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Sample records for small consanguineous families

  1. Compound heterozygosity for three common MEFV mutations in a highly consanguineous family with familial Mediterranean fever.

    PubMed

    Seidel, H; Steinlein, O K

    2008-07-01

    Consanguinity is not the only factor influencing the occurrence of autosomal recessive disorders such as familial Mediterranean fever (FMF). The extended, multiple consanguineous Turkish pedigree presented here demonstrates that the population frequency of certain mutations (so-called "ancient" mutations) can be at least equally important. In high-risk populations different combinations of mutations can occur within the same family, increasing not only the intrafamilial clinical variability, but also causing considerable recurrence risks even in marriages with unrelated spouses.

  2. Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases

    PubMed Central

    Kabir, Firoz; Ullah, Inayat; Ali, Shahbaz; Gottsch, Alexander D.H.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families. Methods Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon–intron boundaries of RP1 were sequenced to identify the causal mutation. Results The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples. Conclusions These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. PMID:27307693

  3. Familial Recurrence of 3MC Syndrome in Consanguineous Families: A Clinical and Molecular Diagnostic Approach With Review of the Literature.

    PubMed

    Gardner, Olivia K; Haynes, Karla; Schweitzer, Daniela; Johns, Alexis; Magee, William P; Urata, Mark M; Sanchez-Lara, Pedro A

    2016-06-29

    We report four individuals from two unrelated consanguineous families with 3MC syndrome. In the first family, chromosome microarray data revealed that the two affected sisters, born to first-cousin parents, shared a unique homozygous C-terminal deletion in the COLEC11 gene. Two affected brothers from a second family, also born to first-cousin parents, shared a region of homozygosity that included the second gene known to cause the 3MC syndrome, MASP1. We discuss the diagnostic approach of craniofacial disorders born to consanguineous parents and highlight a literature search and reference a helpful dysmorphology solution powered by FDNA (Facial Dysmorphology Novel Analysis) technology.

  4. Mutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness

    PubMed Central

    Naeem, Muhammad Asif; Gottsch, Alexander D. H.; Ullah, Inayat; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2015-01-01

    Purpose This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families. Methods Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, including fundus examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion analyses were completed by genotyping closely spaced microsatellite markers, and two-point logarithm of odds (LOD) scores were calculated. All coding exons, along with the exon–intron boundaries of GRM6, were sequenced bidirectionally. Results According to the medical history available to us, affected individuals in both families had experienced night blindness from the early years of their lives. Fundus photographs of affected individuals in both the families appeared normal, with no signs of attenuated arteries or bone spicule pigmentation. The scotopic electroretinogram (ERG) response were absent in all of the affected individuals, while the photopic measurements show reduced b-waves. During exclusion analyses, both families localized to a region on chromosome 5q that harbors GRM6, a gene previously associated with autosomal recessive CSNB. Bidirectional sequencing of GRM6 identified homozygous single base pair changes, specifically c.1336C>T (p.R446X) and c.2267G>A (p.G756D) in families PKRP170 and PKRP172, respectively. Conclusions We identified a novel nonsense and a previously reported missense mutation in GRM6 that were responsible for autosomal recessive CSNB in patients of Pakistani decent. PMID:26628857

  5. Small Families

    MedlinePlus

    ... more emphasis on careers for women, more effective methods of contraception, and the rising cost of rearing and educating children. There are some very clear benefits to having a small family; Each child receives more parental attention and educational advantages, which generally raise her self- ...

  6. Genetic dissection of two Pakistani families with consanguineous localized autosomal recessive hypotrichosis (LAH)

    PubMed Central

    Abbas, Seyyedha; Naveed, Abdul Khaliq; Khan, Shakir; Yousaf, Muhammad Jawad; Azeem, Zahid; Razak, Suhail; Qaiser, Fatima

    2014-01-01

    Objective(s): Genetic analysis of two consanguineous Pakistani families with localized autosomal recessive hypotrichosis was performed with the goal to establish genotype-phenotype correlation. Materials and Methods: Genomic DNA extraction had been done from peripheral blood samples. Extracted DNA was then subjected to PCR (polymerase chain reaction) for amplification. Linkage analysis was performed using 8% polyacrylamide gel. Candidate gene was sequenced after gene linkage supported at highly polymorphic microsatellite markers of the diseased region. Results: Both families were initially tested for linkage to known genes, which were involved in human hereditary hypotrichosis, by genotyping Highly polymorphic microsatellite markers. Family B showed partial linkage at P2RY5 gene on chromosome 13q14.11-q21.32; hence, all exonic regions and their introns boundaries were subjected to DNA sequencing for any pathogenic mutation. Conclusion: Both families were tested for linkage by genotyping polymorphic microsatellite markers linked to known alopecia loci. Family A excluded all known diseased regions that is suggestive of some novel chromosomal disorder. However, sequencing of P2RY5 gene in family B showed no pathogenic mutation. PMID:25429336

  7. Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

    PubMed Central

    Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

  8. WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

    PubMed

    Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease.

  9. Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.

    PubMed

    Chograni, M; Alkuraya, F S; Ourteni, I; Maazoul, F; Lariani, I; Chaabouni, H B

    2015-09-01

    The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

  10. Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

    PubMed

    Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

    2016-07-26

    Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.Molecular Psychiatry advance online publication, 26 July 2016; doi:10.1038/mp.2016.109.

  11. Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

    PubMed

    Harripaul, R; Vasli, N; Mikhailov, A; Rafiq, M A; Mittal, K; Windpassinger, C; Sheikh, T I; Noor, A; Mahmood, H; Downey, S; Johnson, M; Vleuten, K; Bell, L; Ilyas, M; Khan, F S; Khan, V; Moradi, M; Ayaz, M; Naeem, F; Heidari, A; Ahmed, I; Ghadami, S; Agha, Z; Zeinali, S; Qamar, R; Mozhdehipanah, H; John, P; Mir, A; Ansar, M; French, L; Ayub, M; Vincent, J B

    2017-04-11

    Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.Molecular Psychiatry advance online publication, 11 April 2017; doi:10.1038/mp.2017.60.

  12. Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

    PubMed Central

    Rubio-Cabezas, Oscar; Patch, Ann-Marie; Minton, Jayne A. L.; Flanagan, Sarah E.; Edghill, Emma L.; Hussain, Khalid; Balafrej, Amina; Deeb, Asma; Buchanan, Charles R.; Jefferson, Ian G.; Mutair, Angham; Hattersley, Andrew T.; Ellard, Sian

    2009-01-01

    Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. PMID:19837917

  13. A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.

    PubMed

    Naseer, Muhammad Imran; Rasool, Mahmood; Jan, Mohammed M; Chaudhary, Adeel G; Pushparaj, Peter Natesan; Abuzenadah, Adel M; Al-Qahtani, Mohammad H

    2016-12-15

    PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of the cell this gene is required for proper expression of GPI-anchored proteins. Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation. Mutations in the PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have identified a large consanguineous family from Saudi origin segregating developmental delay, intellectual disability, epilepsy and microcephaly. Whole exome sequencing with 100× coverage was performed on two affected siblings of the family. Data analysis in the patient revealed a novel missense mutation c.191C>T in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The mutation was reconfirmed and validated by subsequent Sanger sequencing method. The mutation was ruled out in 100 unrelated healthy controls. We suggest that this pathogenic mutation disrupts the proper function of the gene proteins resulting in the disease state.

  14. Novel homozygous large deletion including the 5′ part of the SPATA7 gene in a consanguineous Israeli Muslim Arab family

    PubMed Central

    Mayer, Anja-Kathrin; Mahajnah, Muhammad; Zobor, Ditta; Bonin, Michael; Sharkia, Rajech

    2015-01-01

    Purpose To identify the genetic defect in a consanguineous Israeli Muslim Arab family with juvenile retinitis pigmentosa (RP). Methods DNA samples were collected from the index patient, her parents, her affected sister, and two non-affected siblings. Genome-wide linkage analysis with 250 K single nucleotide polymorphism (SNP) arrays was performed using DNA from the two affected patients. Owing to consanguinity in the family, we applied homozygosity mapping to identify the disease-causing gene. The candidate gene SPATA7 was screened for mutations with PCR amplifications and direct Sanger sequencing. Results Following high-density SNP arrays, we identified several homozygous genomic regions one of which included the SPATA7 gene. Several mutations in SPATA7 have been reported for various forms of retinal dystrophy, including Leber congenital amaurosis (LCA) and juvenile RP. PCR-based sequence content mapping, long-distance PCR amplifications, and subsequent sequencing analysis revealed a homozygous 63.4 kb large deletion that encompasses the 5′ part of the SPATA7 gene including exons 1–5. The mutation showed concordant segregation with the phenotype in the family as expected for autosomal recessive mode of inheritance and is consistent with a diagnosis of juvenile RP. Conclusions We report a novel homozygous large deletion in SPATA7 associated with juvenile RP in a consanguineous Israeli Muslim Arab family. This is the first larger deletion mutation reported for SPATA7. PMID:25814828

  15. Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family

    PubMed Central

    Dias, Miguel de Sousa; Hamel, Christian P.; Meunier, Isabelle; Varin, Juliette; Blanchard, Steven; Boyard, Fiona; Sahel, José-Alain

    2017-01-01

    Purpose To report the clinical and genetic findings of one family with autosomal recessive cone dystrophy (CD) and to identify the causative mutation. Methods An institutional study of three family members from two generations. The clinical examination included best-corrected Snellen visual acuity measurement, fundoscopy, the Farnsworth D-15 color vision test, a full-field electroretinogram (ERG) that incorporated the International Society for Clinical Electrophysiology of Vision standards and methodology, fundus autofluorescence (FAF) and infrared (IR), and spectral-domain optical coherence tomography (SD-OCT). Genetic findings were achieved with DNA analysis using whole exome sequencing (WES) and Sanger sequencing. Results The proband, a 9-year-old boy, presented with a condition that appeared to be congenital and stationary. The clinical presentation initially reflected incomplete congenital stationary night blindness (icCSNB) because of myopia, a decrease in visual acuity, abnormal oscillatory potentials, and reduced amplitudes on the 30 Hz flicker ERG but was atypical because there were no clear electronegative responses. However, no disease-causing mutations in the genes underlying icCSNB were identified. Following WES analysis of family members, a homozygous splice-site mutation in intron 3 of TTLL5 (c.182–3_182–1delinsAA) was found cosegregating within the phenotype in the family. Conclusions The distinction between icCSNB and CD phenotypes is not always straightforward in young patients. The patient was quite young, which most likely explains why the progression of the CD was not obvious. WES analysis provided prompt diagnosis for this family; thus, the use of this technique to refine the diagnosis is highlighted in this study. PMID:28356705

  16. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing

    PubMed Central

    Lal, Dennis; Neubauer, Bernd A.; Toliat, Mohammad R.; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

    2016-01-01

    Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

  17. Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene.

    PubMed

    Lofrano-Porto, Adriana; Barra, Gustavo B; Nascimento, Paula P; Costa, Patrícia G G; Garcia, Erica C; Vaz, Rodrigo F; Batista, Ana R T; Freitas, Ana C R de; Cherulli, Bruno L B; Bahmad, Fayez; Figueiredo, Larissa G; Neves, Francisco A R; Casulari, Luiz Augusto

    2008-11-01

    Pendred Syndrome (PS) is an autossomal recessive disorder characterized by sensorineural deafness, goiter and iodide organification defect. The hearing loss is associated with inner ear abnormalities, ranging from an isolated enlarged vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to be associated with PS. We describe the clinical and molecular characteristics of a large consanguineous family harboring a mutation in the SLC26A4 gene. The proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular goiter and hypothyroidism since puberty. Five other siblings were deaf: one brother had a similar phenotype, three siblings also had goiters but normal thyroid function tests, and one brother had only a subtle thyroid enlargement. Other 4 siblings had no thyroid or hearing disorder. Parents were first degree cousins and had normal hearing. The mother was healthy, except for subclinical hypothyroidism; the father was deceased. A perchlorate test in the proband showed a discharge of 21% of the incorporated iodide 2h after the administration of 1g of KClO4. Audiological examinations showed profound hearing loss in all deaf subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the mother and control. The coding region of the PDS gene (exons 2-21), including exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair (T) deletion at position 1197 of exon 10 was detected in homozygous state in the 6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this mutation, which has been described by Everett et al. The 1197delT mutation is predicted to result in a frameshift and a truncated protein. The existence of PS phenocopies and intrafamilial phenotypic variability are well documented. The definite

  18. Consanguinity, human evolution, and complex diseases

    PubMed Central

    Bittles, A. H.; Black, M. L.

    2010-01-01

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

  19. Novel homozygous mutations in the EVC and EVC2 genes in two consanguineous families segregating autosomal recessive Ellis-van Creveld syndrome.

    PubMed

    Aziz, Abdul; Raza, Syed I; Ali, Salman; Ahmad, Wasim

    2016-01-01

    Ellis-van Creveld syndrome (EVC) is a rare developmental disorder characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, teeth, oral and cardiac abnormalities. It is caused by biallelic mutations in the EVC or EVC2 gene, separated by 2.6 kb of genomic sequence on chromosome 4p16. In the present study, we have investigated two consanguineous families of Pakistani origin, segregating EVC in autosomal recessive manner. Linkage in the families was established to chromosome 4p16. Subsequently, sequence analysis identified a novel nonsense mutation (p.Trp234*) in exon 8 of the EVC2 gene and 15 bp duplication in exon 14 of the EVC gene in the two families. This further expands the mutations in the EVC or EVC2 genes resulting in the EVC syndrome.

  20. Identification of a novel mutation in FOXL2 gene that leads to blepharophimosis ptosis epicanthus inversus and telecanthus syndrome in a Tunisian consanguineous family.

    PubMed

    Chouchene, Ibtissem; Derouiche, Kaouthar; Chaabouni, Afif; Cherif, Lamia; Amouri, Ahlem; Largueche, Leila; Abdelhak, Sonia; El Matri, Leila

    2010-02-01

    Mutations in FOXL2 gene are responsible for blepharophimosis ptosis epicanthus inversus and telecanthus syndrome (BPES). The BPES syndrome is a rare autosomal dominant genetic disease characterized by eyelid malformations associated with premature ovarian failure (BPES type I) or not (BPES type II). The human FOXL2 protein (376 aa) contains a 100 amino-acid DNA-binding forkhead domain (residues 52-152) and a polyalanine tract (residues 221-234). In the present study, we report the molecular investigation of four affected members with BPES syndrome in a Tunisian consanguineous family. To identify the causative mutation, we performed a direct sequencing of the FOXL2 gene. The sequence analysis of the coding exon revealed a novel frameshift mutation g.1113 dup C, c.876 dup C, p.P292 Fs. The mutation is located downstream of the polyalanine tract and causes the protein extension to 532 aa. This study reports for the first time a novel frameshift mutation in two-generation consanguineous Tunisian family with BPES. Our results expand the spectrum of FOXL2 mutations.

  1. Bloom syndrome: An analysis of consanguineous families assigns the locus mutated to chromosome band 15q26. 1

    SciTech Connect

    German, J.; Roe, A.M.; Ellis, N.A. ); Leppert, M.F. )

    1994-07-05

    By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous far more often than expected (P < 0.0001 by x[sup 2]). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a [open quotes]reverse[close quotes] genetics definition of the primary defect in Bloom syndrome.

  2. Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.

    PubMed

    Aziz, Abdul; Irfanullah; Khan, Saadullah; Zimri, Faridullah Khan; Muhammad, Noor; Rashid, Sajid; Ahmad, Wasim

    2014-01-25

    Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM.

  3. A community genetics perspective on consanguineous marriage.

    PubMed

    Bittles, A H

    2008-01-01

    Consanguineous marriage has long been a controversial topic, with particular attention focused on adverse health outcomes. Unfortunately, the studies that have been conducted on consanguinity to date have usually lacked control for important sociodemographic variables, such as maternal age and birth intervals, and in estimating specific disease gene frequency, they have ignored the influence of population sub-division. Inadequate attention has also been paid to the social benefits associated with intra-familial marriage, resulting in a biased overall cost-benefit assessment. Worldwide, some 1,000 million people live in countries where 20 to more than 50% of marriages are consanguineous, and large migrant communities from these regions are now resident in Western Europe, North America and Oceania. The need for comprehensive and more balanced investigations into all aspects of consanguineous marriage is pressing and merits a substantial international collaborative research effort.

  4. Consanguinity and deafness in Omani children.

    PubMed

    Khabori, Mazin Al; Patton, Michael A

    2008-01-01

    This study was based on a national retrospective analysis of 1400 questionnaires on the causes of deafness in Omani children, collected from 1986 to 2000. It was found that 70% of the deaf children were from parents of consanguineous marriages, and 30% from non-consanguineous unions. In those with consanguineous families 70.16% were first cousin marriages, 17.54% were second cousins, and 10.86% were from the same tribe. The proportion arising from first cousin marriages was higher than the background rate of first cousin marriages in Oman. In the total cohort, 45% had other family members with hearing loss. There was a greater chance of other relatives being affected in the consanguineous group as opposed to the non-consanguineous group (29.7% versus 15.3%). In most cases the affected relative was a deaf sibling (67.8%). We have demonstrated a higher rate of consanguinity amongst parents of deaf children in Oman and suggest this is associated with a higher frequency of autosomal recessive deafness in this paediatric population.

  5. Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report

    PubMed Central

    Magaña, Jonathan J; Tapia-Guerrero, Yessica S; Velázquez-Pérez, Luis; Cruz-Mariño, Tania; Cerecedo-Zapata, Cesar M; Gómez, Rocío; Murillo-Melo, Nadia M; González-Piña, Rigoberto; Hernández-Hernández, Oscar; Cisneros, Bulmaro

    2014-01-01

    Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband. PMID:25664129

  6. [Consanguinity and congenital abnormalities].

    PubMed

    Søgaard, Marie; Vedsted-Jakobsen, Agnete

    2003-04-28

    Knowledge of consanguinity is relevant for employees in the Danish national health service, since about 7.5% of the Danish population has another ethnic background than Danish and the majority comes from cultures where consanguineous marriages are not unusual. In the literature it is found that consanguineous couples have a higher risk of having children with congenital malformations. The risk is increased by a factor 2 to 2 1/2. The average risk in Denmark is about 3%. Primarily, the autosomal recessive diseases are expressed in children with consanguineous parents. In order to advise and diagnose it is essential to clarify the consanguinity state. In case of pregnancy with consanguineous parents, we recommend: 1) Counselling to estimate the risk of foetal illness and information about possible examination possibilities. 2) An ultrasound scan at the gestational age of 11-14 weeks in order to measure nuchal translucency and an early malformation scan. 3) An ultrasound scan for malformations at the gestational age of 18-20 weeks. 4) An ultrasound scan especially in order to detect foetal heart malformations at the gestational age of 20-24 weeks.

  7. Integration of Sequence Data from a Consanguineous Family with Genetic Data from an Outbred Population Identifies PLB1 as a Candidate Rheumatoid Arthritis Risk Gene

    PubMed Central

    Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D.; Mouassess, Faten; Achkar, Walid A. L.; Fulton, Robert S.; Denny, Joshua C.; Gupta, Namrata; Mirel, Daniel; Gabriel, Stacy; Li, Gang; Kremer, Joel M.; Pappas, Dimitrios A.; Carroll, Robert J.; Eyler, Anne E.; Trynka, Gosia; Stahl, Eli A.; Cui, Jing; Saxena, Richa; Coenen, Marieke J. H.; Guchelaar, Henk-Jan; Huizinga, Tom W. J.; Dieudé, Philippe; Mariette, Xavier; Barton, Anne; Canhão, Helena; Fonseca, João E.; de Vries, Niek; Tak, Paul P.; Moreland, Larry W.; Bridges, S. Louis; Miceli-Richard, Corinne; Choi, Hyon K.; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Raj, Towfique; De Jager, Philip L.; Raychaudhuri, Soumya; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Siminovitch, Katherine A.; Gregersen, Peter K.; Mardis, Elaine R.; Arayssi, Thurayya; Kazkaz, Layla A.; Plenge, Robert M.

    2014-01-01

    Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10−6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. PMID:24520335

  8. Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.

    PubMed

    Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D; Mouassess, Faten; Achkar, Walid A L; Fulton, Robert S; Denny, Joshua C; Gupta, Namrata; Mirel, Daniel; Gabriel, Stacy; Li, Gang; Kremer, Joel M; Pappas, Dimitrios A; Carroll, Robert J; Eyler, Anne E; Trynka, Gosia; Stahl, Eli A; Cui, Jing; Saxena, Richa; Coenen, Marieke J H; Guchelaar, Henk-Jan; Huizinga, Tom W J; Dieudé, Philippe; Mariette, Xavier; Barton, Anne; Canhão, Helena; Fonseca, João E; de Vries, Niek; Tak, Paul P; Moreland, Larry W; Bridges, S Louis; Miceli-Richard, Corinne; Choi, Hyon K; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Raj, Towfique; De Jager, Philip L; Raychaudhuri, Soumya; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Siminovitch, Katherine A; Gregersen, Peter K; Mardis, Elaine R; Arayssi, Thurayya; Kazkaz, Layla A; Plenge, Robert M

    2014-01-01

    Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

  9. A Homozygous Mutation in GPT2 Associated with Nonsyndromic Intellectual Disability in a Consanguineous Family from Costa Rica.

    PubMed

    Lobo-Prada, Tanya; Sticht, Heinrich; Bogantes-Ledezma, Sixto; Ekici, Arif; Uebe, Steffen; Reis, André; Leal, Alejandro

    2017-01-28

    Intellectual disability is a highly heterogeneous disease that affects the central nervous system and impairs patients' ability to function independently. Despite multiples genes involved in the etiology of disease, most of the genetic background is yet to be discovered. We used runs of homozygosity and exome sequencing to study a large Costa Rican family with four individuals affected with severe intellectual disability and found a novel homozygous missense mutation, p. 96G>R, c. 286G>A, in all affected individuals. This gene encodes for a pyridoxal enzyme involved in the production of the neurotransmitter glutamate and is highly expressed in the white matter of brain and cerebellum. Protein modeling of GPT2 predicted that the mutation is located in a loop where the substrate binds to the active site of the enzyme, therefore, suggesting that the catalytic activity is impaired. With our report of a second mutation we fortify the importance of GPT2 as a novel cause of autosomal recessive nonsyndromic intellectual disability and support the premise that GPT2 is highly important for the neurodevelopment of the central nervous system.

  10. Organ donation consanguinity or universality.

    PubMed

    Kishore, R R

    1996-01-01

    1. Neither the "Diseased Persons" nor the "Genetic Relations" provide an answer to "trading" in human body parts. 2. Live human body constitutes a vital source of supply of organs and tissues and the possibilities of optimum utilisation should be explored. 3. There is no scope for dogmatic postures and open-mindedness should be the approach while dealing with the issue of Organ Transplantation. 4. Society owes a duty to save the file of a dying man and in the event of failure to do so, it is absolutely immoral to interfere with his own arrangements by making unrealistic laws. No immorality is involved if an individual disposes of his spare body parts for a valid consideration to a needy person. 5. The scarcity needs to be urgently overcome otherwise unwarranted trade and crime are liable to thrive. 6. Families are not unconnected or antagonistic fragments of humanity. After thousands of years of continuous efforts the individuals on this earth have attained the stage of organic and functional integration. Atomisation of society on the basis of consanguineous proximities amounts to reversing this holistic trend. Organ transplantation is a functional expression of a highly evolved pursuit with inherent and intimate interaction in the form of organic exchange at the individual level, independent of consanguineous inducements or motivations. As such there is absolutely no scope for restricting organ donations by strangers. 7. Commercialisation should be curbed by making the enforcement agencies more efficient and not by depriving a needy person of his genuine requirements. Legislative craftsmanship lies in providing an answer without curtailing the freedom of the people.

  11. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  12. Missouri Small Farm Family Program. Revised.

    ERIC Educational Resources Information Center

    Enlow, George; And Others

    Records maintained by rural extension designees on the Missouri Small Farm Family Program, (initiated in 1972 by the cooperative extension service to help low income farm families learn to use available resources to improve their quality of life) provided data re: family characteristics, farm improvement progress, and improvement in the quality of…

  13. [Frequency of consanguineous unions in the Tlemcen area (West Algeria)].

    PubMed

    Zaoui, Salah; Biémont, Christian

    2002-01-01

    In order to describe consanguineous unions and their effects in a sample of the Algerian population, we interviewed 3,983 couples in a hospital and from urban and rural areas near Tlemcen. We observed that unions between cousins represented 34.0% of the marriages. The frequency of unions between relatives was lower in the urban (30.6%) than in the rural areas (40.5%). This difference can be explained by changing custom and family relationships in urban areas, and is evidenced by social and anthropologic factors and the attitude towards consanguineous unions.

  14. The rate of consanguineous marriages among parents of schizophrenic patients in the Arab Bedouin population in Southern Israel.

    PubMed

    Dobrusin, Michael; Weitzman, Dahlia; Levine, Joseph; Kremer, Ilana; Rietschel, Marcella; Maier, Wolfgang; Belmaker, Robert H

    2009-01-01

    Consanguinity may contribute to the incidence of schizophrenia in offspring despite the usually accepted polygenic model of schizophrenia inheritance. Bedouin Arab families in southern Israel have a high rate of cousin marriages as do families throughout most Arab societies. We studied consanguinity in the parents of schizophrenic patients admitted in a defined catchment area of southern Israel, compared to a control group of parents of all infants born to Bedouin mothers in this catchment area. There was a small but significant increase in the rate of cousin marriages among the parents of schizophrenia patients compared to parents of infant controls. These results are consistent with claims that inbreeding can contribute to the incidence of schizophrenia even as a polygenic illness. However, the absence of a better matched control group limits confidence in the results.

  15. Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus

    PubMed Central

    Radhakrishna, Uppala; Ratnamala, Uppala; Deutsch, Samuel; Bartoloni, Lucia; Kuracha, Murali R; Singh, Raminder; Banwait, Jasjit; Bastola, Dhundy K; Johar, Kaid; Nath, Swapan K; Antonarakis, Stylianos E

    2012-01-01

    Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus. PMID:22490987

  16. Consanguinity and reproductive health among Arabs

    PubMed Central

    Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

    2009-01-01

    Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity. PMID:19811666

  17. Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan

    PubMed Central

    Pedurupillay, Christeen Ramane J.; Landsend, Erlend Christoffer Sommer; Vigeland, Magnus Dehli; Ansar, Muhammad; Frengen, Eirik; Misceo, Doriana; Strømme, Petter

    2016-01-01

    We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan. PMID:27472364

  18. Consanguinity and Neonatal Death: A Nested Case-Control Study

    PubMed Central

    Chaman, Reza; Gholami Taramsari, Mahshid; Khosravi, Ahmad; Amiri, Mohammad; Holakouie Naieni, Kourosh; Yunesian, Masoud

    2014-01-01

    Objective: Although numerous studies have found higher rates of abortion and still births following consanguinity (familial marriages), the question of whether consanguinity significantly increases the risk of neonatal death has inadequately been addressed.This study aims to evaluate familial marriage effects on neonatal death in rural areas in Iran. Materials and methods: In this nested case-control study, 6900 newbornswho were born in rural areas of Kohgiluyeh and Boyerahmad Province (South-West of Iran)were followed till the end of neonatal period, and neonatal death was the outcome of interest. Subsequently 97 cases and 97 controls were selected in study cohort by using risk set sampling model. Crude and adjusted odds ratios (OR) were estimated by usinga conditional logistic regression model. Results: In the final model, prematurity (OR = 5.57), low birthweight (LBW) (OR = 7.68), consanguinity (first cousins) (OR = 5.23), C-section (OR = 7.27), birth rank more than 3 (OR = 6.95) and birthsinterval less than 24 months (OR = 4.65) showed significant statistical association with neonatal mortality (p < 0.05). Conclusion: According to our findings, after adjusting the effects of other significant risk factors, familial marriageto first cousins is considered asan important risk factor for neonatal death. PMID:25530772

  19. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society

    PubMed Central

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien AC; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-01-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling. PMID:23921534

  20. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

    PubMed

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-04-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling.

  1. Bleeding disorders in the tribe: result of consanguineous in breeding

    PubMed Central

    2010-01-01

    Objective To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages. Design Cross Sectional Study Introduction Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia. Patients & Methods Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested. Results The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders. Conclusion Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community. PMID:20822539

  2. Consanguinity Among Parents of Iranian Deaf Children

    PubMed Central

    Ajallouyan, Mohammad; Radfar, Shokofeh; Nouhi, Sima; Tavallaie, Seid Abbas; Amirsalari, Susan; Yousefi, Jaleh; Hasanali Fard, Mahdieh

    2016-01-01

    Background It seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran. Objectives The aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation. Methods This study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population. Results Sixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases. Conclusions Our data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage. PMID:28191326

  3. Rubisco small subunit gene family in cassava.

    PubMed

    Yeo, T W; Mak, Y M; Ho, K K

    1999-01-01

    Cassava leaves of two different cultivars, Brazil and Buloh, were used to isolate mRNA. The mRNA isolated was successfully used in the construction of cDNA libraries for each of the cultivars. The cDNA libraries were screened for members of ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit gene family and positive clones were sequenced. A total of seven different SSU genes, of which five were from cultivar Brazil and two were from cultivar Buloh, were isolated. Comparison results show that even though all the sequences are highly similar, they can be classified into three subfamilies. Homology between members of the same subfamily is higher than homology between members from the same cultivar.

  4. Consanguineous marriage in PR China: a study in rural Man (Manchu) communities.

    PubMed

    Wang, W; Qian, Cong; Bittles, A H

    2002-01-01

    Although there is a long history of consanguineous marriage in China, information on its prevalence is very limited. The Man (Qing) dynasty ruled China for over 250 years, but no consanguinity studies have been reported on this important population. The objective of the present investigation was to determine the present-day level of consanguineous marriage in the Man community, and to compare the data with existing consanguinity information on other Chinese populations. The study was conducted in a group of 11 rural Man communities in the north-eastern Chinese province of Liaoning. Household-based interviews were conducted by local staff on 513 couples, 418 of whom were Man with another 95 Man-Han inter-ethnic marriages. Basic pedigrees were constructed to determine the biological relationship between each set of spouses. Thirty of the 418 couples were in a consanguineous union, with a mean coefficient of inbreeding alpha = 0.0012. The small population sizes of the study may have contributed to the spatial variation in the patterns of inbreeding. Across generations there was a reduction in consanguineous marriages and an increase in inter-ethnic unions, which paralleled changes in civil marriage regulations.

  5. Consanguinity and disorders of sex development.

    PubMed

    Bashamboo, Anu; McElreavey, Ken

    2014-01-01

    Disorders of sex development (DSD) are defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et al., Pediatrics 2006;118:e488-e500]. Studies conducted in Western countries, with low rates of consanguinity, show that truly ambiguous genitalia have an estimated incidence of 1:5,000 births. There are indications that the prevalence of DSD is higher in endogamous communities. The incidence of ambiguous genitalia in Saudi Arabia has been estimated at 1:2,500 live births; whilst in Egypt, it has been estimated at 1:3,000 live births. This may be due in part to an increase in disorders of androgen synthesis associated with 46,XX DSD. There is clearly a need for further studies to address the frequency of DSD in communities with high levels of consanguinity. This will be challenging, as an accurate diagnosis is difficult and expensive even in specialized centres. In developing countries with high levels of consanguinity, these limitations can be compounded by cultural, social and religious factors. Overall there is an indication that consanguinity may lead to an increase in incidences of both 46,XY and 46,XX DSD, and a co-ordinated study of populations with higher incidences of consanguinity/endogamy is needed to resolve this.

  6. Axial mesodermal dysplasia complex: a new case with parental consanguinity.

    PubMed

    Mota, C R; Azevedo, M; Rocha, G; Manuela, F; Coelho, R; Lima, M R

    2000-01-01

    A female is described with axial mesodermal dysplasia complex (AMDC) born to a consanguineous couple. This is thought to be the first description of a patient with AMDC born to consanguineous parents.

  7. Profiling β Thalassemia Mutations in Consanguinity and Nonconsanguinity for Prenatal Screening and Awareness Programme

    PubMed Central

    Kumar, Ravindra; Arya, Vandana; Agarwal, Sarita

    2015-01-01

    Mutation spectrum varies significantly in different parts and different ethnic groups of India. Social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) play an important role in impeding the gene pool of the disease within the community and so in society by and large. The present paper discusses the role of consanguinity in profiling of beta thalassemia mutation, and thus the approach for prenatal screening and prevention based awareness programme. Clinically diagnosed 516 cases of beta thalassemia were screened at molecular level. A detailed clinical Proforma was recorded with the information of origin of the family, ethnicity, and consanguinity. The present study reports that subjects originating from Uttar Pradesh, Uttarakhand, Bihar, and Jharkhand have c.92+5G>C and c.124_127delTTCT mutation as the commonest mutation compared to the subjects hailing from Madhya Pradesh and Chhattisgarh and Nepal where sickle mutation was found more common. In 40 consanguineous unions more common and specific beta mutations with higher rate of homozygosity have been reported. This consanguinity-based data helps not only in deciding target oriented prenatal diagnostic strategies but also in objective based awareness programmes in prevention of thalassemia major birth. PMID:26576156

  8. Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

    PubMed Central

    Shihab, Hashem A.; Rodriguez, Santiago; Gaunt, Tom R.; Day, Ian N.M.

    2016-01-01

    Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. PMID:27000383

  9. Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

    PubMed

    Jabeen, Nazish; Malik, Sajid

    2014-06-01

    Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe.

  10. [Scattered papules in three Togolese children from a consanguineous marrige: epidermodysplasia verruciformis].

    PubMed

    Saka, B; Mouhari-Touré, A; Kombaté, K; Pitché, P; Tchangaï-Walla, K

    2009-06-01

    Epidermodysplasia verruciformis (EV) is a rare condition characterized by diffuse flat wart-like lesions. It is an autosomal recessive genodermatosis associated with susceptibility to infection by specific human papillomavirus genotypes and a high risk of skin cancer. In this report we describe three cases of EV after a consanguineous marriage in a family with no history of EV.

  11. A Small Library in Family Planning.

    ERIC Educational Resources Information Center

    Planned Parenthood Federation of America, Inc., New York, NY.

    This annotated listing of books is intended as a reference for anyone seeking an authoritative introduction to population and family planning information, as a world, family, or individual concern. For each entry, the International Standard Book Number (ISBN) is provided if available. The number preceding each reference represents the…

  12. Attitude of Saudi Arabian adults towards consanguineous marriage

    PubMed Central

    Alharbi, Omar A.; Al-Shaia, Walaa A.; Al-Hamam, Abdulaziz A.; Al-Marzoug, Hala M.; Ahmed, Anwar E.; Bagha, Muhammed

    2015-01-01

    Background: Research on the attitudes of Saudi adults towards consanguinity is scarce. The study aimed to explore the attitudes towards consanguinity and its associations with socio-demographic characteristics in a sample of Saudi adults. Methods: A cross-sectional study was conducted using a self-administered questionnaire. A total of 386 outpatient waiting-area attendees at King Abdul-Aziz Medical City-Riyadh were included. Participants were asked about their socio-demographic characteristics, attitude towards consanguinity and the reasons behind this. Results: The positive attitude towards consanguinity among the study respondents was 48.1% with 95% confidence interval (42.91–53.33%). Social and traditional culture (59.9%) were found to be the predominant reasons for favoring consanguinity in Saudi Arabia. Evidence against a positive attitude towards consanguinity was noted in respondents who received medical information about consanguinity versus those who had not received medical information (42.3% vs. 57%, p-value = 0.008). According to the multivariate logistic model, the odds of a positive attitude towards consanguinity were 2 times higher for males (adjusted odds ratio [aOR]: 2.2; 95% CI: 1.147, 4.290) and 4.1 times higher in respondents in consanguineous marriages (aOR: 4.1; 95% CI: 2.350, 7.156). The odds of a positive attitude towards consanguinity were 50% less in respondents who received health information on consanguinity compared to those who had not received health information about consanguinity (aOR: 0.50; 95% CI: 0.253, 0.863). Conclusion: One in every two Saudi adults favors consanguinity however, Saudi men and women differ in their attitudes towards consanguinity. Receiving health information on consanguinity was associated with a negative attitude towards this practice. PMID:26835408

  13. IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome.

    PubMed

    Aldahmesh, Mohammed A; Li, Yuanyuan; Alhashem, Amal; Anazi, Shams; Alkuraya, Hisham; Hashem, Mais; Awaji, Ali A; Sogaty, Sameera; Alkharashi, Abdullah; Alzahrani, Saeed; Al Hazzaa, Selwa A; Xiong, Yong; Kong, Shanshan; Sun, Zhaoxia; Alkuraya, Fowzan S

    2014-06-15

    Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease.

  14. Spectra of small Koronis family members

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Rivkin, A.; Trilling, D.; Moskovitz, N.

    2014-07-01

    The space-weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites are long-standing problems in asteroid science. Although the visible and near-infrared spectra of S- and Q-type objects qualitatively show the same absorption features and quantitatively show evidence of the same minerals, the S types display increased spectral slopes and muted absorption features compared to the Q types. This spectral mismatch is consistent with the effects of the space weathering process. Binzel et al. provided the missing link between Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to the transition from Q- to S-type spectra. This result implied that size, and therefore age, is related to the relationship between Q- and S-type. The existence of Q-type objects in the main belt was not confirmed until Mothe-Diniz and Nesvorny (2008) found them in young S-type clusters. To investigate the trend from Q to S in the main belt, we examined space weathering within the old main-belt Koronis family using a spectrophotometric survey (Rivkin et al. 2011, Thomas et al. 2011). Rivkin et al. (2011) identified several potential Q-type objects within the Koronis family. Our Q-type candidates were identified using broad-band spectrophotometry and could not be taxonomically classified on that basis alone. We obtained follow-up visible and near-infrared spectral observations of our potential Q-type objects, (26970) Elias, (45610) 2000 DJ_{48}, and (37411) 2001 XF_{152}, using Gemini and Magellan. We will present the results of these spectral follow-up observations. Observations of (26970) Elias demonstrate that the object is more consistent with the average Q-type spectrum than the average S-type spectrum.

  15. Consanguinity and other marriage market effects of a wealth shock in Bangladesh.

    PubMed

    Mobarak, Ahmed Mushfiq; Kuhn, Randall; Peters, Christina

    2013-10-01

    This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved.

  16. Consanguinity trends and correlates in the Palestinian Territories.

    PubMed

    Assaf, Shireen; Khawaja, Marwan

    2009-01-01

    Secondary analysis of the trends and correlates of consanguinity in the Palestinian Territories was conducted using data from two separate surveys in 1995 and 2004. The analysis was conducted on ever-married women aged 15-54 who were asked about their relation to their husband in both surveys. A total of 16,197 women in 1995 and 4971 women in 2004 were successfully interviewed. Consanguinity was found to be widely practised in the Palestinian Territories with rates of total consanguinity reaching 45% of all marriages in 2004. Analysis was conducted with the data from the two surveys combined and this indicated that consanguinity was significantly decreasing with time after controlling for other variables. Age of the women, their age at marriage, region and locality type they lived in and their standard of living were all found to be significant predictors of consanguinity. The education level of the women was not found to be significant. After controlling for the survey year, women's labour force status was also found to be a non-significant predictor of consanguinity. Although consanguinity was found to be significantly decreasing slowly with time after controlling for other variables, the future trends of consanguinity are not known due to the unstable political situation in the territories, which could have a direct effect on marriage patterns.

  17. Training and HRD Strategies in Family and Non-Family Owned Small Businesses: A Comparative Approach.

    ERIC Educational Resources Information Center

    Matlay, Harry

    2002-01-01

    A survey of 6,000 British small businesses, 600 interviews, and 120 case studies found that 70-80% were family owned; most favored informal management styles. In family-owned businesses, training of nonfamily employees was considered less crucial; investments in the latter were related to long-term business strategies and potential succession.…

  18. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  19. Consanguineous marriages in the province of Antalya, Turkey.

    PubMed

    Alper, O M; Erengin, H; Manguoğlu, A E; Bilgen, T; Cetin, Z; Dedeoğlu, N; Lüleci, G

    2004-01-01

    To assess the trends in the frequency and the medical effects of consanguinity in the south coast of Turkish population using local and national data in the last 11 years. This cross-sectional study was carried out in Manavgat province, which is a major tourism center on the Mediterranean coast of Turkey. The authors studied consanguineous marriages in rural and urban population in the Mediterranean coast, Manavgat province, Turkey, via a 1500 random survey sample of married couples. There has been a significant increase in the incidence of consanguineous marriages in rural areas (40.7%) since 1989 in the southern population of Turkey. The results showed that the most frequent type of marriage was between the first cousins. It is found that there is no statistically significant difference between the consanguineous and non-consanguineous marriages in the different age groups. The results were discussed on the basis of educational status, reasons for having consanguineous marriages and the general medical effects as well as with the relation of congenital malformations. The custom of consanguineous unions in the Mediterranean population of Turkey is still extremely high, and preventive measures should be done to decrease its frequency and associated complications.

  20. Posttranslational lipid modification of Rho family small GTPases.

    PubMed

    Mitin, Natalia; Roberts, Patrick J; Chenette, Emily J; Der, Channing J

    2012-01-01

    The Rho family comprises a major branch of the Ras superfamily of small GTPases. A majority of Rho GTPases are synthesized as inactive, cytosolic proteins. They then undergo posttranslational modification by isoprenoid or fatty acid lipids, and together with additional carboxyl-terminal sequences target Rho GTPases to specific membrane and subcellular compartments essential for function. We summarize the use of biochemical and cellular assays and pharmacologic inhibitors instrumental for the study of the role of posttranslational lipid modifications and processing in Rho GTPase biology.

  1. Ras Family Small GTPase-mediated Neuroprotective Signaling in Stroke

    PubMed Central

    Shi, Geng-Xian; Andres, Douglas A.; Cai, Weikang

    2012-01-01

    Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of stroke, the overall mechanisms governing the balance between cell survival and death are not well-defined. Ras family small GTPases are activated following ischemic insults, and in turn, serve as intrinsic switches to regulate neuronal survival and regeneration. Their ability to integrate diverse intracellular signal transduction pathways makes them critical regulators and potential therapeutic targets for neuronal recovery after stroke. This article highlights the contribution of Ras family GTPases to neuroprotective signaling cascades, including mitogen-activated protein kinase (MAPK) family protein kinase- and AKT/PKB-dependent signaling pathways as well as the regulation of cAMP response element binding (CREB), Forkhead box O (FoxO) and hypoxia-inducible factor 1(HIF1) transcription factors, in stroke. PMID:21521171

  2. Effects of consanguinity on pre-reproductive mortality: does demographic transition matter?

    PubMed

    Alfonso-Sánchez, Miguel A; Peña, José A

    2005-01-01

    The aim of this study was to investigate whether there is an increase on premature deaths due to genetically determined factors at the beginning of a demographic transition. We also analyzed the effects of parental consanguinity on offspring mortality from an epidemiological viewpoint, using parish records for family reconstitution in a Basque population (1800-1990). Among the offspring of unrelated parents, 13.1% died before their first year of life (infant mortality), and 22.8% died before the age of 16 (pre-reproductive mortality). Significant increases in both infant (23.6%) and pre-reproductive (38.5%) deaths were found among the progeny of first cousins or closer relatives, 1C (F > or = 0.0625). The corresponding relative risks of mortality were 1.79 (95% confidence limits: 1.37-2.28) and 1.68 (1.38-2.01), respectively. Estimates of the population attributable risks indicate that 4% of pre-reproductive mortality is ascribable to consanguineous unions, although kinships other than 1C produced only slight increases in offspring mortality. Evidence on the relationship between the demographic transition and the increase in premature deaths due to genetic factors was obtained through a principal component analysis (95.1% of variance accounted for). During the initial stages of the demographic transition, the population experienced substantial elevations in mean family size, natural increase of the population, frequency of close consanguineous matings (1C), and death rate due to congenital anomalies and perinatal diseases. These findings are of interest for the health services of many developing societies in Asia, Africa, and Latin America, which are nowadays immersed in the demographic transition process.

  3. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.

    PubMed

    Onesto, Cercina; Shutes, Adam; Picard, Virginie; Schweighoffer, Fabien; Der, Channing J

    2008-01-01

    There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that block Rho GTPase function indirectly, either by targeting enzymes involved in post-translational processing or downstream protein kinase effectors. We have reported the identification and characterization of the EHT 1864 small molecule as an inhibitor of Rac family small GTPases, placing Rac1 in an inert and inactive state and then impairing Rac1-mediated functions in vivo. Our work suggests that EHT 1864 selectively inhibits Rac1 downstream signaling and cellular transformation by a novel mechanism involving guanine nucleotide displacement. This chapter provides the details for some of the biochemical and biological methods used to characterize the mode of action of EHT 1864 on Rac1 and its impact on Rac1-dependent cellular functions.

  4. Impact of consanguineous marriages in GJB2-related hearing loss in the Iranian population: a report of a novel variant.

    PubMed

    Mahdieh, Nejat; Rabbani, Bahareh; Shirkavand, Atefeh; Bagherian, Hamideh; Movahed, Zahra Shahab; Fouladi, Paanti; Rahiminejad, Faezeh; Masoudifard, Masoumeh; Akbari, Mohammad Taghi; Zeinali, Sirous

    2011-01-01

    Mutations in GJB2 and GJB6 genes are the main causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Here, we investigated GJB2 and GJB6 mutations in 114 patients from 77 affected ARNSHL families including 54 consanguineous marriages and 23 nonrelative marriages in the Iranian population. Clinical studies and genetic counseling were performed for all families. GJB2 and GJB6 genes were directly sequenced. Three known GJB6 large deletions [del(GJB6-D13S1830), del(GJB6-D13S1854), and a 920 kb deletion] were also checked by quantification of a common deleted region within the GJB6 gene. The frequency of consanguinity was 70.13% among the studied families. Biallelic GJB2 mutations were 16.67% in consanguineous marriages and 4.35% in nonrelative marriages. Mutations found were 35delG, delE120, R127H, M163V, W24X, V37I, G12D, V84A, 313-326del14, and E110K. The latter was a novel variant. Neither point mutation nor a large deletion in the GJB6 gene was found in the population. Mean frequency of GJB2 mutations was 17.92%. GJB2 mutations (and not GJB6 mutations) are the major causes of hearing loss in Iran. The role of consanguineous marriages is also highlighted in occurrence of GJB2-related hearing loss. We suggest that other genes may be involved in the population.

  5. Recessive versus imprinted disorder: consanguinity can impede establishing the diagnosis of autosomal dominant pseudohypoparathyroidism type Ib

    PubMed Central

    Turan, Serap; Akin, Leyla; Akcay, Teoman; Adal, Erdal; Sarikaya, Sevil; Bastepe, Murat; Jüppner, Harald

    2010-01-01

    Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright’s hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH-resistance rather than PTH-deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, autosomal dominant disorder even if consanguinity suggests an autosomal recessive mode of inheritance. PMID:20538864

  6. Family Portrait of the Small Inner Satellites of Jupiter

    NASA Technical Reports Server (NTRS)

    1997-01-01

    These images, taken by Galileo's solid state imaging system between November 1996 and June 1997, provide the first ever 'family portrait' of the four small, irregularly shaped moons that orbit Jupiter in the zone between the planet's ring and the larger Galilean satellites. The moons are shown in their correct relative sizes, with north approximately up in all cases. From left to right, arranged in order of increasing distance from Jupiter, are Metis (longest dimension is approximately 60 kilometers or 37 miles across), Adrastea (20 kilometers or 12 miles across), Amalthea (247 kilometers or 154 miles across), and Thebe (116 kilometers or 72 miles across). While Amalthea, the largest of these four tiny moons, was imaged by NASA's two Voyager spacecraft in 1979 with a resolution comparable to what is shown here, the new Galileo observations represent the first time that Metis, Adrastea, and Thebe have been seen as more than points of light.

    The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

    This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://www.jpl.nasa.gov/ galileo.

  7. Consanguinity and genetic diseases in North Africa and immigrants to Europe.

    PubMed

    Anwar, Wagida A; Khyatti, Meriem; Hemminki, Kari

    2014-08-01

    Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease.

  8. First steps in exploring prospective exome sequencing of consanguineous couples.

    PubMed

    Teeuw, Marieke; Waisfisz, Quinten; Zwijnenburg, Petra J G; Sistermans, Erik A; Weiss, Marjan M; Henneman, Lidewij; ten Kate, Leo P; Cornel, Martina C; Meijers-Heijboer, Hanne

    2014-01-01

    Consanguinity is one of the most frequent risk factors for congenital disorders. In theory, prospective exome sequencing of consanguineous couples could identify couples who both are carriers of autosomal recessive diseases, and empower such couples to make informed reproductive decisions. To investigate this, we sent blood samples to our laboratory of four pairs of consanguineous parents having one or more children affected by an autosomal recessive disorder, without revealing any diagnostic information. The study was restricted to find identical, previously described, or evidently pathogenic mutations in both parents of each couple, in over 400 genes known to result in severe autosomal recessive disorders. Out of the six autosomal recessive disorders known to the four couples studied, two were correctly identified. Carrier status of one not previously known autosomal recessive disorder was discovered. As expected, given the pipeline used, large deletions, mutations in genes not present in the gene list, mutations outside the exons and consensus splice sites, and mutations that were not evidently pathogenic and previously not reported, were not identified. The restriction to detecting only couples with identical mutations diminishes the risk of revealing unsolicited findings and shortens the time needed for analysis, but also results in missing couples with different mutations in the same gene. In addition to the proposed pipeline, couples should be offered testing for carrier status of frequent disorders that can present themselves by large deletions, non-exonic mutations or compound heterozygous mutations (e.g. thalassemia, spinal muscular atrophy, cystic fibrosis). Even though sensitivity is reduced, offering exome sequencing prospectively will increase reproductive options for consanguineous couples.

  9. Consanguinity and late fertility: spatial analysis reveals positive association patterns.

    PubMed

    Lisa, Antonella; Astolfi, Paola; Zei, Gianna; Tentoni, Stefania

    2015-01-01

    The role of consanguinity on human complex traits is an important and controversial issue. In this work we focused on the Sardinian population and examined the effect of consanguineous unions on late female fertility. During the last century the island has been characterized by a high incidence of marriages between relatives, favoured by socio economic conditions and geographical isolation, and by high fertility despite a widespread tendency to delay reproduction. Through spatial analysis techniques, we explored the geographical heterogeneity of consanguinity and late fertility, and identified in Central-Eastern Sardinia a common area with an excess of both traits, where the traits are positively associated. We found that their association did not significantly affect women's fertility in the area, despite the expected negative role of both traits. Intriguingly, this critical zone corresponds well to areas reported by previous studies as being peculiar for a high frequency of centenarians and for lower risk in pregnancy outcome. The proposed approach can be generally exploited to identify target populations on which socioeconomic, biodemographic and genetic data can be collected at the individual level, and deeper analyses carried out to disentangle the determinants of complex biological traits and to investigate their association.

  10. CONSANGUINITY AND INBREEDING COEFFICIENT IN TRIBAL PASHTUNS INHABITING THE TURBULENT AND WAR-AFFECTED TERRITORY OF BAJAUR AGENCY, NORTH-WEST PAKISTAN.

    PubMed

    Ahmad, Bashir; Rehman, Atta Ur; Malik, Sajid

    2016-01-01

    The north-western populations of Pakistan in the Federally Administered Tribal Areas (FATA) adjoining the Pakistan-Afghanistan border are an amalgamation of native and migrated Pashtun tribes. These tribal populations are in transition due to war conditions and geo-political turmoil on both sides of the border since the Soviet invasion in 1979. Bio-demographic and epidemiological data for these tribes are scarce. A prospective cross-sectional sample of 967 males was selected from a representative Pashtun population of Bajaur Agency, and information obtained on bio-demographic variables and marital union types. Analysis of these data revealed that consanguinity was 22.34% and the inbreeding coefficient F was calculated to be 0.0134. The inbreeding coefficient was observed to be higher in subjects who were illiterate, had unskilled jobs and who belonged to younger age categories, extended families and the Tarkalani tribe. Further analyses with respect to temporal variables like subject's age, year of marriage and age at marriage revealed that after a transition in marital union types in the early 80s, there has been a declining trend in the rate of consanguineous unions. Further, consanguineous unions in the parental generation were only 5%, but parental marriage types were predictors of subjects' marital union types. The data further establish that, contrary to a general notion about a high consanguinity rate in Pakistan, consanguineous unions are not common in Bajaur Agency and first cousin marriage is not the preferred type. Furthermore, this research shows that there is a great regional variation in the pattern of consanguinity in Pakistan that needs to be documented in order to draw a more comprehensive picture of the inbreeding coefficient in the country.

  11. Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population

    PubMed Central

    2011-01-01

    Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation. Aim of the study consanguinity rates have been determined among 14 families with mucopolysaccharidosis type I, seen in the pediatric departments of different geographic areas of Tunisia (Central and Southern areas) for the period August 2004 - August 2011 in order to investigate the relation between consanguinity and this disorder. Patients and methods Clinical and molecular analyses confirmed the diagnosis for MPS type I in the studied families. Results Most of the Tunisian MPS I patients have been identified at the homozygous status: p.P533R mutation (7 homozygous and one double heterozygous p.L578Q/p.P533R patients; 41.66% of all the investigated MPSI patients), p.F177S (1 homozygous patient; 5.55%), p.L530fs (1 patient; 5.55%), p.Y581X (2 patients; 11.11%), p.F602X (3 patients; 16.66%), p.R628X (1 patient; 5.55%). Another mutation: p.L578Q has been identified at the heterozygous status in the only double heterozygous p.L578Q/p.P533R case. Part of the mutations was the result of a founder effect. These described points are the consequences of the high rate of consanguinity. Conclusion The high frequency of p.P533R mutation could be explained by the high degree of inbreeding. This is due to the richness of the genetic background of the studied population. A multidisciplinary approach is essential to develop adequate preventive program adapted to the social, cultural, and economic context. PMID:22074387

  12. The practice of consanguineous marriage in Oman: prevalence, trends and determinants.

    PubMed

    Islam, M Mazharul

    2012-09-01

    The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health.

  13. Effect of consanguinity on Argentinean Angus beef DNA traceability.

    PubMed

    Baldo, A; Rogberg-Muñoz, A; Prando, A; Mello Cesar, A S; Lirón, J P; Sorarrain, N; Ramelli, P; Posik, D M; Pofcher, E; Ripoli, M V; Beretta, E; Peral-García, P; Vaca, R; Mariani, P; Giovambattista, G

    2010-08-01

    Since the 1990s several authors have envisaged the use of DNA to certify meat origin. Two major parameters must be assessed before a DNA based traceability protocol can be implemented in the food chain: (i) the information content of a DNA marker set in a specific livestock breed or group of breeds; (ii) the minimum number of DNA markers needed to obtain a statistically acceptable match probability. The objective of the present work was to establish the effect of different levels of inbreeding in the matching efficiency, and the minimum number of microsatellite markers needed, in a DNA based meat traceability program, starting from an 11-microsatellite marker panel. Samples were obtained from beef production farms in South America, where animals are typically bred under pasture-based extensive conditions. Three groups of animals with different consanguinity rates were sampled. Exclusion power (Q) was higher than 0.999998 and match probability lower than 3.01E-08, for the whole set of markers within each group. Both values were affected by consanguinity. To reach a two mismatch criteria exclusion power (Q(2)) of 99.99, six markers were needed in unrelated animals whereas seven markers were needed in related animals. To reach Q(2)=99.9999, 8 and 10 microsatellite markers, respectively, were needed. In general, one or two more microsatellite markers were needed to identify consanguineous animals. This study proved the DNA marker set used to be suitable for the identification of the meat from all slaughtered animals in Argentina, per week, month, and year.

  14. The Family Farm in California. Final Report of the Small Farm Viability Project.

    ERIC Educational Resources Information Center

    California State Office of Economic Development, Sacramento. Community Services Administration.

    Most of California's farms are relatively small, family run operations, and their future has been called into question by current agricultural trends. The Small Farm Viability Planning Project was initiated to identify obstacles to small farm economic viability and make recommendations to the state on policies and actions that might reduce these…

  15. Promoting Population Stabilization: Incentives for Small Families. Worldwatch Paper 54.

    ERIC Educational Resources Information Center

    Jacobsen, Judith

    A wide variety of incentive and disincentive programs are presented in an effort to stabilize the population and prevent bankruptcy of physical, economic, and social resources, particularly in countries like India and China. Following an introduction, the document discusses several programs, including (1) the use of small one-time payments for…

  16. Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness.

    PubMed

    Lezirovitz, Karina; Pardono, Eliete; de Mello Auricchio, Maria T B; de Carvalho E Silva, Fernando L; Lopes, Juliana J; Abreu-Silva, Ronaldo S; Romanos, Jihane; Batissoco, Ana C; Mingroni-Netto, Regina C

    2008-01-01

    Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.

  17. Small families mean better health for mothers and kids.

    PubMed

    Mugumya, E

    1994-01-01

    The practice of family planning (FP) has been used since time immemorial to solve community, individual, and familial problems. There are Biblical references to incest being used to ensure the conception of children and to coitus interruptus being used to prevent conception. Pastoralists used cessation of breastfeeding of male calves to promote the conception and birth of more desirable female calves. The condom has ancient precursors made of animal intestines, and the IUD has a prototype in the stone commonly inserted in the uterus of a camel during long journeys to prevent conception. The issues of effectiveness, safety, and convenience that led to these ancient activities also inform the development and use of modern contraception. FP incorporates fertility control, both treatment for infertility and contraception; abortion is regarded as an indicator of a need for FP, not as part of FP. FP is justified on the grounds of human rights, because it allows an individual to choose whether or not to have a child; on the grounds of health, because maternal age and parity affect the health of the mother and child; on socioeconomic grounds, because overpopulation creates drains on already decreasing resources and because birth to unwed mothers creates difficulties for the children and for society; and on the grounds of improving the status of women because unwanted pregnancy causes women to abandon educational and employment opportunities. The maternal and child health and FP services in Uganda provide immunization, nutrition, prenatal and postpartum care, young child clinic services, school health education, and FP services.

  18. Out of Sight, Out of Mind: Homeless Children and Families in Small-Town America.

    ERIC Educational Resources Information Center

    Vissing, Yvonne M.

    Homelessness in small towns and rural areas is on the rise, and a substantial portion of the rural homeless consists of families with children. This book draws on interviews and case studies of over 300 homeless children and their families, primarily in New Hampshire, and on supporting statistics to provide individual and sociological perspectives…

  19. Fertility Related Attitudes of Minority Mothers with Large and Small Families.

    ERIC Educational Resources Information Center

    Linn, Margaret W.; And Others

    The relationship between certain attitudes and the levels of fertility in five cultural groups was explored in this study. The group studied were blacks, Cubans, American Indians, migrant Chicanos, and white Protestants. Mothers, aged 35-45, with one or two children (small family) or five children (large family) were compared. Attitudes measured…

  20. A novel family of small proteins that affect plant development

    SciTech Connect

    John Charles Walker

    2011-04-29

    The DVL genes represent a new group of plant proteins that influence plant growth and development. Overexpression of DVL1, and other members of the DVL family, causes striking phenotypic changes. The DVL proteins share sequence homology in their C-terminal half. Point mutations in the C-terminal domain show it is necessary and deletion studies demonstrate the C-terminal domain is sufficient to confer the overexpression phenotypes. The phenotypes observed, and the conservation of the protein sequence in the plant kingdom, does suggest the DVL proteins have a role in modulating plant growth and development. Our working hypothesis is the DVL proteins function as regulators of cellular signaling pathways that control growth and development.

  1. Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

    PubMed Central

    2010-01-01

    Background The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. Methods/Design This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. Discussion This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous parents of affected children

  2. The prevalence and correlates of consanguineous marriages in Yemen: similarities and contrasts with other Arab countries.

    PubMed

    Jurdi, Rozzet; Saxena, Prem C

    2003-01-01

    Using data on 9762 women from the 1997 Yemen Demographic and Maternal and Child Health Survey, this paper examines the prevalence and socioeconomic correlates of consanguineous marriages in Yemen. The results indicate that 40% of marriages are consanguineous, over 85% of which are between first cousins. The prevalence of consanguineous marriages appears to have increased over time, particularly for the last marriage cohort. As for socioeconomic correlates, the study confirms the inverse association between consanguineous marriages and women's education and occupation, age at marriage and economic status. However, no statistically significant difference in the prevalence of consanguinity has been found by place of residence and geographical region. Somewhat unexpected results have been obtained by husband's background characteristics, with higher educated men and those working in the modern sector of the economy being more likely to be married to cousins.

  3. Domestic violence and consanguineous marriages - perspective from Rawalpindi, Pakistan.

    PubMed

    Shaikh, M Ali; Kayani, A; Shaikh, I Ali

    2014-01-09

    Domestic violence is globally endemic and adversely impacts the health and economic well-being of women and society. This study used the standardized and validated assessment instrument "Woman Abuse Screening Tool" to study the prevalence of various forms of domestic violence among married women. The relationship between domestic violence and consanguineous marriage was studied using the chi-squared test. Cumulatively, 1010 married women were interviewed. Emotional abuse was the most commonly reported abuse, reported by 721 (71.4%) women as either often or sometimes, followed by sexual abuse and physical abuse, reported by 527 (52.2%) and 511 (50.6%) respectively. Being married to one's cousin did not protect married women from being abused either emotionally or physically by their husbands; thsi was statistically significant. There is a need for better understanding of the magnitude and scale of domestic violence in Pakistan by using standardized assessment tools for meaningful comparisons across different parts of the country over time.

  4. Genetic studies of the members of small, dynamical asteroid families

    NASA Astrophysics Data System (ADS)

    Kelley, Michael Shawn

    1999-10-01

    Analyses of spectrophotometric data of asteroids 9 Metis and 113 Amalthea have revealed a probable genetic (compositional) link between these two objects. The nearly identical composition of the silicate components of these two asteroids is consistent with their derivation from a single parent body. Based on the present compositional and morphological interpretations of 9 Metis and 113 Amalthea, and using plausible (chondritic) starting compositions for the parent body, the original parent asteroid is estimated to have been between approximately 300 and 600 kilometers in diameter. Thus Metis and Amalthea are the largest survivors of a highly-evolved, genetic asteroid family from which 86-96% of the original mass has been lost. New data in the wavelength region of approximately 0.4-2.5 μm have been obtained for asteroid 434 Hungaria. This is the most complete visible to near- infrared spectrum to date for this object. The near- infrared portion of the spectrum is smooth, featureless, and agrees well with previous visible region data. Hungaria's relatively high albedo of 46 percent and lack of intense spectral absorption features strictly limits the suite of possible mineral analogs for this asteroid. Based on spectral, meteoritic and petrologic considerations the silicate composition of the surface of Hungaria is mostly likely made up of iron-free enstatite. However, new visible region data appear to exhibit weak, broad spectral absorption features near 0.5, 0.6, and 1 μm. While the features near 0.5 and 1 μm are unreliable and inconsistent, the weak feature near 0.6 μm appears to be real and may help to constrain the composition of Hungaria. Most minerals which exhibit a similar absorption feature, and are commonly found in meteorites, have a much lower albedo. The dark chondritic inclusions in the Cumberland Falls aubrite exhibit a similar feature near 0.6 μm, and this meteorite provides a possible spectral and compositional analog for Hungaria.

  5. Genomic runs of homozygosity record population history and consanguinity.

    PubMed

    Kirin, Mirna; McQuillan, Ruth; Franklin, Christopher S; Campbell, Harry; McKeigue, Paul M; Wilson, James F

    2010-11-15

    The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (N(e)), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental N(e) (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.

  6. Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Calé--a study of 83 cases.

    PubMed

    Gamella, Juan F; Carrasco-Muñoz, Elisa Martín; Núñez Negrillo, Ana María

    2013-09-01

    This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks of Gitanos in southeastern Spain, and analyzes their sustained inbreeding patterns and complex genealogical relationships. It is based in the family and genealogy reconstitution of the Gitano population of 22 contiguous localities using ethnographic and historical demography methods. The study found a prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases belong to three extended kin networks in which consanguineous marriages have been common for generations. In these networks there are other cases of visual and auditive congenital anomalies, and other birth defects such as brachydactily, polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was possible to trace inbreeding links with a depth of three to nine generations. For these cases the estimated alpha (average of the inbreeding coefficient, F) is 0.0222. Relationships between the parents of people affected are of three types: close, as between first or second cousins; distant, as between third or fourth cousins, and non-existent, as in mixed marriages. In most cases, however, persons with albinism are linked by multiple consanguineous links. Albinism seems to be a visible example of a high prevalence of birth defects in this minority, associated with founder effects, sustained inbreeding and high fertility rates. These conditions derive from Gitano's marriage preferences and pronatalist strategies. In turn, these strategies have to be related to the exclusion, persecution and segregation that Spanish Gypsies have suffered for centuries.

  7. Isonymy, consanguinity and repeated pairs of surnames in Aromun populations.

    PubMed

    Schmidt, H D; Efremovska, L; Handziski, Z

    2001-09-01

    The Aromuns represent a small and almost unknown people that live scattered over the Balkan Peninsula. Due to their language, that is very similar to classical Latin, they are in a special position. The Aromuns settled only in more recent times. Until now they lived as shepherds, as caravan guides and merchants and lead a semi-nomadic life. We are currently carrying out studies to determine the genetic structure of this population. To facilitate the interpretation of these data, we are also trying to obtain other important parameters that pertain to migration processes and the genealogical structure of this populations. The data arise from three areas in Albania, the Republic of Macedonia and Romania. The inbreeding coefficient and the proportion of repeated pairs of surnames was calculated through the use of genealogies and the isonymy method. The difference between these three populations are due primarily to confounding by selection of mates and family composition.

  8. Gender, Work-Family Linkages, and Economic Success among Small Business Owners.

    ERIC Educational Resources Information Center

    Loscocco, Karyn A.; Leicht, Kevin T.

    1993-01-01

    Investigated work-family connections and economic success among women and men small business owners. Analyses of data from 3-year panel survey of 99 women and 312 men showed considerable gender similarity in processes through which business and individual characteristics affect personal earnings, although women were disadvantaged in some…

  9. Spectrum of malformations of the hindbrain (cerebellum, pons, and medulla) in a cohort of children with high rate of parental consanguinity.

    PubMed

    Sztriha, László; Johansen, Johan G

    2005-06-01

    We review 25 patients with a spectrum of hindbrain (cerebellum, pons, and medulla) malformations from a cohort of children with high parental consanguinity rate. Twenty-three of the 25 patients were born to consanguineous parents. The patients were classified in four groups. Eleven patients of 6 families had malformation of the hindbrain and midbrain with molar tooth sign (10 patients of 5 families with typical Joubert syndrome), 5 patients showed severe supratentorial anomalies in addition to the hindbrain malformations, 5 patients had pontocerebellar or cerebellar hypoplasia with anterior horn cell disease in the spinal cord (spinal muscular atrophy), and 4 patients showed malformations affecting predominantly the hindbrain without substantial involvement of other systems. A locus for Joubert syndrome was previously identified on chromosome 9q34.3 in two families, and a second locus on chromosome 11p12-q13.3 in another family. A third Joubert syndrome locus has been mapped at 6q23 and a mutation in the AHI1 gene at this site has been found recently in a further family from this cohort. Delineation of homogeneous subgroups of patients with hindbrain malformations and molecular genetic analysis of these groups may lead to identification of further loci, genes and mutations responsible for the malformations.

  10. Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation.

    PubMed

    Fuster, V; Jiménez, A M; Colantonio, S E

    2001-04-01

    The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tiétar) are interpreted considering the geography, population size, and population mobility for each valley

  11. Investigation of current university research concerning energy conversion and conservation in small single-family dwellings

    NASA Technical Reports Server (NTRS)

    Grossman, G. R.; Roberts, A. S., Jr.

    1975-01-01

    An investigation was made of university research concerning energy conversion and conservation techniques which may be applied in small single-family residences. Information was accumulated through published papers, progress reports, telephone conversations, and personal interviews. A synopsis of each pertinent investigation is given. Finally, a discussion of the synopses is presented and recommendations are made concerning the applicability of concepts for the design and construction of NASA-Langley Research Center's proposed Technology Utilization House in Hampton, Virginia.

  12. Challenges in the care for consanguineous couples: an exploratory interview study among general practitioners and midwives

    PubMed Central

    2012-01-01

    Background It is often suggested that an effort must be made to increase awareness among consanguineous couples of their reproductive risk, and to refer them for genetic counseling if needed. Primary care professionals are considered most appropriate for addressing the subject and identifying couples at risk during consultations in their practice. This Dutch study aims to explore the experiences, attitudes and beliefs of such professionals regarding their care for consanguineous couples. Methods Sixteen semi-structured interviews were conducted with midwives and general practitioners. Results Although most primary care professionals considered it their task to inform couples about the risks of consanguinity, during consultations the topic was generally only briefly touched upon and quickly abandoned. Important reasons for this were professionals’ beliefs about religious and social values of couples, their low perception of the couples’ reproductive risk and expected limited feasibility of referral. Feelings of embarrassment regarding addressing consanguinity did not seem to play a significant role. Conclusions Primary care professional beliefs about their clients’ religious and social values, their attitudes toward the risk, and perceived limited options for referral seem to conflict with the professional norm to address the topic of consanguinity. PMID:23102514

  13. Frequency of consanguineous marriages among parents and grandparents of Down patients.

    PubMed

    Devoto, M; Prosperi, L; Bricarelli, F D; Coviello, D A; Croci, G; Zelante, L; Ferranti, G; Tenconi, R; Stomeo, C; Romeo, G

    1985-01-01

    The existence of a rare autosomal gene which in the homozygous state would cause mitotic nondisjunction in the Down zygote has been hypothesized in the past by Alfi et al. (1980). This hypothesis can be supported or contradicted by the study of the frequency of consanguineous marriages among parents of affected children. Our study on 242 children affected with Down syndrome does not show any increase in the frequency of consanguineous marriages among their parents with respect to the general population, and therefore does not support the hypothesis of an autosomal gene controlling mitotic nondisjunction. Our data do not show any increase in the frequency of consanguineous marriages even among paternal and maternal grandparents of the affected children, thus not supporting the other possible explanation of an autosomal recessive condition in one of the patient's parents which would cause meiotic nondisjunction.

  14. An empirical analysis of the effects of consanguineous marriages on economic development.

    PubMed

    Bildirici, Melike; Kökdener, Meltem; Ersin, Oezgür ömer

    2010-01-01

    In this study, development experiences toward economic development are investigated to provide an alternative analysis of economic development, human capital, and genetic inheritance in the light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriage practices and classified by their per capita gross domestic product (GDP) growth. A broad range of countries are analyzed in the study. Arab countries that experienced high rates of growth in their gross national income during the twentieth century but failed to fulfill adequate development measures as reflected in the growth in national income, countries undergoing transition from tight government regulation to free market democracy, and African nations that have experienced complications in the process of development show important differences in the process of economic development. It is shown that the countries that have reached high average development within the context of per capita GDP have overcome problems integral to consanguineous marriage.

  15. The effect of reproductive compensation on recessive disorders within consanguineous human populations.

    PubMed

    Overall, A D J; Ahmad, M; Nichols, R A

    2002-06-01

    We investigate the effects of consanguinity and population substructure on genetic health using the UK Asian population as an example. We review and expand upon previous treatments dealing with the deleterious effects of consanguinity on recessive disorders and consider how other factors, such as population substructure, may be of equal importance. For illustration, we quantify the relative risks of recessive lethal disorders by presenting some simple calculations that demonstrate the effect 'reproductive compensation' has on the maintenance of recessive alleles. The results show how reproductive compensation can effectively counteract the purging of deleterious alleles within consanguineous populations. Whereas inbreeding does not elevate the equilibrium frequency of affected individuals, reproductive compensation does. We suggest this effect must be built into interpretations of the incidence of genetic disease within populations such as the UK Asians. Information of this nature will benefit health care workers who inform such communities.

  16. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.

    PubMed

    Shutes, Adam; Onesto, Cercina; Picard, Virginie; Leblond, Bertrand; Schweighoffer, Fabien; Der, Channing J

    2007-12-07

    There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes the uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that indirectly block Rho GTPase function, by targeting either enzymes involved in post-translational processing or downstream protein kinase effectors. We recently determined that the EHT 1864 small molecule can inhibit Rac function in vivo. In this study, we evaluated the biological and biochemical specificities and biochemical mechanism of action of EHT 1864. We determined that EHT 1864 specifically inhibited Rac1-dependent platelet-derived growth factor-induced lamellipodia formation. Furthermore, our biochemical analyses with recombinant Rac proteins found that EHT 1864 possesses high affinity binding to Rac1, as well as the related Rac1b, Rac2, and Rac3 isoforms, and this association promoted the loss of bound nucleotide, inhibiting both guanine nucleotide association and Tiam1 Rac guanine nucleotide exchange factor-stimulated exchange factor activity in vitro. EHT 1864 therefore places Rac in an inert and inactive state, preventing its engagement with downstream effectors. Finally, we evaluated the ability of EHT 1864 to block Rac-dependent growth transformation, and we determined that EHT 1864 potently blocked transformation caused by constitutively activated Rac1, as well as Rac-dependent transformation caused by Tiam1 or Ras. Taken together, our results suggest that EHT 1864 selectively inhibits Rac downstream signaling and transformation by a novel mechanism involving guanine nucleotide displacement.

  17. Effect of consanguinity on birth weight for gestational age in a developing country.

    PubMed

    Mumtaz, Ghina; Tamim, Hala; Kanaan, Mona; Khawaja, Marwan; Khogali, Mustafa; Wakim, Gerard; Yunis, Khalid A

    2007-04-01

    Consanguinity, the marriage between relatives, has been associated with adverse child health outcomes because it increases homozygosity of recessive alleles. The objective of this study was to assess the effect of consanguinity on the birth weight of newborns in Greater Beirut, Lebanon. Cross-sectional data were collected on 10,289 consecutive liveborn singleton newborns admitted to eight hospitals belonging to the National Collaborative Perinatal Neonatal Network during the years 2000 and 2001. Birth weight was modeled by use of the fetal growth ratio, defined as the ratio of the observed birth weight to the median birth weight for gestational age. A mixed-effect multiple linear regression model was used to predict the net effect of first- and second-cousin marriage on the birth weight for gestational age, accounting for within-hospital clustering of data. After controlling for medical and sociodemographic covariates, the authors found a statistically significant negative association between consanguinity and birth weight at each gestational age. No significant difference was observed in the decrease in birth weight between the first- and second-cousin marriages. Overall, consanguinity was associated with a decrease in birth weight for gestational age by 1.8% (beta = -0.018, 95% confidence interval: -0.027, -0.008). The largest effects on fetal growth were seen with lower parity and smoking during pregnancy.

  18. Small Science: Infants and Toddlers Experiencing Science in Everyday Family Life

    NASA Astrophysics Data System (ADS)

    Sikder, Shukla; Fleer, Marilyn

    2014-09-01

    Vygotsky (1987) stated that the restructured form of everyday concepts learned at home and in the community interact with scientific concepts introduced in formal school settings, leading to a higher level of scientific thinking for school-aged children. But, what does this mean for the scientific learning of infants and toddlers? What kinds of science learning are afforded at home during this early period of life? The study reported in this paper sought to investigate the scientific development of infants-toddlers (10 to 36 months) growing up in Bangladeshi families living in Australia and Singapore. Four families were studied over 2 years. Digital video observations were made of everyday family life and analysed using Vygotsky's theoretical framework of everyday concepts and scientific concepts (51 h of digital observations). While there are many possibilities for developing scientific concepts in infants-toddlers' everyday life, our study found four categories of what we have called small science: multiple possibilities for science; discrete science; embedded science and counter intuitive science. The findings of this study contribute to the almost non-existent literature into infants and toddlers' scientific development and advance new understandings of early childhood science education.

  19. Small Science: Infants and Toddlers Experiencing Science in Everyday Family Life

    NASA Astrophysics Data System (ADS)

    Sikder, Shukla; Fleer, Marilyn

    2015-06-01

    Vygotsky (1987) stated that the restructured form of everyday concepts learned at home and in the community interact with scientific concepts introduced in formal school settings, leading to a higher level of scientific thinking for school-aged children. But, what does this mean for the scientific learning of infants and toddlers? What kinds of science learning are afforded at home during this early period of life? The study reported in this paper sought to investigate the scientific development of infants-toddlers (10 to 36 months) growing up in Bangladeshi families living in Australia and Singapore. Four families were studied over 2 years. Digital video observations were made of everyday family life and analysed using Vygotsky's theoretical framework of everyday concepts and scientific concepts (51 h of digital observations). While there are many possibilities for developing scientific concepts in infants-toddlers' everyday life, our study found four categories of what we have called small science: multiple possibilities for science; discrete science; embedded science and counter intuitive science. The findings of this study contribute to the almost non-existent literature into infants and toddlers' scientific development and advance new understandings of early childhood science education.

  20. A family of small coiled-coil-forming proteins functioning at the late endosome in yeast.

    PubMed

    Kranz, A; Kinner, A; Kölling, R

    2001-03-01

    The multispanning membrane protein Ste6, a member of the ABC-transporter family, is transported to the yeast vacuole for degradation. To identify functions involved in the intracellular trafficking of polytopic membrane proteins, we looked for functions that block Ste6 transport to the vacuole upon overproduction. In our screen, we identified several known vacuolar protein sorting (VPS) genes (SNF7/VPS32, VPS4, and VPS35) and a previously uncharacterized open reading frame, which we named MOS10 (more of Ste6). Sequence analysis showed that Mos10 is a member of a small family of coiled-coil-forming proteins, which includes Snf7 and Vps20. Deletion mutants of all three genes stabilize Ste6 and show a "class E vps phenotype." Maturation of the vacuolar hydrolase carboxypeptidase Y was affected in the mutants and the endocytic tracer FM4-64 and Ste6 accumulated in a dot or ring-like structure next to the vacuole. Differential centrifugation experiments demonstrated that about half of the hydrophilic proteins Mos10 and Vps20 was membrane associated. The intracellular distribution was further analyzed for Mos10. On sucrose gradients, membrane-associated Mos10 cofractionated with the endosomal t-SNARE Pep12, pointing to an endosomal localization of Mos10. The growth phenotypes of the mutants suggest that the "Snf7-family" members are involved in a cargo-specific event.

  1. How a Small Family Run Business Adopted Critical Reflection Action Learning Using Hand Drawn Images to Initiate Organisational Change

    ERIC Educational Resources Information Center

    Shepherd, Gary

    2016-01-01

    In this account of practice I would like to share my experiences of facilitating a Critical Reflection Action Learning (CRAL) set with a small family run business, struggling to make change and expand their services due to the problems they encountered in separating their business lives from their family lives. The account I present here is based…

  2. GASA4, One of the 14-Member Arabidopsis GASA Family of Small Polypeptides, Regulates Flowering and Seed Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Members of the plant-specific gibberellic acid-stimulated Arabidopsis (GASA) gene family play roles in hormone response, defense and development. We have identified six new Arabidopsis GASA genes, bringing the total number of family members to 14. Here we show that these genes all encode small polyp...

  3. National impacts of the Weatherization Assistance Program in single-family and small multifamily dwellings

    SciTech Connect

    Brown, M.A.; Berry, L.G.; Balzer, R.A.; Faby, E.

    1993-05-01

    Since 1976, the US Department of Energy (DOE) has operated one of the largest energy conservation programs in the nation -- the low-income Weatherization Assistance Program. The program strives to increase the energy efficiency of dwellings occupied by low-income persons in order to reduce their energy consumption, lower their fuel bills, increase the comfort of their homes, and safeguard their health. It targets vulnerable groups including the elderly, people with disabilities, and families with children. The most recent national evaluation of the impacts of the Program was completed in 1984 based on energy consumption data for households weatherized in 1981. DOE Program regulations and operations have changed substantially since then: new funding sources, management principles, diagnostic procedures, and weatherization technologies have been incorporated. Many of these new features have been studied in isolation or at a local level; however, no recent evaluation has assessed their combined, nationwide impacts to date or their potential for the future. In 1990, DOE initiated such an evaluation. This evaluation is comprised of three ``impact`` studies (the Single-Family Study, High-Density Multifamily Study, and Fuel-Oil Study) and two ``policy`` studies. Altogether, these five studies will provide a comprehensive national assessment of the Weatherization Assistance Program as it existed in the 1989 Program Year (PY 1989). This report presents the results of the first phase of the Single-Family Study. It evaluates the energy savings and cost effectiveness of the Program as it has been applied to the largest portion of its client base -- low-income households that occupy single-family dwellings, mobile homes, and small (2- to 4-unit) multifamily dwellings. It is based upon a representative national sample that covers the full range of conditions under which the program was implemented in PY 1989.

  4. Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating.

    PubMed

    Tekin, Mustafa; Duman, Türker; Boğoçlu, Gönül; Incesulu, Armağan; Comak, Elif; Ilhan, Inci; Akar, Nejat

    2003-05-01

    Considerable differences exist for the spectrum of GJB2 mutations in different populations. Screening for the c.35delG mutation in 256 independent probands, 154 multiplex (familial) and 102 simplex (sporadic), coming from different regions of Turkey revealed 37 (14.5%) homozygotes. The allele frequency of c.35delG ranged from 5% to 53% in different cities. Parental consanguinity was noted in 34% of c.35delG homozygotes, yet it was 55% in c.35delG negatives (p=0.034). Further screening for GJB2 mutations in multiplex families demonstrated the presence of c.167delT and L90P mutations as well as a novel complex mutation, c.236_239delTGCAinsAGATCCG, in single alleles, leading to compound heterozygosity with c.35delG. The homozygous E120del mutation was found in another case. The V27I polymorphism was detected in five alleles, one of which was associated with the E114G change. Assortative mating was a significant factor predicting to detect biallelic mutations in the GJB2 gene. These results confirm the overwhelming majority of c.35delG in the Turkish deaf individuals as well as the presence of other changes detected in Caucasian and Asian populations.

  5. Local differences in the Archbishopric of Santiago de Compostela (Galicia, Spain) in relation to the consanguinity structure, 1900-1979.

    PubMed

    Sánchez-Sellero, C; Fariña, J; Aínsua, R L; Varela, T A

    2001-08-01

    The microgeographic variability of consanguinity in the Archbishopric of Santiago de Compostela (Galicia) between 1900 and 1979 was studied. This Archbishopric covers 106 local councils integrated by 964 parishes, of which 677 (70.23%) were analyzed. Of the 307,094 marriages counted within this period, 15,739 corresponded to weddings between biologically related couples. Within the Archbishopric, eight geographical regions were considered: six coastal regions (Golfo Artabro, Bergantiños, Fisterra, Xallas, Santiago Oeste, and Rías Baixas) and two inland regions (Santiago Este and Terra de Montes). In order to evaluate the differences and similarities among them, the frequencies of all types of marriages (consanguineous and nonconsanguineous) were considered. First, a hierarchical grouping of the regions based on their chi-squared distances was performed. Then, in order to analyze relationships that are exclusively due to the structure of consanguinity, a correspondence analysis was performed and only the frequency of the different types of consanguineous marriages was taken into account. The results from both statistical analyses indicate special features of the Xallas region, both in the level of inbreeding (8.75%, the highest in the Archbishopric) and in the structure of consanguinity, for which a high proportion of uncle-niece marriages was found (6.22% of all consanguineous marriages). In all cases the structure of consanguinity provides informative nuances on the differences and similarities among population groups.

  6. The Overlap of Small Molecule and Protein Binding Sites within Families of Protein Structures

    PubMed Central

    Davis, Fred P.; Sali, Andrej

    2010-01-01

    Protein–protein interactions are challenging targets for modulation by small molecules. Here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. Specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. Of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250–1000 Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand and protein binding positions. These “bi-functional positions”, which bind both ligands and proteins, are particularly enriched in tyrosine and tryptophan residues, similar to “energetic hotspots” described previously, and are significantly less conserved than mono-functional and solvent exposed positions. Homology transfer identifies ligands whose binding sites overlap at least 20% of the protein interface for 35% of domain–domain and 45% of domain–peptide mediated interactions. The analysis recovered known small-molecule modulators of protein interactions as well as predicted new interaction targets based on the sequence similarity of ligand binding sites. We illustrate the predictive utility of the method by suggesting structural mechanisms for the effects of sanglifehrin A on HIV virion production, bepridil on the cellular entry of anthrax edema factor, and fusicoccin on vertebrate developmental pathways. The results, available at http://pibase.janelia.org, represent a comprehensive collection of structurally characterized modulators of protein interactions, and suggest that homologous structures are a useful resource for the rational design of interaction modulators. PMID:20140189

  7. Small GTP-binding proteins of the ras family: a conserved functional mechanism?

    PubMed

    Chardin, P

    1991-04-01

    Mutated ras genes can acquire a transforming potential and are frequently detected in human tumors. The mammalian ras gene family includes at least 35 distinct members that can be divided into three main groups on the basis of their sequence similarity to ras, rho, or rab genes. All these genes encode small GTP-binding proteins. Rho proteins are implicated in actin organization and control of cell shape, probably by interacting with the cytoskeleton and intracellular membranes. Rab proteins are involved in vesicular traffic, and appear to control the translocation of vesicles from donor to acceptor membranes. The precise function of ras proteins is unknown, although the prevailing view is that they act as transducers of mitogenic signals. We propose that ras proteins, by analogy with rho and rab, are involved in the lateral segregation of multi-protein complexes at the plasma membrane, and we suggest how this process may be important for mitogenic signal transduction.

  8. Homeodomain-interacting protein kinase (Hipk) phosphorylates the small SPOC family protein Spenito.

    PubMed

    Dewald, D N; Steinmetz, E L; Walldorf, U

    2014-12-01

    The Drosophila homeodomain-interacting protein kinase (Hipk) is a versatile regulator involved in a variety of pathways, such as Notch and Wingless signalling, thereby acting in processes including the promotion of eye development or control of cell numbers in the nervous system. In vertebrates, extensive studies have related its homologue HIPK2 to important roles in the control of p53-mediated apoptosis and tumour suppression. Spenito (Nito) belongs to the group of small SPOC family proteins and has a role, amongst others, as a regulator of Wingless signalling downstream of Armadillo. In the present study, we show that both proteins have an enzyme-substrate relationship, adding a new interesting component to the broad range of Hipk interactions, and we map several phosphorylation sites of Nito. Furthermore, we were able to define a preliminary consensus motif for Hipk target sites, which will simplify the identification of new substrates of this kinase.

  9. The RGK family: a regulatory tail of small GTP-binding proteins.

    PubMed

    Kelly, Kathleen

    2005-12-01

    RGK proteins are small Ras-related GTP-binding proteins that function as potent inhibitors of voltage-dependent calcium channels, and two members of the family, Gem and Rad, modulate Rho-dependent remodeling of the cytoskeleton. Within the Ras superfamily, RGK proteins have distinct structural and regulatory characteristics. It is an open question as to whether RGK proteins catalyze GTP hydrolysis in vivo. Binding of calmodulin and the 14-3-3 protein to RGK proteins controls downstream pathways. Here, we discuss the structural and functional properties of RGK proteins and highlight recent work by Beguin and colleagues addressing the mechanism of Gem regulation by calmodulin and 14-3-3.

  10. Small Molecule Inhibition of the TNF Family Cytokine CD40 Ligand Through a Subunit Fracture Mechanism

    SciTech Connect

    L Silvian; J Friedman; K Strauch; T Cachero; E Day; F Qian; B Cunningham; A Fung; L Sun; et al.

    2011-12-31

    BIO8898 is one of several synthetic organic molecules that have recently been reported to inhibit receptor binding and function of the constitutively trimeric tumor necrosis factor (TNF) family cytokine CD40 ligand (CD40L, aka CD154). Small molecule inhibitors of protein-protein interfaces are relatively rare, and their discovery is often very challenging. Therefore, to understand how BIO8898 achieves this feat, we characterized its mechanism of action using biochemical assays and X-ray crystallography. BIO8898 inhibited soluble CD40L binding to CD40-Ig with a potency of IC{sub 50} = 25 {mu}M and inhibited CD40L-dependent apoptosis in a cellular assay. A co-crystal structure of BIO8898 with CD40L revealed that one inhibitor molecule binds per protein trimer. Surprisingly, the compound binds not at the surface of the protein but by intercalating deeply between two subunits of the homotrimeric cytokine, disrupting a constitutive protein-protein interface and breaking the protein's 3-fold symmetry. The compound forms several hydrogen bonds with the protein, within an otherwise hydrophobic binding pocket. In addition to the translational splitting of the trimer, binding of BIO8898 was accompanied by additional local and longer-range conformational perturbations of the protein, both in the core and in a surface loop. Binding of BIO8898 is reversible, and the resulting complex is stable and does not lead to detectable dissociation of the protein trimer. Our results suggest that a set of core aromatic residues that are conserved across a subset of TNF family cytokines might represent a generic hot-spot for the induced-fit binding of trimer-disrupting small molecules.

  11. Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

    PubMed Central

    Chen, Laura P.; Beck, Anita E.; Tsuchiya, Karen D.; Chow, Penny M.; Mirzaa, Ghayda M.; Wiester, Rebecca T.

    2015-01-01

    Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

  12. CONSANGUINITY, GENETICS AND DEFINITIONS OF KINSHIP IN THE UK PAKISTANI POPULATION.

    PubMed

    Bittles, A H; Small, N A

    2016-11-01

    Consanguineous marriage is a controversial topic in many Western societies, with attention mainly focused on the health of immigrant communities from Asia and Africa. In the UK consanguinity is especially prevalent in the Pakistani community, which now numbers over 1.1 million. Less attention has been paid to the influence of hereditary population stratification within Pakistani communities, in particular biraderi (literally brotherhood) membership, which denotes male lineages that largely govern marriage partner choice and hence the transmission of disease genes. The various roles played by biraderi and their relationship to other socio-occupational and kinship terms, such as caste, quom and zat, are often overlooked in health-based studies. The interchangeable use of these different kinship terms without rigorous definition can create identity uncertainty and hinders inter-study comparisons. Where feasible, standardization of terminology would be both desirable and beneficial, with biraderi the preferred default term to identify specific social and genetic relationships within the Pakistani diaspora.

  13. Rate of Parental Consanguineous Marriage among Patients with Visual Impairments in Turkey

    PubMed Central

    AKKAYA, Sezen

    2016-01-01

    We aimed to describe the causes, characteristics, and rate of parental consanguineous marriage associated with patients with visual impairments in Turkey. This study involved 236 patients with visual impairments. The 10th revision of the International Classification of Diseases was used to categorize the causes of visual impairments (based on the main cause in both eyes). The mean age of the patients was 38.5 ± 24.2 years (range, 6–95 years), and most were in the 15–30-year age group (35.6%). There were more male patients (65%) than female patients. Blindness, severe visual impairment, and mild to moderate visual impairment were observed in 30 (12.7%), 84 (35.6%), and 122 (51.6%) patients, respectively. Choroidal and retinal diseases were identified as the main underlying cause of visual impairment (62.7%), followed by nystagmus (23.7%), optic tract and nerve diseases (11.0%), congenital cataracts (0.8%), and glaucoma (1.7%). Parental consanguinity was present for 26.3% of the patients, and it was significantly more common in the 15–30-year age group (50%) compared to the other age groups. In Turkey, the main cause of visual impairment was choroid and retinal diseases in all the age groups above 14 years, while nystagmus was the most common cause in the age group below 15 years. Parental consanguinity was significantly higher among the patients with macular dystrophy and those with retinitis pigmentosa than with retinopathy of prematurity, optic nerve diseases, age-related macular degeneration, and diabetic retinopathy. Genetic factors are known to be involved in the development of these diseases, indicating that the issue of consanguineous marriage remains a problem in Turkey. PMID:28293658

  14. A study of consanguineous marriage as a risk factor for developing comitant strabismus.

    PubMed

    Bagheri, Mansooreh; Farvardin, Majid; Saadat, Mostafa

    2015-04-01

    Inheritance has an important role in the etiology of comitant strabismus. Consanguineous marriage is a leading factor in birth defects in which inheritance has a role. The aim of this study is to reveal if consanguineous marriage increases the risk of developing comitant strabismus. We included 461 patients who underwent primary surgery for comitant strabismus in Shiraz University Khalili Hospital (Fars province, southern Iran) between years 2003 and 2013 in our study. All the patients were living in Shiraz, Iran. Patients were categorized into the following 4 groups: (1) intermittent or constant exotropia, (2) infantile esotropia, (3) non-accommodative acquired esotropia, and (4) accommodative acquired esotropia. A total of 421 healthy children who were born in Shiraz, at the same period of time, were also studied as a control group. Presence and type of the consanguineous marriages were evaluated in the parents of the patients and control group by a questionnaire. Mean of inbreeding coefficient (α) was calculated in each group of patients and was compared with those of control group. The proportion of parental first cousin marriage was 37.7 and 23.5 % among patient and control groups. The mean of inbreeding coefficients (α) were 0.0236, 0.0283, 0.0288, and 0.0236 in four groups of the patients, respectively. The mean of inbreeding coefficient was 0.0263 in total patients, which was significantly higher than 0.0164 of control group (T = 5.27, df = 880, P < 0.001). Patients with non-accommodative acquired esotropia had the highest mean of inbreeding coefficient (α) (0.0288). It seems that recessive form of inheritance plays an important role in the etiology of comitant strabismus. Modified screening programs may be needed for earlier detection of strabismus in the offspring of consanguineous couples.

  15. Small G-protein Signaling in Neuronal Plasticity and Memory Formation: the Specific Role of Ras Family Proteins

    PubMed Central

    Ye, Xiaojing; Carew, Thomas J.

    2010-01-01

    Small G-proteins are an extensive family of proteins that bind and hydrolyze GTP. They are ubiquitous inside cells, regulating a wide range of cellular processes. Recently, many studies have examined the role of small G-proteins, particularly the Ras family of G-proteins, in memory formation. Once thought to be primarily involved in the transduction of a variety of extracellular signals during development, it is now clear that Ras family proteins also play critical roles in molecular processing underlying neuronal and behavioral plasticity. We here review a number of recent studies that explore how the signaling of Ras family proteins contributes to memory formation. Understanding these signaling processes is of fundamental importance both from a basic scientific perspective, with the goal of providing mechanistic insights into a critical aspect of cognitive behavior, and from a clinical perspective, with the goal of providing effective therapies for a range of disorders involving cognitive impairments. PMID:21040840

  16. Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness.

    PubMed

    Ben Arab, Saida; Masmoudi, Saber; Beltaief, Najeh; Hachicha, Slah; Ayadi, Hammadi

    2004-07-01

    Deafness is an important health problem in the Tunisian population, especially in isolates where the prevalence ranges from 2 to 8%. To evaluate the effect of inbred unions on deafness, a study was conducted on 5,020 individuals (160 are deaf) between 2000 and 2002 in the North of Tunisia. The coefficient of inbreeding for all individuals and the levels of inbreeding in ten districts were computed. The higher levels were obtained in the rural districts. Our study revealed that geographic isolation, social traditions, and parental involvement in mode selection all contribute to increase consanguinity in these regions. The mean inbreeding seems to be similar to those estimated in highly inbred isolates in the world. The relative risk of the 35delG mutation, the single most frequent allele for non-syndromic recessive deafness in Tunisia, was estimated from the observed inbreeding coefficient and found to be 10.76 (SD 7.74) for first-cousin marriages, which are the most common form of consanguineous marriage encountered. Our knowledge of the risk rate of deafness and our understanding of consanguinity is required for the prevention of genetic deafness in the Tunisian population.

  17. Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration.

    PubMed

    Li, Yan-Fang; Li, Hong-Fu; Zhang, Yan-Bin; Wu, Ji-Min

    2016-08-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2.

  18. Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration

    PubMed Central

    Li, Yan-Fang; Li, Hong-Fu; Zhang, Yan-Bin; Wu, Ji-Min

    2016-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2. PMID:27446545

  19. Moxidectin and the avermectins: Consanguinity but not identity

    PubMed Central

    Prichard, Roger; Ménez, Cécile; Lespine, Anne

    2012-01-01

    The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination. PMID:24533275

  20. Moxidectin and the avermectins: Consanguinity but not identity.

    PubMed

    Prichard, Roger; Ménez, Cécile; Lespine, Anne

    2012-12-01

    The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination.

  1. A resonant family of dynamically cold small bodies in the near-Earth asteroid belt

    NASA Astrophysics Data System (ADS)

    de la Fuente Marcos, C.; de la Fuente Marcos, R.

    2013-07-01

    Near-Earth objects (NEOs) moving in resonant, Earth-like orbits are potentially important. On the positive side, they are the ideal targets for robotic and human low-cost sample return missions and a much cheaper alternative to using the Moon as an astronomical observatory. On the negative side and even if small in size (2-50 m), they have an enhanced probability of colliding with the Earth causing local but still significant property damage and loss of life. Here, we show that the recently discovered asteroid 2013 BS45 is an Earth co-orbital, the sixth horseshoe librator to our planet. In contrast with other Earth's co-orbitals, its orbit is strikingly similar to that of the Earth yet at an absolute magnitude of 25.8, an artificial origin seems implausible. The study of the dynamics of 2013 BS45 coupled with the analysis of NEO data show that it is one of the largest and most stable members of a previously undiscussed dynamically cold group of small NEOs experiencing repeated trappings in the 1:1 commensurability with the Earth. This new resonant family is well constrained in orbital parameter space and it includes at least 10 other transient members: 2003 YN107, 2006 JY26, 2009 SH2 and 2012 FC71 among them. 2012 FC71 represents the best of both worlds as it is locked in a Kozai resonance and is unlikely to impact the Earth. These objects are not primordial and may have originated within the Venus-Earth-Mars region or in the main-belt, then transition to Amor-class asteroid before entering Earth's co-orbital region. Objects in this group could be responsible for the production of Earth's transient irregular natural satellites.

  2. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal.

    PubMed

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C; Mahmoudi, Tokameh

    2016-01-01

    Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4 + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal.

  3. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal

    PubMed Central

    Stoszko, Mateusz; De Crignis, Elisa; Rokx, Casper; Khalid, Mir Mubashir; Lungu, Cynthia; Palstra, Robert-Jan; Kan, Tsung Wai; Boucher, Charles; Verbon, Annelies; Dykhuizen, Emily C.; Mahmoudi, Tokameh

    2015-01-01

    Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4 + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal. PMID:26870822

  4. Myocilin variations and familial glaucoma in Taxiarchis, a small Greek village

    PubMed Central

    Konstas, Anastasios G. P.; Samples, John R.; Kaltsos, Kostantinos; Economou, Athanasios; Dimopoulos, Antonios; Georgiadou, Irene; Petersen, Michael B.

    2008-01-01

    Purpose To initiate a prospective study of glaucoma in a Greek village reported over 30 years ago to have several large families with primary open-angle glaucoma (POAG). Methods A random group of 126 villagers from Taxiarchis, Greece was examined in the village community center. The detailed evaluation included ophthalmic and general history, measurement of blood pressure, intraocular pressure (IOP), and central corneal thickness (CCT) as well as evaluation of the optic nerve status. Results The incidence of glaucoma approached 18% in this small isolated village. Myocilin variants were present in almost half of the individuals screened with Arg76Lys and Thr377Met being the most common finding (25% and 17%, respectively). Over half of the individuals with the Thr377Met mutation were diagnosed with glaucoma. Two of these patients were homozygous for the Thr377Met mutation. Three individuals with the Arg76Lys polymorphism had glaucoma; however, two of these individuals also had the Thr377Met mutation. Only two patients with pseudoexfoliation were identified. Conclusions The incidence of glaucoma and the Thr377Met MYOC mutation in this population is much higher than that reported for other European populations. PMID:18449353

  5. Consistent Small-Sample Variances for Six Gamma-Family Measures of Ordinal Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Gamma-family measures are bivariate ordinal correlation measures that form a family because they all reduce to Goodman and Kruskal's gamma in the absence of ties (1954). For several gamma-family indices, more than one variance estimator has been introduced. In previous research, the "consistent" variance estimator described by Cliff and…

  6. Service Family Support -- A Small-Scale Project of Educational Psychologists Working with Parents

    ERIC Educational Resources Information Center

    Hogg, Jane; Hart, Anne; Collins, Zoe V.

    2014-01-01

    Being in a Service family can be a difficult position for children and parents alike due to high levels of mobility, parental separation, and the remaining parent's stress and emotional well-being. A Service family is defined as a family with one or both parents employed by the Ministry of Defence (MOD). The current project looked at the…

  7. The squash aspartic proteinase inhibitor SQAPI is widely present in the cucurbitales, comprises a small multigene family, and is a member of the phytocystatin family.

    PubMed

    Christeller, John T; Farley, Peter C; Marshall, Richelle K; Anandan, Ananda; Wright, Michele M; Newcomb, Richard D; Laing, William A

    2006-12-01

    The squash (Cucurbita maxima) phloem exudate-expressed aspartic proteinase inhibitor (SQAPI) is a novel aspartic acid proteinase inhibitor, constituting a fifth family of aspartic proteinase inhibitors. However, a comparison of the SQAPI sequence to the phytocystatin (a cysteine proteinase inhibitor) family sequences showed approximately 30% identity. Modeling SQAPI onto the structure of oryzacystatin gave an excellent fit; regions identified as proteinase binding loops in cystatin coincided with regions of SQAPI identified as hypervariable, and tryptophan fluorescence changes were also consistent with a cystatin structure. We show that SQAPI exists as a small gene family. Characterization of mRNA and clone walking of genomic DNA (gDNA) produced 10 different but highly homologous SQAPI genes from Cucurbita maxima and the small family size was confirmed by Southern blotting, where evidence for at least five loci was obtained. Using primers designed from squash sequences, PCR of gDNA showed the presence of SQAPI genes in other members of the Cucurbitaceae and in representative members of Coriariaceae, Corynocarpaceae, and Begoniaceae. Thus, at least four of seven families of the order Cucurbitales possess member species with SQAPI genes, covering approximately 99% of the species in this order. A phylogenetic analysis of these Cucurbitales SQAPI genes indicated not only that SQAPI was present in the Cucurbitales ancestor but also that gene duplication has occurred during evolution of the order. Phytocystatins are widespread throughout the plant kingdom, suggesting that SQAPI has evolved recently from a phytocystatin ancestor. This appears to be the first instance of a cystatin being recruited as a proteinase inhibitor of another proteinase family.

  8. Expression and strain variation of the novel “Small Open Reading Frame” 3 (smorf) multigene family in Babesia bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Small open reading frame (smorf) genes comprise the second largest Babesia bovis multigene family. All known 44 variant smorf genes are located in close chromosomal proximity to ves1 genes, which encode proteins that mediate cytoadhesion and contribute to immune evasion. In this study, we characte...

  9. Development of EGFR family small molecule inhibitors for anticancer intervention: an overview of approved drugs and clinical candidates.

    PubMed

    Cheng, Weiyan; Hu, Yongzhou; Sheng, Rong

    2014-01-01

    The epidermal growth factor receptor (EGFR) family includes four structurally related receptor tyrosine kinases, termed as HER1 (EGFR, erbB1), HER2 (erbB2), HER3 (erbB3), and HER4 (erbB4). Given its intimate role in the development of several solid tumors, excessive HER signaling provides a unique opportunity for anticancer intervention. Along with extensive pharmacological studies validating the therapeutic potential of targeting the EGFR family for cancer therapy, kinase inhibitors of this family are continuously coming up and entering clinical studies. Herein, we review the EGFR family small molecule kinase inhibitors which have been approved or progressed into clinical studies, mainly focusing on their mechanisms of action, structure-activity relationships, binding modes, synthetic routes, and clinical status.

  10. Contribution of family labour to the profitability and competitiveness of small-scale dairy production systems in central Mexico.

    PubMed

    Posadas-Domínguez, Rodolfo Rogelio; Arriaga-Jordán, Carlos Manuel; Martínez-Castañeda, Francisco Ernesto

    2014-01-01

    The objective of this work was to determine the effect of family labour on the profitability and competitiveness of small-scale dairy farms in the highlands of Central Mexico. Economic data from 37 farms were analysed from a stratified statistical sampling with a Neyman assignment. Three strata were defined taking herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements, Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The policy analysis matrix was used as the method to determine profitability and competitiveness. The coefficient of private profitability (CPP) when the economic cost of family labour is included in the cost structure was 8.0 %, 31.0 % and 46.0 %. When the economic cost of family labour is not included, CPP increase to 47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and 3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and 0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is not included. It is concluded that family labour is a crucial factor in the profitability and competitiveness of small-scale dairy production.

  11. Genetic heterogeneity and consanguinity lead to a “double hit”: Homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa

    PubMed Central

    Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina

    2013-01-01

    Purpose Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. Methods The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. Results The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. Conclusions This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient. PMID:23882135

  12. [Small-scale, homelike care environments for people with dementia: effects on residents, family caregivers and nursing staff].

    PubMed

    Verbeek, H; Zwakhalen, S M G; van Rossum, E; Kempen, G I J M; Hamers, J P H

    2013-12-01

    Institutional dementia care is increasingly directed towards small-scale and homelike care environments, in The Netherlands as well as abroad. In these facilities, a small number of residents, usually six to eight, live together, and normal daily household activities and social participation are emphasized. In a quasi-experimental study, we studied the effects of small-scale, homelike care environments on residents (n = 259), family caregivers (n = 206) and nursing staff (n = 305). We compared two types of institutional nursing care during a 1 year period (baseline assessment and follow-up measurements at 6 and 12 months): (28) small-scale, homelike care environments and (21) psychogeriatric wards in traditional nursing homes. A matching procedure was applied to increase comparability of residents at baseline regarding functional status and cognition. This study was unable to demonstrate convincing overall effects of small-scale, homelike care facilities. On our primary outcome measures, such as quality of life and behaviour of residents and job satisfaction and motivation of nursing staff, no differences were found with traditional nursing homes. We conclude that small-scale, homelike care environments are not necessarily a better care environment than regular nursing homes and other types of living arrangements should be considered carefully. This provides opportunities for residents and their family caregivers to make a choice which care facility suits their wishes and beliefs best.

  13. The Effect of Consanguineous Marriage on Mental Health among the Students of the Shahrekord University of Medical Sciences

    PubMed Central

    Hosseinpour, Maryam; Deris, Fatemeh; Solati-Dehkordi, Kamal; Heidari-Soreshjani, Sheida; Karimi, Negar; Teimori, Hossein

    2016-01-01

    Introduction In Iran, after unintentional accidents, mental health problems are the second leading burden of disease. Consanguineous marriage is very common in Iran and the association between parental consanguinity and mental health is an important issue that has not yet been studied sufficiently in Iran. Aim To investigate the effect of consanguinity and the degree of relationship on different levels of mental health. Materials and Methods In this cross-sectional study, conducted in the Shahrekord University of Medical Sciences, two groups of students were enrolled. The first group consisted of 156 students that had consanguineous parent (case group) and the second group was 156 students whose parents had non-blood relationship (control group). The students were evaluated using General Health Questionnaire (GHQ-28). Statistical analysis was conducted by Pearson’s correlation coefficient, independent t-test and the one-way analysis of variance. Odd ratio was used to estimate the relative risk. Results Over 30% of the individuals were suffering from mental health problems. The most and least common mental health problems in both groups were social dysfunction (54.5% in the case group and the control group 50%) and depression (15.4% in the case group and 17.3% in the control group), respectively. No statistically significant difference was observed in the frequency of overall mental health and its subscales between student with non-consanguineous parent (control group) and the students that had consanguineous parent (case group) (p>0.05) and the status of mental health was not significantly different among student with different degree of kinship (p>0.05). Conclusion The study revealed that social dysfunction was very common among the study students and also there were no relationship between parental consanguineous marriage and mental health. Parental consanguinity and genetic factors may not be the major causes of high prevalence of mental health problems in

  14. Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

    ClinicalTrials.gov

    2016-08-25

    Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  15. Detection of the YORP effect for small asteroids in the Karin family

    NASA Astrophysics Data System (ADS)

    Nesvorny, David; Carruba, Valerio; Vokrouhlicky, David

    2016-10-01

    The Karin family formed by a collisional breakup of a ~40-km parent asteroid only 5.75 Myr ago. The young age can be demonstrated by numerically integrating the orbits of Karin family members backward in time and showing the convergence of orbital elements. Previous work has pointed out that the convergence is not ideal if the backward integration only accounts for the gravitational perturbations from the Solar System planets. It improves when the thermal radiation force known as the Yarkovsky effect is accounted for. This method can be used to estimate the spin obliquities of Karin family members. Here we show that the obliquity distribution of diameter D=1-2 km asteroids in the Karin family is bimodal, as expected if the YORP effect acted to move obliquities toward extreme values (0 or 180 deg). The measured magnitude of the effect is consistent with the standard YORP model. Specifically, the strength of the YORP effect is inferred to be roughly 70% of the nominal YORP strength obtained for a collection of random Gaussian spheroids. The surface thermal conductivity is found to be 0.07-0.2 W/m/K (thermal inertia 300-500 in the SI units). These results are consistent with surfaces composed of rough and rocky regolith. The obliquity values predicted here for 480 members of the Karin cluster can be validated by the lightcurve inversion method. In broader context, the bimodal distribution of obliquities in the Karin cluster can be thought as an initial stage of dynamical evolution that later leads to a characteristically bi-lobed distribution of family members in the semimajor axis (e.g., Eos, Merxia or Erigone families).

  16. Family Involvement in Creative Teaching Practices for All in Small Rural Schools

    ERIC Educational Resources Information Center

    Vigo Arrazola, Begoña; Soriano Bozalongo, Juana

    2015-01-01

    Parental involvement is interpreted as a key form of support that can contribute to the establishment of inclusive practices in schools, but this can be difficult in sparsely populated areas. Using ethnographic methods of participant observation, informal conversations and document analysis, this article therefore focuses on family involvement…

  17. Expansion of the residential conservation service program to multi-family and small commercial buildings

    SciTech Connect

    1980-11-01

    Alternative regulatory provisions are considered which might permit achievement of the building energy conservation regulatory goals at a lower cost. Major issues, regulatory and legislative options, and cost-benefit analyses are discussed for multi-family and commercial buildings. The following are presented: related government programs, urban and community impact analysis, institutional impacts, energy cost, Residential Conservation Service coverage, methods of analysis, and regional studies. (MHR)

  18. Syndrome Keratitis-Ichtyosis-Deafness (KID) chez un enfant togolais issu d'un mariage consanguin

    PubMed Central

    Kombaté, Koussak; Saka, Bayaki; Landoh, Dadja Essoya; Mouhari-Toure, Abass; Akakpo, Séfako; Belei, Eric; Gnassingbé, Wanguena; Djibril, Mohaman Awalou; Tchangaï-Walla, Kissem; Pitché, Palokinam

    2015-01-01

    Le syndrome KID est une affection génétique rare associant kératite, ichtyose et surdité. Nous rapportons un cas dont la surdité s'est compliquée de mutisme chez un enfant togolais issu d'un mariage consanguin.Il s'agissait d'une fillette de 9 ans admise en dermatologie pour une peau sèche et une kératodermie palmoplantaire évoluant depuis l'enfance, une surdité sévère et un mutisme total évoluant depuis la naissance. Il n'y avait pas d'histoire familiale connue de syndrome KID. Les parents de cet enfant sont des cousins germains. A l'examen, on notait une kératodermie palmoplantaire typique en cuir grossier, une peau sèche ichtyosiforme finement squameuse avec un aspect pachydermique aux genoux et un aspect arlequin aux jambes. L'examen ophtalmologique avait noté une blépharo-conjonctivite, une xérophtalmie, une photophobie et une absence de sourcils. L'examen ORL avait objectivé une hypotrophie des pavillons des oreilles, une surdité sévère et un mutisme total. La particularité de cette observation réside dans la sévérité de l'atteinte auditive qui s'est compliquée de mutisme. Notre enfant étant née de parents consanguins sains, sans histoire familiale de KID, nous pensons que le mode de transmission est probablement sporadique. Une étude moléculaire du cas index et de ses parents, non réalisée à cause de notre plateau technique limité aurait pu le confirmer. PMID:26664520

  19. Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members.

    PubMed Central

    Frost, J A; Xu, S; Hutchison, M R; Marcus, S; Cobb, M H

    1996-01-01

    The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway. PMID:8668187

  20. State-of-the-art of small molecule inhibitors of the TAM family: the point of view of the chemist.

    PubMed

    Baladi, Tom; Abet, Valentina; Piguel, Sandrine

    2015-11-13

    The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure-activity relationships, drug-metabolism and pharmacokinetics properties where they exist.

  1. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5

    PubMed Central

    Nakamura, Yusuke; Lathrop, Mark; Leppert, Mark; Dobbs, Marc; Wasmuth, John; Wolff, Erica; Carlson, Mary; Fujimoto, Esther; Krapcho, Karen; Sears, Tena; Woodward, Scott; Hughes, J.; Burt, Randy; Gardner, Eldon; Lalouel, Jean-Marc; White, Ray

    1988-01-01

    Familial adenomatous polyposis (FAP), a Mendelian disorder that includes familial polyposis coli (FPC) and Gardner syndrome (GS), has an autosomal dominant mode of inheritance. It is characterized by hundreds to thousands of adenomatous polyps that can progress to carcinoma of the colon, suggesting that the gene that harbors the FAP germ-line mutation may play an important role in the somatic genetic pathway to colon cancer. The defect responsible for FAP was recently mapped to the long arm of chromosome 5 by linkage between the FPC phenotype and a locus defined by DNA probe pC11p11 (D5S71), located at 5q21–22. Because an important next step in the paradigm for identification of a disease gene is to obtain a more precise localization, we isolated and mapped by linkage six additional polymorphic DNA markers in the FAP region. Subsequent linkage analysis in six pedigrees, three having the FPC phenotype and three segregating GS, placed the FAP locus very close to a new marker, YN5.48 (D5S81), that is approximately 17 centimorgans distal to C11p11 on the genetic map. The analysis revealed no evidence of genetic heterogeneity between the two phenotypes, a question that had not been clearly resolved by the earlier studies. The new set of markers in the near vicinity of the FAP locus represents a further step toward isolation of the genetic defect and provides the opportunity for preclinical diagnosis of risk status for colon cancer among individuals in families that are segregating adenomatous polyposis. PMID:2903664

  2. New Opportunitie s for Small Satellite Programs Provided by the Falcon Family of Launch Vehicles

    NASA Astrophysics Data System (ADS)

    Dinardi, A.; Bjelde, B.; Insprucker, J.

    2008-08-01

    The Falcon family of launch vehicles, developed by Space Exploration Technologies Corporation (SpaceX), are designed to provide the world's lowest cost access to orbit. Highly reliable, low cost launch services offer considerable opportunities for risk reduction throughout the life cycle of satellite programs. The significantly lower costs of Falcon 1 and Falcon 9 as compared with other similar-class launch vehicles results in a number of new business case opportunities; which in turn presents the possibility for a paradigm shift in how the satellite industry thinks about launch services.

  3. Working Families at the Margins: The Uncertain Future of America's Small Towns. Hearing Before the Select Committee on Children, Youth, and Families. House of Representatives, One Hundred First Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

    Poverty affects many rural two-parent families, even with one or both parents working. High suicide rates, increased violence, families separated in order to find work, homelessness, and hunger afflict the rural and small town poor. This document contains testimony from poor and homeless rural people; the director of the Center on Budget and…

  4. Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East.

    PubMed

    Tanner, Stephan M; Li, Zhongyuan; Bisson, Ryan; Acar, Ceren; Oner, Cihan; Oner, Reyhan; Cetin, Mualla; Abdelaal, Mohamed A; Ismail, Essam A; Lissens, Willy; Krahe, Ralf; Broch, Harald; Gräsbeck, Ralph; de la Chapelle, Albert

    2004-04-01

    Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the Eastern Mediterranean region. The disease can be caused by mutations in either the cubilin (CUBN; MGA1; MIM# 602997) or the amnionless (AMN; MIM# 605799) gene. To explain the peculiar geographical distribution, we hypothesized that mutations in one of the genes would mainly be responsible for the disease in Scandinavia, and mutations in the other gene in the Mediterranean region. We studied 42 sibships and found all cases in Finland to be due to CUBN (three different mutations) and all cases in Norway to be due to AMN (two different mutations), while in Turkey, Israel, and Saudi Arabia, there were two different AMN mutations and three different CUBN mutations. Haplotype evidence excluded both CUBN and AMN conclusively in five families and tentatively in three families, suggesting the presence of at least one more gene locus that can cause MGA. We conclude that the Scandinavian cases are typical examples of enrichment by founder effects, while in the Mediterranean region high degrees of consanguinity expose rare mutations in both genes. We suggest that in both regions, physician awareness of this disease causes it to be more readily diagnosed than elsewhere; thus, it may well be more common worldwide than previously thought.

  5. Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

    PubMed

    Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

    2015-11-01

    Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes.

  6. Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.

    PubMed

    Gu, Xun; Wang, Yufeng; Gu, Jianying

    2002-06-01

    The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome.

  7. Label-based routing for a family of small-world Farey graphs.

    PubMed

    Zhai, Yinhu; Wang, Yinhe

    2016-05-11

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure.

  8. Label-based routing for a family of small-world Farey graphs

    NASA Astrophysics Data System (ADS)

    Zhai, Yinhu; Wang, Yinhe

    2016-05-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure.

  9. Label-based routing for a family of small-world Farey graphs

    PubMed Central

    Zhai, Yinhu; Wang, Yinhe

    2016-01-01

    We introduce an informative labelling method for vertices in a family of Farey graphs, and deduce a routing algorithm on all the shortest paths between any two vertices in Farey graphs. The label of a vertex is composed of the precise locating position in graphs and the exact time linking to graphs. All the shortest paths routing between any pair of vertices, which number is exactly the product of two Fibonacci numbers, are determined only by their labels, and the time complexity of the algorithm is O(n). It is the first algorithm to figure out all the shortest paths between any pair of vertices in a kind of deterministic graphs. For Farey networks, the existence of an efficient routing protocol is of interest to design practical communication algorithms in relation to dynamical processes (including synchronization and structural controllability) and also to understand the underlying mechanisms that have shaped their particular structure. PMID:27167605

  10. Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706).

    PubMed

    Krsticevic, Flavia J; Arce, Débora P; Ezpeleta, Joaquín; Tapia, Elizabeth

    2016-10-13

    In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP) synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq) and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706) genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues.

  11. Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706)

    PubMed Central

    Krsticevic, Flavia J.; Arce, Débora P.; Ezpeleta, Joaquín; Tapia, Elizabeth

    2016-01-01

    In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP) synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq) and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706) genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues. PMID:27565886

  12. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    SciTech Connect

    Leão, Mariana; Gomes, Sara; Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Monti, Paola; Fronza, Gilberto; Pereira, Clara; Saraiva, Lucília

    2015-01-01

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.

  13. Methylation of sulfhydryl groups: a new function for a family of small molecule plant O-methyltransferases

    PubMed Central

    Coiner, Heather; Schröder, Gudrun; Wehinger, Elke; Liu, Chang-Jun; Noel, Joseph P.; Schwab, Wilfried; Schröder, Joachim

    2010-01-01

    Summary In plants, type I and II S-adenosyl-L-methionine-dependent O-methyltransferases (OMTs) catalyze most hydroxyl group methylations of small molecules. A homology-based RT-PCR strategy using Catharanthus roseus (Madagascar periwinkle) RNA previously identified six new type I plant OMT family members. We now describe the molecular and biochemical characterization of a seventh protein. It shares 56–58% identity with caffeic acid OMTs (COMTs), but it failed to methylate COMT substrates, and had no activity with flavonoids. However, the in vitro incubations revealed unusually high background levels without added substrates. A search for the responsible component revealed that the enzyme methylated dithiothreitol (DTT), the reducing agent added for enzyme stabilization. Unexpectedly, product analysis revealed that the methylation occurred on a sulfhydryl moiety, not on a hydroxyl group. Analysis of 34 compounds indicated a broad substrate range, with a preference for small hydrophobic molecules. Benzene thiol (Km 220 μM) and furfuryl thiol (Km 60 μM) were the best substrates (6–7-fold better than DTT). Small isosteric hydrophobic substrates with hydroxyl groups, like phenol and guaiacol, were also methylated, but the activities were at least 5-fold lower than with thiols. The enzyme was named C. roseus S-methyltransferase 1 (CrSMT1). Models based on the COMT crystal structure suggest that S-methylation is mechanistically identical to O-methylation. CrSMT1 so far is the only recognized example of an S-methyltransferase in this protein family. Its properties indicate that a few changes in key residues are sufficient to convert an OMT into a S-methyltransferase (SMT). Future functional investigations of plant methyltransferases should consider the possibility that the enzymes may direct methylation at sulfhydryl groups. PMID:16623883

  14. Larsen syndrome in two generations of an Italian family.

    PubMed Central

    Ventruto, V; Festa, F; Sebastio, L; Sebastio, G

    1976-01-01

    This paper describes a familial case of Larsen syndrome. Typical anomalies were present in the propositus and 2 of his 6 daughters. In addition, all patients had progressive deafness and the 2 daughters had cleft palate. The certain exclusion of any consanguinity between the couple, suggests, in this instance, the dominant mode of transmission of the syndrome. Images PMID:1018317

  15. Cloning and characterization of a small family 19 chitinase from moss (Bryum coronatum).

    PubMed

    Taira, Toki; Mahoe, Yoko; Kawamoto, Noriko; Onaga, Shoko; Iwasaki, Hironori; Ohnuma, Takayuki; Fukamizo, Tamo

    2011-05-01

    Chitinase-A (BcChi-A) was purified from a moss, Bryum coronatum, by several steps of column chromatography. The purified BcChi-A was found to be a molecular mass of 25 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric point of 3.5. A cDNA encoding BcChi-A was cloned by rapid amplification of cDNA ends and polymerase chain reaction. It consisted of 1012 nucleotides and encoded an open reading frame of 228 amino acid residues. The predicted mature BcChi-A consists of 205 amino acid residues and has a molecular weight of 22,654. Sequence analysis indicated that BcChi-A is glycoside hydrolase family-19 (GH19) chitinase lacking loops I, II, IV and V, and a C-terminal loop, which are present in the catalytic domain of plant class I and II chitinases. BcChi-A is a compact chitinase that has the fewest loop regions of the GH19 chitinases. Enzymatic experiments using chitooligosaccharides showed that BcChi-A has higher activity toward shorter substrates than class II enzymes. This characteristic is likely due to the loss of the loop regions that are located at the end of the substrate-binding cleft and would be involved in substrate binding of class II enzymes. This is the first report of a chitinase from mosses, nonvascular plants.

  16. Inhibition of TGF-β signaling in tumor cells by small molecule Src family kinase inhibitors.

    PubMed

    Bartscht, Tobias; Rosien, Benjamin; Rades, Dirk; Kaufmann, Roland; Biersack, Harald; Lehnerta, Hendrik; Ungefroren, Hendrik

    2017-01-02

    In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated shown that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear. In contrast, the anti-TGF-β effect of yet another Src/Abl inhibitor, bosutinib, is more variable with respect to the type of the TGF-β response and the cell type affected, and lacks a clear dose-dependency. In the light of their strong anti-activin receptor-like kinase 5 kinase effect, PP1 and PP2 should not be used when studying the role of c-Src as downstream mediators in TGF-β/activin receptor-like kinase 5 signaling. On the other hand, based upon in vitro findings, it is conceivable that part of the therapeutic effects of AZM475271 and dasatinib seen in preclinical and clinical studies with solid tumors was caused by inhibition of prometastatic TGF-β rather than Src signaling. If AZM475271 and dasatinib can indeed act as dual Src / TGF-β inhibitors in vivo, this may be beneficial for prevention of metastatic disease in more advanced tumor stages.

  17. Evaluation of a Teaching Kit for Family and Consumer Science Classrooms: Motivating Students to Use a Food Thermometer with Small Cuts of Meat

    ERIC Educational Resources Information Center

    Edwards, Zena; Edlefsen, Miriam; Hillers, Virginia; McCurdy, Sandra M.

    2005-01-01

    The U.S. Dept. of Agriculture recommends use of food thermometers to safely cook small cuts of meat, yet most consumers do not use them. Consumers lack knowledge about how and why to use food thermometers with small cuts of meat. Opportunities exist for family and consumer science classes to provide education about thermometers to adolescents, who…

  18. A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis

    PubMed Central

    1996-01-01

    Several members of the rho/rac family of small GTP-binding proteins are known to regulate the distribution of the actin cytoskeleton in various subcellular processes. We describe here a novel rac protein, racE, which is specifically required for cytokinesis, an actomyosin-mediated process. The racE gene was isolated in a molecular genetic screen devised to isolate genes required for cytokinesis in Dictyostelium. Phenotypic characterization of racE mutants revealed that racE is not essential for any other cell motility event, including phagocytosis, chemotaxis, capping, or development. Our data provide the first genetic evidence for the essential requirement of a rho-like protein, specifically in cytokinesis, and suggest a role for these proteins in coordinating cytokinesis with the mitotic events of the cell cycle. PMID:8682867

  19. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping

    SciTech Connect

    Kruglyak, L.; Daly, M.J.; Lander, E.S. |

    1995-02-01

    Homozygosity mapping is a powerful strategy for mapping rare recessive traits in children of consanguineous marriages. Practical applications of this strategy are currently limited by the inability of conventional linkage analysis software to compute, in reasonable time, multipoint LOD scores for pedigrees with inbreeding loops. We have developed a new algorithm for rapid multipoint likelihood calculations in small pedigrees, including those with inbreeding loops. The running time of the algorithm grows, at most, linearly with the number of loci considered simultaneously. The running time is not sensitive to the presence of inbreeding loops, missing genotype information, and highly polymorphic loci. We have incorporated this algorithm into a software package, MAPMAKER/HOMOZ, that allows very rapid multipoint mapping of disease genes in nuclear families, including homozygosity mapping. Multipoint analysis with dozens of markers can be carried out in minutes on a personal workstation. 23 refs., 4 figs., 1 tab.

  20. Frequent overexpression of ErbB--receptor family members in brain metastases of non-small cell lung cancer patients.

    PubMed

    Berghoff, Anna Sophie; Magerle, Manuel; Ilhan-Mutlu, Ayseguel; Dinhof, Carina; Widhalm, Georg; Dieckman, Karin; Marosi, Christine; Wöhrer, Adelheid; Hackl, Monika; Zöchbauer-Müller, Sabine; Preusser, Matthias; Birner, Peter

    2013-12-01

    The ErbB receptor family has been implicated in brain metastases (BM) formation in various cancer types and specific targeted therapies are available. We investigated the overexpression of EGFR, HER2 and HER3 in BM of non-small cell lung cancer (NSCLC) patients to get a better insight on pathobiology of BM and potential drugable targets. We performed immunohistochemical analysis of EGFR, HER2 and HER3 on tissue microarrays of 131 NSCLC-BM. Fifty-one of 131 (38.9%) specimens were considered as positive for EGFR overexpression, 12/131 (9.2%) for HER2 and 27/131 (20.6%) for HER3 respectively. Sixty-nine of 131 (52.7%) of the cases showed overexpression of at least one marker. Four of 131 (3.1%) were positive for all three markers. Strong correlation was observed between HER2 and HER3 overexpression (p = 0.009; Chi-square test after Bonferroni-Holmes correction). No statistically significant correlation of EGFR, HER2 or HER3 overexpression with clinico-pathological parameters including overall survival times was observed. We observed overexpression of ErbB receptor family members, which represent established therapeutic targets in various primary tumours, in approximately half of NSCLC-BM. Further studies should investigate the role of the ErbB pathway in development of and as a therapeutic target in BM of NSCLC patients.

  1. The Role of Irreversible HER Family Inhibition in the Treatment of Patients with Non-Small Cell Lung Cancer

    PubMed Central

    2011-01-01

    Small-molecule tyrosine kinase inhibitors (TKIs) of the human epidermal growth factor receptor (HER) include the reversible epidermal growth factor receptor (EGFR/HER-1) inhibitors gefitinib and erlotinib. EGFR TKIs have demonstrated activity in the treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations; however, multiple mechanisms of resistance limit the benefit of these drugs. Although resistance to EGFR TKIs can be intrinsic and correlated with molecular lesions such as in Kirsten rat sarcoma viral oncogene homolog (KRAS; generally observed in a wild-type EGFR background), acquired resistance to EGFR TKIs can evolve in the setting of activating EGFR mutations, such as in the case of EGFR T790M mutations. Several irreversible inhibitors that target multiple members of the HER family simultaneously are currently in clinical development for NSCLC and may have a role in the treatment of TKI-sensitive and TKI-resistant disease. These include PF00299804, an inhibitor of EGFR/HER-1, HER-2, and HER-4, and afatinib (BIBW 2992), an inhibitor of EGFR/HER-1, HER-2, and HER-4. Results of large, randomized trials of these agents may help to determine their potential for the treatment of NSCLC. PMID:22016476

  2. Wisdom, insight and pragmatism. In the early days of Islam, Muslim society was familiar with the concept of the small family.

    PubMed

    Jullundri, R A

    1996-01-01

    In the context of rapid population growth, Pakistan's main political parties have stressed the importance of the small family norm and the need to adopt modern methods of family planning. Some Ulama, however, have argued that family planning does not conform to the traditions of Islam under the assumption that the levels of sexual perversion and female physical and psychological ailments would increase were family planning widely practiced. The author counters that the opposition of the few Ulama to family planning is based not upon theology and jurisprudence, but rather upon socioeconomic grounds. Islam may be the only divine religion which supports human free will such that a man can organize his affairs according to his own social and economic circumstances. Common belief is, however, that adherence to Islam impedes progress and prosperity. Muslims themselves are responsible for the perpetuation of such an impression. Muslim societies now face several social problems, one of which is their relatively lower acceptance of family planning. Muslim countries share problems in the following areas with regard to family planning: management, women's status in Muslim society, and low educational status.

  3. Ras-like family small GTPases genes in Nilaparvata lugens: Identification, phylogenetic analysis, gene expression and function in nymphal development

    PubMed Central

    Wang, Weixia; Li, Kailong; Wan, Pinjun; Lai, Fengxiang; Fu, Qiang; Zhu, Tingheng

    2017-01-01

    Twenty-nine cDNAs encoding Ras-like family small GTPases (RSGs) were cloned and sequenced from Nilaparvata lugens. Twenty-eight proteins are described here: 3 from Rho, 2 from Ras, 9 from Arf and 14 from Rabs. These RSGs from N.lugens have five conserved G-loop motifs and displayed a higher degree of sequence conservation with orthologues from insects. RT-qPCR analysis revealed NlRSGs expressed at all life stages and the highest expression was observed in hemolymph, gut or wing for most of NlRSGs. RNAi demonstrated that eighteen NlRSGs play a crucial role in nymphal development. Nymphs with silenced NlRSGs failed to molt, eclosion or development arrest. The qRT-PCR analysis verified the correlation between mortality and the down-regulation of the target genes. The expression level of nuclear receptors, Kr-h1, Hr3, FTZ-F1 and E93 involved in 20E and JH signal pathway was impacted in nymphs with silenced twelve NlRSGs individually. The expression of two halloween genes, Cyp314a1 and Cyp315a1 involved in ecdysone synthesis, decreased in nymphs with silenced NlSar1 or NlArf1. Cyp307a1 increased in nymphs with silenced NlArf6. In N.lugens with silenced NlSRβ, NlSar1 and NlRab2 at 9th day individually, 0.0% eclosion rate and almost 100.0% mortality was demonstrated. Further analysis showed NlSRβ could be served as a candidate target for dsRNA-based pesticides for N.lugens control. PMID:28241066

  4. Activation of Relaxin Family Receptor 1 from Different Mammalian Species by Relaxin Peptide and Small-Molecule Agonist ML290

    PubMed Central

    Huang, Zaohua; Myhr, Courtney; Bathgate, Ross A. D.; Ho, Brian A.; Bueno, Amaya; Hu, Xin; Xiao, Jingbo; Southall, Noel; Barnaeva, Elena; Agoulnik, Irina U.; Marugan, Juan J.; Ferrer, Marc; Agoulnik, Alexander I.

    2015-01-01

    Relaxin peptide (RLN), which signals through the relaxin family peptide 1 (RXFP1) GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small-molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by an increase of cAMP production. Guinea pig RXFP1 responded to relaxin but had very low response to ML290 treatment only at highest concentrations used. The rabbit RXFP1 amino acid sequence was the most divergent, with a number of unique substitutions within the ectodomain and the seven-transmembrane domain (7TM). Two splice variants of rabbit RXFP1 derived through alternative splicing of the fourth exon were identified. In contrast to the other species, rabbit RXFP1s were activated by ML290, but not with human, pig, mouse, or rabbit RLNs. Using FLAG-tagged constructs, we have shown that both rabbit RXFP1 variants are expressed on the cell surface. No binding of human Eu-labeled RLN to rabbit RXFP1 was detected, suggesting that in this species, RXFP1 might be non-functional. We used chimeric rabbit–human and guinea pig–human constructs to identify regions important for RLN or ML290 receptor activation. Chimeras with the human ectodomain and rabbit 7TM domain were activated by RLN, whereas substitution of part of the guinea pig 7TM domain with the human sequence only partially restored ML290 activation, confirming the allosteric mode of action for the two ligands. Our data demonstrate that macaque and pig models can be used for ML290 testing. PMID:26347712

  5. Familial chondrocalcinosis in the Chiloe Islands, Chile.

    PubMed Central

    Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

    1975-01-01

    Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

  6. Community engagement and education: addressing the needs of South Asian families with genetic disorders.

    PubMed

    Khan, Nasaim; Kerr, Gifford; Kingston, Helen

    2016-10-01

    Consanguineous marriage is common among the South Asian heritage community in the UK. While conferring social and cultural benefits, consanguinity is associated with an increased risk of autosomal recessive disorders and an increase in childhood death and disability. We have previously developed a genetic service to address the needs of this community. We report the extension of this service to include community-based initiatives aimed at promoting understanding of genetic issues related to consanguinity and improving access to genetic services. Our approach was to develop integrated clinical, educational and community engagement initiatives that would be sustainable on a long-term basis. The service provided for South Asian families by a specialist genetic counsellor was extended, and a series of genetics education and awareness sessions were provided for a diverse range of frontline healthcare workers. Two community genetic outreach worker posts were established to facilitate the engagement of the local South Asian population with genetics. The education and awareness sessions helped address the lack of genetic knowledge among primary health care professionals and community workers. Engagement initiatives by the genetic outreach worker raised awareness of genetic issues in the South Asian community and families affected by autosomal recessive disorders. All three elements of the extended service generated positive feedback. A three-stranded approach to addressing the needs of consanguineous families affected by autosomal recessive disorders as recommended by the World Health Organisation is suggested to be an acceptable, effective and sustainable approach to delivery of service in the UK.

  7. The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

    PubMed

    Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

    2003-03-01

    Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

  8. Age-standardized Incidence Rates for Leukemia Associated with Consanguineous Marriages in 68 Countries, an Ecological Study

    PubMed Central

    Saadat, Mostafa

    2015-01-01

    Consanguineous marriage that defines as a union between biologically related persons has a variety of known deleterious correlations with factors that affect public health within human populations. To investigate the association between the mean of inbreeding coefficient (α) and incidence of leukemia, the present ecological study on 68 countries was carried out. Statistical analysis showed that the age-standardized incidence rate of leukemia positively correlated with log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with log10α (r=−0.609, df=66, P<0.001). Controlling log10GNI per capita, a significant negative correlation between log10α and the age-standardized incidence rate of leukemia was observed (r=−0.392, df=65, P=0.001). The countries were stratified according to their annual GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling for log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was still significant (r=−0.600, df=36, P<0.001). It should be noted that there was no significant association between the age-standardized mortality rate due to leukemia and log10α (P>0.05). The present finding indicates that the rate of leukemia, age-standardized for incidence, is lower in countries with a high prevalence of consanguineous marriages. PMID:25960855

  9. Consanguinity rate and delay in diagnosis in Turkish patients with combined immunodeficiencies: a single-center study.

    PubMed

    Azarsiz, Elif; Gulez, Nesrin; Edeer Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil

    2011-02-01

    Combined immunodeficiency diseases comprise a group of disorders with different molecular basis. Clinical and immunological phenotypes for each group are extremely heterogenous. The frequency of combined immunodeficiencies may vary in different countries. The most frequent forms of combined immunodeficiency show inherited defects in development of T and/or B lymphocytes. These defects are classified according to immunologic phenotype and are categorized into T-B+ or T-B- including forms with or without natural killer lymphocytes. We report here twenty-three patients (female/male: 12/11) with combined immunodeficiency showing different immunological and clinical phenotypes, majority of whom were admitted because of severe upper and lower respiratory tract infections. Mean age of the study group, mean age at onset of the symptoms, and diagnosis were 47.5 ± 42.2, 11.2 ± 17.3, and 19.5 ± 23.8 months, respectively. There was nearly 8 months time delay between beginning of symptoms and diagnosis. Within the combined immunodeficiency phenotypes, T-B-NK+ category was the most frequent phenotype. Consanguinity was positive in 73.9% (n = 17) of patients while it was about 80.0% (n = 8) in deceased ten children. Bone marrow or umblical cord stem cell transplantation was applied to 11 of them. Three patients deceased after transplantation and seven patients deceased without transplantation. Twelve patients are being followed by prophylactic treatment. In conclusion; combined immunodeficiencies are frequent in our country because of high rate of consanguinity. T-B- combined immunodeficiencies are more often observed, and infants presenting severe infections beginning in the first 3 months of life have to be examined for combined immunodeficiencies. Shortening of time delay in diagnosis will increase success of life-saving treatment.

  10. Birth-spacing patterns in Huaning County, Yunnan Province, PRC: is the adoption of a small family norm sustainable?

    PubMed

    Löfstedt, Petra; Ghilagaber, Gebrenegus; Johansson, Annika

    2007-01-01

    China's family planning programs have emphasized delayed marriage and longer spacing between births. Since 1970, the fertility has declined from 6 to 1.8 births and the mean age at first marriage has gone up but the recommended spacing intervals have not been fully realized. Despite the fertility decline it is being debated among scholars whether China has completed a sustainable demographic transition or not, especially in rural areas. The aim of this study was to analyze trends in the timing and patterns of marriage and childbearing in relation to successive family planning policies. A cluster random sample of 1,336 women aged 15-64 at the time of the survey (2000) was selected in one rural county in Yunnan province. Life-table techniques were used to analyze the cumulative proportion of women marrying and having a certain number of births. Cox's hazard regression model was used to estimate the effects of various covariates on the "hazard" for a woman to have a second birth. Our findings demonstrate how childbearing patterns have changed in the direction of delayed marriage, a decreased interval between first marriage and first child, and significantly longer spacing between the first and second child. This transformation of childbearing patterns corresponds well with the requirements of the policies. Considering the characteristics of Yunnan, it seems likely that the changing fertility behavior has been more influenced by a strictly enforced family planning policy than by societal changes leading to the adoption of a new, smaller family norm.

  11. Familial aggregation of colorectal cancer in Egypt.

    PubMed

    Soliman, A S; Bondy, M L; Levin, B; El-Badawy, S; Khaled, H; Hablas, A; Ismail, S; Adly, M; Mahgoub, K G; McPherson, R S; Beasley, R P

    1998-09-11

    We have investigated the familial aggregation of colorectal cancer and hereditary nonpolyposis colorectal cancer (HNPCC) in Egypt because of the high incidence of colorectal cancer in Egyptian children and young adults and the prevalence of consanguinity there. In a pilot study, we conducted detailed interviews with 111 Egyptian colorectal cancer patients and 111 healthy Egyptian controls about their family histories of colorectal cancer, and other cancers, consanguinity, age at diagnosis, symptoms and recurrence. Eight patients (7.2%) had one or more first- or second-degree relatives under age 40 with colorectal cancer, suggestive of HNPCC by the Amsterdam criteria. One of these families had a typical history of HNPCC, with 4 relatives having colorectal cancer in 3 generations; 3 of these relatives were younger than age 45 at colon cancer diagnosis, and other relatives had extracolonic tumors. Another 14 patients (12.6%) had a first- or second-degree relative with a family history of other neoplasms such as endometrial, urinary and hepatobiliary cancers that could also be related to HNPCC. Four patients with early-onset colon cancer and a family history of other HNPCC-related cancers reported that their parents were first-degree cousins.

  12. From "New Genetics" to Everyday Knowledge: Ideas about How Genetic Diseases Are Transmitted in Two Large Brazilian Families

    ERIC Educational Resources Information Center

    Santos, Silvana; Bizzo, Nelio

    2005-01-01

    This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected…

  13. Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities

    PubMed Central

    Ahmed-Belkacem, Abdelhakim; Colliandre, Lionel; Ahnou, Nazim; Nevers, Quentin; Gelin, Muriel; Bessin, Yannick; Brillet, Rozenn; Cala, Olivier; Douguet, Dominique; Bourguet, William; Krimm, Isabelle; Pawlotsky, Jean-Michel; Guichou, Jean- François

    2016-01-01

    Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections. PMID:27652979

  14. Familial Gigantiform Cementoma

    PubMed Central

    Ma, Chunyue; Wang, Hongwei; He, Guang; Qin, Xingjun

    2016-01-01

    Abstract Familial gigantiform cementoma is an exceedingly rare but distinct subtype of cemento-osseous-fibrous lesion. Undocumented radiographic changes and related bone metabolism disorder are herein hypothesized and discussed. We present an adolescent case with recurrent familial gigantiform cementoma who received surgical intervention in our hospital. Apart from typical multiquadrant and expansile abnormalies involving both jaws, he also suffered from several times of fractures in lower extremity. Furthermore, radiographic examinations of calvaria, pelvis, femoris, tibia, and fibula all revealed radiolucent areas signifying diffuse osteopenic bone losses. Some of his consanguineous relatives bore the same burden of fractures during pubertal period. Considering these polyostotic conditions, a correlation of congenital bone metabolism disorder in cases with familial gigantiform cementoma, named “calcium steal disorder,” was thus proposed. Familial gigantiform cementoma is closely associated with “calcium steal disorder.” Whole-body dual-energy absorptiometry should be considered as a routine examination for fracture-related risk prediction. PMID:26945411

  15. Consanguinity in Centre d'Étude du Polymorphisme Humain (CEPH) pedigrees.

    PubMed

    Stevens, Eric L; Heckenberg, Greg; Baugher, Joseph D; Roberson, Elisha D O; Downey, Thomas J; Pevsner, Jonathan

    2012-06-01

    A set of Centre d'Étude du Polymorphisme Humain (CEPH) cell lines serves as a large reference collection that has been widely used as a benchmark for allele frequencies in the analysis of genetic variants, to create linkage maps of the human genome, to study the genetics of gene expression, to provide samples to the HapMap and 1000 Genomes projects, and for a variety of other applications. An explicit feature of the CEPH collection is that these multigenerational families represent reference panels of known relatedness, consisting mostly of three-generation pedigrees with large sibships, two parents, and grandparents. We applied identity-by-state (IBS) and identity-by-descent (IBD) methods to high-density genotype data from 186 CEPH individuals in 13 families. We identified unexpected relatedness between nominally unrelated grandparents both within and between pedigrees. For one pair, the estimated Cotterman coefficient of relatedness k1 exceeded 0.2, consistent with one-eighth sharing (eg, first-cousins). Unexpectedly, significant IBD2 values were discovered in both second-degree and parent-child relationships. These were accompanied by regions of homozygosity in the offspring, which corresponded to blocks lacking IBS0 in purportedly unrelated parents, consistent with inbreeding. Our findings support and extend a 1999 report, based on the use of short tandem-repeat polymorphisms, that several CEPH families had regions of homozygosity consistent with autozygosity. We benchmarked our IBD approach (called kcoeff) against both RELPAIR and PREST software packages. Our findings may affect the interpretation of previous studies and the design of future studies that rely on the CEPH resource.

  16. An annotated catalogue of the gamasid mites associated with small mammals in Asiatic Russia. The family Laelapidae s. str. (Acari: Mesostigmata: Gamasina).

    PubMed

    Vinarski, Maxim V; Korallo-Vinarskaya, Natalia P

    2016-05-16

    Twenty-nine species of mites of the family Laelapidae s. str. have been recorded as associated with small mammals (rodents, insectivores) in Asiatic Russia (Siberia and the Russian Far East). These species belong to two subfamilies (Laelapinae, Myonyssinae) and six genera: Androlaelaps Berlese, 1903, Dipolaelaps Zemskaya & Piontkovskaya, 1960, Laelaps C.L. Koch, 1836, Hyperlaelaps Zakhvatkin, 1948, Myonyssus Tiraboschi, 1904, Oryctolaelaps Lange, 1955. A list of the species, with data on synonymy, geographic ranges, and relationships with mammal hosts is provided. Some considerations concerning patterns of distribution of the parasitic Laelaptidae of Asiatic Russia are presented as well as their classifications from the point of view of known host association records.

  17. A small family of sushi-class retrotransposon-derived genes in mammals and their relation to genomic imprinting.

    PubMed

    Youngson, Neil A; Kocialkowski, Sylvia; Peel, Nina; Ferguson-Smith, Anne C

    2005-10-01

    Ty3/gypsy retrotransposons are rare in mammalian genomes despite their abundance in invertebrate and other vertebrate classes. Here we identify a family of nine conserved mammalian genes with homology to Ty3/gypsy retrotransposons but which have lost their ability to autonomously retrotranspose. Of these, five map to the X chromosome while the remaining four are autosomal. Comparative phylogenetic analyses show them to have strongest homology to the sushi-ichi element from Fugu rubripes. Two of the autosomal gene members, Peg10 and Rtl1, are known to be imprinted, being expressed from the paternally inherited chromosome homologue. This suggests, consistent with the host-parasite response theory of the evolution of the imprinting mechanism, that parental-origin specific epigenetic control may be mediated by genomic "parasitic" elements such as these. Alternatively, these elements may preferentially integrate into regions that are differentially modified on the two homologous chromosomes such as imprinted domains and the X chromosome and acquire monoallelic expression. We assess the imprinting status of the remaining autosomal members of this family and show them to be biallelically expressed in embryo and placenta. Furthermore, the methylation status of Rtl1 was assayed throughout development and was found to resemble that of actively, silenced repetitive elements rather than imprinted sequences. This indicates that the ability to undergo genomic imprinting is not an inherent property of all members of this family of retroelements. Nonetheless, the conservation but functional divergence between the different members suggests that they have undergone positive selection and acquired distinct endogenous functions within their mammalian hosts.

  18. Economic Openness and the Marginalization of Small Family Farmers: Aligning Curriculum To Meet the Needs of Rural Adolescents in Brazil.

    ERIC Educational Resources Information Center

    Moore, Audrey-Marie Schuh

    Economic liberalization and the rise of global competition have increased the importance of agricultural, technical, and business skills for small farmers in Brazil. However, many rural farmers are unable to attend agricultural technical schools due to low educational attainment. The first section of this paper discusses the impact that…

  19. Mechanism for attenuation of DNA binding by MarR family transcriptional regulators by small molecule ligands.

    PubMed

    Perera, Inoka C; Lee, Yong-Hwan; Wilkinson, Steven P; Grove, Anne

    2009-07-31

    Members of the multiple antibiotic resistance regulator (MarR) family control gene expression in a variety of metabolic processes in bacteria and archaea. Hypothetical uricase regulator (HucR), which belongs to the ligand-responsive branch of the MarR family, regulates uricase expression in Deinococcus radiodurans by binding a shared promoter region between uricase and HucR genes. We show here that HucR responds only to urate and, to a lesser extent, to xanthine by attenuated DNA binding, compared to other intermediates of purine degradation. Using molecular-dynamics-guided mutational analysis, we identified the ligand-binding site in HucR. Electrophoretic mobility shift assays and intrinsic Trp fluorescence have identified W20 from the N-terminal helix and R80 from helix 3, which serves as a scaffold for the DNA recognition helix, as being essential for ligand binding. Using structural data combined with in silico and in vitro analyses, we propose a mechanism for the attenuation of DNA binding in which a conformational change initiated by charge repulsion due to a bound ligand propagates to DNA recognition helices. This mechanism may apply generally to MarR homologs that bind anionic phenolic ligands.

  20. Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

    PubMed

    Bartsch, D K; Dietzel, K; Bargello, M; Matthaei, E; Kloeppel, G; Esposito, I; Heverhagen, J T; Gress, T M; Slater, E P; Langer, P

    2013-03-01

    Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2-10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small "imaging" BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.

  1. Catastrophic disruption in the solar system - Asteroid collisional history, origin of Hirayama families and disruption of small satellites

    NASA Technical Reports Server (NTRS)

    Davis, D. R.

    1986-01-01

    The process of collisional catastrophic disruption has played a significantly role in structuring the solar system. Diverse populations of bodies such as the asteroid belt, small satellites of Jupiter and Saturn and perhaps even the rings of Saturn have been created or substantially changed by catastrophic distruption. Understanding the outcome of large scale impacts is essential to learning about the early history of the solar system in the asteroid zone and the reason why a planet failed to form there.

  2. Respiratory Protection Behavior and Respiratory Indices among Poultry House Workers on Small, Family-Owned Farms in North Carolina: A Pilot Project.

    PubMed

    Kearney, Gregory D; Gallagher, Barbara; Shaw, Robert

    2016-01-01

    The aim of this pilot study was to evaluate respiratory behavior and respiratory indices of poultry workers on family-owned, poultry farms with 10 or less employees in North Carolina. A field study was conducted to collect data on participants (N = 24) using spirometry, fractional exhaled nitric oxide (Feno), and an interviewer-administered questionnaire. The majority of workers (76%) ranked respiratory protection as being important, yet 48% reported never or rarely wearing respiratory protection when working in dusty conditions. A large percent of workers reported eye (55%) and nasal (50%) irritation and dry cough (50%). On average, pulmonary lung function and Feno tests were normal among nonsmokers. In bivariate analysis, significant associations were identified between working 7 days on the farm (P = .01), with eye irritation, and working 5 or fewer years in poultry farming (P = .01). Poultry workers on family-owned farms spend a considerable amount of work time in poultry houses and report acute respiratory-related health symptoms. Administrative controls among small, family-owned poultry farms are necessary to improve and promote safety and health to its employees.

  3. Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

    PubMed Central

    Moldenhauer Minillo, Renata; Sobreira, Nara; de Fatima de Faria Soares, Maria; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Alvarez Perez, Ana B.

    2014-01-01

    Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

  4. The production of Multiple Small Peptaibol Families by Single 14-Module Peptide Synthetases in Trichoderma/Hypocrea

    SciTech Connect

    Degenkolb, Thomas; Aghchehb, Razieh Karimi; Dieckmann, Ralf; Neuhof, Torsten; Baker, Scott E.; Druzhinina, Irina S.; Kubicek, Christian P.; Brückner, Hans; von Dohren, Hans

    2012-03-01

    The most common peptaibibiotic structures are 11-residue peptaibols found widely distributed in the genus Trichoderma/Hypocrea. Frequently associated are 14-residue peptaibols sharing partial sequence identity. Genome sequencing projects of 3 Trichoderma strains of the major clades reveal the presence of up to 3 types of nonribosomal peptide synthetases with 7, 14, or 18-20 amino acid adding modules. We here provide evidence that the 14-module NRPS type found in T. virens, T. reesei (teleomorph Hypocrea jecorina) and T. atroviride produces both 11- and 14- residue peptaibols based on the disruption of the respective NRPS gene of T. reesei, and bioinformatic analysis of their amino acid activating domains and modules. The structures of these peptides may be predicted from the gene structures and have been confirmed by analysis of families of 11- and 14-residue peptaibols from the strain 618, termed hypojecorins A (23 sequences determined, 4 new) and B (3 new sequences), and the recently established trichovirins A from T. virens. The distribution of 11- and 14-residue products is strain-specific and depends on growth conditions as well. Possible mechanisms of module skipping are discussed.

  5. Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology.

    PubMed

    Borochowitz, Z; Langer, L O; Gruber, H E; Lachman, R; Katznelson, M B; Rimoin, D L

    1993-02-01

    We report on a "new" severe short-limb bone dysplasia which can be labeled descriptively a spondylo-meta-epiphyseal dysplasia. The 3 patients were born to 2 unrelated Sepharadic Jewish families and a Puerto Rican family. Clinical abnormalities include small stature with short limbs including short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiological abnormalities include platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes over time. Chondroosseous morphology and ultrastructure document sparse matrix and degenerating chondrocytes surrounded by dense amorphous material in the 1 patient studied. Consanguinity is present in 1 family. In addition to the described patient, 2 other short-limb sibs, who did not survive infancy, were born into this family. Even in the absence of any photographic or radiologic documentation of these other 2 infants, autosomal recessive mode of inheritance seems probable.

  6. Identification of small molecule agonists of human relaxin family receptor 1 (RXFP1) by utilizing a homogenous cell-based cAMP assay

    PubMed Central

    Chen, Catherine Z.; Southall, Noel; Xiao, Jingbo; Marugan, Juan J.; Ferrer, Marc; Hu, Xin; Jones, Raisa E.; Feng, Shu; Agoulnik, Irina U.

    2016-01-01

    The relaxin hormone is involved in a variety of biological functions including female reproduction and parturition, regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) RXFP1, relaxin family receptor 1, is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. While agonists of the receptor could have a wide range of pharmacological utility, up to date, there are no reported small molecule agonists for relaxin receptors. Here, we report the development of quantitative high-throughput platform for RXFP1 agonist screen based on homogenous cell-based HTRF cAMP assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365,677 compounds. Neither compound showed activity in a counter screen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists. PMID:23212924

  7. The bldC Developmental Locus of Streptomyces coelicolor Encodes a Member of a Family of Small DNA-Binding Proteins Related to the DNA-Binding Domains of the MerR Family

    PubMed Central

    Hunt, Alison C.; Servín-González, Luis; Kelemen, Gabriella H.; Buttner, Mark J.

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed ΔbldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although ΔbldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein. PMID:15629942

  8. The bldC developmental locus of Streptomyces coelicolor encodes a member of a family of small DNA-binding proteins related to the DNA-binding domains of the MerR family.

    PubMed

    Hunt, Alison C; Servín-González, Luis; Kelemen, Gabriella H; Buttner, Mark J

    2005-01-01

    The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed DeltabldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although DeltabldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein.

  9. The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.

    PubMed

    Pacurari, Maricica; Addison, Joseph B; Bondalapati, Naveen; Wan, Ying-Wooi; Luo, Dajie; Qian, Yong; Castranova, Vincent; Ivanov, Alexey V; Guo, Nancy Lan

    2013-08-01

    Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA‑200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis. Nevertheless, miR-200 family target genes that promote metastasis in non-small cell lung cancer (NSCLC) remain largely unknown. Here, we sought to investigate whether the microRNA-200 family regulates our previously identified NSCLC prognostic marker genes associated with metastasis, as potential molecular targets. Novel miRNA targets were predicted using bioinformatics tools based on correlation analyses of miRNA and mRNA expression in 57 squamous cell lung cancer tumor samples. The predicted target genes were validated with quantitative RT-PCR assays and western blot analysis following re-expression of miR-200a, -200b and -200c in the metastatic NSCLC H1299 cell line. The results show that restoring miR-200a or miR-200c in H1299 cells induces downregulation of DLC1, ATRX and HFE. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. The miR-200 family and these potential targets are functionally involved in canonical pathways of immune response, molecular mechanisms of cancer, metastasis signaling, cell-cell communication, proliferation and DNA repair in Ingenuity pathway analysis (IPA). These results indicate that re-expression of miR-200 downregulates our previously identified NSCLC prognostic biomarkers in metastatic NSCLC cells. These results provide new insights into miR-200 regulation in lung cancer metastasis and consequent clinical outcome, and may provide a potential basis for innovative therapeutic approaches for the treatment of this

  10. Rem2, a member of the RGK family of small GTPases, is enriched in nuclei of the basal ganglia

    PubMed Central

    Liput, Daniel J.; Lu, Van B.; Davis, Margaret I.; Puhl, Henry L.; Ikeda, Stephen R.

    2016-01-01

    Rem2 is a member of the RGK subfamily of RAS small GTPases. Rem2 inhibits high voltage activated calcium channels, is involved in synaptogenesis, and regulates dendritic morphology. Rem2 is the primary RGK protein expressed in the nervous system, but to date, the precise expression patterns of this protein are unknown. In this study, we characterized Rem2 expression in the mouse nervous system. In the CNS, Rem2 mRNA was detected in all regions examined, but was enriched in the striatum. An antibody specific for Rem2 was validated using a Rem2 knockout mouse model and used to show abundant expression in striatonigral and striatopallidal medium spiny neurons but not in several interneuron populations. In the PNS, Rem2 was abundant in a subpopulation of neurons in the trigeminal and dorsal root ganglia, but was absent in sympathetic neurons of superior cervical ganglia. Under basal conditions, Rem2 was subject to post-translational phosphorylation, likely at multiple residues. Further, Rem2 mRNA and protein expression peaked at postnatal week two, which corresponds to the period of robust neuronal maturation in rodents. This study will be useful for elucidating the functions of Rem2 in basal ganglia physiology. PMID:27118437

  11. The VP3 factor from viruses of Birnaviridae family suppresses RNA silencing by binding both long and small RNA duplexes.

    PubMed

    Valli, Adrian; Busnadiego, Idoia; Maliogka, Varvara; Ferrero, Diego; Castón, José R; Rodríguez, José Francisco; García, Juan Antonio

    2012-01-01

    RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery.

  12. Familial occurrence of an association of multiple intestinal atresia and choanal atresia: a new syndrome?

    PubMed

    Ferrarini, Alessandra; Osterheld, Maria-Chiara; Vial, Yvan; de Viragh, Pierre A; Cotting, Jacques; Martinet, Danielle; Beckmann, Jacques S; Fellmann, Florence

    2009-12-01

    We report on two familial cases from a non-consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post-mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high-resolution array CGH revealed no visible anomalies.

  13. Medical History, Lifestyle, Family History, and Occupational Risk Factors for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

    PubMed Central

    Benavente, Yolanda; Blair, Aaron; Vermeulen, Roel; Cerhan, James R.; Costantini, Adele Seniori; Monnereau, Alain; Nieters, Alexandra; Clavel, Jacqueline; Call, Timothy G.; Maynadié, Marc; Lan, Qing; Clarke, Christina A.; Lightfoot, Tracy; Norman, Aaron D.; Sampson, Joshua N.; Casabonne, Delphine; Cocco, Pierluigi; de Sanjosé, Silvia

    2014-01-01

    Background Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are two subtypes of non-Hodgkin lymphoma. A number of studies have evaluated associations between risk factors and CLL/SLL risk. However, these associations remain inconsistent or lacked confirmation. This may be due, in part, to the inadequate sample size of CLL/SLL cases. Methods We performed a pooled analysis of 2440 CLL/SLL cases and 15186 controls from 13 case-control studies from Europe, North America, and Australia. We evaluated associations of medical history, family history, lifestyle, and occupational risk factors with CLL/SLL risk. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We confirmed prior inverse associations with any atopic condition and recreational sun exposure. We also confirmed prior elevated associations with usual adult height, hepatitis C virus seropositivity, living or working on a farm, and family history of any hematological malignancy. Novel associations were identified with hairdresser occupation (OR = 1.77, 95% CI = 1.05 to 2.98) and blood transfusion history (OR = 0.79, 95% CI = 0.66 to 0.94). We also found smoking to have modest protective effect (OR = 0.9, 95% CI = 0.81 to 0.99). All exposures showed evidence of independent effects. Conclusions We have identified or confirmed several independent risk factors for CLL/SLL supporting a role for genetics (through family history), immune function (through allergy and sun), infection (through hepatitis C virus), and height, and other pathways of immune response. Given that CLL/SLL has more than 30 susceptibility loci identified to date, studies evaluating the interaction among genetic and nongenetic factors are warranted. PMID:25174025

  14. Identification and biochemical characterization of Rap2C, a new member of the Rap family of small GTP-binding proteins.

    PubMed

    Paganini, Simona; Guidetti, Gianni Francesco; Catricalà, Silvia; Trionfini, Piera; Panelli, Simona; Balduini, Cesare; Torti, Mauro

    2006-01-01

    The Rap family of small GTP-binding proteins is composed by four different members: Rap1A, Rap1B, Rap2A and Rap2B. In this work we report the identification and characterization of a fifth member of this family of small GTPases. This new protein is highly homologous to Rap2A and Rap2B, binds labeled GTP on nitrocellulose, and is recognized by a specific anti-Rap2 antibody, but not by an anti-Rap1 antibody. The protein has thus been named Rap2C. Binding of GTP to recombinant purified Rap2C was Mg(2+)-dependent. However, accurate comparison of the kinetics of nucleotide binding and release revealed that Rap2C bound GTP less efficiently and possessed slower rate of GDP release compared to the highly homologous Rap2B. Moreover, in the presence of Mg(2+), the relative affinity of Rap2C for GTP was only about twofold higher than that for GDP, while, under the same conditions, Rap2B was able to bind GTP with about sevenfold higher affinity than GDP. When expressed in eukaryotic cells, Rap2C localized at the plasma membrane, as dictated by the presence of a CAAX motif at the C-terminus. We found that Rap2C represented the predominant Rap2 protein expressed in circulating mononuclear leukocytes, but was not present in platelets. Importantly, Rap2C was found to be expressed in human megakaryocytes, suggesting that the protein may be down-regulated during platelets generation. This work demonstrates that Rap2C is a new member of the Rap2 subfamily of proteins, able to bind guanine nucleotides with peculiar properties, and differently expressed by various hematopoietic subsets. This new protein may therefore contribute to the still poorly clarified cellular events regulated by this subfamily of GTP-binding proteins.

  15. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone.

    PubMed

    Yang, Xiudong; Yan, Wenjuan; Tian, Ye; Ma, Pan; Opperman, Lynne A; Wang, Xiaofang

    2016-01-01

    Recent studies have identified family with sequence similarity member 20C (FAM20C) as a kinase that phosphorylates the Ser in Ser-X-Glu/phospho-Ser (pSer) motifs in the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs). There is no in vivo evidence that validates this finding, and it is unclear whether FAM20C is the only kinase for SIBLINGs. We extracted bone noncollagenous proteins (NCPs) from Fam20C-knockout (KO) mice and analyzed the phosphorylation levels. The total NCPs were separated into osteopontin-, bone sialoprotein-, and dentin matrix protein-1-enriched fractions by anion-exchange chromatography and analyzed by SDS-PAGE, native PAGE, and Western immunoblot analysis. The NCP phosphorylation level in the KO mice was lower than that in the wild-type (WT). On the native gel, the SIBLINGs from KO mice showed a lower migration rate (Mr) than those from the WT. Calf intestine phosphatase treatment shifted SIBLINGs from the WT mice to the level adjacent to the KO, but failed to shift the latter, suggesting a phosphorylation loss of SIBLINGs in the KO mice. Mass spectrometry identified less pSers in the SIBLINGs from the KO mice [including the region of the acidic Ser- and aspartate-rich motif (ASARM) peptides]. In an intriguing finding, several pSers in the Ser-X-Glu motifs in the KO mice maintained their phosphorylation, whereas several others in non-Ser-X-Glu motifs did not. Phospho-Tyrs and phospho-Thrs in the SIBLINGs did not appear to be associated with FAM20C. Our results indicate that FAM20C is the primary, but not the only, kinase for the SIBLINGs.-Yang, X., Yan, W., Tian, Y., Ma, P., Opperman, L. A., Wang, X. Family with sequence similarity member 20C is the primary but not the only kinase for the small-integrin-binding ligand N-linked glycoproteins in bone.

  16. myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course.

    PubMed Central

    Johnson, B E; Ihde, D C; Makuch, R W; Gazdar, A F; Carney, D N; Oie, H; Russell, E; Nau, M M; Minna, J D

    1987-01-01

    44 small cell lung cancer cell lines established from 227 patients were studied for myc family DNA amplification (c-myc, N-myc, and L-myc). Two of 19 lines (11%) established from untreated patients' tumors had DNA amplification (one N-myc and one L-myc), compared with 11 of 25 (5 c-myc, 3 N-myc, and 3 L-myc) cell lines (44%) established from relapsed patients' tumors (P = 0.04). The 19 patients who had tumor cell lines established before chemotherapy treatment survived a median of 14 wk compared with 48 wk for the 123 extensive stage patients who did not have cell lines established (P less than 0.001). Relapsed patients whose cell lines had c-myc DNA amplification survived a shorter period (median of 33 wk) than patients whose cell lines did not have c-myc amplification (median of 53 wk; P = 0.04). We conclude that myc family DNA amplification is more common in tumor cell lines established from treated than untreated patients' tumors, and c-myc amplification in treated patients' tumor cell lines is associated with shortened survival. Images PMID:3034978

  17. Consanguinity and the sib-pair method: An approach using identity by descent between and within individuals

    SciTech Connect

    Genin, E.; Clerget-Darpoux, F.

    1996-11-01

    To test for linkage between a trait and a marker, one can consider identical marker alleles in related individuals, for instance, sibs. For recessive diseases, it has been shown that some information may be gained from the identity by descent (IBD) of the two alleles of an affected inbred individual at the marker locus. The aim of this paper is to extend the sib-pair method of linkage analysis to the situation of sib pairs sampled from consanguineous populations. This extension takes maximum advantage of the information provided by both the IBD pattern between sibs and allelic identity within each sib of the pair. This is possible through the use of the condensed identity coefficients. Here, we propose a new test of linkage based on a {Chi}{sup 2}. We compare the performance of this test with that of the classical {Chi}{sup 2} test based on the distribution of sib pairs sharing 0, 1, or 2 alleles IBD. For sib pairs from first-cousin matings, the proposed test can better detect the role of a disease-susceptibility (DS) locus. Its power is shown to be greater than that of the classical test, especially for models where the DS allele may be common and incompletely penetrant; that is to say for situations that may be encountered in multifactorial diseases. A study of the impact of inbreeding on the expected proportions of sib pairs sharing 0, 1, or 2 alleles IBD is also performed here. Ignoring inbreeding, when in fact inbreeding exists, increases the rate of type I errors in tests of linkage. 21 refs., 8 figs., 9 tabs.

  18. Rapidly expanding genetic diversity and host range of the Circoviridae viral family and other Rep encoding small circular ssDNA genomes

    PubMed Central

    Delwart, Eric; Li, Linlin

    2011-01-01

    The genomes of numerous circoviruses and distantly related circular DNA viruses encoding a rolling circle replication initiator protein (Rep) have been characterized from the tissues of mammals, fish, insects, and plants (geminivirus and nanovirus), human and animal feces, in an algae cell, and in diverse environmental samples. We review the genome organization, phylogenetic relationships and initial prevalence studies of cycloviruses, a proposed new genus in the Circoviridae family. Viral fossil rep sequences were also identified integrated on the chromosomes of mammals, frogs, lancelets, crustaceans, mites, gastropods, roundworms, placozoans, hydrozoans, protozoans, land plants, fungi, algae, and phytoplasma bacterias and their plasmids, reflecting their past host range. An ancient origin for viruses with rep-encoding single stranded small circular genomes, predating the diversification of eukaryotes, is discussed. The cellular hosts and pathogenicity of many recently described rep-containing circular genomes remain to be determined. Future studies of the virome of single cell and multi-cellular eukaryotes are likely to further extend the known diversity and host-range of small rep-containing circular viral genomes. PMID:22155583

  19. Asteroid families

    NASA Astrophysics Data System (ADS)

    Nesvorný, David; Bottke, William F.; Vokrouhlický, David; Morbidelli, Alessandro; Jedicke, Robert

    An asteroid family is a group of asteroids with similar orbits and spectra that was produced by a collisional breakup of a large parent body. To identify asteroid families, researchers look for clusters of asteroid positions in the space of proper orbital elements. These elements, being more constant over time than osculating orbital elements, provide a dynamical criterion of whether a group of bodies has a common ancestor. More than fifty asteroid families have been identified to date. Their analysis produced several important insights into the physics of large scale collisions, dynamical processes affecting small bodies in the Solar System, and surface and interior properties of asteroids.

  20. A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity

    PubMed Central

    Karnib, Hussein H.; Gharavi, Ali G.; Aftimos, Georges; Mahfoud, Ziyad; Saad, Reem; Gemayel, Elias; Masri, Badiaa; Assaad, Shafika; Badr, Kamal F.; Ziyadeh, Fuad N.

    2010-01-01

    Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible. Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important

  1. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    SciTech Connect

    Tan, Min; Wu, Junjie; Cai, Yong

    2013-09-06

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC.

  2. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    ClinicalTrials.gov

    2016-10-13

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  3. Src-Family Kinases Are Activated in Non-Small Cell Lung Cancer and Promote the Survival of Epidermal Growth Factor Receptor-Dependent Cell Lines

    PubMed Central

    Zhang, Jie; Kalyankrishna, Shailaja; Wislez, Marie; Thilaganathan, Nishan; Saigal, Babita; Wei, Wei; Ma, Long; Wistuba, Ignacio I.; Johnson, Faye M.; Kurie, Jonathan M.

    2007-01-01

    The role of Src-family kinases (SFKs) in non-small cell lung cancer (NSCLC) has not been fully defined. Here we addressed this question by examining SFK phosphorylation in NSCLC biopsy samples and using genetic and pharmacological approaches to inhibit SFK expression and activity in cultured NSCLC cells. Immunohistochemical analysis of NSCLC biopsy samples using a Tyr416 phosphorylation-specific, pan-SFK antibody revealed staining in 123 (33%) of 370 tumors. Because c-Src is known to be both an upstream activator and downstream mediator of epidermal growth factor receptor (EGFR), we next investigated SFK phosphorylation in a panel of NSCLC cell lines, including ones that depend on EGFR for survival. The EGFR-dependent NSCLC cell lines HCC827 and H3255 had increased phosphorylation of SFKs, and treatment of these cells with an SFK inhibitor (PP1 or SKI-606) induced apoptosis. PP1 decreased phosphorylation of EGFR, ErbB2, and ErbB3 and strikingly enhanced apoptosis by gefitinib, an EGFR inhibitor. HCC827 cells transfected with c-Src short hairpin RNA exhibited diminished phosphorylation of EGFR and ErbB2 and decreased sensitivity to apoptosis by PP1 or gefitinib. We conclude that SFKs are activated in NSCLC biopsy samples, promote the survival of EGFR-dependent NSCLC cells, and should be investigated as therapeutic targets in NSCLC patients. PMID:17200208

  4. Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 Suppresses Proliferation and Induces Apoptosis in Non-Small-Cell Lung Cancer

    PubMed Central

    Li, Yintao; Xu, Yali; Ye, Kuanping; Wu, Nan; Li, Junfeng; Liu, Naijia; He, Min; Lu, Bin; Zhou, Wenbai; Hu, Renming

    2016-01-01

    Our previous studies demonstrated that depletion of tubulin polymerization promoting protein family member 3 (TPPP3) inhibits proliferation and induces apoptosis of HeLa cells. However, the expression and roles of TPPP3 in cancers remain largely unknown. In this study, we investigated the expression of TPPP3 in clinicopathological correlations in non-small-cell lung cancer (NSCLC) samples by immunohistochemistry. TPPP3 expression was significantly upregulated in NSCLC tissues, and high TPPP3 expression was positively associated with tumor size, lymph node metastasis, clinical stage, and poor survival. Furthermore, knockdown of TPPP3 by shRNA significantly inhibited cell proliferation and induced cell apoptosis and cell cycle arrest in vitro. In addition, depletion of TPPP3 inhibited lung cancer growth in vivo in the xenografts of H1299 cells; this effect was accompanied by the suppression of Ki67 expression. Our data suggested that TPPP3 might act as an oncogene in NSCLC. TPPP3 warrants consideration as a therapeutic candidate with anti-tumor potential. PMID:27390593

  5. Suppression of wingless-type MMTV integration site family, member 1 expression by small interfering RNA inhibits U251 glioma cell growth in vitro

    PubMed Central

    DONG, LUN; DUAN, XIAO-CHUN; HAN, CHONG-XU; ZHANG, HENGZHU; WU, YONGKANG

    2015-01-01

    A Wingless-type MMTV integration site family, member 1 (Wnt-1) RNA interference expression vector was constructed during the present study, which was used to transfect the glioma U251 cell line and investigate its effect on glioma. Two 21-base oligonucleotides complementary to the coding sequence that was flanking the loop sequence were designed to form a DNA hairpin template for the target small interfering RNA (siRNA). The siRNA templates were cloned into the siRNA expression vector, pGPU6/green fluorescent protein (GFP)/Neo and the sequence was confirmed by DNA sequencing. The pGPU6/GFP/Neo-short hairpin RNA (shRNA)-Wnt-1 vector was subsequently transfected into U251 cells, and reverse transcription polymerase chain reaction and western blot analysis were used to evaluate the Wnt-1 gene silencing effect on U251 cell growth by MTT assay and flow cytometry. The Wnt-1 protein expression was significantly reduced following transfection with the recombinant plasmid, as determined by western blot analysis of the transfected U251 cells. This transfection exhibited a significantly higher death rate, as shown by MTT. Thus, the present study demonstrated that the pGPU6/GFP/Neo-shRNA-Wnt-1 vector inhibited Wnt-1 protein expression. However, further investigations regarding the Wnt signaling pathway in glioma pathogenesis are required. PMID:25435937

  6. Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB.

    PubMed

    Li, S; Liu, Z C; Yin, S J; Chen, Y T; Yu, H L; Zeng, J; Zhang, Q; Zhu, F

    2013-09-05

    Numerous studies have shown that human endogenous retrovirus W family (HERV-W) envelope gene (env) is related to various diseases but the underlying mechanism has remained poorly understood. Our previous study showed that there was abnormal expression of HERV-W env in sera of patients with schizophrenia. In this paper, we reported that overexpression of the HERV-W env elevated the levels of small conductance Ca(2+)-activated K(+) channel protein 3 (SK3) in human neuroblastoma cells. Using a luciferase reporter system and RNA interference method, we found that functional cAMP response element site was required for the expression of SK3 triggered by HERV-W env. In addition, it was also found that the SK3 channel was activated by HERV-W env. Further study indicated that cAMP response element-binding protein (CREB) was required for the activation of the SK3 channel. Thus, a novel signaling mechanism of how HERV-W env influences neuronal activity and contributes to mental illnesses such as schizophrenia was proposed.

  7. Deletion of the gene family of small chlorophyll-binding proteins (ScpABCDE) offsets C/N homeostasis in Synechocystis PCC 6803.

    PubMed

    Tibiletti, Tania; Hernández-Prieto, Miguel A; Matthijs, Hans C P; Niyogi, Krishna K; Funk, Christiane

    2016-04-01

    In the family of chlorophyll binding proteins, single helix small CAB-like proteins (SCPs) are found in all organisms performing oxygenic photosynthesis. Here, we investigated the function of these stress-inducible proteins in the cyanobacterium Synechocystis sp. PCC 6803. We compared physiological, proteome and transcriptome traits of a Photosystem I (PSI) deletion strain, which constitutively induces SCPs, and a PSI-less/ScpABCDE(-) without SCPs. The SCP mutant cells were larger in size, showed irregular thylakoid structure and differed in cell-surface morphology. Deletion of scp genes strongly affected the carbon (C) and nitrogen (N) balance, resulting in accumulation of carbohydrates and a decrease in N-rich compounds (proteins and chlorophyll). Data from transcriptomic and metabolomic experiments revealed a role of SCPs in the control of chlorophyll biosynthesis. Additionally, SCPs diminished formation of reactive oxygen species, thereby preventing damage within Photosystem II. We conclude that the lack of SCP-function to remove free chlorophyll under stress conditions has a large impact on the metabolism of the entire cell.

  8. The Small Noncoding RNA Processing Machinery of Two Living Fossil Species, Lungfish and Coelacanth, Gives New Insights into the Evolution of the Argonaute Protein Family

    PubMed Central

    Biscotti, Maria Assunta; Forconi, Mariko; Gerdol, Marco; Pallavicini, Alberto; Schartl, Manfred; Barucca, Marco

    2017-01-01

    Argonaute (AGO) family proteins play many roles in epigenetic programming, genome rearrangement, mRNA breakdown, inhibition of translation, and transposon silencing. Despite being a hotspot in current scientific research, their evolutionary history is still poorly understood and consequently the identification of evolutionary conserved structural features should also generate useful information for better understanding their functions. We report here for the first time the transcript sets of the two subfamilies, Ago and Piwi, in the West African lungfish Protopterus annectens and in the Indonesian coelacanth Latimeria menadoensis, two key species in the evolutionary lineage leading to tetrapods. The phylogenetic analysis of 142 inferred protein sequences in 22 fully sequenced species and the analysis of microsynteny performed in the major vertebrate lineages indicate an intricate pattern for the evolution of both subfamilies that has been shaped by whole genome duplications and lineage specific gains and losses. The argonaute subfamily was additionally expanded by local gene duplications at the base of the jawed vertebrate lineage. The subfamily of Piwi proteins is involved in several processes such as spermatogenesis, piRNA biogenesis, and transposon repression. Expression assessment of AGO genes and genes coding for proteins involved in small RNA biogenesis suggests a limited activity of the Piwi pathway in lungfish in agreement with the lungfish genome containing mainly old and inactive transposons. PMID:28206606

  9. Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

    PubMed

    Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

    2016-12-01

    Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis.

  10. [Familial congenital hypomagnesemia revealed by neonatal convulsions].

    PubMed

    Ndiaye, M; Dehanin, T; Sow, A-D; Sène, M-S; Basse, A-M; Fall, A-L; Seck, L-B; Touré, K; Diop, A-G; Sow, H-D; Ndiaye, M-M

    2013-11-01

    Congenital hypomagnesemia is a rare disease, with an impact on cognitive and neurological development. We report on three familial cases of congenital hypomagnesemia, two boys and one girl who belong to the same consanguineous family. They all presented neonatal seizures and a psychomotor developmental delay. Cerebral computed tomography showed cerebral atrophy and calcifications in one case and magnetic resonance imaging found predominant cerebellar atrophy in the two other cases. All three patients also had hypocalcemia, hyperphosphoremia, and hypomagnesemia. The parathyroid hormone blood level was low in two cases and normal in the third. One 7-month old patient died. The others received a supplementation of calcium and magnesium, which normalized calcemia, phosphatemia but not magnesemia, which remained low despite high doses. They have both developed cognitive and behavioral impairments.

  11. New Perspectives on the Rural Economy. Hearing on New Perspectives on the Rural Economy before the Subcommittee on Rural Economy and Family Farming of the Committee on Small Business. United States Senate, One Hundredth Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Small Business.

    Testimony and prepared statements presented at a hearing before the Senate Subcommittee on Rural Economy and Family Farming focused on the concerns of rural small business. Witnesses included Senators from Montana, Illinois, New York, Oklahoma, South Dakota, Wisconsin, Minnesota, and Iowa, and nine representatives of business, state government,…

  12. Phase I Study of Navitoclax (ABT-263), a Novel Bcl-2 Family Inhibitor, in Patients With Small-Cell Lung Cancer and Other Solid Tumors

    PubMed Central

    Gandhi, Leena; Camidge, D. Ross; Ribeiro de Oliveira, Moacyr; Bonomi, Philip; Gandara, David; Khaira, Divis; Hann, Christine L.; McKeegan, Evelyn M.; Litvinovich, Elizabeth; Hemken, Philip M.; Dive, Caroline; Enschede, Sari H.; Nolan, Cathy; Chiu, Yi-Lin; Busman, Todd; Xiong, Hao; Krivoshik, Andrew P.; Humerickhouse, Rod; Shapiro, Geoffrey I.; Rudin, Charles M.

    2011-01-01

    Purpose Resistance to chemotherapy-induced apoptosis represents a major obstacle to cancer control. Overexpression of Bcl-2 is seen in multiple tumor types and targeting Bcl-2 may provide therapeutic benefit. A phase I study of navitoclax, a novel inhibitor of Bcl-2 family proteins, was conducted to evaluate safety, pharmacokinetics, and preliminary efficacy in patients with solid tumors. Patients and Methods Patients enrolled to intermittent dosing cohorts received navitoclax on day −3, followed by dosing on days 1 to 14 of a 21-day cycle. Patients on continuous dosing received a 1-week lead-in dose of 150 mg followed by continuous daily administration. Blood samples were collected for pharmacokinetic analyses, biomarker analyses, and platelet monitoring. Results Forty-seven patients, including 29 with small-cell lung cancer (SCLC) or pulmonary carcinoid, were enrolled between 2007 and 2008, 35 on intermittent and 12 on continuous dosing cohorts. Primary toxicities included diarrhea (40%), nausea (34%), vomiting (36%), and fatigue (34%); most were grade 1 or 2. Dose- and schedule-dependent thrombocytopenia was seen in all patients. One patient with SCLC had a confirmed partial response lasting longer than 2 years, and eight patients with SCLC or carcinoid had stable disease (one remained on study for 13 months). Pro-gastrin releasing peptide (pro-GRP) was identified as a surrogate marker of Bcl-2 amplification and changes correlated with changes in tumor volume. Conclusion Navitoclax is safe and well tolerated, with dose-dependent thrombocytopenia as the major adverse effect. Preliminary efficacy data are encouraging in SCLC. Efficacy in SCLC and the utility of pro-GRP as a marker of treatment response will be further evaluated in phase II studies. PMID:21282543

  13. Under-Five Child Mortality and Morbidity Associated with Consanguineous Child Marriage in Pakistan: Retrospective Analysis using Pakistan Demographic and Health Surveys, 1990-91, 2006-07, 2012-13.

    PubMed

    Mustafa, Mudasir; Zakar, Rubeena; Zakar, Muhammad Zakria; Chaudhry, Ashraf; Nasrullah, Muazzam

    2017-01-02

    Objective To assess the combined effect of consanguineous and child marriages (CCM) on children health, which has not previously been explored, either globally or locally. Methods We analyzed secondary data from a series of cross-sectional, nationally representative Pakistan Demographic and Health Surveys 1990-91, 2006-07, and 2012-13. A total of 5406 mothers with 10,164 children were included in the analysis. Child health was assessed by variables such as history of diarrhea, acute respiratory infection (ARI), ARI with fever, Under-5 child mortality (U5CM) and small-size birth (SSB). Associations among variables were assessed by calculating unadjusted Odd Ratios (OR) and adjusted OR (AOR). Results A majority (n = 6,247, 61%) of the births were to mothers having CCM as compare to non-CCM (3917, 39%). There was a significant association between CCM and U5CM during 1990-91 (AOR 1.24, 95% CI 1.03-1.49) and 2006-07 (AOR 1.25, 95% CI 1.05-1.51), and infant mortality in 1990-91 (AOR 1.39, 95% CI 1.05-1.85) and 2006-07 (AOR 1.61, 95% CI 1.17-2.21). A significant association was also found between CCM and SSB infants in the period 2006-07 (AOR 1.19, 95% CI 1.01-1.42) and 2012-13 (AOR 1.22, 95% CI 1.02-1.46). We noted no effect of CCM on diarrhea, ARI, and ARI with fever. Conclusion CCM increases the likelihood of U5CM, infant mortality and SSB infants. Further quantitative and qualitative research should be conducted to assess the effects of environmental, congenital and genetic factors on the health of children born to mothers in CCM.

  14. Microcephaly, dysmorphic features, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds, and small cerebellum in four patients.

    PubMed

    Kayserili, Hülya; Altunoglu, Umut; Yesil, Gozde; Rosti, Rasim Özgür

    2016-06-01

    Pontocerebellar hypoplasia (PCH) can occur as an isolated entity or part of a syndrome. PCH has been reported with facial dysmorphism, ocular anomalies, and genital anomalies, but the co-occurrence of all four has not been previously described. We report on four patients, born to two consanguineous families that are not related to one another, with distinctive facial features (short forehead, laterally extended, medially flared eyebrows), corneal dystrophy, underdevelopment of labioscrotal folds, and nonprogressive PCH. In addition, the patients show hair extruding from the lactiferous ducts, which to our knowledge has not been described before. The parental consanguinity, affected siblings of both genders, and absent manifestations in parents, indicate an autosomal recessive pattern of inheritance as most likely. © 2016 Wiley Periodicals, Inc.

  15. Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Korean Family by Targeted Exome Sequencing

    PubMed Central

    Chang, Mun Young; Kim, Ah Reum; Kim, Nayoung K.D.; Lee, Chung; Lee, Kyoung Yeul; Jeon, Woo-Sung; Koo, Ja-Won; Oh, Seung Ha; Park, Woong-Yang; Kim, Dongsup; Choi, Byung Yoon

    2015-01-01

    Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development. PMID:26242193

  16. Child Care: Promoting Quality in Family Child Care. Report to the Chairman, Subcommittee on Regulation, Business Opportunities, and Technology, Committee on Small Business, House of Representatives.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC. Health, Education, and Human Services Div.

    A recent study of family child care documented that a significant number of providers were giving inadequate care. As a result, this study sought to: (1) identify public and private initiatives to enhance the quality of family child care and determine how the initiatives are financed; (2) describe the federal role in supporting quality…

  17. Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia

    PubMed Central

    Ramasamy, Ranjith; Bakircioğlu, M. Emre; Cengiz, Cenk; Karaca, Ender; Scovell, Jason; Jhangiani, Shalini N.; Akdemir, Zeynep C.; Bainbridge, Matthew; Yu, Yao; Huff, Chad; Gibbs, Richard A.; Lupski, James R.; Lamb, Dolores J.

    2015-01-01

    Objective To investigate the genetic cause of nonobstructive azoospermia (NOA) in a consanguineous Turkish family through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations. Design Whole-exome sequencing Setting Research laboratory Patient(s) We sequenced the exomes of two siblings in a consanguineous family with NOA. Intervention(s) All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. Main Outcome Measure Discovery of a mutation that could potentially cause NOA Results A novel non-synonymous mutation in neuronal PAS 2 domain (NPAS2) was identified in a consanguineous family from Turkey. This mutation in exon 14 (chr2: 101592000 C>G) of NPAS2 is likely a disease-causing mutation as it is predicted to be damaging, is a novel variant, and segregates with the disease. Family segregation of the variants showed the presence of homozygous mutation in the three brothers with NOA and heterozygous mutation in mother, one brother and one sister who were both fertile. The mutation is not found in the single nucleotide polymorphism (SNP) database, the 1000 Genomes Project, Baylor College of Medicine cohort of 500 Turkish patients (not a population specific polymorphism) or matching 50 fertile controls. Conclusions Using WES, we identified a novel homozygous mutation in NPAS2 as a likely disease-causing variant in a Turkish family diagnosed with NOA. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases which conventional genetic approaches have previously failed to conclude a molecular diagnosis. PMID:25956372

  18. Inbreeding coefficients for X-linked and autosomal genes in consanguineous marriages in Spanish populations: the case of Guipúzcoa (Basque Country).

    PubMed

    Calderón, R; Aresti, U; Ambrosio, B; González-Martín, A

    2009-03-01

    Inbreeding patterns over the past two centuries have been studied more extensively in Spain and Italy than anywhere else in Europe. Consanguinity studies in mainland Spain have shown that populations settled along the Cantabrian cornice share inbreeding patterns that distinguish them from other populations further south. A visual representation of spatial variations of two key inbreeding variables is presented here for the first time via contour maps. This paper also analyzes time trends of mean inbreeding coefficients for X-linked (F(x)) and autosomal genes (F) (1862-1995) together with variations in F(x)/F ratios in Guipúzcoa, the most autochthonous Spanish Basque province. Because close cousin marriages are a mark of identity of the study population, we evaluated the contribution of uncle-niece/aunt-nephew (M12) and first cousin (M22) marriages to F(x) and F values and compared the frequencies of M12 and M22 pedigree subtypes and their corresponding F(x)/F ratios to those found in other Spanish populations. The mean Fx and F inbreeding levels in Guipúzcoa for the 134-year period analyzed were 1.51 x 10(-3) and 1.04 x 10(-3), respectively, and the F(x)/F ratio was seen to be very stable over time. Our findings show that major similarities exist for close consanguineous marriage subtypes between Basque and non-Basque Spanish populations, despite significant geographic variability in terms of first cousin pedigrees. The distortion seems to be caused by Guipúzcoa. The F(x)/F ratios for first cousins in Spanish populations were higher than expected (1.25), with values ranging from 1.34 to 1.48. The findings of the present study may be useful for advancing knowledge on the effects of the interaction between biology and culture and for exploring associations between mating patterns and the prevalence of certain diseases.

  19. Assessment of fertility and infertility in boron-exposed Turkish subpopulations: 3. Evaluation of fertility among sibs and in "borate families".

    PubMed

    Sayli, B S

    2001-09-01

    As a part of a work to reveal the health effects of boron and its compounds, fertility and infertility states of sibs of probands, contacted and interviewed in the field, and of their spouses were given. The purposes were to prevent duplications seemingly inevitable in a relatively small community with prevailing consanguinity while analyzing marriages over respective generations and to reveal if there occurred an aggregation of infertile couples. Any family without offspring after about the second year of marriage was considered primary infertile as adopted throughout the study and such families were ascertained through the individual pedigree charts set up according to the instructions of the proband, he (she) himself (herself) being excluded. The rates of childless families of this type were 0.0-3.4% among male and 0.9-3.8% among female sibs of the participant, and 2.3-10.0% among male and 0.0-5.6% among female sibs of his (her) spouse with averages of 2.3% of 1589, 2.6% of 1589, 4.0% of 1314, and 3.3% of 1436 instances, respectively. The differences were insignificant and the rates were not different from those concerning probands themselves and that of a comparable segment of the Turkish population. "Borate families/kindreds" with two or more members engaged in the borate industry were also assessed in order to detect if there was a significant clustering of infertiles within the kindred. Although it was difficult to compare with a matched group, few couples were examples of familial concentration of infertility. These results provided further support that boron exposure does not affect human reproduction primarily and most probably secondarily.

  20. From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families

    NASA Astrophysics Data System (ADS)

    Santos, Silvana; Bizzo, Nelio

    2005-07-01

    This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

  1. Exploring the genetic basis of 3MC syndrome: Findings in 12 further families.

    PubMed

    Urquhart, Jill; Roberts, Rebecca; de Silva, Deepthi; Shalev, Stavit; Chervinsky, Elena; Nampoothiri, Sheela; Sznajer, Yves; Revencu, Nicole; Gunasekera, Romesh; Suri, Mohnish; Ellingford, Jamie; Williams, Simon; Bhaskar, Sanjeev; Clayton-Smith, Jill

    2016-05-01

    The 3MC syndromes are a group of rare autosomal recessive disorders where the main clinical features are cleft lip and palate, hypertelorism, highly arched eyebrows, caudal appendage, postnatal growth deficiency, and genitourinary tract anomalies. Ophthalmological abnormalities, most notably anterior chamber defects may also be seen. We describe the clinical and molecular findings in 13 individuals with suspected 3MC syndrome from 12 previously unreported families. The exclusion of the MASP1 and COLEC11 Loci in two individuals from different consanguineous families and the absence of mutations in four further individuals sequenced for both genes raises the possibility that that there is further genetic heterogeneity of 3MC syndrome.

  2. Family welfare.

    PubMed

    Sinha, N K

    1992-01-01

    Between 1901-1921, India gained 12.9 million people because mortality remained high. The death rate fell between 1921-1951, but birth rates remained the same. Therefore 110 million people were added--2 times the population increase between 1891-1921. Between 1951-1981, the population increased to 324 million. Socioeconomic development was responsible for most of the downward trend in the birth rate during the 20th century. Even though large families were the norm in early India, religious leaders encouraged small family size. The 1st government family planning clinics in the world opened in Mysore and Bangalore in 1930. Right before Independence, the Bhore Committee made recommendations to reduce population growth such as increasing the age of marriage for girls. Since 1951 there has been a change in measures and policies geared towards population growth with each of the 7 5-Year Plans because policy makers applied what they learned from each previous plan. The 1st 5-Year Plan emphasized the need to understand what factors contribute to population growth. It also integrated family planning services into health services of hospitals and health centers. The government was over zealous in its implementation of the sterilization program (2nd 5-Year Plan, 1956-1961), however, which hurt family planning programs for many years. As of early 1992, sterilization, especially tubectomy, remained the most popular family planning method, however. The 7th 5-Year Plan changed its target of reaching a Net Reproductive Rate of 1 by 2001 to 2006-2011. It set a goal of 100% immunization coverage by 1990 but it did not occur. In 1986, the Ministry of Health and Family Welfare planned to make free contraceptives available in urban and rural areas and to involve voluntary organizations. The government needs to instill measures to increase women's status, women's literacy, and age of marriage as well as to eliminate poverty, ensure old age security, and ensure child survival and

  3. Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

    PubMed

    Ouechtati, Farah; Merdassi, Ahlem; Bouyacoub, Yosra; Largueche, Leila; Derouiche, Kaouther; Ouragini, Houyem; Nouira, Sonia; Tiab, Leila; Baklouti, Karim; Rebai, Ahmed; Schorderet, Daniel F; Munier, Francis L; Zografos, Leonidas; Abdelhak, Sonia; El Matri, Leila

    2011-01-01

    Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

  4. Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia.

    PubMed

    Vongsuvanh, R; Hooper, A J; Coakley, J C; Macdessi, J S; O'Loughlin, E V; Burnett, J R; Gaskin, K J

    2007-11-01

    Abetalipoproteinaemia (ABL) and homozygous familial hypobetalipoproteinaemia (FHBL) are rare inherited disorders associated with low or undetectable levels of apolipoprotein B (apoB)-containing lipoproteins. Patients present with the symptoms and sequelae of fat malabsorption, including fat-soluble vitamin deficiencies. We describe two novel mutations: one an APOB gene mutation causing FHBL and the other a microsomal triglyceride transfer protein (MTP) gene mutation causing ABL. Two siblings of consanguineous parents were homozygous for an apoB mutation 4339delT causing an apoB-30.9 truncation. In another family, a boy born to consanguineous parents was homozygous for a 319 bp in-frame deletion of MTP exon 15 (c.2076-39_2303 + 52del319). All three children presented with malabsorption and liver dysfunction and had similar very low serum lipid, apoB, and fat-soluble vitamin levels. The FHBL parents had low serum lipid and apoB profiles distinguishing the disorder from the normal levels in ABL parents. Future patients presenting with FHBL or ABL should be genotyped to provide further insight into the varying clinical severity related to molecular heterogenicity in these two conditions.

  5. A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate

    PubMed Central

    Yamazaki, Kiyohiro; Yoshino, Yuta; Mori, Yoko; Ochi, Shinichiro; Yoshida, Taku; Ishimaru, Takashi; Ueno, Shu-ichi

    2015-01-01

    Nasu-Hakola disease (NHD) is a rare autosomal recessive neuropsychiatric disorder characterized by bone cysts, fractures, and cognitive impairment. Two genes are responsible for the development of NHD; TYROBP and TREM2. Although it presents with typical signs and symptoms, diagnosing this disease remains difficult. This case report describes a male with NHD with no family or past history of bone fractures who was diagnosed using exome sequencing. His frontal lobe psychiatric symptoms recovered partially following treatment with sodium valproate, but not with an antipsychotic. PMID:26598595

  6. A Novel Family in Medicago truncatula Consisting of More Than 300 Nodule-Specific Genes Coding for Small, Secreted Polypeptides with Conserved Cysteine Motifs1[w

    PubMed Central

    Mergaert, Peter; Nikovics, Krisztina; Kelemen, Zsolt; Maunoury, Nicolas; Vaubert, Danièle; Kondorosi, Adam; Kondorosi, Eva

    2003-01-01

    Transcriptome analysis of Medicago truncatula nodules has led to the discovery of a gene family named NCR (nodule-specific cysteine rich) with more than 300 members. The encoded polypeptides were short (60–90 amino acids), carried a conserved signal peptide, and, except for a conserved cysteine motif, displayed otherwise extensive sequence divergence. Family members were found in pea (Pisum sativum), broad bean (Vicia faba), white clover (Trifolium repens), and Galega orientalis but not in other plants, including other legumes, suggesting that the family might be specific for galegoid legumes forming indeterminate nodules. Gene expression of all family members was restricted to nodules except for two, also expressed in mycorrhizal roots. NCR genes exhibited distinct temporal and spatial expression patterns in nodules and, thus, were coupled to different stages of development. The signal peptide targeted the polypeptides in the secretory pathway, as shown by green fluorescent protein fusions expressed in onion (Allium cepa) epidermal cells. Coregulation of certain NCR genes with genes coding for a potentially secreted calmodulin-like protein and for a signal peptide peptidase suggests a concerted action in nodule development. Potential functions of the NCR polypeptides in cell-to-cell signaling and creation of a defense system are discussed. PMID:12746522

  7. Geographical Range of Rio Mamoré Virus (Family Bunyaviridae, Genus Hantavirus) in Association with the Small-Eared Pygmy Rice Rat (Oligoryzomys microtis)

    PubMed Central

    Richter, Martin H.; Hanson, John Delton; Cajimat, Maria N.; Milazzo, Mary Louise

    2010-01-01

    Abstract Hantavirus HTN·007 was originally isolated from a small-eared pygmy rice rat (Oligoryzomys microtis) captured in northeastern Peru. The results of analyses of nucleotide and amino acid sequence data in this study indicated that HTN·007 is a strain of Rio Mamoré virus (RIOMV) which is enzootic in small-eared pygmy rice rat populations in Bolivia. As such, the results of this study extend our knowledge of the geographical range of RIOMV and support the notion that the small-eared pygmy rice rat is the principal host of RIOMV. PMID:20687859

  8. Vorticella Linnaeus, 1767 (Ciliophora, Oligohymenophora, Peritrichia) is a grade not a clade: redefinition of Vorticella and the families Vorticellidae and Astylozoidae using molecular characters derived from the gene coding for small subunit ribosomal RNA.

    PubMed

    Sun, Ping; Clamp, John; Xu, Dapeng; Kusuoka, Yasushi; Miao, Wei

    2012-01-01

    Recent phylogenetic analyses of the peritrich genus Vorticella have suggested that it might be paraphyletic, with one Vorticella species - Vorticella microstoma grouping with the swimming peritrichs Astylozoon and Opisthonecta in a distant clade. These results were based on very limited taxon sampling and thus could not be accepted as conclusive evidence for revising the generic classification. We tested paraphyly of the genus Vorticella by making a new analysis with a broad range of samples from three continents that yielded 52 new sequences of the gene coding for small subunit rRNA. Our results, together with the available sequences in Genbank, form a comprehensive set of data for the genus Vorticella. Analyses of these data showed that Vorticella microstoma morphotypes, Astylozoon, and Opisthonecta form a well-supported, monophyletic clade, that is distinct from and basal to the family Vorticellidae containing other species of Vorticella. Paraphyly of the genus Vorticella and family Vorticellidae was strongly confirmed by these results. Furthermore, the two clades of Vorticella identified by the SSU rRNA gene are so genetically diverse whereas the genetic distances within the one containing Vorticella microstoma morphotypes, Astylozoon, and Opisthonecta were so slight, which marked it as a separate family that must be defined by molecular characters in the absence of unifying morphological and morphogenetic characters. An emended characterization and status of the genus Vorticella, the families Vorticellidae and Astylozoidae are presented and discussed.

  9. Co-existence of phenylketonuria either with maple syrup urine disease or Sandhoff disease in two patients from Iran: emphasizing the role of consanguinity.

    PubMed

    Abiri, Maryam; Talebi, Saeed; Uitto, Jouni; Youssefian, Leila; Vahidnezhad, Hassan; Shirzad, Tina; Salehpour, Shadab; Zeinali, Sirous

    2016-10-01

    Most inborn errors of metabolism (IEMs) are inherited in an autosomal recessive manner. IEMs are one of the major concerns in Iran due to its extensive consanguineous marriages. Herein, we report two patients with two co-existent IEMs: a girl affected by classic phenylketonuria (PKU) and maple syrup urine disease (MSUD) and a male patient affected with Sandhoff disease and PKU, where Sandhoff disease was suspected due to the presence of a cherry-red spot in the eyes at 6 months which is unrelated to PKU. Sequencing of candidate genes in the first patient revealed one novel and three recurrent compound heterozygous mutations of p.Ser231Pro and p.Ala300Ser in the PAH gene and p.Glu330Lys and p.Arg170Cys mutations in the BCKDHB gene. Genetic testing results in the second patient showed previously reported homozygous mutations of p.Arg261Gln in the PAH and p.Arg533Cys mutation in the HEXB gene. Genetic testing confirmed the clinical diagnosis of both diseases in both patients. To the best of our knowledge; this is the first report of the co-existence of two distinct genetic disorders in two individuals from Iran. Co-existent different IEMs in patients complicated the clinical diagnosis and management of the diseases.

  10. Challenges and solutions for gene identification in the presence of familial locus heterogeneity

    PubMed Central

    Rehman, Atteeq U; Santos-Cortez, Regie Lyn P; Drummond, Meghan C; Shahzad, Mohsin; Lee, Kwanghyuk; Morell, Robert J; Ansar, Muhammad; Jan, Abid; Wang, Xin; Aziz, Abdul; Riazuddin, Saima; Smith, Joshua D; Wang, Gao T; Ahmed, Zubair M; Gul, Khitab; Shearer, A Eliot; Smith, Richard J H; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hinnant, John; Khan, Shaheen N; Fisher, Rachel A; Ahmad, Wasim; Friderici, Karen H; Riazuddin, Sheikh; Friedman, Thomas B; Wilch, Ellen S; Leal, Suzanne M

    2015-01-01

    Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification. PMID:25491636

  11. Family Therapy

    MedlinePlus

    Tests and Procedures Family therapy By Mayo Clinic Staff Family therapy is a type of psychological counseling (psychotherapy) that helps family members improve communication and resolve conflicts. Family therapy is usually provided ...

  12. Family Life

    MedlinePlus

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  13. Crystallization and preliminary X-ray diffraction analysis of XAC1151, a small heat-shock protein from Xanthomonas axonopodis pv. citri belonging to the α-crystallin family

    SciTech Connect

    Hilario, Eduardo; Teixeira, Elaine Cristina; Pedroso, Gisele Audrei; Bertolini, Maria Célia; Medrano, Francisco Javier

    2006-05-01

    XAC1151, a small heat-shock protein from X. axonopodis pv. citri belonging to the α-crystallin family, was crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium phosphate. X-ray diffraction data were collected to 1.65 Å resolution using a synchrotron-radiation source. The hspA gene (XAC1151) from Xanthomonas axonopodis pv. citri encodes a protein of 158 amino acids that belongs to the small heat-shock protein (sHSP) family of proteins. These proteins function as molecular chaperones by preventing protein aggregation. The protein was crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium phosphate. X-ray diffraction data were collected to 1.65 Å resolution using a synchrotron-radiation source. The crystal belongs to the rhombohedral space group R3, with unit-cell parameters a = b = 128.7, c = 55.3 Å. The crystal structure was solved by molecular-replacement methods. Structure refinement is in progress.

  14. The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A Genetic and Phenotypic Study of Pakistani Families

    PubMed Central

    Keser, Vafa; Khan, Ayesha; Siddiqui, Sorath; Lopez, Irma; Ren, Huanan; Qamar, Raheel; Nadaf, Javad; Majewski, Jacek; Chen, Rui; Koenekoop, Robert K.

    2017-01-01

    Purpose To evaluate consanguineous pedigrees from Pakistan with a clinical diagnosis of nonsyndromic congenital retinal nonattachment (NCRNA) and identify genes responsible for the disease as currently only one NCRNA gene is known (atonal basic helix-loop-helix transcription factor 7: ATOH7). Methods We implemented a three-step genotyping platform: single nucleotide polymorphism genotyping to identify loss of heterozygosity regions in patients, Retinal Information Network panel screening for mutations in currently known retinal genes. Negative patients were then subjected to whole exome sequencing. Results We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. Surprisingly, we then found mutations in familial exudative vitreoretinopathy (FEVR) genes; low-density lipoprotein receptor-related protein 5 mutations (six families), tetraspanin 12 mutations (two families), and NDP mutations (two families). Thus, 62% of the patients were successfully genotyped in our study with seven novel and six previously reported mutations in known retinal genes. Conclusions Although the clinical diagnosis of all children was NCRNA with severe congenital fibrotic retinal detachments, the molecular diagnosis determined that the disease process was in fact a very severe form of FEVR in 10 families. Because severe congenital retinal detachment has not been previously associated with all the FEVR genes, we have thus expanded the phenotypic spectrum of FEVR, a highly variable retinal detachment phenotype that has clinical overlap with NCRNA. We identified seven novel mutations. We also established for the first time genetic overlap between the Iranian and Pakistani populations. We identified eight NCRNA families that do not harbor mutations in any known retinal genes, suggesting novel causal genes in these families. PMID:28192794

  15. Autosomal recessive peripheral sensory neuropathy in 3 non-Ashkenazi Jewish families.

    PubMed Central

    Tamari, I; Goodman, R M; Sarova, I; Hertz, M; Adar, R; Zvibach, T

    1980-01-01

    Three unrelated Oriental Jewish families with a total of eight subjects with progressive hereditary sensory neuropathy are reported. The parents were all unaffected and because of parental consanguinity in each of the three families it is postulated that this rare neurological disorder is transmitted in an autosomal recessive manner. In one family both parents showed an abnormal response to pain stimulation with normal motor and sensory nerve conduction velocity. This response may be an expression of the carrier state for this hereditary disease. Only five other families (non-Jewish) have been reported as having this form of peripheral hereditary sensory neuropathy. These observations suggest that one type, the progressive form, of peripheral hereditary sensory neuropathy may be more common in Oriental Jews. Images PMID:6937618

  16. Not Your Family Farm

    ERIC Educational Resources Information Center

    Tenopir, Carol; Baker, Gayle; Grogg, Jill E.

    2007-01-01

    The information industry continues to consolidate, just as agribusiness has consolidated and now dominates farming. Both the family farm and the small information company still exist but are becoming rarer in an age of mergers, acquisitions, and increased economies of scale. Small companies distinguish themselves by high quality, special themes,…

  17. Structure, expression, and phylogenetic relationships of a family of ypt genes encoding small G-proteins in the green alga Volvox carteri.

    PubMed

    Fabry, S; Jacobsen, A; Huber, H; Palme, K; Schmitt, R

    1993-09-01

    In addition to the previously described gene yptV1 encoding a small G-protein we have now identified and sequenced four more ras-related ypt genes (yptV2-yptV5) from the green alga Volvox carteri. The four new genes encode polypeptides consisting of 203 to 217 amino-acid residues that contain the typical sequence elements (GTP-binding domains, effector domain) of the ypt/rab subgroup of the Ras superfamily. Comparison of the derived amino-acid sequences from the V. carteri ypt gene products and their Ypt homologs from other species revealed similarity values ranging from 60% to 85%, whereas intraspecies similarities were found to approach only 55%. The coding sequences are interrupted by 5-7 introns of variable size (70-1000 nucleotides) occupying different positions in the genes. Reverse-transcribed samples of stage-specific RNAs were PCR-amplified with primers specific to yptV1, yptV3, yptV4, and yptV5 to determine if yptV transcription might be restricted to either cell type or to a specific stage of the life cycle. These experiments demonstrated that each of these genes is expressed throughout the entire Volvox life cycle and in both the somatic and the reproductive cells of the alga. The transcription start sites of yptV1 and yptV5 were mapped by primer extension. Expression of recombinant yptV cDNA in E. coli yielded recombinant proteins that bound GTP specifically, demonstrating a property which is typical for small G-proteins. The derived YptV polypeptide sequences were used to group them into four distinct classes of Ras-like proteins. These are the first proteins of the Ras superfamily to be identified in a green alga. We discuss the possible role of the YptV-proteins in the intracellular vesicle transport of Volvox.

  18. Intra-Family Gamete Donation: A Solution to Concerns Regarding Gamete Donation in China?

    PubMed

    Liao, Juhong; Devolder, Katrien

    2016-09-01

    Gamete donation from third parties is controversial in China as it severs blood ties, which are considered of utmost importance in Confucian tradition. In recent years, infertile couples are increasingly demonstrating a preference for the use of gametes donated by family members to conceive children-known as "intra-family gamete donation." The main advantage of intra-family gamete donation is that it maintains blood ties between children and both parents. To date there is no practice of intra-family gamete donation in China. In this paper, we investigate intra-family adoption in China in order to illustrate that intra-family gamete donation is consistent with Confucian tradition regarding the importance of maintaining blood ties within the family. There are several specific ethical issues raised by intra-family gamete donation. It may, for example, result in consanguinity and the semblance of incest, lead to confused family relationships, and raise concerns about possible coercion of familial donors. Confucian tradition provides a new approach to understand and deal with these ethical issues in a way that Western tradition does not. As a result, we suggest intra-family gamete donation could be an acceptable solution to the problem of infertility in China. However, further discussion and open debates on the ethical issues raised by intra-family gamete donation are needed in China.

  19. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  20. Familial hypertriglyceridemia

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000397.htm Familial hypertriglyceridemia To use the sharing features on this page, please enable JavaScript. Familial hypertriglyceridemia is a common disorder passed down through families. ...

  1. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  2. Family Arguments

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  3. Family Literacy

    ERIC Educational Resources Information Center

    Holloway, John H.

    2004-01-01

    Research indicates that family literacy programs can provide opportunities for educational success for parents and children. The benefits reaped by the children in family literacy workshops are presented.

  4. Crystallization and preliminary X-ray diffraction analysis of XAC1151, a small heat-shock protein from Xanthomonas axonopodis pv. citri belonging to the alpha-crystallin family.

    PubMed

    Hilario, Eduardo; Teixeira, Elaine Cristina; Pedroso, Gisele Audrei; Bertolini, Maria Célia; Medrano, Francisco Javier

    2006-05-01

    The hspA gene (XAC1151) from Xanthomonas axonopodis pv. citri encodes a protein of 158 amino acids that belongs to the small heat-shock protein (sHSP) family of proteins. These proteins function as molecular chaperones by preventing protein aggregation. The protein was crystallized using the sitting-drop vapour-diffusion method in the presence of ammonium phosphate. X-ray diffraction data were collected to 1.65 angstroms resolution using a synchrotron-radiation source. The crystal belongs to the rhombohedral space group R3, with unit-cell parameters a = b = 128.7, c = 55.3 angstroms. The crystal structure was solved by molecular-replacement methods. Structure refinement is in progress.

  5. A small GTPase of the Rab family is required for root hair formation and preinfection stages of the common bean-Rhizobium symbiotic association.

    PubMed

    Blanco, Flavio Antonio; Meschini, Eitel Peltzer; Zanetti, María Eugenia; Aguilar, O Mario

    2009-09-01

    Legume plants are able to establish a symbiotic relationship with soil bacteria from the genus Rhizobium, leading to the formation of nitrogen-fixing root nodules. Successful nodulation requires both the formation of infection threads (ITs) in the root epidermis and the activation of cell division in the cortex to form the nodule primordium. This study describes the characterization of RabA2, a common bean (Phaseolus vulgaris) cDNA previously isolated as differentially expressed in root hairs infected with Rhizobium etli, which encodes a protein highly similar to small GTPases of the RabA2 subfamily. This gene is expressed in roots, particularly in root hairs, where the protein was found to be associated with vesicles that move along the cell. The role of this gene during nodulation has been studied in common bean transgenic roots using a reverse genetic approach. Examination of root morphology in RabA2 RNA interference (RNAi) plants revealed that the number and length of the root hairs were severely reduced in these plants. Upon inoculation with R. etli, nodulation was completely impaired and no induction of early nodulation genes (ENODs), such as ERN1, ENOD40, and Hap5, was detected in silenced hairy roots. Moreover, RabA2 RNAi plants failed to induce root hair deformation and to initiate ITs, indicating that morphological changes that precede bacterial infection are compromised in these plants. We propose that RabA2 acts in polar growth of root hairs and is required for reorientation of the root hair growth axis during bacterial infection.

  6. MiR-30 Family Potentially Targeting PI3K-SIAH2 Predicted Interaction Network Represents a Novel Putative Theranostic Panel in Non-small Cell Lung Cancer

    PubMed Central

    Chan, Lawrence W. C.; Wang, Fengfeng; Meng, Fei; Wang, Lili; Wong, Sze Chuen Cesar; Au, Joseph S. K.; Yang, Sijun; Cho, William C. S.

    2017-01-01

    Non-small cell lung cancer (NSCLC) comprises about 84% of all lung cancers. Many treatment options are available but the survival rate is still very low due to drug resistance. It has been found that phosphoinositide-3-kinase (PI3K) affects sensitivity to tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Expression level of seven in absentia homolog 2 (SIAH2), an E3 ubiquitin-protein ligase, is upregulated in NSCLC and correlated with tumor grade. However, the relationship between PI3K and SIAH2 remains unclear and therefore it is not known whether they can act as treatment co-targets and theranostic dual markers for overcoming TKI resistance. It is worthy to note that PI3K and SIAH2 are potentially regulated by a common group of microRNAs in miR-30 family. Our bioinformatics analyses showed upregulated SIAH2 expression in NSCLC based on mass spectrometry data, explored its indirect interaction with PI3K and predicted their targeting microRNAs in common. We have also explored the potential role of miR-30 family in the modulation of PI3K-SIAH2 interaction in NSCLC. PMID:28210267

  7. Muslim families and family therapy.

    PubMed

    Daneshpour, M

    1998-07-01

    Muslim immigrant families living in the United States may well come to the attention of mental health professionals. This article examines the applicability of the Anglo-American models of family therapy to Muslim immigrant families. The most significant differences in value systems between the Muslim and Anglo-American cultures is Muslim families' preference for greater connectedness, a less flexible and more hierarchical family structure, and an implicit communication style. Systemic thinking, which deals with the pattern of relationships, is valid for all families regardless of cultural differences. However, the preferred directions of change for Muslim families need to be integrated into the assessment and goals for family therapy.

  8. Efficacy of afatinib, an irreversible ErbB family blocker, in the treatment of intracerebral metastases of non-small cell lung cancer in mice

    PubMed Central

    Zhang, Shi-rong; Zhu, Lu-cheng; Jiang, Yan-ping; Zhang, Jing; Xu, Ru-jun; Xu, Ya-si; Xia, Bing; Ma, Sheng-lin

    2017-01-01

    Few effective therapeutic options are currently available for the treatment of non-small cell lung cancer (NSCLC) with brain metastases (BM). Recent evidence shows that NSCLC patients with BMs respond well to afatinib, but little is known about the underlying mechanisms. In this study, we evaluated the efficacy of afatinib in treatment of BMs in mice and investigated whether afatinib could actively penetrate the brain-blood barrier and bind to its target. NSCLC BM model was established in nude mice by intracerebral injection of PC-9.luc cells. The tumors were measured weekly using in vivo quantitative bioluminescence. The mice are administrated afatinib (15, 30 mg·kg−1·d−1, ig) for 14 d. The antitumor efficacy of afatinib was determined by tumor growth inhibition (TGI), which was calculated as [1−(change of tumor volume in treatment group/control group)×100]. Pharmacokinetic characteristics were measure in mice receiving a single dose of afatinib (30 mg/kg, ig). Pharmacodynamics of afatinib was also assessed by detecting the expression of pEGFR (Tyr1068) in brain tumor foci using immunohistochemistry. Administration of afatinib (15, 30 mg·kg−1·d−1) dose-dependently inhibited PC-9 tumor growth in the brain with a TGI of 90.2% and 105%, respectively, on d 14. After administration of afatinib (30 mg/kg), the plasma concentration of afatinib was 91.4±31.2 nmol/L at 0.5 h, reached a peak (417.1±119.9 nmol/L) at 1 h, and was still detected after 24 h. The cerebrospinal fluid (CSF) concentrations followed a similar pattern. The T1/2 values of afatinib in plasma and CSF were 5.0 and 3.7 h, respectively. The AUC(0–24 h) values for plasma and CSF were 2375.5 and 29.1 nmol/h, respectively. The plasma and CSF concentrations were correlated (r=0.844, P<0.01). Pharmacodynamics study showed that the expression levels of pEGFR were reduced by 90% 1 h after afatinib administration. The Emax was 86.5%, and the EC50 was 0.26 nmol/L. A positive correlation between

  9. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  10. Byler-like familial cholestasis in an extended kindred.

    PubMed

    Bourke, B; Goggin, N; Walsh, D; Kennedy, S; Setchell, K D; Drumm, B

    1996-09-01

    Progressive familial intrahepatic cholestasis (PFIC) occurs in many communities and races. A form of PFIC in five children from two consanguineous marriages in an Irish kindred is described. In addition, a review of clinical information from the records of three deceased members of the kindred strongly implies that they also suffered from PFIC. The children had a history of neonatal diarrhoea, sepsis, and intermittent jaundice that ultimately became permanent. They suffered intractable pruritus and growth retardation. Despite evidence of severe cholestasis, serum gamma-glutamyl transferase and cholesterol were normal in these children. Sweat sodium concentration were raised in three children. Liver histology showed severe intrahepatic cholestasis and hepatocellular injury. Urinary bile acid analysis revealed a non-specific pattern consistent with chronic cholestasis. These children suffer from a form of PFIC remarkably similar to that occurring in members of the Byler kindred.

  11. Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling relatives: a new prospect of exploiting extended family search.

    PubMed

    Hamidieh, A A; Dehaghi, M Ostadali; Paragomi, P; Navaei, S; Jalali, A; Eslami, G Ghazizadeh; Behfar, M; Ghavamzadeh, A

    2015-04-01

    The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In patients without fully-matched siblings, HLA registries or cord blood banks are alternative strategies with some restrictions. Owing to the high rate of consanguineous marriage in our country, between 2006 and 2013, extended family searches were undertaken in Hematology-Oncology Research Center and Stem Cell Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental consanguinity and no available HLA identical sibling. Fully-matched other-relative donors were found for 109 cases. We retrospectively studied the HSCT outcome in these patients. Median time to neutrophil engraftment was 13 days (range: 9-31days). In 83 patients, full chimerism and in 17 patients, mixed chimerism was achieved. Acute GvHD (aGvHD) grade II-IV appeared in 36 patients (33%). The frequency of aGvHD development in various familial subgroups was NS. Five patients expired before day+100. In the surviving 104 cases, chronic GvHD developed in 20 patients (19.2%). The distantly related subgroup had significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free survival (DFS) were 76.7±4.5% and 71.7±4.7%, respectively. No significant difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial relationships. Our considerable rate of fully-matched non-sibling family members and the favorable outcome support the rationale for extended family search in regions where consanguineous marriage is widely practiced.

  12. Clinical features and molecular genetics of two Tunisian families with abetalipoproteinemia.

    PubMed

    Hammer, Monia Benhamed; El Euch-Fayache, Ghada; Nehdi, Houda; Feki, Moncef; Maamouri-Hicheri, Wieme; Hentati, Fayçal; Amouri, Rim

    2014-02-01

    Abetalipoproteinemia (ABL) is a rare monogenic disease characterized by very low plasma levels of cholesterol and triglyceride and almost complete absence of apolipoprotein B (apoB)-containing lipoproteins. Typically, patients present with failure to thrive, acanthocytosis, pigmented retinopathy and neurological features. It has been shown that ABL results from mutations in the gene encoding the microsomal triglyceride transfer protein (MTTP). Sanger sequencing of MTTP was performed for two unrelated consanguineous Tunisian families with two affected individuals each, presenting a more severe ABL phenotype than previously reported in the literature. The patients were found to be homozygous for two novel mutations. In the first family, a nonsense mutation, c.2313T>A, leading to a truncated protein (p.Y771X) was identified. In the second family, a splice mutation, IVS 9+2T>G, was found. These mutations are believed to abolish the assembly and secretion of apoB-containing lipoproteins.

  13. Molecular study of 33 families with Fraser syndrome new data and mutation review.

    PubMed

    van Haelst, M M; Maiburg, M; Baujat, G; Jadeja, S; Monti, E; Bland, E; Pearce, K; Hennekam, R C; Scambler, P J

    2008-09-01

    Fraser syndrome (FS) is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract. FS is considered to be the human equivalent of the murine blebbing mutants: in the mouse mutations at five loci cause a phenotype that is comparable to FS in humans, and thus far mutations in two syntenic human genes, FRAS1 and FREM2, have been identified to cause FS. Here we present the molecular analysis of 48 FS patients from 18 consanguineous and 15 nonconsanguineous families. Linkage analysis in consanguineous families indicated possible linkage to FRAS1 and FREM2 in 60% of the cases. Mutation analysis identified 11 new mutations in FRAS1 and one FREM2 mutation. Manifestations of these patients and previously reported cases with an FRAS1 mutation were compared to cases without detectable FRAS1 mutations to study genotype-phenotype correlations. Although our data suggest that patients with an FRAS1 mutation have more frequently skull ossification defects and low insertion of the umbilical cord, these differences are not statistically significant. Mutations were identified in only 43% of the cases suggesting that other genes syntenic to murine genes causing blebbing may be responsible for FS as well.

  14. Muslim Families and Family Therapy.

    ERIC Educational Resources Information Center

    Daneshpour, Manijeh

    1998-01-01

    Examines the applicability of the Anglo-American models of family therapy to Muslim immigrant families. The differences in value systems are the Muslim families' preferences for greater connectedness, a less flexible and more hierarchical family structure, and an implicit communication style. Suggests that directions for change for Muslims need to…

  15. Family Violence and Family Physicians

    PubMed Central

    Herbert, Carol P.

    1991-01-01

    The acronym IDEALS summarizes family physicians' obligations when violence is suspected: to identify family violence; document injuries; educate families and ensure safety for victims; access resources and coordinate care; co-operate in the legal process; and provide support for families. Failure to respond reflects personal and professional experience and attitudes, fear of legal involvement, and lack of knowledge. Risks of intervention include physician burnout, physician overfunctioning, escalation of violence, and family disruption. PMID:21228987

  16. Mariage consanguin et morbi-mortalité, courte revue de la littérature à partir d'une association exceptionnelle: syndrome de Usher et Neurofibromatose de Von Recklinghausen

    PubMed Central

    Atipo-Tsiba, Pépin-Williams

    2016-01-01

    Le syndrome de Usher est défini par l'association d'une surdité de perception congénitale de sévérité variable évolutive ou non et d'une rétinopathie pigmentaire progressivement cécitante. La Neurofibromatose de Von Recklinghausen ou Neurofibromatose de type I est la principale forme clinique des neurofibromatoses avec environ 90% des cas. Ces deux maladies sont d'origine génétique avec des prévalences très basses. La probabilité pour qu'un seul et même individu souffre à la fois de ces maladies est exceptionnelle. Comme toutes les maladies génétiques, la consanguinité augmente de façon assez sensible la probabilité de leur apparition. Le mariage consanguin est encore largement répondu au Maghreb et dans certaines régions d'Afrique de l'Ouest. Cette observation rapporte un cas exceptionnel de cette association chez un homme de 40 ans originaire de la Mauritanie né d'une union consanguine. PMID:27231508

  17. Cancerous leptomeningitis and familial congenital hypopituitarism.

    PubMed

    Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

    2016-05-01

    People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

  18. Family Violence

    MedlinePlus

    ... Deployment & Transition Home » Health & Wellness » Family Violence Family Violence Recognize the warning signs . Know how to report. ... Love Every Day Making Relationships Work National Domestic Violence Hotline Signs of Child Abuse INSTALLATION PROGRAM DIRECTORY ...

  19. Family Involvement.

    ERIC Educational Resources Information Center

    Liontos, Lynn Balster

    1992-01-01

    Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

  20. Family Support.

    ERIC Educational Resources Information Center

    Wieck, Colleen, Ed.; McBride, Marijo, Ed.

    1990-01-01

    This "Feature Issue" of the quarterly journal "Impact" presents 19 brief articles on family support systems in the United States for persons with developmental disabilities and their families. Emphasis is on provisions of Public Law 99-457. Articles include: "Family Support in the United States: Setting a Course for the…

  1. Italian families and family interventions.

    PubMed

    Casacchia, Massimo; Roncone, Rita

    2014-06-01

    In Italy, as in many countries, relatives are closely involved in caring for persons with physical and mental disorders. The Italian scenario lends itself to routine involvement of family members in psychiatric treatment because, despite becoming smaller and smaller, Italian families keep close ties, and men and women do not leave the parental home until relatively late. The authors describe the impact of international family psychosocial research on the Italian mental health services (MHSs) and the main psychosocial interventions currently in use, including family psychoeducational interventions and the "Milan family therapy approach." They also highlight the contribution Italian researchers have given to the study of important variables in integrated mental disorder care, such as family burden of care, relatives' attitudes, family functioning, and satisfaction with the MHSs. Finally, they discuss the difficulties of implementing and disseminating family interventions within the Italian MHS, despite the growing evidence of their effectiveness.

  2. A second family with autosomal recessive spondylometaphyseal dysplasia and early death.

    PubMed

    Mégarbané, André; Mehawej, Cybel; El Zahr, Amir; Haddad, Soha; Cormier-Daire, Valérie

    2014-04-01

    We report on a consanguineous Lebanese family in which two sibs had pre- and post-natal growth retardation, developmental delay, large anterior fontanel, prominent forehead, low-set ears, depressed nasal bridge, short nose, anteverted nares, increased nasal width, prominent abdomen, and short limbs. Radiographs disclosed the presence of wormian bones, platyspondyly, decreased interpedicular distance at the lumbar vertebrae, square iliac bones, horizontal acetabula, trident acetabula, hypoplastic ischia, partial agenesis of the sacrum, ribs with cupped ends, short long bones with abnormal modeling, slight widening of the distal femoral metaphyses, and delayed epiphyseal ossification. Both sibs had a severe cardiomegaly and died at around 24 months from a heart failure. Differential diagnosis suggests that this is a second family presenting a newly described early lethal chondrodysplasia first reported by [Mégarbané et al. (2008); Am J Med Genet Part A 146A:2916-2919].

  3. Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex123

    PubMed Central

    Maeta, Kazuhiro; Edamatsu, Hironori; Nishihara, Kaori; Ikutomo, Junji; Bilasy, Shymaa E.

    2016-01-01

    Abstract Cerebral neocortex development in mammals requires highly orchestrated events involving proliferation, differentiation, and migration of neural progenitors and neurons. Rapgef2 and Rapgef6 constitute a unique family of guanine nucleotide exchange factors for Rap1 small GTPase, which is known to play crucial roles in migration of postmitotic neurons. We previously reported that conditional knockout of Rapgef2 in dorsal telencephalon (Rapgef2-cKO) resulted in the formation of an ectopic cortical mass (ECM) resembling that of subcortical band heterotopia. Here we show that double knockout of Rapgef6 in Rapgef2-cKO mice (Rapgef2/6-dKO) results in marked enlargement of the ECM. While Rapgef2-cKO affects late-born neurons only, Rapgef2/6-dKO affects both early-born and late-born neurons. The Rapgef2-cKO cortex at embryonic day (E) 15.5, and the Rapgef2/6-dKO cortex at E13.5 and E15.5 show disruption of the adherens junctions (AJs) on the apical surface, detachment of radial glial cells (RGCs) from the apical surface and disorganization of the radial glial fiber system, which are accompanied by aberrant distribution of RGCs and intermediate progenitors, normally located in the ventricular zone and the subventricular zone, respectively, over the entire cerebral cortex. Moreover, intrauterine transduction of Cre recombinase into the Rapgef2flox/flox brains also results in the apical surface AJ disruption and the RGC detachment from the apical surface, both of which are effectively suppressed by cotransduction of the constitutively active Rap1 mutant Rap1G12V. These results demonstrate a cell-autonomous role of the Rapgef2/6-Rap1 pathway in maintaining the apical surface AJ structures, which is necessary for the proper development of neural progenitor cells. PMID:27390776

  4. A functional interplay between the small GTPase Rab11a and mitochondria-shaping proteins regulates mitochondrial positioning and polarization of the actin cytoskeleton downstream of Src family kinases.

    PubMed

    Landry, Marie-Claude; Champagne, Claudia; Boulanger, Marie-Chloé; Jetté, Alexandra; Fuchs, Margit; Dziengelewski, Claire; Lavoie, Josée N

    2014-01-24

    It is believed that mitochondrial dynamics is coordinated with endosomal traffic rates during cytoskeletal remodeling, but the mechanisms involved are largely unknown. The adenovirus early region 4 ORF4 protein (E4orf4) subverts signaling by Src family kinases (SFK) to perturb cellular morphology, membrane traffic, and organellar dynamics and to trigger cell death. Using E4orf4 as a model, we uncovered a functional connection between mitochondria-shaping proteins and the small GTPase Rab11a, a key regulator of polarized transport via recycling endosomes. We found that E4orf4 induced dramatic changes in the morphology of mitochondria along with their mobilization at the vicinity of a polarized actin network typifying E4orf4 action, in a manner controlled by SFK and Rab11a. Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the fission factor dynamin-related protein 1 (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP. Knockdown of FIP1/RCP or inhibition of Drp1 markedly impaired mitochondrial remodeling and actin assembly, involving Rab11a-mediated mitochondrial dynamics in E4orf4-induced signaling. A similar mobilization of mitochondria near actin-rich structures was mediated by Rab11 and Drp1 in viral Src-transformed cells and contributed to the biogenesis of podosome rosettes. These findings suggest a role for Rab11a in the trafficking of Drp1 to mitochondria upon SFK activation and unravel a novel functional interplay between Rab11a and mitochondria during reshaping of the cell cytoskeleton, which would facilitate mitochondria redistribution near energy-requiring actin-rich structures.

  5. Roles within the Family

    MedlinePlus

    ... Family Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families ...

  6. Improving Family Communications

    MedlinePlus

    ... Family Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families ...

  7. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  8. Family Reunification

    ERIC Educational Resources Information Center

    Wulczyn, Fred

    2004-01-01

    Reunifying children placed in foster care with their birth parents is a primary goal of the child welfare system. Yet, relatively little is known about the reunification process. This article analyzes new data on trends in family reunification and discovers: (1) Although most children still exit foster care through family reunification, exit…

  9. Family Empowerment.

    ERIC Educational Resources Information Center

    Sinclair, Mary F., Ed.; And Others

    1992-01-01

    This feature issue of IMPACT focuses on the empowerment of families with a member who has a developmental disability. It presents strategies and models for a collaborative, respectful approach to service provision, and presents the experiences of families in seeking support and assistance. Feature articles include "Two Generations of…

  10. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  11. Family, Extended

    ERIC Educational Resources Information Center

    Patton, Jessica Rae

    2006-01-01

    Parents are a child's first and most influential teacher. People hear this truism often, yet nowhere has the author seen it more taken to heart than at Tower Street Elementary School. The school's efforts to form a true partnership with students' families--from involving families in the first day of school, to the principal making home visits, to…

  12. Family Potyviridae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

  13. Family intervention for schizophrenia

    PubMed Central

    Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

    2014-01-01

    Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of

  14. Clinical exome sequencing: results from 2819 samples reflecting 1000 families

    PubMed Central

    Trujillano, Daniel; Bertoli-Avella, Aida M; Kumar Kandaswamy, Krishna; Weiss, Maximilian ER; Köster, Julia; Marais, Anett; Paknia, Omid; Schröder, Rolf; Garcia-Aznar, Jose Maria; Werber, Martin; Brandau, Oliver; Calvo del Castillo, Maria; Baldi, Caterina; Wessel, Karen; Kishore, Shivendra; Nahavandi, Nahid; Eyaid, Wafaa; Al Rifai, Muhammad Talal; Al-Rumayyan, Ahmed; Al-Twaijri, Waleed; Alothaim, Ali; Alhashem, Amal; Al-Sannaa, Nouriya; Al-Balwi, Mohammed; Alfadhel, Majid; Rolfs, Arndt; Abou Jamra, Rami

    2017-01-01

    We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care. PMID:27848944

  15. Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations.

    PubMed

    Kumar, A; Blanton, S H; Babu, M; Markandaya, M; Girimaji, S C

    2004-10-01

    Patients with primary microcephaly, an autosomal recessive trait, have mild to severe mental retardation without any other neurological deficits. It is a genetically heterogeneous disorder with six known loci: MCPH1 to MCPH6. Only the genes for MCPH1 and MCPH5 have been identified so far. We have ascertained nine consanguineous families with primary microcephaly from India. To establish linkage of these nine families to known MCPH loci, microsatellite markers were selected from the candidate regions of each of the six known MCPH loci and used to genotype the families. The results were suggestive of linkage of three families to the MCPH5 locus and one family to the MCPH2 locus. The remaining five families were not linked to any of the known loci. DNA-sequence analysis identified one known (Arg117X) and two novel (Trp1326X and Gln3060X) mutations in the three MCPH5-linked families in a homozygous state. Three novel normal population variants (i.e., c.7605G > A, c.4449G > A, and c.5961 A > G) were also detected in the ASPM gene.

  16. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  17. Familial dysautonomia

    MedlinePlus

    Riley-Day syndrome; FD; Hereditary sensory and autonomic neuropathy - type III (HSAN III); Autonomic crises - familial dysautonomia ... PA: Elsevier; 2016:chap 107. Sarnat HB. Autonomic neuropathies. In: Kliegman RM, Stanton BF, St. Geme JW, ...

  18. Unusual families.

    PubMed

    Golombok, Susan

    2005-03-01

    The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers.

  19. Family dysfunction

    PubMed Central

    Hayaki, Chie; Anno, Kozo; Shibata, Mao; Iwaki, Rie; Kawata, Hiroshi; Sudo, Nobuyuki; Hosoi, Masako

    2016-01-01

    Abstract Previous studies have shown differences in the psychosocial factors related to chronic localized pain (CLP) and chronic widespread pain (CWP). However, no studies have done an evaluation of differences between CLP and CWP from the viewpoint of family functioning. We did a cross-sectional study in a tertiary care setting to investigate possible differences in the relation of CWP and CLP to family functioning. Patients with CLP (N = 126) or CWP (N = 75) were assessed for family functioning by the Family Assessment Device (FAD) and a comparison was done. Logistic regression analysis was used to estimate associations of family functioning subscales with pain status (CWP vs CLP), controlling for demographic variables, pain variables; pain duration, pain ratings, pain disability, and psychological factors; depression, anxiety, and catastrophizing. The odds ratios (ORs) for the presence of CWP were calculated. Compared to patients with CLP, patients with CWP showed a lower functional status for Roles and Affective Involvement. The ORs for CWP were significantly higher in lower functioning Roles (OR: 2.38, 95% CI: 1.21–4.65) and Affective Involvement (OR: 2.86, 95% CI: 1.56–5.24) after adjusting for demographic variables. The significant association of CWP to Roles and Affective Involvement remained after controlling for the pain variables and psychological factors. This study shows that the families of patients with CWP have poorer family functioning than those with CLP. Our findings suggest that early identification and interventions for the family dysfunction of chronic pain patients are important to the treatment and prevention of CWP. PMID:27930535

  20. Family Child Care Licensing Study, 2003.

    ERIC Educational Resources Information Center

    Hollestelle, Kay; Koch, Pauline D.

    This report presents the findings of the 2003 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2002 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

  1. Family Child Care Licensing Study, 2001.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

  2. The Family Child Care Licensing Study, 1999.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This report presents the findings of the 1999 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1998 study. Data on small family child care homes and group or large family child care homes are organized in 22 categories: (1) number of regulated homes; (2)…

  3. Family Child Care Licensing Study, 2000.

    ERIC Educational Resources Information Center

    Kelly, Nia, Comp.

    This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

  4. Family Child Care Licensing Study, 2002.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This report presents the findings of the 2002 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2001 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

  5. Co-expression of pregnane X receptor and ATP-binding cassette sub-family B member 1 in peripheral blood: A prospective indicator for drug resistance prediction in non-small cell lung cancer

    PubMed Central

    KONG, QINGNUAN; HAN, ZENGLEI; ZUO, XIAOLI; WEI, HONGJUN; HUANG, WEIQING

    2016-01-01

    The aim of the present study was to investigate the protein expression profiling of pregnane X receptor (PXR) and ATP-binding cassette sub-family B member 1 (ABCB1; also known as MDR1 or P-gp), present in the peripheral blood mononuclear cells (PBMCs) and cancerous tissues of cases of non-small cell lung cancer (NSCLC). Furthermore, the study aimed to assess the feasibility of predicting drug resistance through the medium of PBMCs. Of the subjects included in the study, 37 were histopathologically diagnosed with NSCLC and 17 were control patients without cancer. ThinPrep liquid-based smears with cytosine were applied in the examination of the PBMCs and proved quite effective in preserving the morphology and surface antigens of the lymphocytes. Measurements of expression levels in the PBMCs and cancerous tissues were obtained by immunohistochemical means. The results showed that, with the exception of the selective PXR expression in the normal lung tissues, the two types of proteins existed extensively throughout the PBMCs, normal tissues and tumors. Among the cancer patients, prior to chemotherapy, a significant rise in ABCB1 expression could be observed in the PBMCs, together with a similar rise in ABCB1 and PXR expression in the tumor specimens. Marked upregulation of the two proteins was detected in the PBMCs following 1 cycle of first-line chemotherapy. ABCB1 expression, correlated with PXR, persisted mostly in the PBMCs and tissue samples. When bound to and activated by ligands, PXR translocates from the cytoplasm to the nucleus of the cells. PXR subsequently binds to its DNA response elements as a heterodimer with the retinoid X receptor. A PXR translocation of moderate or low differentiation was identified in 3 cases of adenocarcinoma, which were co-expressing the two genes in the PBMCs prior to chemotherapy. During follow-up visits, tumor recurrence was observed within 3 months in 5 cases, which were characterized by PXR translocation. These findings

  6. Co-expression of pregnane X receptor and ATP-binding cassette sub-family B member 1 in peripheral blood: A prospective indicator for drug resistance prediction in non-small cell lung cancer.

    PubMed

    Kong, Qingnuan; Han, Zenglei; Zuo, Xiaoli; Wei, Hongjun; Huang, Weiqing

    2016-05-01

    The aim of the present study was to investigate the protein expression profiling of pregnane X receptor (PXR) and ATP-binding cassette sub-family B member 1 (ABCB1; also known as MDR1 or P-gp), present in the peripheral blood mononuclear cells (PBMCs) and cancerous tissues of cases of non-small cell lung cancer (NSCLC). Furthermore, the study aimed to assess the feasibility of predicting drug resistance through the medium of PBMCs. Of the subjects included in the study, 37 were histopathologically diagnosed with NSCLC and 17 were control patients without cancer. ThinPrep liquid-based smears with cytosine were applied in the examination of the PBMCs and proved quite effective in preserving the morphology and surface antigens of the lymphocytes. Measurements of expression levels in the PBMCs and cancerous tissues were obtained by immunohistochemical means. The results showed that, with the exception of the selective PXR expression in the normal lung tissues, the two types of proteins existed extensively throughout the PBMCs, normal tissues and tumors. Among the cancer patients, prior to chemotherapy, a significant rise in ABCB1 expression could be observed in the PBMCs, together with a similar rise in ABCB1 and PXR expression in the tumor specimens. Marked upregulation of the two proteins was detected in the PBMCs following 1 cycle of first-line chemotherapy. ABCB1 expression, correlated with PXR, persisted mostly in the PBMCs and tissue samples. When bound to and activated by ligands, PXR translocates from the cytoplasm to the nucleus of the cells. PXR subsequently binds to its DNA response elements as a heterodimer with the retinoid X receptor. A PXR translocation of moderate or low differentiation was identified in 3 cases of adenocarcinoma, which were co-expressing the two genes in the PBMCs prior to chemotherapy. During follow-up visits, tumor recurrence was observed within 3 months in 5 cases, which were characterized by PXR translocation. These findings

  7. Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

    PubMed Central

    de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

    2016-01-01

    Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

  8. A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia.

    PubMed

    Al Tassan, Nada; Khalil, Dania; Shinwari, Jameela; Al Sharif, Latifa; Bavi, Prashant; Abduljaleel, Zainularifeen; Abu Dhaim, Nada; Magrashi, Amna; Bobis, Steve; Ahmed, Hala; Alahmed, Samaher; Bohlega, Saeed

    2012-02-01

    Autosomal recessive ataxias are heterogeneous group of disorders characterized by cerebellar atrophy and peripheral sensorimotor neuropathy. Molecular characterization of this group of disorders identified a number of genes contributing to these overlapping phenotypes. Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive form of ataxia caused by mutations in the SETX gene. We report on a consanguineous family with autosomal recessive inheritance and clinical characteristics of AOA2, and no mutations in the SETX gene. We mapped the AOA locus in this family to chromosome 17p12-p13. Sequencing of all genes in the refined region identified a homozygous missense mutation in PIK3R5 that was absent in 477 normal controls. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis.

  9. Identifying mutations in Tunisian families with retinal dystrophy

    PubMed Central

    Habibi, Imen; Chebil, Ahmed; Falfoul, Yosra; Allaman-Pillet, Nathalie; Kort, Fedra; Schorderet, Daniel F.; El Matri, Leila

    2016-01-01

    Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population. PMID:27874104

  10. A Novel Member of a Zinc Transporter Family Is Defective in Acrodermatitis Enteropathica

    PubMed Central

    Wang, Kun; Zhou, Bing; Kuo, Yien-Ming; Zemansky, Jason; Gitschier, Jane

    2002-01-01

    The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an ∼3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as “hZIP4,” which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc. PMID:12032886

  11. A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.

    PubMed

    Wang, Kun; Zhou, Bing; Kuo, Yien-Ming; Zemansky, Jason; Gitschier, Jane

    2002-07-01

    The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.

  12. A novel mutation in a large family causes a unique phenotype of Mucolipidosis IV.

    PubMed

    AlBakheet, AlBandary; Qari, Aliya; Colak, Dilek; Rasheed, Anas; Kaya, Namik; Al-Sayed, Moeenaldeen

    2013-09-10

    Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder reported among Ashkenazi Jews and to a lesser extent in other ethnic groups. Several mutations have been reported in MCOLN1 which is the only known gene associated with the disorder. Here we report the first Saudi patient with Mucolipidosis type IV from a consanguineous family with two branches having a total of five patients carrying a novel transition mutation, c.1307A>G (p.Y436C) in exon 11. The clinical course of the patient was nonspecific and a lysosomal storage disorder was not highly suspected due to lack of coarse facial features, organomegaly and skeletal findings of dysostosis multiplex. The detailed bioinformatics analysis on the deleterious effects of the mutation is discussed. Emphasis is made on the importance of brain magnetic resonance imaging (MRI) findings and serum gastrin level as key clues to the diagnosis of this often subtle neurodevelopmental disorder.

  13. A novel homozygous HOXB1 mutation in a Turkish family with hereditary congenital facial paresis.

    PubMed

    Sahin, Yavuz; Güngör, Olcay; Ayaz, Akif; Güngör, Gülay; Sahin, Bedia; Yaykasli, Kursad; Ceylaner, Serdar

    2017-02-01

    Hereditary congenital facial paresis (HCFP) is characterized by isolated dysfunction of the facial nerve (CN VII) due to congenital cranial dysinnervation disorders. HCFP has genetic heterogeneity and HOXB1 is the first identified gene. We report the clinical, radiologic and molecular investigations of three patients admitted for HCFP in a large consanguineous Turkish family. High-throughput sequencing and Sanger sequencing of all patients revealed a novel homozygous mutation p.Arg230Trp (c.688C>T) within the HOXB1 gene. The report of the mutation brings the total number of HOXB1 mutations identified in HCFP to four. The results of this study emphasize that in individuals with congenital facial palsy accompanied by hearing loss and dysmorphic facial features, HOXB1 mutation causing HCFP should be kept in mind.

  14. Family Hypnotherapy.

    ERIC Educational Resources Information Center

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

  15. Serving Families.

    ERIC Educational Resources Information Center

    Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

    Parent Services Project (PSP), the first comprehensive program of resources and mental health activities for parents offered at child care centers in the San Francisco Bay Area (California), has expanded to centers in six states, serving over 19,000 families. This report describes the program's history, aims, and achievements, along with specific…

  16. Family Violence.

    ERIC Educational Resources Information Center

    Sorgen, Carol, Ed.

    1979-01-01

    This quarterly publication, issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), contains articles dealing with family violence and alcohol abuse, children of alcoholic parents, training programs for counselors, and confidentiality of client records. The three articles on alcohol abuse suggest that: (1) there is a clear…

  17. Family Disruptions

    MedlinePlus

    ... and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family as ... these out-of-town trips. Spend as much time as it takes to explain where you are ... before and during your travels. You need to acknowledge and accept her feelings: " ...

  18. FAMILY TYMOVIRIDAE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

  19. FAMILY LAUXANIIDAE.

    PubMed

    Silva, Vera Cristina

    2016-06-14

    An updated Catalogue of the Lauxaniidae of Colombia is presented. This acalyptratae family is poorly known in Colombia, with only 36 described species in 33 genera. This paper expands the distribution of 24 species to Colombia. At total, 63 species are reported here for Colombia.

  20. Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in two siblings born from consanguineous parents.

    PubMed

    Houcinat, N; Llanas, B; Moutton, S; Toutain, J; Cailley, D; Arveiler, B; Combe, C; Lacombe, D; Rooryck, C

    2015-11-01

    The use of array-comparative genomic hybridization (array-CGH) in routine clinical work has allowed the identification of many new copy number variations (CNV). The 16p13.11 duplication has been implicated in various congenital anomalies and neurodevelopmental disorders, but it has also been identified in healthy individuals. We report a clinical observation of two brothers from related parents each carrying a homozygous 16p13.11 duplication. The propositus had mild intellectual disability and posterior urethral valves with chronic renal disease. His brother was considered a healthy child with only learning disabilities and poor academic performances. However, a routine medical examination at 25-years-old revealed a mild chronic renal disease and ureteropelvic junction obstruction. Furthermore, the father presented with a unilateral renal agenesis, thus it seemed that a "congenital anomalies of kidney and urinary tract" (CAKUT) phenotype segregated in this family. This may be related to the duplication, but we cannot exclude the involvement of additional genetic or non-genetic factors in the urological phenotype. Several cohort studies showed association between this chromosomal imbalance and different clinical manifestations, but rarely with CAKUT. The duplication reported here was similar to the larger one of 3.4 Mb previously described versus the more common of 1.6 Mb. It encompassed at least 11 known genes, including the five ohnologs previously identified. Our observation, in addition to expanding the clinical spectrum of the duplication provides further support to understanding the underlying pathogenic mechanism.

  1. Family Structure and Family Processes in Mexican American Families

    PubMed Central

    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

    2010-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct, CD/ODD and MDD symptoms, and greater parent-child conflict than their counterparts in two parent families. Single parent mothers reported greater economic hardship, depression and family stress. Family stress and parent-child conflict emerged as significant mediators of the association between family structure and early adolescent outcomes, suggesting important processes linking MA single parent families and adolescent adjustment. PMID:21361925

  2. Family Therapy and Disturbed Families.

    ERIC Educational Resources Information Center

    Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

    Presented at a conference at which authors represented major theoretical positions in the field, most of the papers use family therapy as an important source of observations or ideas, or as a means to pinpoint methodological problems. Papers are grouped in sections as follows: four which introduce the reader to the field of specialization, provide…

  3. Family medicine curriculum

    PubMed Central

    Klein, Douglas; Schipper, Shirley

    2008-01-01

    PROBLEM ADDRESSED The Family Medicine Residency Program at the University of Alberta has used academic sessions and clinical-based teaching to prepare residents for private practice. Before the new curriculum, academic sessions were large group lectures given by specialists. These sessions lacked consistent quality, structured topics, and organization. OBJECTIVE OF PROGRAM The program was designed to improve the quality and consistency of academic sessions by creating a new curriculum. The goals for the new curriculum included improved organizational structure, improved satisfaction from the participants, improved resident knowledge and confidence in key areas of family medicine, and improved performance on licensing examinations. PROGRAM DESCRIPTION The new curriculum is faculty guided but resident organized. Twenty-three core topics in family medicine are covered during a 2-year rotating curriculum. Several small group activities, including problem-based learning modules, journal club, and examination preparation sessions, complement larger didactic sessions. A multiple-source evaluation process is an essential component of this new program. CONCLUSION The new academic curriculum for family medicine residents is based on a variety of learning styles and is consistent with the principles of adult learning theory. This structured curriculum provides a good basis for further development. Other programs across the country might want to incorporate these ideas into their current programming. PMID:18272637

  4. Family Centers

    DTIC Science & Technology

    1992-12-30

    quality service delivery to meet the needs of the DoD personnel and their families, in accordance with DoD Directive 1342.17 (reference (a)). 4...facility, and program standards. f. Develop and forward to ASD(FM&P), for review and approval, a comprehensive evaluation system to measure the...of future services and the continuation, expansion, or termination of others. (3) Service-wide measurement criteria for monitoring and evaluating the

  5. Familial Hypercholesterolemia

    PubMed Central

    Bouhairie, Victoria Enchia; Goldberg, Anne Carol

    2015-01-01

    Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in physicians and patients in order to reduce the burden of this disorder. PMID:25939291

  6. Juvenile familial endocrinopathy

    PubMed Central

    Drury, M. I.; Keelan, Deborah M.; Timoney, F. J.; Irvine, W. J.

    1970-01-01

    A case of primary hypothyroidism, idiopathic Addison's disease, idiopathic hypoparathyroidism (with preceding moniliasis), Addisonian pernicious anaemia and primary ovarian failure is described. She died at the age of 24 years following an illness compatible with adrenal crisis. At post-mortem there was no recognizable adrenal or ovarian tissue; there was only a minute portion of probable parathyroid tissue and the uterus was infantile. Her serum contained antibodies reactive with adrenal cortex, steroid-producing cells in the gonads, placental trophoblasts and thyroid epithelial cytoplasm and intrinsic factor. Her brother, who was known to have gluten enteropathy, died aged 11 years following an illness compatible with adrenal crisis. His adrenal glands were grossly atrophic at autopsy. The parents were consanguinous and both showed either clinical or serological evidence of organ specific autoimmune disease. PMID:5202743

  7. Asteroid families - Physical properties and evolution

    NASA Technical Reports Server (NTRS)

    Chapman, Clark R.; Paolicchi, Paolo; Zappala, Vincenzo; Binzel, Richard P.; Bell, Jeffrey F.

    1989-01-01

    Asteroid families are considered to be fragments from collisional destruction of precursor bodies. However, results available on the inferred mineralogy, size distributions, and spins of family members do not confirm the expectations of the traditional model. Only a handful of nearly 100 proposed families, most of them populous, have distributions of inferred mineralogies consistent with simple cosmochemical models for parent bodies. It is suggested that most catastrophic collisions may not result in observable families, but rather in a spray of smaller particles, thus accounting for the small number of confirmed and consistent families, despite evidence for extensive collisional evolution of asteroids.

  8. [Unverricht-Lündborg disease: clinical and electrophysiologic study of 19 Maghreb families].

    PubMed

    Gouider, R; Ibrahim, S; Fredj, M; Gargouri, A; Saïdi, H; Ouezzani, R; Malafosse, A; Yahiaoui, M; Grid, D; Mrabet, A

    1998-07-01

    We describe clinical, electrophysiological and genetic features in 44 patients with Unverricht-Lündborg disease from 19 families living in North African countries (Tunisia, Algeria and Morocco). The mean age of patients was 25.3 years; mean age was at onset 11.3 years. The disease began more frequently with seizures (91 per cent) or myoclonus (80 p. 100) than ataxia (16 p. 100). Subsequently myoclonus and generalized seizures were present in all patients, cerebellar signs were absent in four cases. EEG findings included normal background activity (90 p. 100), spontaneous fast generalized spikes (93 p. 100) and photosensitivity (70 p. 100). Antiepileptic polytherapy (clonazepam and/or phenobarbital and/or valporic acid) was used in 84 per cent of cases. Antiepileptic drugs were more effective in controlling epileptic seizures (less than one seizure/month in 60 p. 100) than myocloni which persisted daily in 64 p. 100 of cases. Mean duration of the disease was 13.5 years. One patient died of status epilepticus. Consanguinity was noted in 17 families (first degree in 15 families). Linkage to chromosome 21q 22.3 was confirmed in 11 families. We noted an inter and intrafamilial variability of clinical signs and disease course.

  9. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    PubMed

    Zhang, Li; Liang, Jianfeng; Yu, Yanbing

    Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China.

  10. Shodagor Family Strategies : Balancing Work and Family on the Water.

    PubMed

    Starkweather, Kathrine E

    2017-03-11

    The Shodagor of Matlab, Bangladesh, are a seminomadic community of people who live and work on small wooden boats, within the extensive system of rivers and canals that traverse the country. This unique ecology places particular constraints on family and economic life and leads to Shodagor parents employing one of four distinct strategies to balance childcare and provisioning needs. The purpose of this paper is to understand the conditions that lead a family to choose one strategy over another by testing predictions about socioecological factors that impact the sexual division of labor, including a family's stage in the domestic cycle, aspects of the local ecology, and the availability of alloparents. Results show that although each factor has an impact on the division of labor individually, a confluence of these factors best explains within-group, between-family differences in how mothers and fathers divide subsistence and childcare labor. These factors also interact in particular ways for Shodagor families, and it appears that families choose their economic strategies based on the constellation of constraints that they face. The results of these analyses have implications for theory regarding the sexual division of labor across cultures and inform how Shodagor family economic and parenting strategies should be contextualized in future studies.

  11. Multigene families in African swine fever virus: family 360.

    PubMed Central

    González, A; Calvo, V; Almazán, F; Almendral, J M; Ramírez, J C; de la Vega, I; Blasco, R; Viñuela, E

    1990-01-01

    A group of cross-hybridizing DNA segments contained within the restriction fragments RK', RL, RJ, and RD' of African swine fever virus DNA were mapped and sequenced. Analysis of these sequences revealed the presence of a family of homologous open reading frames in regions close to the DNA ends. The whole family is composed of six open reading frames with an average length of 360 coding triplets (multigene family 360), four of which are located in the left part of the genome and two of which are in the right terminal EcoRI fragment. In close proximity to the right terminal inverted repeat, we found an additional small open reading frame which was homologous to the 5'-terminal portion of the other open reading frames, suggesting that most of that open reading frame has been deleted. These repeated sequences account for the previously described inverted internal repetitions (J.M. Sogo, J.M. Almendral, A. Talavera, and E. Viñuela, Virology 133:271-275, 1984). Most of the genes of multigene family 360 are transcribed in African swine fever virus-infected cells. A comparison of the predicted protein sequences of family 360 indicated that several residues are conserved, suggesting that an overall structure is maintained for every member of the family. The transcription direction of each open reading frame, as well as the evolutionary relationships among the genes, suggests that the family originated by gene duplication and translocation of sequences between the DNA ends. Images PMID:2325203

  12. Changing Trends In Family Practice Obstetrics

    PubMed Central

    Ranson, Peter J.

    1978-01-01

    Since trends in some countries show less involvement of the family doctor in obstetrics, and even more reliance on the obstetrician/gynecologist as the primary care physician for women, this study was designed to find out if obstetrics could be adequately practiced in a small rural hospital by family physicians with occasional surgical help. Also, a questionnaire was sent to 200 family physicians, 100 in Ottawa and 100 in Vancouver, to ascertain their involvement in obstetrics.

  13. First report of a novel missense CLDN19 mutations causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a Chinese family.

    PubMed

    Yuan, Tao; Pang, Qianqian; Xing, Xiaoping; Wang, Xi; Li, Yuhui; Li, Jingjun; Wu, Xueyan; Li, Mei; Wang, Ou; Jiang, Yan; Dong, Jin; Xia, Weibo

    2015-04-01

    Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the CLDN16 or CLDN19 genes, encoding claudin-16 and claudin-19 in the thick ascending limb of Henle's loop. In patients with claudin-19 mutations, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described. In this report, we presented a 12-year-old girl with rickets, polyuria, and polydipsia. She was the daughter of consanguineous parents, and she had a history of recurred hypocalcemic and hypomagnesemic tetany. On physical examination, bilateral horizontal nystagmus and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypocalcemia, hypercalciuria, nephrocalcinosis, and renal stone. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous missense mutation c.241C>T in the CLDN19 gene. In conclusion, in a patient with hypomagnesemia, hypercalciuria, nephrocalcinosis, and ocular findings, a diagnosis of FHHNC caused by claudin-19 mutation should be considered. This is the first study of FHHNC in Chinese population. Our findings of the novel mutation c.241C>T in exon 2 add to the list of more than 16 mutations of CLDN19 gene reported.

  14. Family Child Care Licensing Study, 1998.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This report details a survey of state child care regulatory agencies. Data on both small family child care homes (FCCH) and group or large family child care homes (LCCH or GCCH) are included and organized into 22 categories: (1) number of regulated homes; (2) definitions and regulatory requirements; (3) unannounced inspection procedure; (4)…

  15. Family Child Care Licensing Study, 1997.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This report details the findings of an annual survey of state child care regulatory agencies. The survey gathered data on both small family child care homes and group or large family child care homes in each of the 50 states, the District of Columbia, Puerto Rico and the Virgin Islands. The report's introduction lists the survey categories and…

  16. Teaching English to Refugees: A Family Model.

    ERIC Educational Resources Information Center

    Andre, Elise; Brown, Dorothy S.

    The instructional program in English as a second language (ESL) followed by a family of 12 Hmong refugees in a small midwestern town is described. Eight of the younger members of the family met for one hour three times each week. Instruction was under the guidance of two teachers, thus allowing for individual help. Other volunteers assisted from…

  17. Integrating Family Resilience and Family Stress Theory.

    ERIC Educational Resources Information Center

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  18. The Family Hero in Black Alcoholism Families.

    ERIC Educational Resources Information Center

    Brisbane, Francis L.

    1989-01-01

    Uses data from 20 case studies of Black adult female children of alcoholic parents to discuss Family Hero role often assumed by oldest or only female child in Black alcoholism families. Explains how female-dominated survival role of Family Hero in Black families is significantly more related to racial and cultural factors than numbers alone may…

  19. Positive Family Functioning.

    ERIC Educational Resources Information Center

    Sussman, Marvin B.

    The persistence of the nuclear family as the primary social unit in the United States and most all other societies, especially complex ones, is a fact. Values shape the definition of family, especially the "good family," and the "great debate" of this period on family failure, family corruption and the family's near demise originates in…

  20. Family Orientation in Family Medicine Training

    PubMed Central

    Talbot, Yves R.; Tannenbaum, David

    1990-01-01

    Teaching about the family has become an important part of the family medicine curriculum. The family orientation index, a 39-item questionnaire, was designed to evaluate the family orientation of services and care provided as well as the teaching and research. The questionnaire was distributed to 55 program directors at 16 Canadian universities. The response rate was 84%. The results indicate that the family orientation of services is less than optimal. PMID:21233938

  1. Family ties: constructing family time in low-income families.

    PubMed

    Tubbs, Carolyn Y; Roy, Kevin M; Burton, Linda M

    2005-03-01

    "Family time" is reflected in the process of building and fortifying family relationships. Whereas such time, free of obligatory work, school, and family maintenance activities, is purchased by many families using discretionary income, we explore how low-income mothers make time for and give meaning to focused engagement and relationship development with their children within time constraints idiosyncratic to being poor and relying on welfare. Longitudinal ethnographic data from 61 low-income African American, European American, and Latina American mothers were analyzed to understand how mothers construct family time during daily activities such as talking, play, and meals. We also identify unique cultural factors that shape family time for low-income families, such as changing temporal orientations, centrality of television time, and emotional burdens due to poverty. Implications for family therapy are also discussed.

  2. Familial hyperargininaemia.

    PubMed Central

    Terheggen, H G; Lowenthal, A; Lavinha, F; Colombo, J P

    1975-01-01

    A third case of hyperargininaemia occurring in one family was studied from birth. In cord blood serum arginine concentration was only slightly raised, but arginase activity in red blood cell haemolysates was very low. In the urine on day 2 a typical cystinuria pattern was present. Arginine concentration in serum increased to 158 mumol/100 ml on the 41st day of life. Later determinations of the arginase activity in peripheral blood showed values below the sensitivity of the method. Blood ammonia was consistently high, and cystinuria was present. The enzymatic defect was further displayed by intravenous loading tests with arginine. Serum urea values were predominantly normal or near the lower limit of normal, suggesting the presence of other metabolic pathways of urea synthesis. In urine there was no excretion of guanidinosuccinic acid, while the excretion of other monosubstituted guanidine derivatives was increased, pointing to a connexion with hyperargininaemia. Owing to parental attitude, a low protein diet (1-5 g/kg) was introduced only late. The infant developed severe mental retardation, athetosis, and spasticity. PMID:1124944

  3. To integrate family planning into the building up of mental civilization by offering comprehensive services.

    PubMed

    1988-03-01

    The government of Nangong City, a newly instituted city with a relatively large proportion of agricultural workers has integrated family planning into the building up of mental civilization. As a result, in 1986, the family planning practice rate was 98.4%. One way the government accomplished this was by developing production to eliminate poverty, to show that population development has a significant impact on socioeconomic development. To help change people's attitudes about family planning, the government 1) used publicity, such as speechmaking, mass media, and courses in population theory; 2) awarded those who made contributions; 3) carried out publicity and education in accordance with characteristics of different groups of people; and 4) encouraged bridegrooms to live with their wives' families if the wives' parents had had no son. Another technique the government used as the popularization of scientific knowledge about population theory, physiology and hygiene, birth control, and eugenics and health in births. A 4th method was to popularize knowledge of laws and regulations, such as of early marriage and consanguineous marriage. 5th, the government developed social security undertakings: 1) giving priority to single-child families and 2) taking care of the elderly. Finally, the government improved maternal and child care by 1) providing premarital health care; 2) creating a project for healthier births and better upbringing; 3) family planning workers showing warm concern for reproductive women; and 4) controlling women's diseases and providing health care knowledge, as well as family planning services. These 6 activities have resulted in 1) the decreasing momentum of per capita arable land being controlled, 2) 1-child couples having more time to learn, 3) the development of educational undertakings, 4) a change in people's traditional practices, and 5) improvement in the understanding of patriotism.

  4. Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins

    SciTech Connect

    Rogers, G.R.; Lee, M.; Compton, J.G.

    1995-11-01

    Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.

  5. Family and family therapy in Russia.

    PubMed

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  6. Family Therapy and Ideology.

    ERIC Educational Resources Information Center

    Bernal, Guillermo; Ysern, Eduardo

    1986-01-01

    Argues that the family and the enterprise of family therapy are social systems and under the influence of the ideology particular to a given society. The strategic family therapy treatment of a family with a drug-addicted member serves as an example to clarify the ideological themes of contemporary family therapy. (Author/BL)

  7. Accumulation of "small dense" low density lipoproteins (LDL) in a homozygous patients with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor.

    PubMed Central

    März, W; Baumstark, M W; Scharnagl, H; Ruzicka, V; Buxbaum, S; Herwig, J; Pohl, T; Russ, A; Schaaf, L; Berg, A

    1993-01-01

    The interaction of LDL and LDL subfractions from a patient homozygous for familial defective apoB-100 (FDB) has been studied. His LDL cholesterol ranged from 2.65 to 3.34 g/liter. In cultured fibroblasts, binding, internalization, and degradation of the patient's LDL was diminished, but not completely abolished. The patient's apolipoprotein E concentration was low, and the amount of apolipoprotein E associated with LDL was not elevated over normal. LDL were separated into six subfractions: LDL-1 (1.019-1.031 kg/liter), LDL-2 (1.031-1.034 kg/liter), LDL-3 (1.034-1.037 kg/liter), LDL-4 (1.037-1.040 kg/liter), LDL-5 (1.040-1.044 kg/liter), and LDL-6 (> 1.044 kg/liter). LDL-5 and LDL-6 selectively accumulated in the patient's plasma. Concentrations of LDL-1 to 3 were normal. The LDL receptor-mediated uptake of LDL-1 and LDL-2 could not be distinguished from normal LDL. LDL-3 and LDL-4 displayed reduced uptake; LDL-5 and LDL-6 were completely defective in binding. When apolipoprotein E-containing particles were removed by immunoabsorption before preparing subfractions, LDL-3 and LDL-4, but not LDL-1 and LDL-2, retained some receptor binding activity. We conclude that in FDB, LDL-1 and LDL-2 contain sufficient apolipoprotein E to warrant normal cellular uptake. In LDL-3 and LDL-4, the defective apoB-100 itself displays some receptor binding; LDL-5 and LDL-6 are inable to interact with LDL receptors and accumulate in plasma. Images PMID:8254047

  8. Effects of family connection and family individuation.

    PubMed

    Bell, Linda G; Bell, David C

    2009-09-01

    This prospective longitudinal study explores the differential effects of family connection and family individuation measured during adolescence on later midlife well-being. Home interviews were held in the 1970s with 99 families of 245 adolescents. Connection and individuation in the family system were measured by self-report, a projective exercise, and coding of taped family interactions. Twenty-five years later, telephone interviews were conducted with 54 men and 120 women (representing 82 families) who had been adolescents in the 1970s interviews. Family connection (measured during adolescence) was associated with self-acceptance and positive relationships at midlife partially mediated by marriage. Family individuation (measured during adolescence) was associated with personal autonomy at midlife.

  9. Revamping Family Preservation Services for Native Families.

    ERIC Educational Resources Information Center

    Coleman, Heather; Unrau, Yvonne A.; Manyfingers, Brenda

    2001-01-01

    Examines the philosophy and program structures of family preservation services (FPS) in the context of providing services to Native American families with child welfare issues. Explores Native cultural concepts of family, child rearing, time, and spirituality. Outlines cross-cultural training needs for FPS workers related to cultural awareness,…

  10. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  11. The expanding family Marseilleviridae.

    PubMed

    Aherfi, Sarah; La Scola, Bernard; Pagnier, Isabelle; Raoult, Didier; Colson, Philippe

    2014-10-01

    The family Marseilleviridae encompasses giant viruses that replicate in free-living Acanthamoeba amoebae. Since the discovery of the founding member Marseillevirus in 2007, 7 new marseilleviruses have been observed, including 3 from environmental freshwater, one from a dipteran, and two from symptom-free humans. Marseilleviruses have ≈250-nm-large icosahedral capsids and 346-386-kb-long mosaic genomes that encode 444-497 predicted proteins. They share a small set of core genes with Mimivirus and other large and giant DNA viruses that compose a monophyletic group, first described in 2001. Comparative genomics analyses indicate that the family Marseilleviridae currently includes three lineages and a pan-genome composed of ≈600 genes. Antibodies against marseilleviruses and viral DNA have been observed in a significant proportion of asymptomatic individuals and in the blood and lymph nodes of a child with adenitis; these observations suggest that these giant viruses may be blood borne and question if they may be pathogenic in humans.

  12. 26 CFR 1.1366-3 - Treatment of family groups.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Treatment of family groups. 1.1366-3 Section 1... (CONTINUED) INCOME TAXES Small Business Corporations and Their Shareholders § 1.1366-3 Treatment of family groups. (a) In general. Under section 1366(e), if an individual, who is a member of the family of one...

  13. Choosing a Family Doctor

    MedlinePlus

    ... of the whole family. Family doctors create caring relationships with patients and their families. They really get ... questions.Remember, it takes time to build a relationship with your doctor. Last Updated: May 2014 This ...

  14. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  15. Familial Pulmonary Fibrosis

    MedlinePlus

    ... Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  16. National Military Family Association

    MedlinePlus

    ... have good news and bad news for military families. MORE Military Families Brace for What’s Next In Syria President Trump ordered an airstrike in Syria leaving military families wondering what's next. More April is the Month ...

  17. Normal Functioning Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  18. Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries

    PubMed Central

    Moore, Michael J.; Neubig, Kurt M.; Williams, Norris H.; Whitten, W. Mark; Kim, Joo-Hwan

    2015-01-01

    Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability. PMID:26558895

  19. Seven New Complete Plastome Sequences Reveal Rampant Independent Loss of the ndh Gene Family across Orchids and Associated Instability of the Inverted Repeat/Small Single-Copy Region Boundaries.

    PubMed

    Kim, Hyoung Tae; Kim, Jung Sung; Moore, Michael J; Neubig, Kurt M; Williams, Norris H; Whitten, W Mark; Kim, Joo-Hwan

    2015-01-01

    Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability.

  20. The 1993 Family Day Care Licensing Study. Family Day Care Advocacy Project.

    ERIC Educational Resources Information Center

    Children's Foundation, Washington, DC.

    This study contains the results of a nationwide survey of state regulatory agencies conducted to update family day care licensing information gathered in 1992. Following a list of definitions for terms used in the study and a brief overview of each state's regulatory requirements for small and large family day care providers, the main section…

  1. Familial mesothelioma: a report of two families

    SciTech Connect

    Hammar, S.P.; Bockus, D.; Remington, F.; Freidman, S.; LaZerte, G.

    1989-02-01

    Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from an identical histologic type of peritoneal mesothelioma. Our report, as with those previously recorded, suggests that genetic factors may be important in the genesis of some mesotheliomas.

  2. Familial Mediterranean Fever

    MedlinePlus

    Diseases and Conditions Familial Mediterranean fever By Mayo Clinic Staff Familial Mediterranean fever is an inflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, ...

  3. Sequence analysis and characterization of pOM1, a small cryptic plasmid from Butyrivibrio fibrisolvens, and its use in construction of a new family of cloning vectors for Butyrivibrios.

    PubMed Central

    Hefford, M A; Kobayashi, Y; Allard, S E; Forster, R J; Teather, R M

    1997-01-01

    As a preliminary step in the development of vector systems, we have isolated and begun to characterize small, cryptic plasmids from several strains of the rumen bacterium Butyrivibrio fibrisolvens. We present here the complete nucleotide sequence of Butyrivibrio plasmid pOM1, which was isolated from B. fibrisolvens Bu49. While it is very similar in size to the previously characterized Butyrivibrio plasmids pRJF1 and pRJF2, pOM1 exhibits a restriction pattern which is quite distinct. Analysis of sequence data reveals that pOM1 contains only two open reading frames of significant length (ORF1 and ORF2), both of which are required for self-replication and maintenance. The protein encoded in ORF1 shows homologies with Pre (plasmid recombination enzyme) proteins encoded in plasmids from gram-positive organisms such as Staphylococcus aureus, Streptococcus agalactiae, Lactobacillus plantarum, and Bacillus thuringiensis. The putative translation product of ORF2, on the other hand, resembles Rep (replication) proteins of a different group of gram-positive plasmids, for which the Staphylococcus plasmid pSN2 is a prototype. Unlike the other characterized-Butyrivibrio plasmids, pOM1 appears to replicate via a rolling-circle mechanism. Experimental evidence showing the presence of a single-stranded replication intermediate consistent with this mechanism is presented. pOM1 has been used in the construction of a new Escherichia coli-B. fibrisolvens shuttle vector, pSMerm1, which has been successfully used to introduce a cloned gene into B. fibrisolvens harboring the pRJF1 plasmid. PMID:9143105

  4. Efficacy of the Irreversible ErbB Family Blocker Afatinib in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)–Pretreated Non–Small-Cell Lung Cancer Patients with Brain Metastases or Leptomeningeal Disease

    PubMed Central

    Tufman, Amanda; Wehler, Thomas; Pelzer, Theo; Wiewrodt, Rainer; Schütz, Martin; Serke, Monika; Stöhlmacher-Williams, Jan; Märten, Angela; Maria Huber, Rudolf; Dickgreber, Nicolas J.

    2015-01-01

    Introduction: Afatinib is an effective first-line treatment in patients with epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) and has shown activity in patients progressing on EGFR-tyrosine kinase inhibitors (TKIs). First-line afatinib is also effective in patients with central nervous system (CNS) metastasis. Here we report on outcomes of pretreated NSCLC patients with CNS metastasis who received afatinib within a compassionate use program. Methods: Patients with NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment received afatinib. Medical history, patient demographics, EGFR mutational status, and adverse events including tumor progression were documented. Results: From 2010 to 2013, 573 patients were enrolled and 541 treated with afatinib. One hundred patients (66% female; median age, 60 years) had brain metastases and/or leptomeningeal disease with 74% having documented EGFR mutation. Median time to treatment failure for patients with CNS metastasis was 3.6 months, and did not differ from a matched group of 100 patients without CNS metastasis. Thirty-five percent (11 of 31) of evaluable patients had a cerebral response, five (16%) responded exclusively in brain. Response duration (range) was 120 (21–395) days. Sixty-six percent (21 of 32) of patients had cerebral disease control on afatinib. Data from one patient with an impressive response showed an afatinib concentration in the cerebrospinal fluid of nearly 1 nMol. Conclusion: Afatinib appears to penetrate into the CNS with concentrations high enough to have clinical effect on CNS metastases. Afatinib may therefore be an effective treatment for heavily pretreated patients with EGFR-mutated or EGFR–TKI-sensitive NSCLC and CNS metastasis. PMID:25247337

  5. Effectiveness of Cognitive/Behavioral Small Group Intervention for Reduction of Depression and Stress in Non-Hispanic White and Hispanic/Latino Women Dementia Family Caregivers: Outcomes and Mediators of Change

    PubMed Central

    Gray, Heather L.; Dupart, Tamarra; Jimenez, Daniel; Thompson, Larry W.

    2014-01-01

    This study enrolled 184 middle-aged and older women (95 Non-Hispanic White and 89 Hispanic/Latino) who provided in-home hands-on care to an elderly relative with Alzheimer's disease or another form of dementia. Within ethnic group they were randomly assigned to either a CBT-based small group intervention program called “Coping with Caregiving” (CWC) that taught a variety of cognitive and behavioral skills to reduce stress and depression, or to a minimal telephone based control condition (TSC). Intervention lasted about 4 months; one post-treatment assessment was completed 6 months after baseline by interviewers blind to the intervention condition. Interviews and interventions were conducted in English or Spanish by trained staff. Results indicated that those in the CWC (regardless of ethnicity) showed greater improvement from pre to post intervention than those in the TSC on measures of depressive symptoms, overall life stress, and caregiving-specific stress. In order to investigate if these changes may have been related to one proposed mechanism of change in CBT (skill utilization), a new measure was constructed. Change in frequency of use and perceived helpfulness of adaptive coping skills were assessed in all caregivers. Results indicated that caregivers in CWC reported greater frequency of use, and greater perceived helpfulness, of these skills at post intervention compared to caregivers in the TSC. Improvement measured by dependent measures was correlated with an increase in these indices for those in the CWC. Tests for mediation suggest that effective skill utilization may mediate the effect of treatment on outcome. Implications of these findings are discussed and recommendations provided for future research. PMID:25067886

  6. Strengthening Family Practices for Latino Families

    PubMed Central

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9–12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto Rican families. PMID:20871785

  7. Family science: What is it?

    SciTech Connect

    Whitlow, B.

    1994-12-31

    Family science is an informal science education program designed to teach science skills by having children and parents learn and enjoy science together. Aimed at addressing the underrepresentation of women and ethnic and racial minorities in science-based careers, FAMILY SCIENCE involves parents and children in kindergarten through eighth grade in science activities that demonstrate the role science plays in their daily life and future. Family involvement is the key to the program`s effectiveness. Family classes are usually offered in a series of one- to two-hour class meetings for parents and their children after school, evenings, and weekends. During classes, parents and children work in pairs and small groups to solve problems, work cooperatively, and talk science. The activities provide experiences for the entire family that build skills, confidence, and interest in science. In addition, guest speakers and career activities illustrate for parents in the workforce the significance of math and science in their own jobs, and for kids, it highlights the diversity of jobs and the relevance of math and science.

  8. Medicaid and Family Wealth Transfer

    PubMed Central

    Lee, Jinkook; Kim, Hyungsoo; Tanenbaum, Sandra

    2006-01-01

    Purpose: This study examines whether the relationship between making familial wealth transfers and becoming a Medicaid recipient sheds light on the current debate about Medicaid estate planning, whereby some elders transfer their assets to their families to qualify for Medicaid. Design and Methods: Using the Health and Retirement Study, we tracked a national sample of community-based elders who did not receive Medicaid at the 1993 baseline interview but became Medicaid recipients during a 10-year time period and examined wealth transfers for these new Medicaid beneficiaries. Results: Among elders aged 70 or older who did not receive Medicaid in 1993, 16.4% became Medicaid recipients over 10 years. Among these new Medicaid recipients, 17.9% transferred their wealth to family members before receiving Medicaid benefits, with an average transfer amount of $8,507 during the 2 years prior to receiving Medicaid benefits. In addition, 15.2% of community-residing elders entered a nursing home during the 10-year period, and 26.3% of these were covered by Medicaid. Of these new Medicaid recipients living in nursing homes, 12.6% transferred wealth to their families in the mean amount of $4,112. Implications: Familial wealth transfers do occur before changes in Medicaid eligibility in a small, but nontrivial, number of cases, but the amount transferred is modest, especially among nursing home residents. This finding implies that policies to reduce Medicaid long-term-care expenditures by limiting such transfers may not be very effective. PMID:16452279

  9. IDENTIFYING COLLISIONAL FAMILIES IN THE KUIPER BELT

    SciTech Connect

    Marcus, Robert A.; Ragozzine, Darin; Murray-Clay, Ruth A.; Holman, Matthew J.

    2011-05-20

    The identification and characterization of numerous collisional families-clusters of bodies with a common collisional origin-in the asteroid belt has added greatly to the understanding of asteroid belt formation and evolution. More recent study has also led to an appreciation of physical processes that had previously been neglected (e.g., the Yarkovsky effect). Collisions have certainly played an important role in the evolution of the Kuiper Belt as well, though only one collisional family has been identified in that region to date, around the dwarf planet Haumea. In this paper, we combine insights into collisional families from numerical simulations with the current observational constraints on the dynamical structure of the Kuiper Belt to investigate the ideal sizes and locations for identifying collisional families. We find that larger progenitors (r {approx} 500 km) result in more easily identifiable families, given the difficulty in identifying fragments of smaller progenitors in magnitude-limited surveys, despite their larger spread and less frequent occurrence. However, even these families do not stand out well from the background. Identifying families as statistical overdensities is much easier than characterizing families by distinguishing individual members from interlopers. Such identification seems promising, provided the background population is well known. In either case, families will also be much easier to study where the background population is small, i.e., at high inclinations. Overall, our results indicate that entirely different techniques for identifying families will be needed for the Kuiper Belt, and we provide some suggestions.

  10. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

    SciTech Connect

    Thomas, P.M.; Cote, G.J.; Hallman, D.M.; Mathew, P.M.

    1995-02-01

    Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [{theta} = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to be assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release. 37 refs., 2 figs., 4 tabs.

  11. Identification of a novel ZNF469 mutation in a large family with Ehlers-Danlos phenotype.

    PubMed

    Al-Owain, Mohammed; Al-Dosari, Mohammed S; Sunker, Asma; Shuaib, Taghreed; Alkuraya, Fowzan S

    2012-12-15

    Brittle cornea syndrome (BCS) is a genetically heterogeneous disorder characterized by extreme corneal fragility and thinning, which may lead to spontaneous or trauma-induced corneal rupture. BCS-1 and BCS-2 are caused by recessive mutations in ZNF469 and PRDM5, respectively. Both genes play a role in the regulatory pathway of corneal development and maintenance. We report a consanguineous family with five patients affected with the cardinal ocular features of BCS and significant musculoskeletal findings primarily in the form of joint hypermobility and severe kyphoscoliosis. The patients had thin velvety skin, hallux valgus, variable sensorineural hearing loss and arachnodactyly. Interestingly, one of the patients additionally had phenylketonuria and showed a milder ophthalmological and musculoskeletal phenotype than his affected siblings. The urinary pyridinoline and deoxypyridinoline concentrations and their ratios were mildly elevated indicating increased bone-collagen turnover. A novel homozygous 14 bp duplication in exon 2 of ZNF469 (c.8817_8830dup) was uncovered by direct sequencing. This family highlights the phenotypic overlap between BCS and Ehlers-Danlos syndrome.

  12. The Changing Family Structure.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1993

    1993-01-01

    This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand:…

  13. The Family in Treatment.

    ERIC Educational Resources Information Center

    Dunlop, Jean D.

    This paper describes Laurelhurst Manor's family treatment program to help families affected by chemical dependency, a 7-month program which treats family members from the perspective of developmental stages and family roles. The center, located in Portland, Oregon, is a 40-bed, free-standing facility having a 20-bed adolescent unit and a 20-bed…

  14. Black Families. Third Edition.

    ERIC Educational Resources Information Center

    McAdoo, Harriette Pipes, Ed.

    The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say…

  15. Family Participation in Policymaking.

    ERIC Educational Resources Information Center

    Caplan, Elizabeth, Ed.; Blankenship, Kelly, Ed.; McManus, Marilyn, Ed.

    1998-01-01

    This bulletin focuses on family participation in mental health policymaking and highlights state efforts to increase family involvement. Articles include: (1) "Promoting Family Member Involvement in Children's Mental Health Policy Making Bodies," which describes how different states are promoting family member involvement in various statutory and…

  16. Families in Transition .

    ERIC Educational Resources Information Center

    Bundy, Michael L., Ed.; Gumaer, James, Ed.

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  17. Clinical and molecular characterization of seven Egyptian families with autosomal recessive robinow syndrome: Identification of four novel ROR2 gene mutations.

    PubMed

    Aglan, Mona; Amr, Khalda; Ismail, Samira; Ashour, Adel; Otaify, Ghada A; Mehrez, Mennat Allah I; Aboul-Ezz, Eman H A; El-Ruby, Mona; Mazen, Inas; Abdel-Hamid, Mohamed S; Temtamy, Samia A

    2015-12-01

    Robinow syndrome (RS) is a rare genetic disorder characterized by limb shortening, genital hypoplasia, and craniofacial/orodental abnormalities. The syndrome follows both autosomal dominant and recessive patterns of inheritance with similar phenotypic presentation and overlapping features. Autosomal recessive Robinow syndrome (ARRS) is caused by mutations in the ROR2 gene. Here, we present the clinical, radiological and molecular findings of 11 Egyptian patients from 7 unrelated consanguineous families with clinical features of ARRS. Mutation analyses of ROR2 gene identified five pathogenic mutations distributed all over the gene. The identified mutations included four novel (G326A, D166H, S677F, and R528Q) and one previously reported (Y192D). Our results extend the number of ROR2 mutations identified so far, suggest a founder effect in the Egyptian population, and emphasize the important role of genetic testing in proper counseling and patients' management.

  18. Nontraditional family romance.

    PubMed

    Corbett, K

    2001-07-01

    Family stories lie at the heart of psychoanalytic developmental theory and psychoanalytic clinical technique, but whose family? Increasingly, lesbian and gay families, multiparent families, and single-parent families are relying on modern reproductive technologies to form families. The contemplation of these nontraditional families and the vicissitudes of contemporary reproduction lead to an unknowing of what families are, including the ways in which psychoanalysts configure the family within developmental theory. This article focuses on the stories that families tell in order to account for their formation--stories that include narratives about parental union, parental sexuality, and conception. The author addresses three constructs that inform family stories and that require rethinking in light of the category crises posed by and for the nontraditional family: (1) normative logic, (2) family reverie and the construction of a family romance, and (3) the primal scene. These constructs are examined in tandem with detailed clinical material taken from the psychotherapy of a seven-year-old boy and his two mothers.

  19. Law and family planning.

    PubMed

    Kirby, M D

    1984-03-17

    This discussion of law and family planning reviews some recent reports of the Australain Law Reform Commission (ALRC), the law as it affects family planning and the sexuality of young people with reference to the Irish dilemma, the law's approach in Ingland, Canada, and the US. The ALRC works only on references recived by it from the Federal Attorney General. No reference so far received has been specific to the issues of family planning, but some past and present projects are partly relevant. The most recent report of the ALRC, tabled in Federal Parliament in December 1983 related to privacy protection. An issue that arose in this inquiry related to the subject of the rights to privacy of young people. In a discussion paper the ALRC had suggestd that young persons between the ages of 12-16 should have certain defined legal protection of privacy, even against their parents. Specifically, the ALRC was thinking of medical advice and school counseling. Obviously the issue of contraceptive advice was raised in this context, and never has a tenative proposal of the ALRC engendered so much bitter criticism. The Commission modified its proposal on this topic and the details of the revised proposals are disclosed in its report. Clearly, the rights of young people in regard to sexual advice, education, and treatment are matters of great controversy and strongly divided community opinion. In Australia there are some who are totally opposed to family planning for themselves, their children, and even for others. Such opposition exists in the medical profession. Presumably, such people base their views on strongly held moral principles. They generally believe that contraception interferes in the ways of nature. Far from being promoted by open discussion and instruction in the schools, such matters are intimate concerns of a small circle, principally the family. In dealing with those aspects that concern the rights of parents in thes matters, attention turns to England's Gillick

  20. The Family Relationships Grid: Measuring Family Structure.

    ERIC Educational Resources Information Center

    Copeland, Anne P.; And Others

    This study examined the Family Relationships Grid (FRG), a new measure of family structure that evaluates alliances, identification, isolation, and the relative strength of sibling and marital relationships. Subjects were 52 female and 35 male adolescents who were recruited through a university course and who each had at least one sibling.…

  1. Putting the "family" back into family therapy.

    PubMed

    Breunlin, Douglas C; Jacobsen, Elizabeth

    2014-09-01

    In this article, we examine the field of family therapy by drawing a distinction between two forms of practice: Whole Family Therapy (WFT), defined as treating the whole family, and Relational Family Therapy (RFT), defined as working with a subsystem of the family or an individual while retaining a systemic lens. Our thesis is that the practice of WFT has been in decline for some time and steps must be taken to keep it from becoming a defunct practice. We consider the trajectory of WFT and RFT throughout the development of family therapy through reference to the people, the literature, training, and practice patterns associated with family therapy. We remind the reader of the many benefits of WFT and suggest that today WFT is likely to be practiced in conjunction with RFT and individual therapy. Since training of family therapists today is largely located in degree-granting programs, we identify constraints to including WFT in such programs. We conclude by offering suggestions that can enhance a program's ability to train students in WFT.

  2. Strengthening Family Practices for Latino Families

    ERIC Educational Resources Information Center

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  3. Family Therapy for the "Truncated" Nuclear Family.

    ERIC Educational Resources Information Center

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  4. Creating a Family Health History

    MedlinePlus

    ... please turn Javascript on. Creating a Family Health History Why Create a Family Health History? Click for more information A Family Tree for ... Click for more information What a Family Health History May Reveal You can use a family health ...

  5. Charcot-Marie-Tooth Disease Type 4H Resulting from Compound Heterozygous Mutations in FGD4 from Nonconsanguineous Korean Families.

    PubMed

    Hyun, Young Se; Lee, Jinho; Kim, Hye Jin; Hong, Young Bin; Koo, Heasoo; Smith, Alec S T; Kim, Deok-Ho; Choi, Byung-Ok; Chung, Ki Wha

    2015-11-01

    Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive demyelinating subtype of peripheral enuropathies caused by mutations in the FGD4 gene. Most CMT4H patients are in consanguineous Mediterranean families characterized by early onset and slow progression. We identified two CMT4H patients from a Korean CMT cohort, and performed a detailed genetic and clinical analysis in both cases. Both patients from nonconsanguineous families showed characteristic clinical manifestations of CMT4H including early onset, scoliosis, areflexia, and slow disease progression. Exome sequencing revealed novel compound heterozygous mutations in FGD4 as the underlying cause in both families (p.Arg468Gln and c.1512-2A>C in FC73, p.Met345Thr and c.2043+1G>A (p.Trp663Trpfs*30) in FC646). The missense mutations were located in highly conserved RhoGEF and PH domains which were predicted to be pathogenic in nature by in silico modeling. The CMT4H occurrence frequency was calculated to 0.7% in the Korean demyelinating CMT patients. This study is the first report of CMT4H in Korea. FGD4 assay could be considered as a means of molecular diagnosis for sporadic cases of demyelinating CMT with slow progression.

  6. Clinical, laboratory, and immunological studies of a family with a high prevalence of generalized prepubertal and juvenile periodontitis.

    PubMed

    López, N J

    1992-05-01

    A study of a consanguineous family with a high prevalence of localized juvenile periodontitis (LJP) and generalized prepubertal periodontitis (GPP) was done over a 7-and-a-half year period. The parents had adult periodontitis, while 2 daughters, aged 13 and 15, had LJP. Furthermore, 2 other daughters, ages 14 and 10, and a son, aged 9, were affected by GPP. Two remaining siblings were not affected. Clinical and radiographic examinations on all family members were done, and chemotaxis for blood neutrophils was assessed. Laboratory tests, immunological examinations, and evaluation for neutrophil functions were done on the GPP patients. Microbiological cultures were performed on 2 of the GPP patients, as well as in the mother. The mother, the 2 LJP patients, and 1 of the unaffected siblings had depressed PMN chemotaxis. The other family members, including the 3 GPP patients, had normal PMN chemotaxis. GPP patients did not have any systemic disease, and evidence of major defects in the immunological functions was not detected. LJP patients were successfully treated with root planing, subgingival curettage, and tetracycline therapy. Intensive periodontal therapy, combined with systemic administration of antibiotics, was not effective in halting periodontal tissue destruction in the 3 GPP patients. Results indicate that the underlying cause of GPP is not always related to leukocyte dysfunction. Since Actinobacillus actinomycetemcomitans was the most frequent pathogen found in subgingival microflora of 2 of the GPP patients, it is assumed that it may play a key role in the etiology of GPP.

  7. Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Xia, Hong; Huang, Xiangjun; Guo, Yi; Hu, Pengzhi; He, Guangxiang; Deng, Xiong; Xu, Hongbo; Yang, Zhijian; Deng, Hao

    2015-01-01

    Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder, generally manifested with prelingual hearing loss and absence of other clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-generation consanguineous Chinese family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the phenotypes in the ARNSHL family and was absent in two hundred normal controls. The variant was predicted to interfere with the formation of the Myosin XVa-whirlin-Eps8 complex at the tip of stereocilia, which is indispensable for stereocilia elongation. Our data suggest that the homozygous MYO15A c.9316dupC variant might be the pathogenic mutation, and exome sequencing is a powerful molecular diagnostic strategy for ARNSHL, an extremely heterogeneous disorder. Our findings extend the mutation spectrum of the MYO15A gene and have important implications for genetic counseling for the family. PMID:26308726

  8. The Determination of Navy Family Housing Requirements

    DTIC Science & Technology

    1992-04-01

    AD-A253 487 The Determination of Navy Family Housing Requirements NA10IR1 DTIC D:~TI Eric M. Small UL E0 19925 L" Karen M. Dahut ODV fVP, gp20380...identification code (UIC), used to identify each operational unit. UICs for Navy (and Marine Corps) units are assigned by CNO; dummy UICs are assigned to non...w8226l///l//l lll/!/l/ l April 1992 The Determination of Navy Family Housing Requirements NA1OIRI Eric M. Small Karen M. Dahut Prepared pursuant to

  9. Invest in Family*

    PubMed Central

    Shah, Nilesh; De Sousa, Avinash

    2015-01-01

    The family is an integral part of one's life. It is very essential that every individual employed or unemployed invests time therein. The family is a source of support and growth for an individual, and the lack of family support or loneliness may be a causative factor in the genesis of psychiatric disorders, especially depression. In India, family plays a paramount role when it comes to mental health of the individual. Tips on how one should invest time in one's family along with the role of a family in one's personal and social structure are discussed. PMID:25838732

  10. A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections

    PubMed Central

    Glocker, Erik-Oliver; Hennigs, Andre; Nabavi, Mohammad; Schäffer, Alejandro A.; Woellner, Cristina; Salzer, Ulrich; Pfeifer, Dietmar; Veelken, Hendrik; Warnatz, Klaus; Tahami, Fariba; Jamal, Sarah; Manguiat, Annabelle; Rezaei, Nima; Amirzargar, Ali Akbar; Plebani, Alessandro; Hannesschläger, Nicole; Gross, Olaf; Ruland, Jürgen; Grimbacher, Bodo

    2009-01-01

    BACKGROUND Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. METHODS We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. RESULTS We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin-17). Functional studies based on genetic reconstitution of myeloid cells from Card9−/− mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. CONCLUSIONS An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. PMID:19864672

  11. Assessing Postpartum Family Functioning

    PubMed Central

    Midmer, Deana; Talbot, Yves

    1988-01-01

    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals. PMID:21253238

  12. Unique Family Living Situations

    MedlinePlus

    ... if the family home changes for reasons of divorce, death, or economics? Factors, such as shifting between ... blending families when a parent remarries after a divorce or death of a spouse, or moving in ...

  13. Government and the Family

    ERIC Educational Resources Information Center

    Mondale, Walter F.

    1975-01-01

    In order to deal successfully with the changes and pressures placed upon families, article considered the extent government policies are helping or hurting families, and what kind of support services are available. (Author/RK)

  14. Family Caregiver Alliance

    MedlinePlus

    ... on your schedule. Look for our launch soon! FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... Group) Smart Patients Caregivers Community In partnership with Family Caregiver Alliance Learn more Caregiver Research Caregivers exhibit ...

  15. Socioeconomic factors in family planning.

    PubMed

    Eger, G

    1976-03-01

    In a developing country with an average life expectancy of 50 years or higher (an age already reached by several less developed nations) unl imited procreation is no longer necessary to insure the survival of 1 or 2 sons. Data from Pakistan computed from the Population Growth Estimation Experiment of 1962-1965 shows that the male mortality ratio for infants under 1 year was 232/1000 but for 1-4 years it was 25/1000 and for 5-14 years, 3/1000. Further study showed that women had an average of about 5 living children and some of these children already had children of their own as a result of early marriage. If a 27-year-old father has a 2-year-old son there is a 77.2% chance the child will survive him. If replacement is permitted in case of death, a campaign of "at least 2 sons" would result in Pakistan of an average family size of 3.6 children, far fewer than is now the case. This strategy should be more acceptable to parents than the present recommendation to restrict the number of children to 2 or 3. There also needs to be economic incentives for small families. Under present conditions the cost per child is small to the average rural family and the reward in prestige is great. The People's Republic of China has used negative incentives effectively. Positive incentives should be just as effective but they must be high enough to offset the current rewards of childbearing. There is also need to find out why so many couples do not practice family planning even though they approve of it and how administrative structure influences the success of a program. It has already been shown in Pakistan that repeat visits bring in far more acceptors than just 1 visit and repeated personal contacts should be maintained with the target population.

  16. Family Violence: An Overview.

    ERIC Educational Resources Information Center

    National Center on Child Abuse and Neglect (DHHS/OHDS), Washington, DC.

    Family violence is a widespread problem; research has shown multiple factors are associated with family violence. Types of family violence include spouse abuse; elder abuse and neglect; child abuse and neglect; parent abuse; and sibling abuse. There are three types of spouse abuse: physical abuse, sexual violence, and psychological/emotional…

  17. Fatherhood and Family Support.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1996-01-01

    On the assumption that fathers have been relatively absent from family support programs, this publication of the Family Resource Coalition addresses the role of fathers in family support programs, examines the impact of fathers on their children, and describes programs involving fathers successfully. Articles include: (1) "What's Behind the…

  18. Changing Family Forms.

    ERIC Educational Resources Information Center

    Seibert, M. Therese; Willetts, Marion C.

    2000-01-01

    Explores the definition of family. Considers three facets of the contemporary family measured by U.S. Census statistics: (1) marriage and divorce trends; (2) declining fertility; and (3) the rise in single-headed families. Addresses the societal changes (economic, cultural, legal, and technological) that have influenced the changes in family…

  19. Launching Family Message Journals.

    ERIC Educational Resources Information Center

    Wollman-Bonilla, Julie

    This lesson introduces Family Message Journals, a tool for encouraging family involvement and supporting writing to reflect and learn. First and second graders are led into composing through demonstration, guided writing, and finally independent writing of messages that they will bring home for family to read and write a reply. During the three…

  20. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  1. Families in Transition.

    ERIC Educational Resources Information Center

    Britton, Patti O., Ed.; McGee, Michael, Ed.

    1987-01-01

    This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

  2. Family Planning & Literacy.

    ERIC Educational Resources Information Center

    International Planned Parenthood Federation, London (England).

    This publication is an International Planned Parenthood Federation (IPPF) annotated bibliography of books and articles concerned with family planning and literacy. The subject is divided into four major listings: (1) Literacy; (2) Education; (3) Literacy and Family Planning; and (4) Functional Literacy/Family Planning Projects and Programs.…

  3. Books in the Family.

    ERIC Educational Resources Information Center

    Swinger, Alice K.

    1989-01-01

    Opportunities for parents to encourage reading in the family are noted and ways to enhance the reading experience are discussed, including writing letters to book characters, singing combined with reading aloud, supplementing school subjects with enjoyable reading, sharing books at family gatherings, and using family experiences for book…

  4. Family Customs and Traditions.

    ERIC Educational Resources Information Center

    MacGregor, Cynthia

    Recognizing the importance of maintaining open communication with immediate and extended family members, this book provides a compilation of ideas for family traditions and customs that are grounded in compassion and human kindness. The traditions were gathered from families in the United States and Canada who responded to advertisements in…

  5. Familial lipoprotein lipase deficiency

    MedlinePlus

    ... for anyone with a family history of this disease. Prevention There is no known prevention for this rare, inherited disorder. Awareness of risks may allow early detection. Following a very low-fat diet can improve the ... Type I hyperlipoproteinemia; Familial chylomicronemia; Familial ...

  6. Year of the Family.

    ERIC Educational Resources Information Center

    California Agriculture, 1994

    1994-01-01

    This special issue focuses on problems and challenges confronting the California family and on research and extension efforts to provide at least partial answers. Research briefs by staff include "Challenges Confront the California Family" (state trends in poverty, divorce, single-parent families, child abuse, delinquency, teen births,…

  7. Individual and Family Development.

    ERIC Educational Resources Information Center

    Carlson, Jean; Simpson, Elizabeth

    This curriculum guide, in working paper form, for a semester-long three-credit course in individual and family development is one of nine technical core courses in an associate degree consumer/family manager program. The course studies individual and family development through the life cycle. Emphasis is on the relationship of basic needs to the…

  8. Treatment of violent families.

    PubMed Central

    Bell, C. C.; Chance-Hill, G.

    1991-01-01

    Family violence is responsible for a significant proportion of homicides, a major cause of premature deaths in African-Americans. This article reviews the prevalence of family violence and explores associated risk factors. Principles and tips of treatment, along with a cognitive framework to guide the actual therapy, are outlined. Finally, issues of preventing family violence are discussed. PMID:2038079

  9. Strengthening America's Families.

    ERIC Educational Resources Information Center

    Alvarado, Rose; Kumpfer, Karol

    2000-01-01

    Improving parenting practices and the family environment is the most effective, enduring strategy for combating juvenile delinquency. Describes the Office of Juvenile Justice and Delinquency Prevention's Strengthening America's Families Initiative. Highlights several family-focused prevention programs identified as exemplary, explaining how they…

  10. A story of family.

    PubMed

    Condon, Barbara Backer

    2010-07-01

    The author of this column gives a vivid description of Parse's humanbecoming family model as lived in community. The story of M'Barek (Mark), who was imprisoned for 18 years, draws readers to a new understanding of family and community. Through the process of storytelling, Parse's essences of family are discussed.

  11. Incarceration and Family Stress as Understood through the Family Process Theory: Evidence from Hong Kong.

    PubMed

    Chui, Wing Hong

    2016-01-01

    The myriad of negative effects brought about by the incarceration of a family member have consistently been demonstrated in research. However, previous works have tended to focus on the perspectives of family members separately, rather than exploring the dynamic relationships within the family as an entire unit. Moreover, such research is still limited in the Chinese cultural context. Thus, the current study aimed to examine the applicability of the Family Process Theory on a small sample of Chinese fathers who were imprisoned and have returned to their communities, conceptualizing the challenges faced by their families under the theoretical elements of rules of transformation, rituals, ambiguous loss, and boundary ambiguity. A total of 17 participants were recruited through the assistance of service organizations, and data were collected via semi-structured interviews. As congruent with the theory, inmates' families were found to come across problems particularly in the transitioning phase and establishment of new rituals, while ambiguity surrounding the incarceration and the blurred role of the father led to problems with fatherhood identity both during and after the incarceration. Recommendations are made, in line with these findings and the suggestions of ex-prisoners, for services to have more of a focus on preserving the integrity of inmates' families. Given the right circumstances, families can even serve as a motivator for incarcerated fathers to improve themselves and mature, leveraging the important supportive role of the family and the fear of again being separated from one's family as effective deterrents to recidivism.

  12. Incarceration and Family Stress as Understood through the Family Process Theory: Evidence from Hong Kong

    PubMed Central

    Chui, Wing Hong

    2016-01-01

    The myriad of negative effects brought about by the incarceration of a family member have consistently been demonstrated in research. However, previous works have tended to focus on the perspectives of family members separately, rather than exploring the dynamic relationships within the family as an entire unit. Moreover, such research is still limited in the Chinese cultural context. Thus, the current study aimed to examine the applicability of the Family Process Theory on a small sample of Chinese fathers who were imprisoned and have returned to their communities, conceptualizing the challenges faced by their families under the theoretical elements of rules of transformation, rituals, ambiguous loss, and boundary ambiguity. A total of 17 participants were recruited through the assistance of service organizations, and data were collected via semi-structured interviews. As congruent with the theory, inmates’ families were found to come across problems particularly in the transitioning phase and establishment of new rituals, while ambiguity surrounding the incarceration and the blurred role of the father led to problems with fatherhood identity both during and after the incarceration. Recommendations are made, in line with these findings and the suggestions of ex-prisoners, for services to have more of a focus on preserving the integrity of inmates’ families. Given the right circumstances, families can even serve as a motivator for incarcerated fathers to improve themselves and mature, leveraging the important supportive role of the family and the fear of again being separated from one’s family as effective deterrents to recidivism. PMID:27378979

  13. Family practice in Turkey.

    PubMed

    Ozsahin, Akatli Kursad

    2014-03-01

    The national project 'Transformation in Health' was started in 2005 to provide expert primary care by family physicians, and decrease expenses in Turkey. The number of family physicians was far below the need, so public physicians were promoted to family physician status after a 10-day intensive course. The government declared some satisfactory results, but privately paid family physicians were not accepted into the system. Furthermore, the government stopped paying for their services from private settings. Some family physicians became unemployed as the major payer for all forms of medical care in Turkey denied their services. The process showed it's value in time. Nevertheless, family physicians should be the core of this transformation as family medicine is an academic and a scientific discipline and a primary care-oriented specialty with its own specific educational content, research and base of evidence, which cannot be achieved through standard medical education.

  14. Responding to Diversity? Refugee Families and Schools.

    ERIC Educational Resources Information Center

    Vincent, Carol; Warren, Simon

    This paper reports on a small-scale, recently completed qualitative project conducted in the United Kingdom that focuses on links between refugee families and the schools their children attend. The project attempted to study the relationships between refugee parents and education professionals in order to identify factors that encourage or hinder…

  15. Family SMEs in Ireland as Learning Organizations

    ERIC Educational Resources Information Center

    Birdthistle, Naomi

    2008-01-01

    Purpose: The purpose of this paper is to investigate whether small and medium-sized family businesses in Ireland have the potential to be classified as learning organizations. Design/methodology/approach: The research methodology adopted for this study is that of multiple-case studies. In this research, personal interviews were selected as the…

  16. Family Communication Awareness/Suicide Prevention.

    ERIC Educational Resources Information Center

    Jensen, Dennis; Griffith, Steve

    What happened in the small farm community of Elk Point, South Dakota, on January 8, 1986, was unimaginable--a father shot his family and then walked to work and shot himself. Upon learning of the murder/suicide, the Elk Point School District faced the difficult questions of what teachers should say to students, how the district should deal with…

  17. Multiplex families with epilepsy

    PubMed Central

    Afawi, Zaid; Oliver, Karen L.; Kivity, Sara; Mazarib, Aziz; Blatt, Ilan; Neufeld, Miriam Y.; Helbig, Katherine L.; Goldberg-Stern, Hadassa; Misk, Adel J.; Straussberg, Rachel; Walid, Simri; Mahajnah, Muhammad; Lerman-Sagie, Tally; Ben-Zeev, Bruria; Kahana, Esther; Masalha, Rafik; Kramer, Uri; Ekstein, Dana; Shorer, Zamir; Wallace, Robyn H.; Mangelsdorf, Marie; MacPherson, James N.; Carvill, Gemma L.; Mefford, Heather C.; Jackson, Graeme D.; Scheffer, Ingrid E.; Bahlo, Melanie; Gecz, Jozef; Heron, Sarah E.; Corbett, Mark; Mulley, John C.; Dibbens, Leanne M.; Korczyn, Amos D.

    2016-01-01

    Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID:26802095

  18. Exome sequencing identifies a novel homozygous CLN8 mutation in a Turkish family with Northern epilepsy.

    PubMed

    Sahin, Yavuz; Güngör, Olcay; Gormez, Zeliha; Demirci, Huseyin; Ergüner, Bekir; Güngör, Gülay; Dilber, Cengiz

    2017-03-01

    Neuronal ceroid lipofuscinosis (NCL), one of the most common neurodegenerative childhood-onset disorders, is characterized by autosomal-recessive inheritance, epileptic seizures, progressive psychomotor deterioration, visual impairment, and premature death. Based on the country of origin of the patients, the clinical features/courses, and the molecular genetics background of the disorder, 14 distinct NCL subtypes have been described to date. CLN8 mutation was first identified in Finnish patients, and the condition was named Northern Epilepsy (NE); however, the severe phenotype of the CLN8 gene was subsequently found outside Finland and named 'variant late-infantile' NCL. In this study, five patients and their six healthy relatives from a large Turkish consanguineous family were enrolled. The study involved detailed clinical, radiological and molecular genetic evaluations. Whole-exome sequencing and homozygosity mapping revealed a novel homozygous CLN8 mutation, c.677T>C (p.Leu226Pro). We defined NE cases in Turkey, caused by a novel mutation in CLN8. WES can be an important diagnostic method in rare cases with atypical courses.

  19. Familial Constitutional Rearrangement of Chromosomes 4 & 8: Phenotypically Normal Mother and Abnormal Progeny

    PubMed Central

    Kunwar, Fulesh

    2016-01-01

    Balanced chromosome translocations carriers mostly do not have recognizable phenotypic expression but may have more risk of recurrent spontaneous abortions &/or children with serious birth defects due to unbalanced chromosome complements. Unbalanced chromosomal rearrangements have variable clinical expression and are rare. We present here a case report of three siblings affected with intellectual disability and minor dysmorphic features of face and limbs, born to a non-consanguineous couple in which mother had 5 abortions. The constitutional chromosome analysis revealed balanced translocation t (4;8) in mother and all the three siblings were karyotypically normal. Chromosomal microarray in one of the probands revealed partial monosomy 8pter-p23 and a partial trisomy 4pter-p16. Phenotypic features were recorded in 3 probands using Human Phenotype Ontology terms to query web-based tool Phenomizer. The harmonized description using globally accepted ontology is very important especially in case of rare genetic conditions and the heterogeneous phenotypes which make it even more challenging. The prevalence of sub-microscopic unbalanced translocations may be under-reported due to lesser use of molecular genetic analysis. The familial expression of abnormal phenotypes including intellectual disability make the individuals candidate for molecular genetic analysis and phenotyping to help defer the status of idiopathic mental retardation and identify sub-entity of genetic condition. PMID:27190830

  20. Refined mapping of the gene causing Familial Mediterranean fever, by linkage and homozygosity studies

    SciTech Connect

    Aksentijevich, I.; Pras, E.; Gruberg, L.; Helling, S.; Prosen, L.; Pras, M.; Kastner, D.L. ); Shen, Y.; Holman, K.; Sutherland, G.R.; Richards, R.I. ); Ramsburg, M.; Dean, M. ); Amos, C.I. )

    1993-08-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. The authors recently reported linkage of the gene causing FMF (designated [open quotes]MEF[close quotes]) to two markers on chromosome 16p. To map MEF more precisely, they have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. They also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. 30 refs., 6 figs., 2 tabs.

  1. Mitogenic cardiomyopathy: a lethal neonatal familial dilated cardiomyopathy characterized by myocyte hyperplasia and proliferation.

    PubMed

    Chang, Kenneth T E; Taylor, Glenn P; Meschino, Wendy S; Kantor, Paul F; Cutz, Ernest

    2010-07-01

    Pediatric cardiomyopathies are a heterogenous group of conditions of which dilated cardiomyopathies are the most common clinicomorphologic subtype. However, the etiology and pathogenesis of many cases of dilated cardiomyopathies remain unknown. We describe a series of 5 cases of a rare but clinically and histologically distinctive dilated cardiomyopathy that was uniformly lethal in early infancy. The 5 cases include 2 pairs of siblings. There was parental consanguinity in 1 of the 2 pairs of siblings. Death occurred in early infancy (range, 22-67 days; mean, 42 days) after a short history of general lethargy, decreased feeding, respiratory distress, or cyanosis. There was no specific birth or early neonatal problems. Autopsy revealed congestive cardiac failure and enlarged, dilated hearts with ventricular dilatation more pronounced than atrial dilatation, and endocardial fibroelastosis. Histology showed prominent hypertrophic nuclear changes of cardiac myofibers and markedly increased myocyte mitotic activity including occasional atypical mitoses. Immunohistochemical staining for Mib1 showed a markedly increased proliferative index of 10% to 20%. Ancillary investigations, including molecular studies, did not reveal a primary cause for the cardiomyopathies. This distinctive dilated cardiomyopathy characterized by unusual histologic features of myocyte nuclear hypertrophy and marked mitotic activity is lethal in early infancy. Its occurrence in 2 pairs of siblings suggests familial inheritance. Although the underlying molecular pathogenesis remains to be elucidated, it is important to recognize this distinctive entity for purposes of genetic counseling.

  2. Molecular study of the 5 {alpha}-reductase type 2 gene in three European families with 5 {alpha}-reductase deficiency

    SciTech Connect

    Boudon, C.; Lumbroso, S.; Lobaccaro, J.M. ||

    1995-07-01

    The molecular basis of 5{alpha}-reductase (5{alpha}R) deficiency was investigated in four patients from three European families. In the French family, the first patient was raised as a female, and gonadectomy was performed before puberty. The second sibling, also raised as female, differed in that gonadal removal was performed after the onset of pubertal masculinization. The other two patients, both from Polish families, developed masculinization of external genitalia during puberty. All patients developed a female sexual identity. In all cases, no known consanguinity or family history of 5{alpha}R deficiency was reported. The genomic DNAs of the patients were sequenced after polymerase chain reaction amplification of the five exons of the 5{alpha}R type 2 gene. We found two homozygous mutations responsible for gutamine to arginine and histidine to arginine substitution in families 1 and 3, respectively. In family 2, we found a heterozygous mutation responsible for an asparagine to serine substitution at position 193. The glutamine/arginine 126 mutation in the French family was previously reported in a Creole ethnic group, and the Polish histidine/arginine 231 mutation was previously reported in a patient from Chicago, Moreover, all of the mutations created new restriction sites, which were used to determine the kindred carrier status in the three families. Because 5{alpha}R deficiency is known to be heterogenous disease in terms of clinical and biochemical expression, our data suggest that molecular biology analysis of the type 2 gene could be an essential step in diagnosing 5{alpha}R deficiency. 22 refs., 3 figs., 1 tab.

  3. Opening Doors: Understanding School and Family Influences on Family Involvement

    ERIC Educational Resources Information Center

    Carlisle, Erin; Stanley, Lindsey; Kemple, Kristen Mary

    2005-01-01

    Family involvement in schooling can benefit young children, teachers, and families. Family involvement in schools can be influenced by both school-related and family-related factors. School-related factors include teachers' attitudes toward families, and school and teacher expectations. Family-related factors include ethnicity, prior school…

  4. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  5. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  6. Extended family medicine training

    PubMed Central

    Slade, Steve; Ross, Shelley; Lawrence, Kathrine; Archibald, Douglas; Mackay, Maria Palacios; Oandasan, Ivy F.

    2016-01-01

    Abstract Objective To examine trends in family medicine training at a time when substantial pedagogic change is under way, focusing on factors that relate to extended family medicine training. Design Aggregate-level secondary data analysis based on the Canadian Post-MD Education Registry. Setting Canada. Participants All Canadian citizens and permanent residents who were registered in postgraduate family medicine training programs within Canadian faculties of medicine from 1995 to 2013. Main outcome measures Number and proportion of family medicine residents exiting 2-year and extended (third-year and above) family medicine training programs, as well as the types and numbers of extended training programs offered in 2015. Results The proportion of family medicine trainees pursuing extended training almost doubled during the study period, going from 10.9% in 1995 to 21.1% in 2013. Men and Canadian medical graduates were more likely to take extended family medicine training. Among the 5 most recent family medicine exit cohorts (from 2009 to 2013), 25.9% of men completed extended training programs compared with 18.3% of women, and 23.1% of Canadian medical graduates completed extended training compared with 13.6% of international medical graduates. Family medicine programs vary substantially with respect to the proportion of their trainees who undertake extended training, ranging from a low of 12.3% to a high of 35.1% among trainees exiting from 2011 to 2013. Conclusion New initiatives, such as the Triple C Competency-based Curriculum, CanMEDS–Family Medicine, and Certificates of Added Competence, have emerged as part of family medicine education and credentialing. In acknowledgment of the potential effect of these initiatives, it is important that future research examine how pedagogic change and, in particular, extended training shapes the care family physicians offer their patients. As part of that research it will be important to measure the breadth and uptake of

  7. Family dynamics and family psychotherapy of psychosomatic.

    PubMed

    Wirsching, M; Stierlin, H

    1979-01-01

    Family therapy of psychosomatic disorders is oftern difficult and comparable to the therapy of psychotic patients. Nonetheless, the results published today by authors such as Minuchin and Selvini and our own experiences are promising indeed. We have found that what seemed to be a deep-rooted psychic structure changed rapidly and enduringly if the relationship field changed. Amelioration of symptoms is in many cases easily attained if they are understood in their function within a relational system. Also, we regard the system or family approach as a chance for medical practice. The general practioner who usually deals with family systems has, in our view, an ideal position to bring about change if he uses his authority and trust properly. He has to obtain a positive, not pathology-oriented view and should use family and social resources in spite of engaging in an often fruitless and endless contact with the designated patient, which only serves to maintain and even to increase the homeostatic lock of the family system.

  8. Creating a family health history

    MedlinePlus

    Family health history; Create a family health history; Family medical history ... Many factors affect your health. These include your: Genes Diet and exercise habits Environment Family members tend to share certain behaviors, genetic traits, and habits. ...

  9. Risk of other Cancers in Families with Melanoma: Novel Familial Links

    PubMed Central

    Frank, Christoph; Sundquist, Jan; Hemminki, Akseli; Hemminki, Kari

    2017-01-01

    A family history of cutaneous melanoma (‘melanoma’) is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma. PMID:28198461

  10. Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation.

    PubMed Central

    Takeda, K; Balzano, S; Sakurai, A; DeGroot, L J; Refetoff, S

    1991-01-01

    Generalized resistance to thyroid hormone (GRTH) is a syndrome characterized by impaired tissue responsiveness to thyroid hormone. Two distinct point mutations in the hormone binding domain of the thyroid hormone receptor (TR) beta have recently been identified in two unrelated families with GRTH. One, Mf, involves a replacement of the normal glycine-345 for arginine in exon 7 and another, Mh, replaces the normal proline-453 for histidine in exon 8. To probe for the presence of the Mf and Mh defect in 19 unrelated families with GRTH, we applied separate polymerase chain reactions using allele-specific oligonucleotide primers containing the normal and each of the two mutant nucleotides at the 3'-position. A total of 24 affected subjects and 13 normal family members were studied. The mode of inheritance was dominant in 13 families, was unknown in 5 families, and was clearly recessive in 1 family in which only the consanguineous subjects were affected. Primers containing the substitutions specific for Mf and Mh amplified exons 7 and 8, respectively, only in affected members of each of the two index families. Primers containing the normal sequences amplified exons 7 and 8 of the TR beta gene in all subjects except affected members of one family. In this family with recessively inherited GRTH, neither exon could be amplified using any combinations of primers and DNA blot revealed absence of all coding exons. These results indicate a major deletion of the TR beta gene, including both DNA and hormone binding domains. Since heterozygous members of this family are not affected, the presence of a single normal allele is sufficient for normal function of the TR beta. These data also support the hypothesis that in the dominant mode of GRTH inheritance the presence of an abnormal TR beta interferes with the function of the normal TR beta. Distinct mutations are probably responsible for GRTH in unrelated families. Images PMID:1991834

  11. Family factors for child meal skipping in low-income families in Korea.

    PubMed

    Bae, Hwa-ok; Kim, Meesook; Hong, Soon-Myung

    2010-04-01

    The present study proposed to examine whether family factors are associated with child meal skipping in Korea. Family factors were divided into risk factors and protective factors on conceptual and theoretical bases. The sample was obtained from the Survey of Meal Service for Poor Children conducted by the Korea Institute for Health and Social Affairs in 2007. A final sample was composed of 944 children in low-income families who are served by the public meal program. Child meal skipping was positively associated with risk factors and negatively associated with protective factors, as hypothesized. Single-father family, middle or small urban area, presence of caretaker after school, health level of caretaker, caretaker's concern about child's diet, and degree of family cohesion significantly predicted child meal skipping. The authors suggest a few implications for practice based on the study findings.

  12. Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families.

    PubMed

    Issa, Yasmin A; Kamal, Lara; Rayyan, Amal Abu; Dweik, Dima; Pierce, Sarah; Lee, Ming K; King, Mary-Claire; Walsh, Tom; Kanaan, Moien

    2016-10-01

    Tooth development is controlled by the same processes that regulate formation of other ectodermal structures. Mutations in the genes underlying these processes may cause ectodermal dysplasia, including severe absence of primary or permanent teeth. Four consanguineous Palestinian families presented with oligodontia and hair and skin features of ectodermal dysplasia. Appearance of ectodermal dysplasia was consistent with autosomal recessive inheritance. Exome sequencing followed by genotyping of 56 informative relatives in the 4 families suggests that the phenotype is due to homozygosity for KREMEN1 p.F209S (c.626 T>C) on chromosome 22 at g.29,521,399 (hg19). The variant occurs in the highly conserved extracellular WSC domain of KREMEN1, which is known to be a high affinity receptor of Dickkopf-1, a component of the Dickkopf-Kremen-LRP6 complex, and a potent regulator of Wnt signaling. The Wnt signaling pathway is critical to development of ectodermal structures. Mutations in WNT10A, LRP6, EDA, and other genes in this pathway lead to tooth agenesis with or without other ectodermal anomalies. Our results implicate KREMEN1 for the first time in a human disorder and provide additional details on the role of the Wnt signaling in ectodermal and dental development.

  13. Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome.

    PubMed

    Bouyacoub, Yosra; Zribi, Hela; Azzouz, Hatem; Nasrallah, Fehmi; Abdelaziz, Rim Ben; Kacem, Monia; Rekaya, Ben; Messaoud, Olfa; Romdhane, Lilia; Charfeddine, Cherine; Bouziri, Mustapha; Bouziri, Sonia; Tebib, Neji; Mokni, Mourad; Kaabachi, Naziha; Boubaker, Samir; Abdelhak, Sonia

    2013-10-15

    Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner-Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the present study, we report clinical features and molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in two young patients, both born to consanguineous unions between first-degree cousins. These two unrelated families originated from Northern and Southern Tunisia. The clinical diagnosis was based on the observation of several complications related to Richner-Hanhart syndrome: recurrent eye redness, tearing and burning pain, photophobia, bilateral pseudodendritic keratitis, an erythematous and painful focal palmo-plantar hyperkeratosis and a mild delay of mental development. The diagnosis was confirmed by biochemical analysis. Sequencing of the TAT gene revealed the presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs 6). Early diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and the severity of long-term complications of hypertyrosinemia such as intellectual disability.

  14. Bringing Back Community: Family Support from the Bottom up

    ERIC Educational Resources Information Center

    Wigfall, Valerie

    2006-01-01

    This paper presents findings of an evaluation of a one-off, small scale, pilot project. Picking up where Sure Start, the government programme for families of newborns to threes, leaves off, "Families in Focus" works with children aged four to 16 on a disadvantaged council estate in London. Through this route, the programme also reaches…

  15. Societal Complexity and Familial Complexity: Evidence for the Curvilinear Hypothesis

    ERIC Educational Resources Information Center

    Blumberg, Rae Lesser; Winch, Robert F.

    1972-01-01

    The hypothesis is supported that the most extended, complex familial systems should be found among societies in an intermediate range of societal complexity, particularly among settled agricultural peoples. Among the simple hunting-gathering groups and in modern industrial states is found the nuclear family system: small, independent, nonextended…

  16. Effect of location on family medicine residents' training.

    PubMed Central

    Lebel, D.; Hogg, W.

    1993-01-01

    A survey of family medicine residents trained at community-based or hospital-based centres suggested differences in experience and in career plans. Community-based residents saw more patients in the same family, believed they knew the community better, made more housecalls, expected to use allied health professionals more frequently, and were more likely to choose a small community practice. PMID:8499787

  17. Advancing family psychology.

    PubMed

    Fiese, Barbara H

    2016-02-01

    To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year.

  18. State of family planning.

    PubMed

    Schreiber, Courtney A; Traxler, Sarah

    2015-06-01

    Family planning and reproductive health services are uniquely impacted by policy and politics in the United States. Recent years have witnessed an unprecedented number of abortion restrictions, and research funding has decreased in related areas. Despite this, both the science and the implementation of improved family planning and abortion methods have progressed in the past decade. This article reviews the current state of family planning, as well as technologies and patient care opportunities for the future.

  19. The Growth of a Family

    PubMed Central

    Carroll, June C.; Biringer, Anne

    1991-01-01

    Caring for a family during pregnancy and birth is an ideal opportunity for family physicians to assess family functioning and help the family adjust to the birth of a new child. Stress and support systems can influence the course of pregnancy, including obstetric and perinatal outcomes. A family-centered approach can help patients during this critical stage of family development. PMID:21229107

  20. The Hoffmeister asteroid family

    NASA Astrophysics Data System (ADS)

    Carruba, V.; Novaković, B.; Aljbaae, S.

    2017-03-01

    The Hoffmeister family is a C-type group located in the central main belt. Dynamically, it is important because of its interaction with the ν1C nodal secular resonance with Ceres, which significantly increases the dispersion in inclination of family members at a lower semimajor axis. As an effect, the distribution of inclination values of the Hoffmeister family at a semimajor axis lower than its centre is significantly leptokurtic, and this can be used to set constraints on the terminal ejection velocity field of the family at the time it was produced. By performing an analysis of the time behaviour of the kurtosis of the vW component of the ejection velocity field [γ2(vW)], as obtained from Gauss' equations, for different fictitious Hoffmeister families with different values of the ejection velocity field, we were able to exclude that the Hoffmeister family should be older than 335 Myr. Constraints from the currently observed inclination distribution of the Hoffmeister family suggest that its terminal ejection velocity parameter VEJ should be lower than 25 m s-1. Results of a Yarko-YORP Monte Carlo method to family dating, combined with other constraints from inclinations and γ2(vW), indicate that the Hoffmeister family should be 220^{+60}_{-40} Myr old, with an ejection parameter VEJ = 20 ± 5 m s-1.

  1. [Nuclear families in Turkey].

    PubMed

    Unalan, T

    1988-01-01

    This study examines the household or family types in Turkey in 1983, especially nuclear families. Nuclear families constitute 61.6% of all households in Turkey, and the majority of them are in the West and the Central regions. The highest % of nuclear families was found in the Mediterranean regions, and the lowest in the Black Sea region. Among all nuclear families, 87% of them consist of husband, wife and children, whereas 13% of them have only husband and wife. Nuclear families without children are common in urban areas and in the West while nuclear families with children are mostly found in rural areas and in the East and the Black Sea regions. Nuclear families with 3 or more children constitute 32% of all nuclear households in the West. On the other hand, the corresponding % is 73 for the Eastern region. As a result, it is concluded that nuclear families have significant regional and residential differentiations and households with the same formation in a developed and a less developed region should have different social, economic, and cultural characteristics.

  2. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  3. Small Scale Organic Techniques

    ERIC Educational Resources Information Center

    Horak, V.; Crist, DeLanson R.

    1975-01-01

    Discusses the advantages of using small scale experimentation in the undergraduate organic chemistry laboratory. Describes small scale filtration techniques as an example of a semi-micro method applied to small quantities of material. (MLH)

  4. Family Language Policy: A Case Study of a Russian-Hebrew Bilingual Family--Toward a Theoretical Framework

    ERIC Educational Resources Information Center

    Kopeliovich, Shulamit

    2010-01-01

    This article presents an in-depth, small-scale qualitative study of a Hebrew-Russian bilingual family with 8 children, and compares the parents' perspective on the family language policy with their children's evaluation of it. Spolsky's (2004, 2009) model of language policy enables tracing the development of the parents' language…

  5. Small bowel bacterial overgrowth

    MedlinePlus

    Overgrowth - intestinal bacteria; Bacterial overgrowth - intestine; Small intestinal bacterial overgrowth; SIBO ... intestine does not have a high number of bacteria. Excess bacteria in the small intestine may use ...

  6. Family Sense of Coherence and Family Adaptation.

    ERIC Educational Resources Information Center

    Antonovsky, Aaron; Sourani, Talma

    1988-01-01

    Administered family Sense of Coherence (SOC) scale to 60 married Israeli males who were disabled by injury or illness and to their spouses. Data provide strong support for hypothesis that strength of SOC would be associated with adaptation, and showed considerable degree of consensus among spouses. (Author/NB)

  7. The Rafita asteroid family

    NASA Astrophysics Data System (ADS)

    Aljbaae, S.; Carruba, V.; Masiero, J. R.; Domingos, R. C.; Huaman, M.

    2017-01-01

    The Rafita asteroid family is an S-type group located in the middle main belt, on the right side of the 3J:-1A mean-motion resonance. The proximity of this resonance to the family left side in semi-major axis caused many former family members to be lost. As a consequence, the family shape in the (a, 1/D) domain is quite asymmetrical, with a preponderance of objects on the right side of the distribution. The Rafita family is also characterized by a leptokurtic distribution in inclination, which allows the use of methods of family age estimation recently introduced for other leptokurtic families such as Astrid, Hansa, Gallia, and Barcelona. In this work we propose a new method based on the behavior of an asymmetry coefficient function of the distribution in the (a, 1/D) plane to date incomplete asteroid families such as Rafita. By monitoring the time behavior of this coefficient for asteroids simulating the initial conditions at the time of the family formation, we were able to estimate that the Rafita family should have an age of 490 ± 200 Myr, in good agreement with results from independent methods such as Monte Carlo simulations of Yarkovsky and Yorp dynamical induced evolution and the time behaviour of the kurtosis of the sin (i) distribution. Asteroids from the Rafita family can reach orbits similar to 8% of the currently known near Earth objects. ≃1% of the simulated objects are present in NEO-space during the final 10 Myr of the simulation, and thus would be comparable to objects in the present-day NEO population.

  8. Strengthening Families: Exploring the Impacts of Family Camp Experiences on Family Functioning and Parenting

    ERIC Educational Resources Information Center

    Garst, Barry A.; Baughman, Sarah; Franz, Nancy K.; Seidel, Richard W.

    2013-01-01

    Research suggests that family camp experiences can enhance family relationships. Families often participate in family camp experiences for a vacation, as part of a therapeutic and/or intervention strategy, or to gain general enrichment or engagement. To better understand the impacts of family camp experiences on family functioning, a mixed-methods…

  9. Smooth School Transitions: Tips for Military Families

    MedlinePlus

    ... Family Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families ...

  10. The lipocalin protein family: structure and function.

    PubMed Central

    Flower, D R

    1996-01-01

    The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel beta-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily: the calycins. Members of the lipocalin family are characterized by several common molecular-recognition properties: the ability to bind a range of small hydrophobic molecules, binding to specific cell-surface receptors and the formation of complexes with soluble macromolecules. The varied biological functions of the lipocalins are mediated by one or more of these properties. In the past, the lipocalins have been classified as transport proteins; however, it is now clear that the lipocalins exhibit great functional diversity, with roles in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and, as carrier proteins, to act in the general clearance of endogenous and exogenous compounds. PMID:8761444

  11. Narrative Family Therapy.

    ERIC Educational Resources Information Center

    Walsh, William M.; Keenan, Robert

    1997-01-01

    States that narrative family therapy is informed by social constructionism and postmodern worldviews, and is a relatively significant departure from mainstream psychotherapy. Discusses the use of narrative family therapy. Uses the story of Adam and Eve in the Garden of Eden as an example. (MKA)

  12. Families, Risk, and Competence.

    ERIC Educational Resources Information Center

    Lewis, Michael, Ed.; Feiring, Candice, Ed.

    The problems of studying families arise from the difficulty in studying systems in which there are multiple elements interacting with each other and with the child. This book attests to the growing sophistication of the conceptualization and measurement techniques for understanding family processes. Chapters in the first part of the book,…

  13. Workshops on Family Communication.

    ERIC Educational Resources Information Center

    Galvin, Kathleen M.

    Intended to help speech communication professionals become involved in developing, implementing, and evaluating marital or family enrichment programs, this booklet discusses the theory and practice of using marital enrichment programs to increase family harmony. The first section contains an overview of selected enrichment programs, as well as…

  14. Changing Families, Changing Workplaces

    ERIC Educational Resources Information Center

    Bianchi, Suzanne M.

    2011-01-01

    American families and workplaces have both changed dramatically over the past half-century. Paid work by women has increased sharply, as has family instability. Education-related inequality in work hours and income has grown. These changes, says Suzanne Bianchi, pose differing work-life issues for parents at different points along the income…

  15. Education and the Family.

    ERIC Educational Resources Information Center

    Kaplan, Leonard, Ed.

    This book is the report of the Family Ties Commission, which was established by the Association of Teacher Educators to study the relationship between home and school. Following the preface and two introductory essays, "Education and My Family" (K.B. O'Rourke as told to E. Johnson) and "Preparing for Successful Children" (B. Clawson), the book is…

  16. The Working Family.

    ERIC Educational Resources Information Center

    Boethius, Monica

    1984-01-01

    The working family is today by far the most common family type in Sweden. However, just over 50 percent of the children of working parents have access to day care. Because Swedish income tax policy is based on the concept that all adults will support themselves and does not take into account the number of persons supported on an income, one parent…

  17. Employers, Families and Education.

    ERIC Educational Resources Information Center

    Partnership for Family Involvement in Education (ED), Washington, DC.

    Family involvement in education is good for business, critical to children's school achievement, and important in creating strong and vibrant communities. This report discusses the role of businesses and employers in helping partners and family members be more involved in children's learning. Throughout the report, programs at specific companies…

  18. America's Family Time Famine.

    ERIC Educational Resources Information Center

    Mattox, Jr., William R.

    1990-01-01

    Parents spend increasingly less time with their children because of the pressures of dual careers and single parenthood. Economic pressures and social values have affected sharing of family time. Studies show both parents and children consider spending time together the most important element in improving family life. (BC)

  19. Family Science Night

    ERIC Educational Resources Information Center

    Hansen, Holly; Alderman, Helen Christine

    2016-01-01

    The goal of the Family Science Night (FSN) described in this article was to involve culturally and linguistically diverse families in school life so that students would be more vocal, successful, and interactive in science class. The project would also demonstrate to the students that their teacher valued their input in the classroom. The setting…

  20. Therapy for Family Systems.

    ERIC Educational Resources Information Center

    Rosmann, Michael R.

    A family therapy model, based on a conceptualization of the family as a behavioral system whose members interact adaptively so that an optimal level of functioning is maintained within the system, is described. The divergent roots of this conceptualization are discussed briefly, as are the treatment approaches based on it. The author's model,…

  1. Patent Family Databases.

    ERIC Educational Resources Information Center

    Simmons, Edlyn S.

    1985-01-01

    Reports on retrieval of patent information online and includes definition of patent family, basic and equivalent patents, "parents and children" applications, designated states, patent family databases--International Patent Documentation Center, World Patents Index, APIPAT (American Petroleum Institute), CLAIMS (IFI/Plenum). A table…

  2. Democratization of the Family.

    ERIC Educational Resources Information Center

    Beck, Ulrich

    1997-01-01

    Discusses several issues related to a modern approach in the interpretation of civil freedom and its relationship to the notion of family. First, presents some definitions and distinctions regarding the sociology of political freedom, which it suggests should become the sociology of citizenship. Then, applies those ideas to families, particularly…

  3. Marriage or Family Therapy.

    ERIC Educational Resources Information Center

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  4. Measuring Family Dynamics.

    ERIC Educational Resources Information Center

    Kunce, Joseph T.; Priesmeyer, Marydeth L.

    1985-01-01

    Investigated dimensions of family dynamics via test construction and cross validation, with a developmental sample (N=93) and a validity generalization sample (N=65). Developed two scales that correlated significantly with perceptions of family stability and quality in the developmental and validity generalization samples. (BH)

  5. Family Support and Education

    ERIC Educational Resources Information Center

    Goldstein, Lou Ann

    2013-01-01

    Family involvement is essential to the developmental outcome of infants born into Neonatal Intensive Care Unit (NICU). In this article, evidence has been presented on the parent's perspective of having an infant in the NICU and the context of family. Key points to an educational assessment are also reviewed. Throughout, the parent's concerns and…

  6. Black Families. Interdisciplinary Perspectives.

    ERIC Educational Resources Information Center

    Cheatham, Harold E., Ed.; Stewart, James B., Ed.

    Since the early 1960s, the black family has been characterized as pathological. This six-part collection of 18 research studies presents alternative approaches to understanding the special characteristics of black families. Part I, "Theoretical and Methodological Perspectives," comprises a comparison of the pioneering work of W. E. B. Du…

  7. Family-Friendly Art

    ERIC Educational Resources Information Center

    Williams, Patterson; Garcia, Maria

    2004-01-01

    In the late 1980s, the Denver Art Museum initiated efforts to make the museum a destination for families. From 1997 to 2001, with a generous grant from The Pew Charitable Trusts, these efforts came to fruition. From the moment they walk through the doors, families' needs are anticipated. For example, they can pick up a welcoming brochure, Free…

  8. The Family Constellation Scale.

    ERIC Educational Resources Information Center

    Lemire, David

    The Family Constellation Scale (FC Scale) is an instrument that assesses perceived birth order in families. It can be used in counseling to help initiate conversations about various traits and assumptions that tend to characterize first-born, middle-born children, youngest-born, and only children. It provides both counselors and clients insights…

  9. Balancing Family and Work.

    ERIC Educational Resources Information Center

    Yahnke, Sally; And Others

    The purpose of this monograph is to present a series of activities designed to teach strategies needed for effectively managing the multiple responsibilities of family and work. The guide contains 11 lesson plans dealing with balancing family and work that can be used in any home economics class, from middle school through college. The lesson…

  10. Marinating the Family.

    ERIC Educational Resources Information Center

    Hensel, Karen A.

    1982-01-01

    Describes the New York Aquarium's program specifically designed for family learning and teaching. The program's goal is to create an environment where child-parent roles are dropped and where the philosophy that no one of us is as smart as all of us prevails. Strategies for family involvement are outlined. (MH)

  11. Reaching Rural Families.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1995

    1995-01-01

    This newsletter issue focuses on programming undertaken to address the health and educational needs of rural families in developing and developed nations. After examining the nature of rural families and rural poverty, the newsletter discusses: (1) the Mon Women's Organization in Thailand; (2) The "Contact With Kids" parent education…

  12. Latino Families Learning Together.

    ERIC Educational Resources Information Center

    Osterling, Jorge P.; Violand-Sanchez, Emma; von Vacano, Marcela

    1999-01-01

    The push for the English-only literacy approach sends the wrong message to language-minority families. The Arlington (Virginia) Public Schools have established first-language pilot programs to accelerate Latino students' academic achievement and have welcomed community-based educational initiatives. A family-literacy program motivates parents to…

  13. Family Perspectives on Prematurity

    ERIC Educational Resources Information Center

    Zero to Three (J), 2003

    2003-01-01

    In this article, seven families describe their experiences giving birth to and raising a premature baby. Their perspectives vary, one from another, and shift over time, depending on each family's circumstances and the baby's developmental course. Experiences discussed include premature labor, medical interventions and the NICU, bringing the baby…

  14. Explaining Family Interactions.

    ERIC Educational Resources Information Center

    Fitzpatrick, Mary Anne, Ed.; Vangelisti, Anita L., Ed.

    A detailed review of current research and state-of-the-art ideas concerning both communication processes and family functioning is presented in this collection of articles. The volume is organized around three sections. Part 1, "The Development of Family Communication Patterns," contains: (1) "Communication in Infancy"…

  15. Transient familial hyperbilirubinemia

    MedlinePlus

    ... please enable JavaScript. Transient familial hyperbilirubinemia is a metabolic disorder that is passed down through families. Babies with ... M. Editorial team. Related MedlinePlus Health Topics Jaundice Metabolic Disorders Browse the Encyclopedia A.D.A.M., Inc. ...

  16. Intervention in Disintegrating Families.

    ERIC Educational Resources Information Center

    Wootton, Ray W.

    A special demonstration project attempted to find means of assisting hard-core multi-problem families in a predominantly rural Idaho county. A single agency was formed to coordinate community activities and provide a variety of services for the needs of the total family. Project personnel included a director, social worker, home economist, public…

  17. Families on the Grow.

    ERIC Educational Resources Information Center

    Lee, Irene K.; Phillips, Marjorie M.

    This correspondence course was designed to help parents better understand their growing children and themselves as parents. The introduction briefly sketches the importance of the family in child development. Each of the five illustrated lessons contains 7 to 12 pages on one aspect of family life. Each lesson contains a set of objectives, a…

  18. Golden Matrix Families

    ERIC Educational Resources Information Center

    Fontaine, Anne; Hurley, Susan

    2011-01-01

    This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

  19. Helping Friends and Family

    MedlinePlus

    ... chapter Join our online community Helping Friends and Family Part of living well with Alzheimer’s is adjusting to your “new normal” and helping family and friends do the same. Knowing what to ...

  20. [Focus: Family Communication].

    ERIC Educational Resources Information Center

    Barnes, Richard E., Ed.

    1977-01-01

    This issue of the "Journal of the Wisconsin Communication Association" focuses on family communication and contains the following articles: "Marital Typologies: An Alternative Approach to the Study of Communication in Enduring Relations" by Mary Anne Fitzpatrick, "Intimate Communication and the Family" by Marilyn D. LaCourt, and "A Study in…

  1. The FGF family: biology, pathophysiology and therapy

    PubMed Central

    Beenken, Andrew; Mohammadi, Moosa

    2013-01-01

    The family of fibroblast growth factors (FGFs) regulates a plethora of developmental processes, including brain patterning, branching morphogenesis and limb development. Several mitogenic, cytoprotective and angiogenic therapeutic applications of FGFs are already being explored, and the recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in bile acid, glucose and phosphate homeostasis has sparked renewed interest in the pharmacological potential of this family. This Review discusses traditional applications of recombinant FGFs and small-molecule FGF receptor kinase inhibitors in the treatment of cancer and cardiovascular disease and their emerging potential in the treatment of metabolic syndrome and hypophosphataemic diseases. PMID:19247306

  2. Small Business Management Volume IV: Final Report. An Adult Education Program. Development, Demonstration and Evaluation of Management Education Programs for Small Business Entrepreneurs, Including Minorities.

    ERIC Educational Resources Information Center

    Persons, Edgar A.; Swanson, Gordon I.

    The purpose of the small business management program is to help families improve the effectiveness of their business operation and enable them to reach family and business goals. Similar to a successful program in farm management education operational in Minnesota since 1952, the program includes classroom instruction, small group instruction,…

  3. Welfare and the family size decision of low-income, two-parent families.

    PubMed

    Gensler, H

    1997-10-01

    This study determines the increase in family size given an increase in the per child welfare benefit for a family with children in the US. The family size decision was modeled as a discrete choice decision. Data were obtained from the 1980-91 March Current Population Surveys of the US Census Bureau on 13,516 low-income, nonmilitary, non-farm, two-parent families with at least one dependent child. Low income was any amount under twice the official poverty level. Parents were limited to ages 18-40 years. Alaska and Hawaii were excluded. The data sets for 1979-90 were pooled. The sample included 10% Blacks and 27% receiving some amount of welfare. Average ages were 28.9 years for mothers and 30.8 years for fathers. The average number of children was 2.43. Findings from the ordered probit model indicate that education had a negative impact on family size, and age and race had positive impacts. Wages did not have a significant effect. The state unemployment rate and the average state income had negative effects. Unearned income had a small but significant effect on family size. The marginal welfare benefit had a positive impact. Findings reinforce the wealth hypothesis, that wealthier societies have smaller family sizes. Family size declines with increases in wages and education, which reflect increases in opportunity costs for time. Family size increases with age, as rearing children is labor-intensive. Family size increases with unearned income and welfare benefits that make childbearing affordable. It is argued that poor people in developed societies behave more consistently like poor people in developing countries. A 100% increase in the per child welfare benefit resulted in a 2% increase in the number of children. The policy implication is that a considerable increase in welfare benefits will have only trivial behavioral impacts for the poor on family size decisions.

  4. Family Reconstruction: The Family within-a Group Experience.

    ERIC Educational Resources Information Center

    Satir, Virginia; And Others

    1988-01-01

    Presents Virginia Satir's Family Reconstruction, a group therapy experience that blends and extends her 1982 process therapy and 1983 conjoint family therapy approaches. Describes the family reconstruction process, the review of family reconstruction data in the pregroup interview, the family reconstruction process in the counseling group, and the…

  5. 75 FR 17946 - Family Report, MTW Family Report

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... URBAN DEVELOPMENT Family Report, MTW Family Report AGENCY: Office of the Chief Information Officer, HUD... understand demographic, family profile, income, and housing information for participants in the Public... Following Information Title of Proposal: Family Report, MTW Family Report. OMB Approval Number:...

  6. THE SCHULHOF FAMILY: SOLVING THE AGE PUZZLE

    SciTech Connect

    Vokrouhlický, David; Ďurech, Josef; Pravec, Petr; Kušnirák, Peter; Hornoch, Kamil; Vraštil, Jan; Krugly, Yurij N.; Inasaridze, Raguli Ya.; Ayvasian, Vova; Zhuzhunadze, Vasili; Pray, Donald; Husárik, Marek; Pollock, Joseph T.; Nesvorný, David

    2016-03-15

    The Schulhof family, a tight cluster of small asteroids around the central main belt body (2384) Schulhof, belongs to a so far rare class of very young families (estimated ages less than 1 Myr). Characterization of these asteroid clusters may provide important insights into the physics of the catastrophic disruption of their parent body. The case of the Schulhof family has been up to now complicated by the existence of two proposed epochs of its origin. In this paper, we first use our own photometric observations, as well as archival data, to determine the rotation rate and spin axis orientation of the largest fragment (2384) Schulhof. Our data also allow us to better constrain the absolute magnitude of this asteroid, and thus also improve the determination of its geometric albedo. Next, using the up-to-date catalog of asteroid orbits, we perform a new search of smaller members in the Schulhof family, increasing their number by 50%. Finally, the available data are used to access Schulhof's family age anew. We now find that the younger of the previously proposed two ages of this family is not correct, resulting from a large orbital uncertainty of single-opposition members. Our new runs reveal a single age solution of about 800 kyr with a realistic uncertainty of 200 kyr.

  7. HALF-BROTHERS IN THE SCHULHOF FAMILY?

    SciTech Connect

    Vokrouhlicky, David; Nesvorny, David E-mail: davidn@boulder.swri.edu

    2011-07-15

    Disruptive collisions in the asteroid belt produced groups of fragments known as the asteroid families. The studies of identified asteroid families help us to better understand issues related to impact physics, space weathering, asteroid interior, and collisional evolution of the main belt. Here, we analyze a family near the central main belt asteroid (2384) Schulhof. We show that the previously found group of objects around (81337) 2000 GP36 is actually a sub-cluster in the larger Schulhof family. Using backward integrations we demonstrate that the orbits of sub-cluster asteroids converge to that of (2384) Schulhof at 780 {+-} 100 kyr ago, suggesting that the breakup event happened very recently. Interestingly, a similar analysis of the two newly discovered members of the Schulhof family may indicate a second event {approx}< 100 kyr ago (e.g., secondary collision, fission, satellite instability). If confirmed, the formation history of the Schulhof family would suggest that small asteroids may have very colorful lifetimes. Additional astrometric observations of the two new member asteroids will be needed to improve their present orbit and better constrain their past histories.

  8. Five Weekend National Family Medicine Fellowship

    PubMed Central

    Talbot, Yves; Batty, Helen; Rosser, Walter W.

    1997-01-01

    PROBLEM ADDRESSED Many faculty development programs are thought time-consuming and inaccessible to academic family physicians or physicians wanting to move into academic positions. This is largely due to difficulty in leaving their practices for extended periods. Canadian family medicine needs trained leaders who can work in teams and are well grounded in the principles of their discipline as they relate to education, management, research, and policy making. OBJECTIVE OF PROGRAM To develop a team of leaders in family medicine. MAIN COMPONENTS OF PROGRAM The Five Weekend National Family Medicine Fellowship Program focuses on the essentials of education, management, communication, critical appraisal skills, and the principles of family medicine to develop leadership and team-building skills for faculty and community-based family physicians entering academic careers. This unique 1-year program combines intensive weekend seminars with small-group projects between weekends. It emphasizes a broader set of skills than just teaching, has regional representation, and focuses on leadership and teamwork using a time-efficient format. CONCLUSION The program has graduated 34 Fellows over the last 3 years. More than 90% of the 35 projects developed through course work have been presented in national or provincial peer-reviewed settings. Quantitative ratings of program structure, course content, and course outcomes have been positive. PMID:9426934

  9. Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy.

    PubMed

    Compton, Alison G; Albrecht, Douglas E; Seto, Jane T; Cooper, Sandra T; Ilkovski, Biljana; Jones, Kristi J; Challis, Daniel; Mowat, David; Ranscht, Barbara; Bahlo, Melanie; Froehner, Stanley C; North, Kathryn N

    2008-12-01

    We have previously reported a group of patients with congenital onset weakness associated with a deficiency of members of the syntrophin-alpha-dystrobrevin subcomplex and have demonstrated that loss of syntrophin and dystrobrevin from the sarcolemma of skeletal muscle can also be associated with denervation. Here, we have further studied four individuals from a consanguineous Egyptian family with a lethal congenital myopathy inherited in an autosomal-recessive fashion and characterized by a secondary loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma, central nervous system involvement, and fetal akinesia. We performed homozygosity mapping and candidate gene analysis and identified a mutation that segregates with disease within CNTN1, the gene encoding for the neural immunoglobulin family adhesion molecule, contactin-1. Contactin-1 transcripts were markedly decreased on gene-expression arrays of muscle from affected family members compared to controls. We demonstrate that contactin-1 is expressed at the neuromuscular junction (NMJ) in mice and man in addition to the previously documented expression in the central and peripheral nervous system. In patients with secondary dystroglycanopathies, we show that contactin-1 is abnormally localized to the sarcolemma instead of exclusively at the NMJ. The cntn1 null mouse presents with ataxia, progressive muscle weakness, and postnatal lethality, similar to the affected members in this family. We propose that loss of contactin-1 from the NMJ impairs communication or adhesion between nerve and muscle resulting in the severe myopathic phenotype. This disorder is part of the continuum in the clinical spectrum of congenital myopathies and congenital myasthenic syndromes.

  10. A family quarrel? "Developmentalism" or family planning.

    PubMed

    Carder, M

    1974-01-01

    The switch in emphasis in population policies from family planning to the development of socioeconomic policies that would encourage smaller families--summed up in the word "developmentalism"--is charted from a 1967 paper by Kinsley Davis to its culmination at the 1974 World Population Conference, when even as staunch a supporter of family planning as John D. Rockefeller came out in support of placing population policy in the context of economic and social development. The real question is, however: To what extent does developmentalism represent a true shift in policy and how much is simply a more sophisticated rhetoric designed to deflect the growing opposition to population control? On the one hand, the endorsement by a man of Rockefeller's stature indicates a significant change. On the other, the changes which the implementation of developmentalism would entail seem irreconcilable with the present political and economic structures of underdeveloped nations and of relations between them and the more developed countries. Further, developmentalism is neither as progressive as its advocates suggest, nor as threatening as its opponents cry. It is, in fact, a prescription for enhancing the effectiveness of family planning through a form of social engineering from the top; its details--more aid, investment, and trade--would involve an expanded Western role in the Third World. It is even suggested that developmentalism might be a cover for the creation of a more stratified society, where marginal members are restricted to their own quarters in an effort to secure political stability and economic growth. In the end, developmentalism might be shortlived, as pressure to step up birth control programs is felt from many quarters.

  11. Meeting information needs of families of critical care patients.

    PubMed

    Barbret, L C; Westphal, C G; Daly, G A

    1997-01-01

    Families of patients in critical care experience extreme anxiety and frustration while awaiting their loved ones' recovery or stabilization. To study the hypothesis that meeting families' informational needs can reduce their anxiety and help them cope with the initial crisis, a small task force at a Midwest acute care facility, using a CQI approach, studied possible solutions. Initial findings showed low satisfaction for families of critically ill patients with the present system of imparting information to them. After initiation of a storyboard to present information by the critical care team, families reported increased satisfaction and greater knowledge recall.

  12. Familial heterotaxia: What is the inheritance in this family?

    SciTech Connect

    Delatycki, M.B.; Sheffield, L.J.

    1997-04-14

    Recently, Alonso and colleagues reported on a number of cases of autosomal dominant heterotaxia in the American Journal of Medical Genetics. We would like to report a case of familial heterotaxia whose inheritance is unclear. II-2 and II-3 are sisters married to men who are related neither to themselves nor to each other. III-1 was diagnosed on antenatal ultrasonography as having complex congenital heart disease. Foetal blood sampling was carried out and was normal (46,XX). Postnatally she was found to have a complete atrioventricular septal defect, separate apical VSD, small left ventricle, interrupted inferior vena cava, hypoplastic aortic arch, and aortic coarctation. The child developed necrotising enterocolitis on day 2 and died at age 11 days. Autopsy confirmed these findings; the abdominal organs were all in their normal sites with a single spleen of normal size. 6 refs., 1 fig.

  13. [Family oriented nursing care].

    PubMed

    Lima-Rodríguez, Joaquin Salvador; Lima-Serrano, Marta; Sáez-Bueno, Africa

    2009-01-01

    Nursing has experienced an important methodological development, in which it gives priority to the individual, although at a socioeconomic level a marked interest is seen in the health care of the family unit and the NANDA (North American Nursing Diagnosis Association), NIC (Nursing Interventions Classification) and NOC (Nursing Outcomes Classification) nursing guidelines, using diagnoses, criteria of results and interventions orientated towards this aim. We consider to the family as an opened system consisted of human elements, with a common history, which they form a functional unit been ruled by own procedure. In this paper we look at those aspects that must be taken into account in nursing assessment of families from a systemic perspective, including some tools for data collection and analysis of information. In addition, we identify specific areas of intervention. We believe that the family must be studied from a nursing care point of view with its own characteristics as opposed to those possessed individually by each of its members. We also believe that, when assessment is centred on the Henderson unaided activities study or the Gordon functional health patterns, they are not useful in assessing the family unit. This work offers an assessment method centred on the family unit, which helps to identify the nursing diagnoses applicable to it. Our proposal, which has been successfully used by nursing students over the last few years, hopes to contribute to quality clinical practice with a tool orientated towards the family.

  14. Families Get Involved! Learning Partners.

    ERIC Educational Resources Information Center

    Office of Educational Research and Improvement (ED), Washington, DC. Media and Information Services.

    Noting that families who are involved in their children's education make a difference in their child's performance, this two-page information sheet encourages families to get involved by listing the benefits of family involvement on one side and the ways adult family members can help in the school on the other. As a result of family participation:…

  15. Family Centered Maternity Care

    PubMed Central

    Enkin, Murray W.

    1973-01-01

    Current practices of obstetrical care tend to hinder rather than facilitate family development and maturation. A program of family centred maternity care is described. Husbands are invited to prenatal visits, and are involved in intensive preparation for labor and delivery. Their presence and active participation in labor, delivery, and postpartum course are encouraged. This, along with a rooming-in policy for the baby, and the utilization of the postpartum period for an intensive training in parenthood, appears to produce a safe and satisfying obstetrical experience for the family. PMID:20468914

  16. Men and family planning in Portugal.

    PubMed

    Vicente, A

    1993-10-01

    Although family planning services in Portugal are open to everybody, male and female, and they are free of charge, it is mostly women who are using the services, since family planning services have integrated maternal health care. Between 1978 and 1981, the Commission for the Portuguese Commission for Equality and Women's Rights implemented a family planning information, education, and communication project under technical and financial aid by the United Nations Population Fund. During a training course for a group of 12 women, which took place in the small town Vialonga near Lisbon in 1992, all women said that their husbands did not play any role in family planning. The choice of the method was their sole responsibility. In 1988, data were gathered by the General Direction of Primary Health Care from the local health services. 17.6% of women used the pill, and 28% practiced coitus interruptus. Condom use amounted to 5.7%. Other methods were the IUD (7.3%), natural methods (3.6%), spermicides (2.6%), the diaphragm (0.3%), and sterilization (female 3.6%; male 0.3%). In 1992, the Commission published a study on family planning, involving 638 men and 882 women, which concluded that the responsibility for family planning was no longer exclusively with women and that young, single people were in favor of family planning information sessions. The Portuguese Constitution states that the state shall promote a wider knowledge of family planning methods and responsible parenthood. The Health Secretary of State ordered the integration of family planning into the National Health Service in 1976. A 1984 law, Sex Education and Family Planning, and a 1985 Government Order constitute the legal framework for the practice of family planning. The Commission for Equality and Women's Rights has been implementing information, education, and communication activities since 1976. One of the members of the Consultative Council is the Association for Family Planning, which has also been

  17. The case of the missing Ceres family

    NASA Astrophysics Data System (ADS)

    Rivkin, A.; Asphaug, E.; Bottke, W.

    2014-07-01

    Most of the largest asteroids in the main belt are associated with an impact-generated dynamical family. The Vesta family dominates the inner asteroid belt with its numbers [1,2], and was a critical piece of evidence in tying the HED meteorites to Vesta. In addition to Vesta (the third-largest asteroid), Pallas (the second-largest asteroid), Hygiea (the fourth-largest asteroid), and the largest S-class asteroid, (15) Eunomia, all have dynamical families [3--6]. In total, ten of the 14 known 250+ km bodies in the past or present asteroid belt are associated with dynamical families, either of the smaller ''cratering'' type, dominated by a major body and relatively small fragments, or large disruptions that indicate gravity-dominated catastrophic events. It is curious, then, that the very largest body in the asteroid belt, Ceres, is missing from this list of parents. Ceres is unassociated with any sort of family at all as far as we know [4]. This alone is perhaps not sufficient to draw any conclusion, but motivates us towards the considerations we make here. We will use relevant published works to demonstrate that Ceres' collisional history is very likely to include large enough impacts to create a family [8--10], that a Ceres family would be found if extant [2], and that a Ceres family would not be easily erased once created if it is like the rocky bodies comprising ''typical'' asteroid families [7]. There is observational and model evidence that Ceres is a differentiated body, with an icy mantle atop a rocky core [11--13]. However, the surface of Ceres is too warm to maintain ice for significantly long periods of time (save very near the poles), and the retreat of ice does not effectively halt until it reaches a depth of rough order 100--1000 m (depending upon latitude and surface temperature) beneath an insulating lag deposit [14,15]. To first order, an icy Ceres family is subject to the same sublimation rates as Ceres itself. Can its members have simply sublimed

  18. Variable Myopathic Presentation in a Single Family with Novel Skeletal RYR1 Mutation

    PubMed Central

    Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

    2013-01-01

    We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca2+ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient’s muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies. PMID:23894444

  19. Variable myopathic presentation in a single family with novel skeletal RYR1 mutation.

    PubMed

    Attali, Ruben; Aharoni, Sharon; Treves, Susan; Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

    2013-01-01

    We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax = 3.86 at θ = 0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca(2+) stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient's muscle concomitant with a reduction of the DHPRα1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies.

  20. Thioredoxin Reductase 2 (TXNRD2) Mutation Associated With Familial Glucocorticoid Deficiency (FGD)

    PubMed Central

    Prasad, Rathi; Chan, Li F.; Hughes, Claire R.; Kaski, Juan P.; Kowalczyk, Julia C.; Savage, Martin O.; Peters, Catherine J.; Nathwani, Nisha; Clark, Adrian J. L.; Metherell, Louise A.

    2014-01-01

    Context: Classic ACTH resistance, due to disruption of ACTH signaling, accounts for the majority of cases of familial glucocorticoid deficiency (FGD). Recently FGD cases caused by mutations in the mitochondrial antioxidant, nicotinamide nucleotide transhydrogenase, have highlighted the importance of redox regulation in steroidogenesis. Objective: We hypothesized that other components of mitochondrial antioxidant systems would be good candidates in the etiology of FGD. Design: Whole-exome sequencing was performed on three related patients, and segregation of putative causal variants confirmed by Sanger sequencing of all family members. A TXNRD2-knockdown H295R cell line was created to investigate redox homeostasis. Setting: The study was conducted on patients from three pediatric centers in the United Kingdom. Patients: Seven individuals from a consanguineous Kashmiri kindred, six of whom presented with FGD between 0.1 and 10.8 years, participated in the study. Interventions: There were no interventions. Main Outcome Measure: Identification and functional interrogation of a novel homozygous mutation segregating with the disease trait were measured. Results: A stop gain mutation, p.Y447X in TXNRD2, encoding the mitochondrial selenoprotein thioredoxin reductase 2 (TXNRD2) was identified and segregated with disease in this extended kindred. RT-PCR and Western blotting revealed complete absence of TXNRD2 in patients homozygous for the mutation. TXNRD2 deficiency leads to impaired redox homeostasis in a human adrenocortical cell line. Conclusion: In contrast to the Txnrd2-knockout mouse model, in which embryonic lethality as a consequence of hematopoietic and cardiac defects is described, absence of TXNRD2 in humans leads to glucocorticoid deficiency. This is the first report of a homozygous mutation in any component of the thioredoxin antioxidant system leading to inherited disease in humans. PMID:24601690

  1. Autosomal dominant familial spastic paraplegia: Tight linkage to chromosome 15q

    SciTech Connect

    Fink, J.K.; Wu, C.T.B.; Jones, S.M.

    1994-09-01

    Familial spastic paraplegia (FSP) (MIM No.18260) constitutes a clinically and genetically diverse group of disorders that share the primary feature of progressive, severe, lower extremity spasticity. FSP is classified according to the mode of inheritance and whether progressive spasticity occurs in isolation ({open_quotes}uncomplicated FSP{close_quotes}) or with other neurologic abnormalities ({open_quotes}complicated FSP{close_quotes}), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, or deafness. Recently, autosomal dominant, uncomplicated FSP was shown to be genetically heterogeneous and tightly linked to a group of microsatellite markers on chromosome 14q in one large kindred. We examined 126 members of a non-consanguineous North American kindred of Irish descent. FSP was diagnosed in 31 living subjects who developed insidiously progressive gait disturbance between ages 12 and 35 years. Using genetic linkage analysis to microsatellite DNA polymorphisms, we showed that the FSP locus on chromosome 14q was exluded from linkage with the disorder in our family. Subsequently, we searched for genetic linkage between the disorder and microsatellite DNA polymorphisms spanning approximately 50% of the genome. We observed significantly positive, two-point maximum lod scores (Z) for markers on chromosome 15q: D15S128 (Z=9.70, {theta}=0.05), D15S165 (Z=3.30, {theta}=0.10), and UT511 (Z=3.86, {theta}=0.10). Our data clearly establishes that one locus for autosomal dominant, uncomplicated FSP is mapped to the pericentric region of chromosome 15q. Identifying genes responsible for chromosome 15q-linked and chromosome 14q-linked FSP will greatly advance our understanding of this condition and hopefully other inherited and degenerative brain and spinal cord disorders that are also characterized by axonal degeneration.

  2. Chemoprevention in familial adenomatous polyposis.

    PubMed

    Kim, Brian; Giardiello, Francis M

    2011-08-01

    Familial adenomatous polyposis (FAP) predictably leads to adenomas and eventual adenocarcinomas in the lower gastrointestinal tract and less frequently, the upper gastrointestinal tract. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas in the upper and lower gastrointestinal tract, as well as to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery with colectomy and ileorectal anastamosis (IRA). The nonsteroidal anti-inflammatory drug (NSAID) sulindac and selective cyclooxygenase-2 (COX-2) inhibitor celecoxib reduce polyposis of the retained rectum after colectomy with IRA. Reports of cardiovascular risks of some NSAIDs and selective COX-2 inhibitors have led to promising studies of lower doses in combination with ursodeoxycholic acid, statin, and difluoromethylornithine. Curcumin and eicosapentaenoic acid show efficacy in small clinical trials of FAP chemoprevention. This article will review the concept of chemoprevention and the current clinical literature in FAP chemoprevention.

  3. A Novel Mutation of LAMB2 in a Multi-Generational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome

    PubMed Central

    Mohney, Brian G.; Pulido, Jose S.; Lindor, Noralane M.; Hogan, Marie C.; Consugar, Mark B.; Peters, Justin; Pankratz, V. Shane; Nasr, Samih H.; Smith, Stephen J.; Gloor, James; Kubly, Vickie; Spencer, Dorothy; Nielson, Rebecca; Puffenberger, Erik G.; Strauss, Kevin A.; Morton, D. Holmes; Eldahdah, Lama; Harris, Peter C.

    2011-01-01

    Purpose To describe a novel laminin beta-2 (LAMB2) mutation associated with nephritic syndrome and severe retinal disease without microcoria in a large, multi-generational family with Pierson syndrome. Design Retrospective chart review and prospective family examination. Participants An extended consanguineous family of 52 members. Methods The eyes, urine, and serum DNA were evaluated in all family members after discovering 2 patients, both less than 10 years of age, with bilateral retinal detachments and concurrent renal dysfunction. Linkage analysis was performed in the 9 living affected individuals, 7 using the Illumina Human Hap370 Duo Bead Array and 2 using GeneChip 10K mapping arrays. Main Outcome Measures The prevalence and severity of ocular and kidney involvement and genetic findings. Results Eleven affected family members were identified (9 living), all manifesting chronic kidney disease and bilateral chrioretinal pigmentary changes, with or without retinal detachments, but without microcoria or neurodevelopmental deficits, segregating in an autosomal recessive pattern. The causative gene was localized to a 9Mb region on chromosome 3. Comprehensive gene sequencing revealed a novel LAMB2 variant (c. 440A>G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls. The mutation is located in a highly conserved site in the N-terminal domain VI of LAMB2. Conclusions This study describes a novel mutation of LAMB2 and further expands the spectrum of eye and renal manifestations associated with defects in the laminin beta-2 chain. PMID:21236492

  4. Family Treatment for Schizophrenia

    PubMed Central

    FALLOON, IAN R. H.; MCGILL, CHARISTINE W.; MATTHEWS, SUSAN M.; KEITH, SAMUEL J.; SCHOOLER, NINA R.

    1996-01-01

    The NIMH Treatment Strategies in Schizophrenia (TSS) collaborative study group investigated the efficacy of antisychotic drug maintenance strategies involving reduced medication exposure in interaction with applied and supportive family management for the long-term treatment of schizophrenia. Therapy was provided at five centers by 25 clinicians who did not participate in the development of the therapies. They were trained by two of the authors, I.R.H.F and C.W.M, in applied family management, a homebased treatment derived from the behavioral family therapy developed by them. Clinicians’ characteristics, selection, and training methods, as well as patient rehospitalization rates, are reported for the two family management conditions. The TSS study represents a bridge between the development of a novel therapy and its dissemination in general clinical practice. PMID:22700264

  5. The Family Training Concept

    ERIC Educational Resources Information Center

    Porter, Gwendolyn H.

    1974-01-01

    The author describes a program in which the families of migrant workers were educated, trained, and placed in permanent jobs. This program also provided health, counseling, and child care services. (RWP)

  6. General Dynamics Atlas family

    NASA Astrophysics Data System (ADS)

    Oates, James

    Developments concerning the Atlas family of launch vehicles over the last three or four years are summarized. Attention is given to the center of gravity, load factors, acoustics, pyroshock, low-frequency sinusoidal vibration, and high-frequency random vibration.

  7. Balancing Work & Family.

    ERIC Educational Resources Information Center

    Lee, Chris

    1991-01-01

    Describes the responses of some companies to increasing demands for family-work balance in terms of flexibility in working hours and leave policies, child care, and fringe benefits. Identifies some of the effects on the "bottom line." (SK)

  8. Familial calcific periarthritis.

    PubMed Central

    Hajiroussou, V J; Webley, M

    1983-01-01

    A family of 4 is described in which both children had calcific periarthritis affecting the shoulders, and the mother had radiological evidence of periarticular calcification near the left greater trochanter. PMID:6882045

  9. Children and Families: 1984?

    ERIC Educational Resources Information Center

    Bronfenbrenner, Urie

    1981-01-01

    In order to develop normally, children need emotional involvement and shared activities with one or more adult(s). Public policy in the United States, unlike that of most industrialized societies, is not supportive of family life. (Author/GC)

  10. Family troubles - resources

    MedlinePlus

    The following organizations are good resources for information on child abuse , incest, domestic violence, and family troubles: National Domestic Violence Hotline -- www.thehotline.org Prevent Child Abuse America -- ...

  11. Asbestos: Protect Your Family

    MedlinePlus

    ... Facebook Twitter Google+ Pinterest Contact Us Protect Your Family How to Identify Materials That May Contain Asbestos ... Improper removal may actually increase your and your family’s exposure to asbestos fibers. Top of Page Asbestos ...

  12. Small and Part-Time Farmers in the Southern Region.

    ERIC Educational Resources Information Center

    O'Sullivan, John M.

    2000-01-01

    The loss of small farms in the South was dramatic from 1987 to 1997, with family farming becoming an increasingly rare phenomenon. Small farms are important to the local economic base. They purchase inputs locally, keep the tax base low, and reduce the need for public services. Diversity among farm managers is increasing in the South, with greater…

  13. Wellness in Small Businesses. WBGH Worksite Wellness Series.

    ERIC Educational Resources Information Center

    Behrens, Ruth A.

    Increasing numbers of small businesses are providing wellness activities for their employees. By instituting wellness programs, small businesses can improve employee morale, engender a commitment from employees, enhance the feeling of "family" among employees, improve worker productivity, and contain health care costs. Wellness programs are…

  14. Genome assembly of bell pepper endornavirus from small RNA.

    PubMed

    Sela, Noa; Luria, Neta; Dombrovsky, Aviv

    2012-07-01

    The family Endornaviridae infects diverse hosts, including plants, fungi, and oomycetes. Here we report for the first time the assembly of bell pepper endornavirus by next-generation sequencing of viral small RNA. Such a population of small RNA indicates the activation of the viral immunity silencing machinery by this cryptic virus, which probably encodes a novel silencing suppressor.

  15. Small Business in America: The Year 2000 and Beyond.

    ERIC Educational Resources Information Center

    Institute for Enterprise Advancement, Washington, DC.

    Small businesses are meeting the challenges of a changing economy and leading the way in production and job creation. Small businesses especially will continue to benefit from demographic and societal shifts, in particular the emergence of the two-career family that fuels the service industry. Women and minority persons are the newest…

  16. The changing American family.

    PubMed

    Thornton, A; Freedman, D

    1983-10-01

    This Bulletin documents recent changes in American family patterns resulting both from longterm trends in urbanization, industrialization, and economic growth and the disruption of the Great Depression and World War 2, as well as changed attitudes toward marriage, parenthood, divorce, and the roles of women. Following a postwar boom in the 1950s and 1960s, marriage rates have now fallen to levels observed in the early 20th century. Since 1970, the number of unmarried couples living together has more than tripled to 1.9 million in 1983. The divorce rate has now stabilized after more than doubling since 1960, but at the current level, 1/2 of all recent marriages will end in divorce. Most divorced persons remarry fairly quickly, often creating complex families of "step-relatives." With 19% of households with minor children now headed by a women with no husband present, up to 1/2 of all children will live for sometime in a fatherless family before age 18. Over 1/2 of all married women, including 49% of married mothers of preschool children, now hold a paid job outside the home. Working wives boost a family's income by an average 40% but still are expected to shoulder most responsiblility for home and childcare. White women now in their 20s say they expect to have an average of 2 children, but are delaying childbearing to such an extent that 29% could end up childless. Most of the elderly live on their own but usually near children whom they see frequently. Despite changes in traditional family patterns, Americans consistently report that a happy marriage and good family are the most important aspects of life. And though most Americans now live with few or no family members, they maintain active contact with a large network of family.

  17. Familiality in brain tumors

    PubMed Central

    Blumenthal, Deborah T.; Cannon-Albright, Lisa A.

    2008-01-01

    Background: Familiality in brain tumors is not definitively substantiated. Methods: We used the Utah Population Data Base (UPDB), a genealogy representing the Utah pioneers and their descendants, record-linked to statewide cancer records, to describe the familial nature of primary brain cancer. We examined the familial clustering of primary brain tumors, including subgroups defined by histologic type and age at diagnosis. The UPDB includes 1,401 primary brain tumor cases defined as astrocytoma or glioblastoma, all with at least three generations of genealogy data. We tested the hypothesis of excess relatedness of brain tumor cases using the Genealogical Index of Familiality method. We estimated relative risks for brain tumors in relatives using rates of brain tumors estimated internally. Results: Significant excess relatedness was observed for astrocytomas and glioblastomas considered as a group (n = 1,401), for astrocytomas considered separately (n = 744), but not for glioblastomas considered separately (n = 658). Significantly increased risks to first- and second-degree relatives for astrocytomas were identified for relatives of astrocytomas considered separately. Significantly increased risks to first-degree relatives, but not second degree, were observed for astrocytoma and glioblastoma cases considered together, and for glioblastoma cases considered separately. Conclusions: This study provides strong evidence for a familial contribution to primary brain cancer risk. There is evidence that this familial aspect includes not only shared environment, but also a heritable component. Extended high-risk brain tumor pedigrees identified in the UPDB may provide the opportunity to identify predisposition genes responsible for familial brain tumors. GLOSSARY GBM = glioblastoma; GIF = Genealogical Index of Familiality; HGG = high-grade gliomas; ICD-O = International Classification of Disease–Oncology; LGG = low-grade gliomas; RR = relative risks; SEER = Surveillance

  18. Swedish Family Policy.

    ERIC Educational Resources Information Center

    Herrstrom, Staffan

    1986-01-01

    Family policy remains one of the leading issues of Swedish domestic politics. All parties are agreed that families with children must be given a better deal in the wake of the economic crisis. But how is this to be done and how quickly can it be achieved? Is the expansion of day nursery facilities to be speeded up, or are parents to be given a…

  19. Sexual Health Care in Family Medicine

    PubMed Central

    Cohen, Gerald; Cohen, May

    1985-01-01

    Although patients frequently present with sexual concerns, family doctors generally do not handle them well. Sexual issues may present in many ways: as specific concerns; as a component of non-sexual complaints or as a factor in relationship or marital problems. The family doctor must include sexual enquiry and counselling as part of overall health care, and in the management of illnesses. In order to be effective counsellors, physicians must examine their own attitudes, and become knowledgeable about sexuality and myths influencing sexual behavior, and skillful at interviewing and sexual history-taking. The family doctor can become adept at giving patients permission to discuss their sexuality, and at providing information and strategies to enhance sensual enjoyment and communication with partners. Small group training sessions incorporating discussion and role-playing effectively teach physicians skills and strategies in sexual counselling. PMID:21274058

  20. Family Over Rules? An Ethical Analysis of Allowing Families to Overrule Donation Intentions.

    PubMed

    Shaw, David; Georgieva, Denie; Haase, Bernadette; Gardiner, Dale; Lewis, Penney; Jansen, Nichon; Wind, Tineke; Samuel, Undine; McDonald, Maryon; Ploeg, Rutger

    2017-03-01

    Millions of people want to donate their organs after they die for transplantation, and many of them have registered their wish to do so or told their family and friends about their decision. For most of them, however, this wish is unlikely to be fulfilled, as only a small number of deaths (1% in the United Kingdom) occur in circumstances where the opportunity to donate organs is possible. Even for those who do die in the "right" way and have recorded their wishes or live in a jurisdiction with a "presumed consent" system, donation often does not go ahead because of another issue: their families refuse to allow donation to proceed. In some jurisdictions, the rate of "family overrule" is over 10%. In this article, we provide a systematic ethical analysis of the family overrule of donation of solid organs by deceased patients, and examine arguments both in favor of and against allowing relatives to "veto" the potential donor's intentions. First, we provide a brief review of the different consent systems in various European countries, and the ramifications for family overrule. Next, we describe and discuss the arguments in favor of permitting donation intentions to be overruled, and then the arguments against doing so. The "pro" arguments are: overrule minimises family distress and staff stress; families need to cooperate for donation to take place; families might have evidence regarding refusal; and failure to permit overrules could weaken trust in the donation system. The "con" arguments are: overrule violates the patient's wishes; the family is too distressed and will regret the decision; overruling harms other patients; and regulations prohibit overrule. We conclude with a general discussion and recommendations for dealing with families who wish to overrule donation. Overall, overrule should only rarely be permitted.