MR recession were included. The final success rate was 86.0% and the rate of undercorrection was 14.0%. The surgical dose-response curves of TED-related ET showed a gentle slope compared with those of standard surgical tables. In the univariable model, simultaneous vertical rectus muscle recession was the only significant factor influencing surgical dose-response of MR recession in TED-related ET (β = -0.397, P = 0.044). In a model adjusted for age, sex, type of surgery, and preoperative horizontal angle of deviation, simultaneous vertical rectus muscle recession showed marginal significance (β = -0.389, P = 0.064). The surgical dose-response curve of TED-related ET was unique. Simultaneous vertical rectus muscle recession was associated with increased surgical dose-response in TED-related ET. PMID:26796354

The Ecology of Student Retention: Undergraduate Students and the Great Recession

ERIC Educational Resources Information Center

Mendoza, Pilar; Malcolm, Zaria; Parish, Nancy

2015-01-01

This study investigated qualitatively how undergraduate students experienced the Great Recession at a flagship university in the South Eastern of United States and how this experience relates to their retention. Results indicate that the Great Recession has significantly impacted students' engagement and commitments. We argue that student…

Effects of student pairing and public review on physical activity during school recess.

PubMed

Zerger, Heather M; Miller, Bryon G; Valbuena, Diego; Miltenberger, Raymond G

2017-07-01

The purpose of this study was to evaluate the effects of student pairing and feedback during recess on children's step counts. During baseline, participants wore a sealed pedometer during recess. During intervention, we paired participants with higher step counts with participants with lower step counts. We encouraged teams to compete for the highest step count each day and provided feedback on their performance during each recess session. Results showed a large mean increase in step count from baseline to intervention. These results suggest that children's steps during recess can be increased with a simple and cost-effective intervention. © 2017 Society for the Experimental Analysis of Behavior.

Recession strategy: renewal efforts up, prospecting down.

PubMed

Groman, J E

1980-02-01

This computer pro offers insights into non-profit strategy during a recession. Renewals, prospecting, basics, visibility and markedting are keywords to plan a successful route through recessionary periods.

Physical Activity During Recess Outdoors and Indoors Among Urban Public School Students, St. Louis, Missouri, 2010–2011

PubMed Central

Tran, Irene; Clark, B. Ruth

2013-01-01

We measured the quantity and intensity of physical activity in 106 urban public school students during recess outdoors, recess indoors in the gym, and recess indoors in the classroom. Students in grades 2 through 5 wore accelerometer pedometers for an average of 6.2 (standard deviation [SD], 1.4) recess periods over 8 weeks; a subsample of 26 also wore heart rate monitors. We determined, on the basis of 655 recess observations, that outdoor recess enabled more total steps per recess period (P < .0001), more steps in moderate-to-vigorous physical activity (P < .0001), and higher heart rates than recess in the gym or classroom. To maximize physical activity quantity and intensity, school policies should promote outdoor recess. PMID:24262028

Synthesis of streamflow recession curves in dry environments

NASA Astrophysics Data System (ADS)

Arciniega, Saul; Breña-Naranjo, Agustín; Pedrozo-Acuña, Adrían

2015-04-01

The elucidation and predictability of hydrological systems can largely benefit by extracting observed patterns in processes, data and models. Such type of research framework in hydrology, also known as synthesis has gained significant attention over the last decade. For instance, hydrological synthesis implies that the identification of patterns in catchment behavior can enhance the extrapolation of hydrological signatures over large spatial and temporal scales. Hydrological signatures during dry periods such as streamflow recession curves (SRC) are of special interest in regions coping with water scarcity. Indeed, the study of SRCs from observed hydrographs allows to extract information about the storage-discharge relationship of a specific catchment and some of their groundwater hydraulic properties. This work aims at performing a synthesis work of SRCs in semi-arid & arid environments across Northern Mexico. Our dataset consisted in observed daily SRCs in 63 catchments with minima human interferences. Three streamflow recession extraction methods (Vogel, Brutsaert and Aksoy-Wittenberg) along with four recession models (Maillet, Boussinesq, Coutagne y Wittenberg) and three parameter estimation techniques (regressions, lower envelope y data binning) were used to determine the combination among different possible methods, processes and models that better describes SRCs in our study sites. Our results show that the extraction method proposed by Aksoy-Wittenberg along with Coutagne's nonlinear recession model provides a better approximation of SRCs across Northern Mexico, whereas regression was found to be the most adequate parameter estimation method. This study suggests that hydrological synthesis turned out to be an useful framework to identify similar patterns and model parameters during dry periods across Mexico's water-limited environments.

Psychological predictors of children' s recess physical activity motivation and behavior.

PubMed

Stellino, Megan Babkes; Sinclair, Christina D

2013-06-01

This study explored the relationship between children's basic psychological needs satisfaction at recess, level of recess physical activity motivation (RPAM), and recess physical activity (RPA). Fifth-grade children (N = 203; 50.2% boys; 71.7% healthy-weight) completed measures of age, gender, basic psychological need satisfaction, and level of self-determined motivation for RPA. Children also wore pedometers during six consecutive 30-min mid-school-day recesses. Multiple regression analyses indicated unique significant predictors of RPAM and RPA according to gender and weight status. RPAM was significantly predicted by all three basic psychological needs for boys and only competence need satisfaction for girls and healthy-weight children. RPA was predicted by RPAM for girls, competence need satisfaction for overweight children, and autonomy need satisfaction for boys and healthy-weight children. Findings support self-determination theory and provide important insight into the variations in psychological predictors of motivation for RPA and actual physical activity behavior based on gender and weight status.

Novel surveillance of psychological distress during the great recession.

PubMed

Ayers, John W; Althouse, Benjamin M; Allem, Jon-Patrick; Childers, Matthew A; Zafar, Waleed; Latkin, Carl; Ribisl, Kurt M; Brownstein, John S

2012-12-15

Economic stressors have been retrospectively associated with net population increases in nonspecific psychological distress (PD). However, no sentinels exist to evaluate contemporaneous associations. Aggregate Internet search query surveillance was used to monitor population changes in PD around the United States' Great Recession. Monthly PD query trends were compared with unemployment, underemployment, homes in delinquency and foreclosure, median home value or sale prices, and S&P 500 trends for 2004-2010. Time series analyses, where economic indicators predicted PD one to seven months into the future, were performed in 2011. PD queries surpassed 1,000,000 per month, of which 300,000 may be attributable to the Great Recession. A one percentage point increase in mortgage delinquencies and foreclosures was associated with a 16% (95%CI, 9-24) increase in PD queries one-month, and 11% (95%CI, 3-18) four months later, in reference to a pre-Great Recession mean. Unemployment and underemployment had similar associations half and one-quarter the intensity. "Anxiety disorder", "what is depression", "signs of depression", "depression symptoms", and "symptoms of depression" were the queries exhibiting the strongest associations with mortgage delinquencies and foreclosures, unemployment or underemployment. Housing prices and S&P 500 trends were not associated with PD queries. A non-traditional measure of PD was used. It is unclear if actual clinically significant depression or anxiety increased during the Great Recession. Alternative explanations for strong associations between the Great Recession and PD queries, such as media, were explored and rejected. Because the economy is constantly changing, this work not only provides a snapshot of recent associations between the economy and PD queries but also a framework and toolkit for real-time surveillance going forward. Health resources, clinician screening patterns, and policy debate may be informed by changes in PD query

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

Effects of oxygen stoichiometry on the scaling behaviors of YBa2Cu3O(x) grain boundary weak-links

NASA Technical Reports Server (NTRS)

Wu, K. H.; Fu, C. M.; Jeng, W. J.; Juang, J. Y.; Uen, T. M.; Gou, Y. S.

1995-01-01

The effects of oxygen stoichiometry on the transport properties of the pulsed laser deposited YBa2Cu3O(x) bicrystalline grain boundary weak-link junctions were studied. It is found that not only the cross boundary resistive transition foot structure can be manipulated repeatedly with oxygen annealing processes but the junction behaviors are also altered in accordance. In the fully oxygenated state i.e with x = 7.0 in YBa2Cu3O(x) stoichiometry, the junction critical current exhibits a power of 2 scaling behavior with temperature. In contrast, when annealed in the conditions of oxygen-deficient state (e.g with x = 6.9 in YBa2Cu3O(x) stoichiometry) the junction critical current switches to a linear temperature dependence behavior. The results are tentatively attributed to the modification of the structure in the boundary area upon oxygen annealing, which, in turn, will affect the effective dimension of the geometrically constrained weak-link bridges. The detailed discussion on the responsible physical mechanisms as well as the implications of the present results on device applications will be given.

Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping

PubMed Central

Siemiatkowska, Anna M.; Arimadyo, Kentar; Moruz, Luminita M.; Astuti, Galuh D.N.; de Castro-Miro, Marta; Zonneveld, Marijke N.; Strom, Tim M.; de Wijs, Ilse J.; Hoefsloot, Lies H.; Faradz, Sultana M.H.; Cremers, Frans P.M.; den Hollander, Anneke I.

2011-01-01

Purpose Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping. Methods DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations. Results In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2). Conclusions Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population. PMID:22128245

7 Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy

PubMed Central

Ratai, Eva; Kok, Trina; Wiggins, Christopher; Wiggins, Graham; Grant, Ellen; Gagoski, Borjan; O'Neill, Gilmore; Adalsteinsson, Elfar; Eichler, Florian

2010-01-01

Background Adult patients with X-linked adrenoleukodystrophy (X-ALD) remain at risk for progressive neurological deterioration. Phenotypes vary in their pathology, ranging from axonal degeneration to inflammatory demyelination. The severity of symptoms is poorly explained by conventional imaging. Objective To test the hypothesis that neurochemistry in normal appearing brain differs among adult phenotypes of X-ALD, and that neurochemical changes correlate with the severity of symptoms. Patients and Methods Using a 7 Tesla scanner we performed structural and proton MRSI in 13 adult patients with X-ALD, including 4 patients with adult cerebral ALD (ACALD), 5 with adrenomyeloneuropathy (AMN) and 4 female heterozygotes. Studies were also performed in nine healthy controls. Results Among adult X-ALD phenotypes, MI/Cr was 46% higher and Cho/Cr 21% higher in normal appearing white matter of ACALD compared to AMN (p < 0.05). Both NAA/Cr and Glu/Cr ratios were lower in AMN patients (p = 0.028 and p = 0.036, respectively) than in controls. There were no significant differences between AMN and female heterozygotes. In cortex, ACALD patients had lower values of NAA/Cr compared to female heterozygotes and controls (p = 0.022). The global MI/Cr ratio demonstrated a significant association with the EDSS (Spearman ρ = 0.66, p = 0.039). Conclusion 7 Tesla proton MRSI reveals differences in the neurochemistry of ACALD but is unable to distinguish AMN from female heterozygotes. MI/Cr correlates with the severity of the symptoms and may be a meaningful biomarker in adult X-ALD. PMID:19001168

Regulatory divergence of X-linked genes and hybrid male sterility in mice.

PubMed

Oka, Ayako; Shiroishi, Toshihiko

2014-01-01

Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations

PubMed Central

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10–13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease. PMID:29201369

X-linked adult-onset adrenoleukodystrophy: Psychiatric and neurological manifestations.

PubMed

Shamim, Daniah; Alleyne, Karen

2017-01-01

Adult-onset adrenoleukodystrophy is a rare x-linked inborn error of metabolism occurring predominantly in males with onset in early 30s. Here, we report a 34-year-old male with first signs of disease in early 20s manifesting as a pure psychiatric disorder. Prior to onset of neurological symptoms, this patient demonstrated a schizophrenia and bipolar-like presentation. The disease progressed over the next 10-13 years and his memory and motor problems became evident around the age of 33 years. Subsequently, diagnostic testing showed the typical magnetic resonance imaging and lab findings for adult-onset adrenoleukodystrophy. This case highlights adult-onset adrenoleukodystrophy which may present as a pure psychiatric disturbance in early adulthood and briefly discusses the prolonged time between the onset of psychiatric symptoms and the onset of neurological disease.

Hospital financial performance in the recent recession and implications for institutions that remain financially weak.

PubMed

Bazzoli, Gloria J; Fareed, Naleef; Waters, Teresa M

2014-05-01

The recent recession had a profound effect on all sectors of the US economy, including health care. We examined how private hospitals fared through the recession and considered how changes in their financial health may affect their ability to respond to future industry challenges. We categorized 2,971 private short-term general medical or surgical hospitals (both nonprofit and for-profit) according to their pre-recession financial health and safety-net status, and we examined their operational status changes and operating and total financial margins during 2006-11. We found that hospitals that were financially weak before the recession remained so during and after the recession. The total margins of nonprofit hospitals (both safety-net and other institutions) declined in 2008 but returned to their pre-recession levels by 2011. The recession did not create additional fiscal pressure on hospitals that were previously financially weak or in safety-net roles. However, both groups continue to have notable financial deficiencies that could limit their abilities to meet the growing demands on the industry.

A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

PubMed

Schernthaner-Reiter, Marie Helene; Adams, David; Trivellin, Giampaolo; Ramnitz, Mary Scott; Raygada, Margarita; Golas, Gretchen; Faucz, Fabio R; Nilsson, Ola; Nella, Aikaterini A; Dileepan, Kavitha; Lodish, Maya; Lee, Paul; Tifft, Cynthia; Markello, Thomas; Gahl, William; Stratakis, Constantine A

2016-05-01

X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiology may harbor splice site mutations that are initially underestimated in their pathogenicity on sequence analysis. • X-linked nephrogenic diabetes insipidus is caused by AVPR2 mutations, and disease severity can vary depending on the functional effect of the mutation. What is New: • We demonstrate here that a splice site mutation in AVPR2 leads to partial X-linked NDI in two brothers. • Treatment with high-dose DDAVP led to improvement of polyuria and polydipsia, weight gain, and growth.

Semiconductor structure and recess formation etch technique

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

Lu, Bin; Sun, Min; Palacios, Tomas Apostol

2017-02-14

A semiconductor structure has a first layer that includes a first semiconductor material and a second layer that includes a second semiconductor material. The first semiconductor material is selectively etchable over the second semiconductor material using a first etching process. The first layer is disposed over the second layer. A recess is disposed at least in the first layer. Also described is a method of forming a semiconductor structure that includes a recess. The method includes etching a region in a first layer using a first etching process. The first layer includes a first semiconductor material. The first etching processmore » stops at a second layer beneath the first layer. The second layer includes a second semiconductor material.« less

Ready for Recess: A Pilot Study to Increase Physical Activity in Elementary School Children

ERIC Educational Resources Information Center

Huberty, Jennifer L.; Siahpush, Mohammad; Beighle, Aaron; Fuhrmeister, Erin; Silva, Pedro; Welk, Greg

2011-01-01

Background: Creating an optimal environment at recess may be necessary to maximize physical activity (PA) participation in youth. The purpose of this study was to determine the initial effectiveness of an elementary school recess intervention on the amount of moderate PA (MPA) and vigorous PA (VPA) during recess and the school day. Methods: This…

A Comparison of Children's Physical Activity Levels in Physical Education, Recess, and Exergaming.

PubMed

Gao, Zan; Chen, Senlin; Stodden, David F

2015-03-01

To compare young children's different intensity physical activity (PA) levels in physical education, recess and exergaming programs. Participants were 140 first and second grade children (73 girls; Meanage= 7.88 years). Beyond the daily 20-minute recess, participants attended 75-minute weekly physical education classes and another 75-minute weekly exergaming classes. Children's PA levels were assessed by ActiGraph GTX3 accelerometers for 3 sessions in the 3 programs. The outcome variables were percentages of time spent in sedentary, light PA and moderate-to-vigorous PA (MVPA). There were significant main effects for program and grade, and an interaction effect for program by grade. Specifically, children's MVPA in exergaming and recess was higher than in physical education. The 2nd-grade children demonstrated lower sedentary behavior and MVPA than the first-grade children during recess; less light PA in both recess and exergaming than first-grade children; and less sedentary behavior but higher MVPA in exergaming than first-grade children. Young children generated higher PA levels in recess and exergaming as compared with physical education. Hence, other school-based PA programs may serve as essential components of a comprehensive school PA program. Implications are provided for educators and health professionals.

Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia

PubMed Central

Kannengiesser, Caroline; Sanchez, Mayka; Sweeney, Marion; Hetet, Gilles; Kerr, Briedgeen; Moran, Erica; Fuster Soler, Jose L.; Maloum, Karim; Matthes, Thomas; Oudot, Caroline; Lascaux, Axelle; Pondarré, Corinne; Sevilla Navarro, Julian; Vidyatilake, Sudharma; Beaumont, Carole; Grandchamp, Bernard; May, Alison

2011-01-01

Background Congenital sideroblastic anemias are rare disorders with several genetic causes; they are characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic sideroblastic anemia is a defect in the X-linked 5-aminolevulinate synthase 2 gene but this is not always present. Recently, variations in the gene for the mitochondrial carrier SLC25A38 were reported to cause a non-syndromic, severe type of autosomal-recessive sideroblastic anemia. Further evaluation of the importance of this gene was required to estimate the proportion of patients affected and to gain further insight into the range and types of variations involved. Design and Methods In three European diagnostic laboratories sequence analysis of SLC25A38 was performed on DNA from patients affected by congenital sideroblastic anemia of a non-syndromic nature not caused by variations in the 5-aminolevulinate synthase 2 gene. Results Eleven patients whose ancestral origins spread across several continents were homozygous or compound heterozygous for ten different SLC25A38 variations causing premature termination of translation (p.Arg117X, p.Tyr109LeufsX43), predicted splicing alteration (c.625G>C; p.Asp209His) or missense substitution (p.Gln56Lys, p.Arg134Cys, p.Ile147Asn, p.Arg187Gln, p.Pro190Arg, p.Gly228Val, p.Arg278Gly). Only three of these variations have been described previously (p.Arg117X, p.Tyr109LeufsX43 and p.Asp209His). All new variants reported here are missense and affect conserved amino acids. Structure modeling suggests that these variants may influence different aspects of transport as described for mutations in other mitochondrial carrier disorders. Conclusions Mutations in the SLC25A38 gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. Missense mutations are shown to be of importance as are mutations that affect protein production

Parental Employment Status and Symptoms of Children Abused during a Recession

ERIC Educational Resources Information Center

Tobey, Trina; McAuliff, Kathleen; Rocha, Celina

2013-01-01

Incidences and severity of child abuse have increased since the start of the recession. This study examined the relationship between employment status and severity of symptoms in children abused during a recession year. Participants included 154 females and 65 males between 2 and 17 years old referred to Dallas Children's Advocacy Center after…

INTRAGROUP AND GALAXY-LINKED DIFFUSE X-RAY EMISSION IN HICKSON COMPACT GROUPS

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

Desjardins, Tyler D.; Gallagher, Sarah C.; Tzanavaris, Panayiotis

2013-02-15

Isolated compact groups (CGs) of galaxies present a range of dynamical states, group velocity dispersions, and galaxy morphologies with which to study galaxy evolution, particularly the properties of gas both within the galaxies and in the intragroup medium. As part of a large, multiwavelength examination of CGs, we present an archival study of diffuse X-ray emission in a subset of nine Hickson compact groups (HCGs) observed with the Chandra X-Ray Observatory. We find that seven of the groups in our sample exhibit detectable diffuse emission. However, unlike large-scale emission in galaxy clusters, the diffuse features in the majority of themore » detected groups are linked to the individual galaxies, in the form of both plumes and halos likely as a result of vigourous star formation or activity in the galaxy nucleus, as well as in emission from tidal features. Unlike previous studies from earlier X-ray missions, HCGs 31, 42, 59, and 92 are found to be consistent with the L{sub X} -T relationship from clusters within the errors, while HCGs 16 and 31 are consistent with the cluster L{sub X} -{sigma} relation, though this is likely coincidental given that the hot gas in these two systems is largely due to star formation. We find that L{sub X} increases with decreasing group H I to dynamical-mass ratio with tentative evidence for a dependence in X-ray luminosity on H I morphology whereby systems with intragroup H I indicative of strong interactions are considerably more X-ray luminous than passively evolving groups. We also find a gap in the L{sub X} of groups as a function of the total group specific star formation rate. Our findings suggest that the hot gas in these groups is not in hydrostatic equilibrium and these systems are not low-mass analogs of rich groups or clusters, with the possible exception of HCG 62.« less

Intragroup and Galaxy-linked Diffuse X-ray Emission In Hickson Compact Groups

NASA Technical Reports Server (NTRS)

Desjardins, Tyler D.; Gallagher, Sarah C.; Tzanavaris, Panayiotis; Mulchaey, John S.; Brandt, William N.; Charlton, Jane C.; Garmire, Gordon P.; Gronwall, Caryl; Cardiff, Ann; Johnson, Kelsey E.;

Juvenile X-linked retinoschisis responsive to intravitreal corticosteroids.

PubMed

Ansari, Waseem H; Browne, Andrew W; Singh, Rishi P

2017-04-01

To report the case of an adult male with X-linked retinoschisis (XLRS) who presented with cystoid macular edema (CME) that responded consistently to treatment with intravitreal steroids. A 39 year old male with unilateral presentation of CME after repair of a retinal detachment secondary to XLRS responded initially to an injection of intravitreal triamcinolone acetonide (IVTA). Central subfield thickness on OCT was reduced. Three months later, the CME recurred and he was unresponsive to topical treatment so repeat IVTA was given, and the CME once again was reduced dramatically. After the next recurrence, intravitreal dexamethasone implant treatment was initiated and successful at treating recurrences in 3 month intervals for 5 additional injections. Finally, an intravitreal fluocinolone acetonide implant was surgically placed with control of CME. Corticosteroids have never been reported to be effective in CME related to XLRS. Here, we document a case of a man who successfully had decrease of intraretinal fluid and schisis with treatment of intravitreal corticosteroids as demonstrated by spectral domain optical coherence tomography.

Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic.

PubMed

Carroll, Joseph; Rossi, Ethan A; Porter, Jason; Neitz, Jay; Roorda, Austin; Williams, David R; Neitz, Maureen

2010-09-15

Blue cone monochromacy (BCM) is an X-linked condition in which long- (L) and middle- (M) wavelength-sensitive cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal cone electroretinograms. Here we imaged the cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M opsin gene expression (effectively acting as a cone opsin knockout). On average, they had cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of opsin in a subset of cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers. Copyright 2010 Elsevier Ltd. All rights reserved.

School recess, social connectedness and health: a Canadian perspective.

PubMed

McNamara, Lauren; Colley, Paige; Franklin, Nicole

2017-04-01

Children need opportunities to establish positive social connections at school, yet many school playgrounds are challenged by social conflict that can undermine these connections. When children's social needs go unmet, the resultant feelings of loneliness, isolation and self-doubt can cumulatively lead to mental and physical illness. Because recess is typically the only time during the school day that children are free to socialize and play, we propose a more thoughtful way of thinking about it: from the lens of belongingness. Schools are, historically, designed for instruction. We argue, however, that we need to attend to children's social needs at school. We highlight current research from social neuroscience, belonging and social connectedness in order to delineate the pathways between daily school recess and developmental health trajectories. We then consolidate an array of research on play, social interaction and school change to suggest four areas that could benefit from consideration in research, practice and policy: (i) the culture of recess, (ii) the importance of healthy role models on the playground, (iii) the necessity of activities, options and variety during recess and (iv) the significance of space and spatial layout (indoor and outdoor). We bridge our discussion with the conception of health as described in the Ottawa Charter and emphasize the need to build alliances across sectors to assist schools in their efforts to support children's overall health needs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A novel UBE2A mutation causes X-linked intellectual disability type Nascimento.

PubMed

Tsurusaki, Yoshinori; Ohashi, Ikuko; Enomoto, Yumi; Naruto, Takuya; Mitsui, Jun; Aida, Noriko; Kurosawa, Kenji

2017-01-01

X-linked intellectual disability (ID) type Nascimento (MIM #300860), also known as ubiquitin-conjugating enzyme E2 A (UBE2A) deficiency syndrome, is a congenital malformation syndrome characterized by moderate to severe ID, speech impairment, dysmorphic facial features, genital anomalies and skin abnormalities. Here, we report a Japanese patient with severe ID and congenital cataract. We identified a novel hemizygous mutation (c.76G>A, p.Gly26Arg) in UBE2A by whole-exome sequencing.

Polysilicon planarization and plug recess etching in a decoupled plasma source chamber using two endpoint techniques

NASA Astrophysics Data System (ADS)

Kaplita, George A.; Schmitz, Stefan; Ranade, Rajiv; Mathad, Gangadhara S.

1999-09-01

The planarization and recessing of polysilicon to form a plug are processes of increasing importance in silicon IC fabrication. While this technology has been developed and applied to DRAM technology using Trench Storage Capacitors, the need for such processes in other IC applications (i.e. polysilicon studs) has increased. Both planarization and recess processes usually have stringent requirements on etch rate, recess uniformity, and selectivity to underlying films. Additionally, both processes generally must be isotropic, yet must not expand any seams that might be present in the polysilicon fill. These processes should also be insensitive to changes in exposed silicon area (pattern factor) on the wafer. A SF6 plasma process in a polysilicon DPS (Decoupled Plasma Source) reactor has demonstrated the capability of achieving the above process requirements for both planarization and recess etch. The SF6 process in the decoupled plasma source reactor exhibited less sensitivity to pattern factor than in other types of reactors. Control of these planarization and recess processes requires two endpoint systems to work sequentially in the same recipe: one for monitoring the endpoint when blanket polysilicon (100% Si loading) is being planarized and one for monitoring the recess depth while the plug is being recessed (less than 10% Si loading). The planarization process employs an optical emission endpoint system (OES). An interferometric endpoint system (IEP), capable of monitoring lateral interference, is used for determining the recess depth. The ability of using either or both systems is required to make these plug processes manufacturable. Measuring the recess depth resulting from the recess process can be difficult, costly and time- consuming. An Atomic Force Microscope (AFM) can greatly alleviate these problems and can serve as a critical tool in the development of recess processes.

The Great American Recession and forgone healthcare: Do widened disparities between African-Americans and Whites remain?

PubMed

Travers, Jasmine L; Cohen, Catherine C; Dick, Andrew W; Stone, Patricia W

2017-01-01

During the Great Recession in America, African-Americans opted to forgo healthcare more than other racial/ethnic groups. It is not understood whether disparities in forgone care returned to pre-recession levels. Understanding healthcare utilization patterns is important for informing subsequent efforts to decrease healthcare disparities. Therefore, we examined changes in racial disparities in forgone care before, during, and after the Great Recession. Data were pooled from the 2006-2013 National Health Interview Survey. Forgone medical, mental, and prescription care due to affordability were assessed among African-Americans and Whites. Time periods were classified as: pre-recession (May 2006-November 2007), early recession (December 2007-November 2008), late recession (December 2008-May 2010) and post-recession (June 2010-December 2013). Multivariable logistic regressions of race, interacted with time periods, were used to identify disparities in forgone care controlling for other demographics, health insurance coverage, and having a usual place for medical care across time periods. Adjusted Wald tests were performed to identify significant changes in disparities across time periods. The sample consisted of 110,746 adults. African-Americans were more likely to forgo medical care during the post- recession compared to Whites (OR = 1.16, CI = 1.06, 1.26); changes in foregone medical care disparities were significant in that they increased in the post-recession period compared to the pre-recession (OR = 1.17, CI = 1.08, 1.28 and OR = 0.89, CI = 0.77, 1.04, respectively, adjusted Wald Test p-value < 0.01). No changes in disparities were seen in prescription and mental forgone care. A persistent increase in forgone medical care disparities existed among African-Americans compared to Whites post-Great Recession and may be a result of outstanding issues related to healthcare access, cost, and quality. While health insurance is an important component of access to care, it

The State of Play: Gallup Survey of Principals on School Recess

ERIC Educational Resources Information Center

Robert Wood Johnson Foundation, 2010

2010-01-01

When most people talk about how to improve education, they tend to focus only on what happens in the classroom. But the most unexpected opportunity to boost learning lies outside the classroom: on the playground at recess. A new, first-of-its-kind Gallup poll reveals that elementary school principals overwhelmingly believe recess has a positive…

Unemployment, the Great Recession, and Apprenticeship Attrition in the U.S.

ERIC Educational Resources Information Center

Bilginsoy, Cihan

2018-01-01

The author estimates the impacts of the local rate of unemployment and the Great Recession on the quit and graduation rates of the U.S. construction trade apprentices over the 2001-2014 period. Trade union participation in training sponsorship had a strong influence on attrition rates. The impacts of the business cycle and the Great Recession on…

Association between sports participation and sedentary behavior during school recess among brazilian adolescents.

PubMed

Silva, Diego Augusto Santos; Dos Santos Silva, Roberto Jerônimo

2015-03-29

The aim of this study was to examine the association between sports participation and sedentary behavior during school recess among Brazilian adolescents. This study included 2,243 adolescents aged 13-18 years (16.2 ± 1.1), 62.2% females and 37.8% males, enrolled in public high schools in Aracaju, Northeastern Brazil. Sedentary behavior during school recess and sport participation was self-reported. Several factors were examined, including sex, age, skin color, socioeconomic status, maternal education and physical activity level. Sixty percent of adolescents had sedentary behavior during school recess and 57.7% of adolescents reported that they did not participate in any team sport. Additionally, adolescents who did not practice any team sport were 40% more likely (OR: 1.4, 95% CI: 1.1, 1.8) to be sedentary during school recess compared to those who participated in two or more team sports. It is recommended that schools encourage students to engage in sports activities and promote more physical activity during school recess to reduce the sedentary behavior and increase physical activity levels in youth.

Recession-based hydrological models for estimating low flows in ungauged catchments in the Himalayas

NASA Astrophysics Data System (ADS)

Rees, H. G.; Holmes, M. G. R.; Young, A. R.; Kansakar, S. R.

The Himalayan region of Nepal and northern India experiences hydrological extremes from monsoonal floods during July to September, when most of the annual precipitation falls, to periods of very low flows during the dry season (December to February). While the monsoon floods cause acute disasters such as loss of human life and property, mudslides and infrastructure damage, the lack of water during the dry season has a chronic impact on the lives of local people. The management of water resources in the region is hampered by relatively sparse hydrometerological networks and consequently, many resource assessments are required in catchments where no measurements exist. A hydrological model for estimating dry season flows in ungauged catchments, based on recession curve behaviour, has been developed to address this problem. Observed flows were fitted to a second order storage model to enable average annual recession behaviour to be examined. Regionalised models were developed, using a calibration set of 26 catchments, to predict three recession curve parameters: the storage constant; the initial recession flow and the start date of the recession. Relationships were identified between: the storage constant and catchment area; the initial recession flow and elevation (acting as a surrogate for rainfall); and the start date of the recession and geographic location. An independent set of 13 catchments was used to evaluate the robustness of the models. The regional models predicted the average volume of water in an annual recession period (1st of October to the 1st of February) with an average error of 8%, while mid-January flows were predicted to within ±50% for 79% of the catchments in the data set.

Genetics Home Reference: autosomal recessive congenital methemoglobinemia

MedlinePlus

... it alters a molecule within these cells called hemoglobin . Hemoglobin carries oxygen to cells and tissues throughout the ... autosomal recessive congenital methemoglobinemia , some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, ...

Lunch, recess and nutrition: responding to time incentives in the cafeteria.

PubMed

Price, Joseph; Just, David R

2015-02-01

In this study, we evaluate if moving recess before lunch has an effect on the amount of fruits and vegetables elementary school students eat as part of their school-provided lunch. Participants were 1st-6th grade students from three schools that switched recess from after to before lunch and four similar schools that continued to hold recess after lunch. We collected data for an average of 14 days at each school (4 days during spring 2011, May 3 through June 1, 2011 and 9 days during fall 2011, September 19 through November 11, 2011). All of the schools were in Orem, UT. Data was collected for all students receiving a school lunch and was based on observational plate waste data. We find that moving recess before lunch increased consumption of fruits and vegetables by 0.16 servings per child (a 54% increase) and increased the fraction of children eating at least one serving of fruits or vegetables by 10 percentage points (a 45% increase). In contrast, the schools in our control group actually experienced a small reduction in fruit and vegetable consumption during the same time period. Our results show the benefits of holding recess before lunch and suggest that if more schools implement this policy, there would be significant increases in fruit and vegetable consumption among students who eat school lunch as part of the National School Lunch Program. Copyright © 2014 Elsevier Inc. All rights reserved.

A recessive genetic model and runs of homozygosity in major depressive disorder

PubMed Central

Power, Robert A.; Keller, Matthew C.; Ripke, Stephan; Abdellaoui, Abdel; Wray, Naomi R.; Sullivan, Patrick F; Breen, Gerome

2014-01-01

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here we undertake an analysis of ROH for MDD using the 9,238 MDD cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (p=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD. PMID:24482242

Single-Exome sequencing identified a novel RP2 mutation in a child with X-linked retinitis pigmentosa.

PubMed

Lim, Hassol; Park, Young-Mi; Lee, Jong-Keuk; Taek Lim, Hyun

2016-10-01

To present an efficient and successful application of a single-exome sequencing study in a family clinically diagnosed with X-linked retinitis pigmentosa. Exome sequencing study based on clinical examination data. An 8-year-old proband and his family. The proband and his family members underwent comprehensive ophthalmologic examinations. Exome sequencing was undertaken in the proband using Agilent SureSelect Human All Exon Kit and Illumina HiSeq 2000 platform. Bioinformatic analysis used Illumina pipeline with Burrows-Wheeler Aligner-Genome Analysis Toolkit (BWA-GATK), followed by ANNOVAR to perform variant functional annotation. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation. Analysis of exome sequence data identified a novel frameshift mutation in RP2 gene resulting in a premature stop codon (c.665delC, p.Pro222fsTer237). Sanger sequencing revealed this mutation co-segregated with the disease phenotype in the child's family. We identified a novel causative mutation in RP2 from a single proband's exome sequence data analysis. This study highlights the effectiveness of the whole-exome sequencing in the genetic diagnosis of X-linked retinitis pigmentosa, over the conventional sequencing methods. Even using a single exome, exome sequencing technology would be able to pinpoint pathogenic variant(s) for X-linked retinitis pigmentosa, when properly applied with aid of adequate variant filtering strategy. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

PubMed

Bademci, Guney; Lasisi, Akeem; Yariz, Kemal O; Montenegro, Paola; Menendez, Ibis; Vinueza, Rodrigo; Paredes, Rosario; Moreta, Germania; Subasioglu, Asli; Blanton, Susan; Fitoz, Suat; Incesulu, Armagan; Sennaroglu, Levent; Tekin, Mustafa

2015-02-25

Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies. Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families. Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families. Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.

X-linked Alport syndrome: An SSCP-based mutation survey over all 51 exons of the COL4A5 gene

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

Renieri, A.; Bruttini, M.; Galli, L.

1996-06-01

The COL4A5 gene encodes the {alpha}5 (type IV) collagen chain and is defective in X-linked Alport syndrome (AS). Here, we report the first systematic analysis of all 51 exons of COL4A5 gene in a series of 201 Italian AS patients. We have previously reported nine major rearrangements, as well as 18 small mutations identified in the same patient series by SSCP analysis of several exons. After systematic analysis of all 51 exons of COL4A5, we have now identified 30 different mutations: 10 glycine substitutions in the triple helical domain of the protein, 9 frameshift mutations, 4 in-frame deletions, 1 startmore » codon, 1 nonsense, and 5 splice-site mutations. These mutations were either unique or found in two unrelated families, thus excluding the presence of a common mutation in the coding part of the gene. Overall, mutations were detected in only 45% of individuals with a certain or likely diagnosis of X-linked AS. This finding suggests that mutations in noncoding segments of COL4A5 account for a high number of X-linked AS cases. An alternative hypothesis is the presence of locus heterogeneity, even within the X-linked form of the disease. A genotype/phenotype comparison enabled us to better substantiate a significant correlation between the degree of predicted disruption of the {alpha}5 chain and the severity of phenotype in affected male individuals. Our study has significant implications in the diagnosis and follow-up of AS patients. 44 refs., 3 figs., 4 tabs.« less

Epidemiology of gingival recession and risk indicators in dental hospital population of Bhimavaram

PubMed Central

Manchala, S. Reddy; Vandana, K. L.; Mandalapu, N. B.; Mannem, S.; Dwarakanath, C. D.

2012-01-01

Objective: Gingival recession (GR) is a common manifestation in most populations, and is considered as an early sign of periodontal disease. GR is an intriguing condition where various factors play an important role in its etiology. Only few studies have been undertaken to assess the prevalence and risk factors for GR in patients visiting dental hospitals. The aim of this study is not only to estimate prevalence, severity, and extent of GR in hospital population, of Vishnu Dental College, Bhimavaram, Andhra Pradesh, India, but also to assess the potential risk factors for the same. Materials and Methods: In this study, 2837 patients were examined of which 627 were included into the study. The age range was 16-80 years. Subjects were interviewed using a structural questionnaire, and full mouth clinical examination was done to assess recession. Results: Of all subjects examined 45.6%, 16.2% of individuals and 13%, 4.8% of teeth per individual showed GR >3 mm. Prevalence and severity of recession was correlated with age. Recession was present but recession threshold ≥3 and ≥5 mm affected only small percentage of teeth in subjects younger than 45 years. Mandibular incisors showed the highest prevalence of GR ≥1 mm with 61% of teeth being affected. Smoking and presence of supragingival calculus were most significantly associated localized and generalized recession. Conclusion: Prevalence of periodontal disease is high among this population based on the presence of gingival recession in most the individuals. High prevalence of GR is significantly associated with supragingival calculus and smoking habits. This suggests a need to improve their periodontal condition through education, motivation, and improving their periodontal health. PMID:24478971

Novel Surveillance of Psychological Distress during the Great Recession

PubMed Central

Ayers, John W.; Althouse, Benjamin M.; Allem, Jon-Patrick; Childers, Matthew A.; Zafar, Waleed; Latkin, Carl; Ribisl, Kurt M.; Brownstein, John S.

2015-01-01

Background Economic stressors have been retrospectively associated with net population increases in nonspecific psychological distress (PD). However, no sentinels exist to evaluate contemporaneous associations. Aggregate Internet search query surveillance was used to monitor population changes in PD around the United States’ Great Recession. Methods Monthly PD query trends were compared with unemployment, underemployment, homes in delinquency and foreclosure, median home value or sale prices, and S&P 500 trends for 2004–2010. Time series analyses, where economic indicators predicted PD one to seven months into the future, were performed in 2011. Results PD queries surpassed 1,000,000 per month, of which 300,000 may be attributable to the Great Recession. A one percentage point increase in mortgage delinquencies and foreclosures was associated with a 16% (95%CI, 9–24) increase in PD queries one-month, and 11% (95%CI, 3–18) four months later, in reference to a pre-Great Recession mean. Unemployment and underemployment had similar associations half and one-quarter the intensity. “Anxiety disorder,” “what is depression,” “signs of depression,” “depression symptoms,” and “symptoms of depression” were the queries exhibiting the strongest associations with mortgage delinquencies and foreclosures, unemployment or underemployment. Housing prices and S&P 500 trends were not associated with PD queries. Limitations A non-traditional measure of PD was used. It is unclear if actual clinically significant depression or anxiety increased during the Great Recession. Alternative explanations for strong associations between the Great Recession and PD queries, such as media, were explored and rejected. Conclusions Because the economy is constantly changing, this work not only provides a snapshot of recent associations between the economy and PD queries but also a framework and toolkit for real-time surveillance going forward. Health resources, clinician

Physiological Arousal in Autism and Fragile X Syndrome: Group Comparisons and Links with Pragmatic Language

ERIC Educational Resources Information Center

Klusek, Jessica; Martin, Gary E.; Losh, Molly

2013-01-01

This study tested the hypothesis that pragmatic (i.e., social) language impairment is linked to arousal dysregulation in autism spectrum disorder (ASD) and fragile X syndrome (FXS). Forty boys with ASD, 39 with FXS, and 27 with typical development (TD), aged 4-15 years, participated. Boys with FXS were hyperaroused compared to boys with TD but did…

Scheduling Recess before Lunch: Exploring the Benefits and Challenges in Montana Schools

ERIC Educational Resources Information Center

Bark, Katie; Stenberg, Molly; Sutherland, Shelly; Hayes, Dayle

2010-01-01

Purpose/Objectives: The purpose of the "Montana Recess Before Lunch Survey" was to explore benefits, challenges, and factors associated with successful implementation of Recess Before Lunch (RBL), from the perspective of school principals. Methods: An online written questionnaire was distributed to all (N = 661) Montana elementary and…

5meCpG epigenetic marks neighboring a primate-conserved core promoter short tandem repeat indicate X-chromosome inactivation.

PubMed

Machado, Filipe Brum; Machado, Fabricio Brum; Faria, Milena Amendro; Lovatel, Viviane Lamim; Alves da Silva, Antonio Francisco; Radic, Claudia Pamela; De Brasi, Carlos Daniel; Rios, Álvaro Fabricio Lopes; de Sousa Lopes, Susana Marina Chuva; da Silveira, Leonardo Serafim; Ruiz-Miranda, Carlos Ramon; Ramos, Ester Silveira; Medina-Acosta, Enrique

2014-01-01

X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigenetic marker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic

5meCpG Epigenetic Marks Neighboring a Primate-Conserved Core Promoter Short Tandem Repeat Indicate X-Chromosome Inactivation

PubMed Central

Machado, Filipe Brum; Machado, Fabricio Brum; Faria, Milena Amendro; Lovatel, Viviane Lamim; Alves da Silva, Antonio Francisco; Radic, Claudia Pamela; De Brasi, Carlos Daniel; Rios, Álvaro Fabricio Lopes; de Sousa Lopes, Susana Marina Chuva; da Silveira, Leonardo Serafim; Ruiz-Miranda, Carlos Ramon; Ramos, Ester Silveira; Medina-Acosta, Enrique

2014-01-01

X-chromosome inactivation (XCI) is the epigenetic transcriptional silencing of an X-chromosome during the early stages of embryonic development in female eutherian mammals. XCI assures monoallelic expression in each cell and compensation for dosage-sensitive X-linked genes between females (XX) and males (XY). DNA methylation at the carbon-5 position of the cytosine pyrimidine ring in the context of a CpG dinucleotide sequence (5meCpG) in promoter regions is a key epigenetic marker for transcriptional gene silencing. Using computational analysis, we revealed an extragenic tandem GAAA repeat 230-bp from the landmark CpG island of the human X-linked retinitis pigmentosa 2 RP2 promoter whose 5meCpG status correlates with XCI. We used this RP2 onshore tandem GAAA repeat to develop an allele-specific 5meCpG-based PCR assay that is highly concordant with the human androgen receptor (AR) exonic tandem CAG repeat-based standard HUMARA assay in discriminating active (Xa) from inactive (Xi) X-chromosomes. The RP2 onshore tandem GAAA repeat contains neutral features that are lacking in the AR disease-linked tandem CAG repeat, is highly polymorphic (heterozygosity rates approximately 0.8) and shows minimal variation in the Xa/Xi ratio. The combined informativeness of RP2/AR is approximately 0.97, and this assay excels at determining the 5meCpG status of alleles at the Xp (RP2) and Xq (AR) chromosome arms in a single reaction. These findings are relevant and directly translatable to nonhuman primate models of XCI in which the AR CAG-repeat is monomorphic. We conducted the RP2 onshore tandem GAAA repeat assay in the naturally occurring chimeric New World monkey marmoset (Callitrichidae) and found it to be informative. The RP2 onshore tandem GAAA repeat will facilitate studies on the variable phenotypic expression of dominant and recessive X-linked diseases, epigenetic changes in twins, the physiology of aging hematopoiesis, the pathogenesis of age-related hematopoietic

Recession, debt and mental health: challenges and solutions

PubMed Central

2009-01-01

Background During the economic downturn, the link between recession and health has featured in many countries' media, political, and medical debate. This paper focuses on the previously neglected relationship between personal debt and mental health. Aims Using the UK as a case study, this paper considers the public health challenges presented by debt to mental health. We then propose solutions identified in workshops held during the UK Government's Foresight Review of Mental Capital and Wellbeing. Results Within their respective sectors, health professionals should receive basic ‘debt first aid’ training, whilst all UK financial sector codes of practice should – as a minimum – recognise the existence of customers with mental health problems. Further longitudinal research is also needed to ‘unpack’ the relationship between debt and mental health. Across sectors, a lack of co-ordinated activity across health, money advice, and creditor organisations remains a weakness. A renewed emphasis on co-ordinated ‘debt care pathways’ and better communication between local health and advice services is needed. Discussion The relationship between debt and mental health presents a contemporary public health challenge. Solutions exist, but will require action and investment at a time of competition for funds. PMID:22477896

Novel RS1 mutations associated with X-linked juvenile retinoschisis

PubMed Central

YI, JUNHUI; LI, SHIQIANG; JIA, XIAOYUN; XIAO, XUESHAN; WANG, PANFENG; GUO, XIANGMING; ZHANG, QINGJIONG

2012-01-01

To identify mutations in the retinoschisin (RS1) gene in families with X-linked retinoschisis (XLRS). Twenty families with XLRS were enrolled in this study. All six coding exons and adjacent intronic regions of RS1 were amplified by polymerase chain reaction (PCR). The nucleotide sequences of the amplicons were determined by Sanger sequencing. Ten hemizygous mutations in RS1 were detected in patients from 14 of the 20 families. Four of the ten mutations were novel, including c:176G>A (p:Cys59Tyr) in exon 3, c:531T>G (p:Tyr177X), c:607C>G (p:Pro203Ala) and c:668G>A (p:Cys223Tyr) in exon 6. These four novel mutations were not present in 176 normal individuals. The remaining six were recurrent mutations, including c:214G>A (p:Glu72Lys), c:304C>T (p:Arg102Trp), c:436G>A (p:Glu146Lys), c:544C>T (p:Arg182Cys), c:599G>A (p:Arg200His) and c:644A>T (p:Glu215Val). Our study expanded the mutation spectrum of RS1 and enriches our understanding of the molecular basis of XLRS. PMID:22245991

Novel RS1 mutations associated with X-linked juvenile retinoschisis.

PubMed

Yi, Junhui; Li, Shiqiang; Jia, Xiaoyun; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Zhang, Qingjiong

2012-04-01

To identify mutations in the retinoschisin (RS1) gene in families with X-linked retinoschisis (XLRS). Twenty families with XLRS were enrolled in this study. All six coding exons and adjacent intronic regions of RS1 were amplified by polymerase chain reaction (PCR). The nucleotide sequences of the amplicons were determined by Sanger sequencing. Ten hemizygous mutations in RS1 were detected in patients from 14 of the 20 families. Four of the ten mutations were novel, including c:176G>A (p:Cys59Tyr) in exon 3, c:531T>G (p:Tyr177X), c:607C>G (p:Pro203Ala) and c:668G>A (p:Cys223Tyr) in exon 6. These four novel mutations were not present in 176 normal individuals. The remaining six were recurrent mutations, including c:214G>A (p:Glu72Lys), c:304C>T (p:Arg102Trp), c:436G>A (p:Glu146Lys), c:544C>T (p:Arg182Cys), c:599G>A (p:Arg200His) and c:644A>T (p:Glu215Val). Our study expanded the mutation spectrum of RS1 and enriches our understanding of the molecular basis of XLRS.

A novel UBE2A mutation causes X-linked intellectual disability type Nascimento

PubMed Central

Tsurusaki, Yoshinori; Ohashi, Ikuko; Enomoto, Yumi; Naruto, Takuya; Mitsui, Jun; Aida, Noriko; Kurosawa, Kenji

2017-01-01

X-linked intellectual disability (ID) type Nascimento (MIM #300860), also known as ubiquitin-conjugating enzyme E2 A (UBE2A) deficiency syndrome, is a congenital malformation syndrome characterized by moderate to severe ID, speech impairment, dysmorphic facial features, genital anomalies and skin abnormalities. Here, we report a Japanese patient with severe ID and congenital cataract. We identified a novel hemizygous mutation (c.76G>A, p.Gly26Arg) in UBE2A by whole-exome sequencing. PMID:28611923

Hunting for Novel X-Linked Breast Cancer Suppressor Genes in Mouse and Human

DTIC Science & Technology

2007-03-01

display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 01/03/07 2 . REPORT TYPE...and correlated significantly with HER- 2 over-expression, regardless of the status of HER- 2 amplification. In toto, the data demonstrate that FOXP3...is an X-linked breast cancer suppressor gene and an important regulator of the HER- 2 /ErbB2 oncogene. 15. SUBJECT TERMS No subject terms provided 16

The construction of a high-density linkage map for identifying SNP markers that are tightly linked to a nuclear-recessive major gene for male sterility in Cryptomeria japonica D. Don

PubMed Central

2012-01-01

Background High-density linkage maps facilitate the mapping of target genes and the construction of partial linkage maps around target loci to develop markers for marker-assisted selection (MAS). MAS is quite challenging in conifers because of their large, complex, and poorly-characterized genomes. Our goal was to construct a high-density linkage map to facilitate the identification of markers that are tightly linked to a major recessive male-sterile gene (ms1) for MAS in C. japonica, a species that is important in Japanese afforestation but which causes serious social pollinosis problems. Results We constructed a high-density saturated genetic linkage map for C. japonica using expressed sequence-derived co-dominant single nucleotide polymorphism (SNP) markers, most of which were genotyped using the GoldenGate genotyping assay. A total of 1261 markers were assigned to 11 linkage groups with an observed map length of 1405.2 cM and a mean distance between two adjacent markers of 1.1 cM; the number of linkage groups matched the basic chromosome number in C. japonica. Using this map, we located ms1 on the 9th linkage group and constructed a partial linkage map around the ms1 locus. This enabled us to identify a marker (hrmSNP970_sf) that is closely linked to the ms1 gene, being separated from it by only 0.5 cM. Conclusions Using the high-density map, we located the ms1 gene on the 9th linkage group and constructed a partial linkage map around the ms1 locus. The map distance between the ms1 gene and the tightly linked marker was only 0.5 cM. The identification of markers that are tightly linked to the ms1 gene will facilitate the early selection of male-sterile trees, which should expedite C. japonica breeding programs aimed at alleviating pollinosis problems without harming productivity. PMID:22424262

Recession and Divorce in the United States, 2008-2011

PubMed Central

Cohen, Philip N.

2015-01-01

Recession may increase divorce through a stress mechanism, or reduce divorce by exacerbating cost barriers or strengthening family bonds. After establishing an individual-level model predicting U.S. women's divorce, the paper tests period effects, and whether unemployment and foreclosures are associated with the odds of divorce using the 2008-2011 American Community Survey. Results show a downward spike in the divorce rate after 2008, almost recovering to the expected level by 2011, which suggests a negative recession effect. On the other hand, state foreclosure rates are positively associated with the odds of divorce with individual controls, although this effect is not significant when state fixed effects are introduced. State unemployment rates show no effect on odds of divorce. Future research will have to determine why national divorce odds fell during the recession while state-level economic indicators were not strongly associated with divorce. Exploratory analysis which shows unemployment decreasing divorce odds for those with college degrees, while foreclosures have the opposite effect, provides one possible avenue for such research. PMID:26023246

Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency.

PubMed

Mauldin, E A; Wang, P; Evans, E; Cantner, C A; Ferracone, J D; Credille, K M; Casal, M L

2015-07-01

A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species. © The Author(s) 2014.

X-Linked Glomerulopathy Due to COL4A5 Founder Variant.

PubMed

Barua, Moumita; John, Rohan; Stella, Lorenzo; Li, Weili; Roslin, Nicole M; Sharif, Bedra; Hack, Saidah; Lajoie-Starkell, Ginette; Schwaderer, Andrew L; Becknell, Brian; Wuttke, Matthias; Köttgen, Anna; Cattran, Daniel; Paterson, Andrew D; Pei, York

2018-03-01

Alport syndrome is a rare hereditary disorder caused by rare variants in 1 of 3 genes encoding for type IV collagen. Rare variants in COL4A5 on chromosome Xq22 cause X-linked Alport syndrome, which accounts for ∼80% of the cases. Alport syndrome has a variable clinical presentation, including progressive kidney failure, hearing loss, and ocular defects. Exome sequencing performed in 2 affected related males with an undefined X-linked glomerulopathy characterized by global and segmental glomerulosclerosis, mesangial hypercellularity, and vague basement membrane immune complex deposition revealed a COL4A5 sequence variant, a substitution of a thymine by a guanine at nucleotide 665 (c.T665G; rs281874761) of the coding DNA predicted to lead to a cysteine to phenylalanine substitution at amino acid 222, which was not seen in databases cataloguing natural human genetic variation, including dbSNP138, 1000 Genomes Project release version 01-11-2004, Exome Sequencing Project 21-06-2014, or ExAC 01-11-2014. Review of the literature identified 2 additional families with the same COL4A5 variant leading to similar atypical histopathologic features, suggesting a unique pathologic mechanism initiated by this specific rare variant. Homology modeling suggests that the substitution alters the structural and dynamic properties of the type IV collagen trimer. Genetic analysis comparing members of the 3 families indicated a distant relationship with a shared haplotype, implying a founder effect. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

DJ-1/PARK7, But Not Its L166P Mutant Linked to Autosomal Recessive Parkinsonism, Modulates the Transcriptional Activity of the Orphan Nuclear Receptor Nurr1 In Vitro and In Vivo.

PubMed

Lu, Lingling; Zhao, Shasha; Gao, Ge; Sun, Xiaohong; Zhao, Huanying; Yang, Hui

2016-12-01

Although mutations of DJ-1 have been linked to autosomal recessive Parkinsonism for years, its physiological function and the pathological mechanism of its mutants are not well understood. We report for the first time that exogenous application of DJ-1, but not its L166P mutant, enhances the nuclear translocation and the transcriptional activity of Nurr1, a transcription factor essential for dopaminergic neuron development and maturation, both in vitro and in vivo. Knockdown of DJ-1 attenuates Nurr1 activity. Further investigation showed that signaling of Raf/MEK/ERK MAPKs is involved in this regulatory process and that activation induced by exogenous DJ-1 is antagonized by U0126, an ERK pathway inhibitor, indicating that DJ-1 modulates Nurr1 activity via the Raf/MEK/ERK pathway. Our findings shed light on the novel function of DJ-1 to enhance Nurr1 activity and provide the first insight into the molecular mechanism by which DJ-1 enhances Nurr1 activity.

Metabolic Syndrome Risks Following the Great Recession in Rural Black Young Adults.

PubMed

Miller, Gregory E; Chen, Edith; Yu, Tianyi; Brody, Gene H

2017-09-06

Some of the country's highest rates of morbidity and mortality from cardiovascular disease are found in lower-income black communities in the rural Southeast. Research suggests these disparities originate in the early decades of life, and partly reflect the influence of broader socioeconomic forces acting on behavioral and biological processes that accelerate cardiovascular disease progression. However, this hypothesis has not been tested explicitly. Here, we examine metabolic syndrome (MetS) in rural black young adults as a function of their family's economic conditions before and after the Great Recession. In an ongoing prospective study, we followed 328 black youth from rural Georgia, who were 16 to 17 years old when the Great Recession began. When youth were 25, we assessed MetS prevalence using the International Diabetes Federation's guidelines. The sample's overall MetS prevalence was 18.6%, but rates varied depending on family economic trajectory from before to after the Great Recession. MetS prevalence was lowest (10.4%) among youth whose families maintained stable low-income conditions across the Recession. It was intermediate (21.8%) among downwardly mobile youth (ie, those whose families were lower income before the Recession, but slipped into poverty). The highest MetS rates (27.5%) were among youth whose families began the Recession in poverty, and sank into more meager conditions afterwards. The same patterns were observed with 3 alternative MetS definitions. These patterns suggest that broader economic forces shape cardiometabolic risk in young blacks, and may exacerbate disparities already present in this community. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Gingival abrasion and recession in manual and oscillating–rotating power brush users

PubMed Central