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Sample records for prolyl oligopeptidase family

  1. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Fajtová, P.; Štefanić, S.; Hradilek, M.; Dvořák, Jan; Vondrášek, J.; Jílková, A.; Ulrychová, L.; McKerrow, J.H.; Caffrey, C.R.; Mareš, M.; Horn, M.

    2015-01-01

    Roč. 9, č. 6 (2015), e0003827 ISSN 1935-2735 Institutional support: RVO:60077344 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.948, year: 2015

  2. Molecular dynamics study of prolyl oligopeptidase with inhibitor in binding cavity

    NARCIS (Netherlands)

    Kaszuba, K.; Róg, T.; St-Pierre, J.-F.; Männistö, P.T.; Karttunen, M.E.J.; Bunker, A.

    2009-01-01

    We used the crystal structure of prolyl oligopeptidase (POP) with bound Z-pro-prolinal (ZPP) inhibitor (Protein Data Bank (PDB) structure 1QFS) to perform an intensive molecular dynamics study of the POP-ZPP complex. We performed 100 ns of simulation with the hemiacetal bond, through which the ZPP

  3. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Fajtová, Pavla; Štefanic, S.; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael; Horn, Martin

    2015-01-01

    Roč. 9, č. 6 (2015), e0003827/1-e0003827/24 ISSN 1935-2735 R&D Projects: GA ČR(CZ) GAP302/11/1481; GA MŠk LO1302 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : Schistosoma mansoni * schistosomiasis * prolyl oligopeptidase * blood fluke Subject RIV: CE - Biochemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 3.948, year: 2015 http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003827

  4. Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.

    Science.gov (United States)

    Nagatsu, Toshiharu

    2017-06-01

    Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.

  5. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  6. Inhibitory effect of verbascoside isolated from Buddleja brasiliensis Jacq. ex Spreng on prolyl oligopeptidase activity.

    Science.gov (United States)

    Filho, Augusto G; Morel, Ademir F; Adolpho, Luciana; Ilha, Vinícius; Giralt, Ernest; Tarragó, Teresa; Dalcol, Ionara I

    2012-10-01

    The phenylpropanoid glycoside verbascoside [2-(3,4-dihydroxyphenylethyl)-1-O-α-L-rhamnopyranosyl-(1→3)-β-D-(4-O-caffeyl)-glucopyranoside] (1) has been isolated as the main constituent of the crude extract of Buddleja brasiliensis Jacq. ex Spreng from Southern Brazil. The crude extract, main fractions and the compound 1 were evaluated for inhibition of the enzymes acetylcholinesterase (AChE), dipeptidyl peptidase-IV (DPP-IV) and prolyl oligopeptidase (POP). Compound 1 showed weak activity against DPP-IV with an IC(50) > 150 µM and was inactive against AChE, with a pMIQ determined by bioautography of 9.6. In contrast, 1 displayed significant inhibition of POP in a dose-dependent manner with an IC(50) value of 1.3 ± 0.2 µM, similar to the positive control, baicalin, with a POP IC(50) of 12 ± 3 µM. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Effects of a Natural Prolyl Oligopeptidase Inhibitor, Rosmarinic Acid, on Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Miaomiao Wei

    2012-03-01

    Full Text Available Rosmarinic acid (RA, a polyphenolic phytochemical, is a natural prolyl oligopeptidase inhibitor. In the present study, we found that RA exerted potent anti-inflammatory effects in in vivo models of acute lung injury (ALI induced by lipopolysaccharide (LPS. Mice were pretreated with RA one hour before challenge with a dose of 0.5 mg/kg LPS. Twenty-four hours after LPS was given, bronchoalveolar lavage fluid (BALF was obtained to measure pro-inflammatory mediator and total cell counts. RA significantly decreased the production of LPS-induced TNF-a, IL-6, and IL-1β compare with the LPS group. When pretreated with RA (5, 10, or 20 mg/kg the lung wet-to-dry weight (W/D ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF were decreased significantly. Furthermore, RA may enhance oxidase dimutase (SOD activity during the inflammatory response to LPS-induced ALI. And we further demonstrated that RA exerts anti-inflammation effect in vivo models of ALI through suppresses ERK/MAPK signaling in a dose dependent manner. These studies have important implications for RA administration as a potential treatment for ALI.

  8. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  9. Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80 as a novel immunogen for Chagas disease vaccine.

    Directory of Open Access Journals (Sweden)

    Augusto E Bivona

    2018-03-01

    Full Text Available Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80 as a new antigen for vaccine development against Chagas disease.In a murine model, we analyzed the immune response triggered by different immunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHC-I peptide. Immunization protocols conferred protection against a T. cruzi lethal challenge. Immunized groups showed a decreased parasitemia and higher survival rate compared with non-immunized control mice. Moreover, during the chronic phase of the infection, immunized mice presented: lower levels of myopathy-linked enzymes, parasite burden, electrocardiographic disorders and inflammatory cells.Considering that

  10. Structural and Biochemical Characterization of the Human Cyclophilin Family of Peptidyl-Prolyl Isomerases

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Tara L.; Walker, John R.; Campagna-Slater, Valérie; Finerty, Jr., Patrick J.; Paramanathan, Ragika; Bernstein, Galina; MacKenzie, Farrell; Tempel, Wolfram; Ouyang, Hui; Lee, Wen Hwa; Eisenmesser, Elan Z.; Dhe-Paganon, Sirano (Toronto); (Colorado)

    2011-12-14

    Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known for being the target of the immunosuppressive drug cyclosporin, used to combat organ transplant rejection. There is great interest in both the substrate specificity of these enzymes and the design of isoform-selective ligands for them. However, the dearth of available data for individual family members inhibits attempts to design drug specificity; additionally, in order to define physiological functions for the cyclophilins, definitive isoform characterization is required. In the current study, enzymatic activity was assayed for 15 of the 17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold was tested. In order to rationalize the observed isoform diversity, the high-resolution crystallographic structures of seven cyclophilin domains were determined. These models, combined with seven previously solved cyclophilin isoforms, provide the basis for a family-wide structure:function analysis. Detailed structural analysis of the human cyclophilin isomerase explains why cyclophilin activity against short peptides is correlated with an ability to ligate cyclosporin and why certain isoforms are not competent for either activity. In addition, we find that regions of the isomerase domain outside the proline-binding surface impart isoform specificity for both in vivo substrates and drug design. We hypothesize that there is a well-defined molecular surface corresponding to the substrate-binding S2 position that is a site of diversity in the cyclophilin family. Computational simulations of substrate binding in this region support our observations. Our data indicate that unique isoform determinants exist that may be exploited for development of selective ligands and suggest that the currently available small-molecule and peptide-based ligands for this class of enzyme are insufficient for isoform

  11. Scientific opinion on the safety of proline-specific oligopeptidase as a novel food pursuant to Regulation (EC) No 258/97

    DEFF Research Database (Denmark)

    Poulsen, Morten

    2017-01-01

    and of the Council, taking into account the comments and objections of a scientific nature raised by Member States. The novel food is an enzyme preparation of prolyl-oligopeptidase produced with a genetically modified Aspergillus niger self clone strain. The target population is the general adult population......Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on proline-specific oligopeptidase (Tolerase® G) as a novel food ingredient submitted pursuant to Regulation (EC) No 258/97 of the European Parliament...

  12. Induced-fit Mechanism for Prolyl Endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Li, Min; Chen, Changqing; Davies, David R.; Chiu, Thang K. (NIH); (LSU); (Chinese Aca. Sci.)

    2010-11-15

    Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the {beta}-propeller and {alpha}/{beta}-hydrolase domains; addition of substrate to preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases.

  13. cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue

    Energy Technology Data Exchange (ETDEWEB)

    Rennex, D.; Hemmings, B.A.; Hofsteenge, J.; Stone, S.R. (Friedrich Miescher-Institut, Basel (Switzerland))

    1991-02-26

    Prolyl endopeptidase is a cytoplasmic serine protease. The enzyme was purified from porcine kidney, and oligonucleotides based on peptide sequences from this protein were used to isolate a cDNA clone from a porcine brain library. This clone contained the complete coding sequence of prolyl endopeptidase and encoded a polypeptide with a molecular mass of 80751 Da. The deduced amino acid sequence of prolyl endopeptidase showed no sequence homology with other known serine proteases. ({sup 3}H)Diisopropyl fluorophosphate was used to identify the active-site serine of prolyl endopeptidase. One labeled peptide was isolated and sequenced. The sequence surrounding the active-site serine was Asn-Gly-Gly-Ser-Asn-Gly-Gly. This sequence is different from the active-site sequences of other known serine proteases. This difference and the lack of overall homology with the known families of serine proteases suggest that prolyl endopeptidase represents a new type of serine protease.

  14. Prolyl hydroxylation in elastin is not random

    DEFF Research Database (Denmark)

    Schmelzer, Christian E H; Nagel, Marcus B M; Dziomba, Szymon

    2016-01-01

    BACKGROUND: This study aimed to investigate the prolyl and lysine hydroxylation in elastin from different species and tissues. METHODS: Enzymatic digests of elastin samples from human, cattle, pig and chicken were analyzed using mass spectrometry and bioinformatics tools. RESULTS: It was confirmed...... at the protein level that elastin does not contain hydroxylated lysine residues regardless of the species. In contrast, prolyl hydroxylation sites were identified in all elastin samples. Moreover, the analysis of the residues adjacent to prolines allowed the determination of the substrate site preferences...... of prolyl 4-hydroxylase. It was found that elastins from all analyzed species contain hydroxyproline and that at least 20%-24% of all proline residues were partially hydroxylated. Determination of the hydroxylation degrees of specific proline residues revealed that prolyl hydroxylation depends on both...

  15. Prolyl hydroxylation in elastin is not random.

    Science.gov (United States)

    Schmelzer, Christian E H; Nagel, Marcus B M; Dziomba, Szymon; Merkher, Yulia; Sivan, Sarit S; Heinz, Andrea

    2016-10-01

    This study aimed to investigate the prolyl and lysine hydroxylation in elastin from different species and tissues. Enzymatic digests of elastin samples from human, cattle, pig and chicken were analyzed using mass spectrometry and bioinformatics tools. It was confirmed at the protein level that elastin does not contain hydroxylated lysine residues regardless of the species. In contrast, prolyl hydroxylation sites were identified in all elastin samples. Moreover, the analysis of the residues adjacent to prolines allowed the determination of the substrate site preferences of prolyl 4-hydroxylase. It was found that elastins from all analyzed species contain hydroxyproline and that at least 20%-24% of all proline residues were partially hydroxylated. Determination of the hydroxylation degrees of specific proline residues revealed that prolyl hydroxylation depends on both the species and the tissue, however, is independent of age. The fact that the highest hydroxylation degrees of proline residues were found for elastin from the intervertebral disc and knowledge of elastin arrangement in this tissue suggest that hydroxylation plays a biomechanical role. Interestingly, a proline-rich domain of tropoelastin (domain 24), which contains several repeats of bioactive motifs, does not show any hydroxyproline residues in the mammals studied. The results show that prolyl hydroxylation is not a coincidental feature and may contribute to the adaptation of the properties of elastin to meet the functional requirements of different tissues. The study for the first time shows that prolyl hydroxylation is highly regulated in elastin. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Redox modulation of thimet oligopeptidase activity by hydrogen peroxide.

    Science.gov (United States)

    Icimoto, Marcelo Y; Ferreira, Juliana C; Yokomizo, César H; Bim, Larissa V; Marem, Alyne; Gilio, Joyce M; Oliveira, Vitor; Nantes, Iseli L

    2017-07-01

    Thimet oligopeptidase (EC 3.4.24.15, TOP) is a cytosolic mammalian zinc protease that can process a diversity of bioactive peptides. TOP has been pointed out as one of the main postproteasomal enzymes that process peptide antigens in the MHC class I presentation route. In the present study, we describe a fine regulation of TOP activity by hydrogen peroxide (H 2 O 2 ). Cells from a human embryonic kidney cell line (HEK293) underwent an ischemia/reoxygenation-like condition known to increase H 2 O 2 production. Immediately after reoxygenation, HEK293 cells exhibited a 32% increase in TOP activity, but no TOP activity was observed 2 h after reoxygenation. In another model, recombinant rat TOP (rTOP) was challenged by H 2 O 2 produced by rat liver mitoplasts (RLMt) alone, and in combination with antimycin A, succinate, and antimycin A plus succinate. In these conditions, rTOP activity increased 17, 30, 32 and 38%, respectively. Determination of H 2 O 2 concentration generated in reoxygenated cells and mitoplasts suggested a possible modulation of rTOP activity dependent on the concentration of H 2 O 2 . The measure of pure rTOP activity as a function of H 2 O 2 concentration corroborated this hypothesis. The data fitted to an asymmetrical bell-shaped curve in which the optimal activating H 2 O 2 concentration was 1.2 nM, and the maximal inhibition (75% about the control) was 1 μm. Contrary to the oxidation produced by aging associated with enzyme oligomerization and inhibition, H 2 O 2 oxidation produced sulfenic acid and maintained rTOP in the monomeric form. Consistent with the involvement of rTOP in a signaling redox cascade, the H 2 O 2 -oxidized rTOP reacted with dimeric thioredoxin-1 (TRx-1) and remained covalently bound to one subunit of TRx-1.

  17. Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships.

    Science.gov (United States)

    Mantovani, Fiamma; Zannini, Alessandro; Rustighi, Alessandra; Del Sal, Giannino

    2015-10-01

    The p53 protein family, comprising p53, p63 and p73, is primarily involved in preserving genome integrity and preventing tumor onset, and also affects a range of physiological processes. Signal-dependent modifications of its members and of other pathway components provide cells with a sophisticated code to transduce a variety of stress signaling into appropriate responses. TP53 mutations are highly frequent in cancer and lead to the expression of mutant p53 proteins that are endowed with oncogenic activities and sensitive to stress signaling. p53 family proteins have unique structural and functional plasticity, and here we discuss the relevance of prolyl-isomerization to actively shape these features. The anti-proliferative functions of the p53 family are carefully activated upon severe stress and this involves the interaction with prolyl-isomerases. In particular, stress-induced stabilization of p53, activation of its transcriptional control over arrest- and cell death-related target genes and of its mitochondrial apoptotic function, as well as certain p63 and p73 functions, all require phosphorylation of specific S/T-P motifs and their subsequent isomerization by the prolyl-isomerase Pin1. While these functions of p53 counteract tumorigenesis, under some circumstances their activation by prolyl-isomerases may have negative repercussions (e.g. tissue damage induced by anticancer therapies and ischemia-reperfusion, neurodegeneration). Moreover, elevated Pin1 levels in tumor cells may transduce deregulated phosphorylation signaling into activation of mutant p53 oncogenic functions. The complex repertoire of biological outcomes induced by p53 finds mechanistic explanations, at least in part, in the association between prolyl-isomerases and the p53 pathway. This article is part of a Special Issue entitled Proline-directed foldases: Cell signaling catalysts and drug targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Characterisation of Aspergillus niger prolyl aminopeptidase

    NARCIS (Netherlands)

    Basten, E.J.W.; Moers, A.P.H.A.; Ooyen, van A.J.J.; Schaap, P.J.

    2005-01-01

    We have cloned a gene (papA) that encodes a prolyl aminopeptidase from Aspergillus niger. Homologous genes are present in the genomes of the Eurotiales A. nidulans, A. fumigatus and Talaromyces emersonii, but the gene is not present in the genome of the yeast Saccharomyces cerevisiae. Cell extracts

  19. Oligopeptidase B from Serratia proteamaculans. III. Inhibition analysis. Specific interactions with metalloproteinase inhibitors.

    Science.gov (United States)

    Mikhailova, A G; Khairullin, R F; Kolomijtseva, G Ya; Rumsh, L D

    2012-03-01

    Inhibition of the novel oligopeptidase B from Serratia proteamaculans (PSP) by basic pancreatic trypsin inhibitor, Zn2+ ions, and o- and m-phenanthroline was investigated. A pronounced effect of calcium ions on the interaction of PSP with inhibitors was demonstrated. Inversion voltamperometry and atomic absorption spectrometry revealed no zinc ions in the PSP molecule. Hydrophobic nature of the enzyme inhibition by o- and m-phenanthroline was established.

  20. Heterologous Expression, Purification and Characterization of an Oligopeptidase A from the Pathogen Leptospira interrogans.

    Science.gov (United States)

    Anu, Prasannan V; Madanan, Madathiparambil G; Nair, Ananthakrishnan J; Nair, Gangaprasad A; Nair, Govinda Pillai M; Sudhakaran, Perumana R; Satheeshkumar, Padikara K

    2018-04-01

    Oligopeptidases are enzymes involved in the degradation of short peptides (generally less than 30 amino acids in size) which help pathogens evade the host defence mechanisms. Leptospira is a zoonotic pathogen and causes leptospirosis in mammals. Proteome analysis of Leptospira revealed the presence of oligopeptidase A (OpdA) among other membrane proteins. To study the role of oligopeptidase in leptospirosis, the OpdA of L. interrogans was cloned and expressed in Escherichia coli with a histidine tag (His-tag). The protein showed maximum expression at 37 °C with 0.5 mM of IPTG after 2 h of induction. Recombinant OpdA protein was purified to homogeneity using Ni-affinity chromatography. The purified OpdA showed more than 80% inhibition with a serine protease inhibitor but the activity was reduced to 30% with the cysteine protease inhibitor. The peptidase activity was increased significantly in the presence of Zn 2+ at a neutral pH. Inhibitor assay indicate the presence of more than one active sites for peptidase activity as reported with the OpdA of E. coli and Salmonella. Over-expression of OpdA in E. coli BL21 (DE3) did not cause any negative effects on normal cell growth and viability. The role of OpdA as virulence factor in Leptospira and its potential as a therapeutic and diagnostic target in leptospirosis is yet to be identified.

  1. Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.

    Science.gov (United States)

    Aprelikova, Olga; Chandramouli, Gadisetti V R; Wood, Matthew; Vasselli, James R; Riss, Joseph; Maranchie, Jodi K; Linehan, W Marston; Barrett, J Carl

    2004-06-01

    Hypoxia and induction of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) is a hallmark of many tumors. Under normal oxygen tension HIF-alpha subunits are rapidly degraded through prolyl hydroxylase dependent interaction with the von Hippel-Lindau (VHL) tumor suppressor protein, a component of E3 ubuiquitin ligase complex. Using microarray analysis of VHL mutated and re-introduced cells, we found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with known HIF target genes, while the other two family members (PHD1 and 2) did not respond to VHL. We further tested the regulation of these genes by HIF-1 and HIF-2 and found that siRNA targeted degradation of HIF-1alpha and HIF-2alpha results in decreased hypoxia-induced PHD3 expression. Ectopic overexpression of HIF-2alpha in two different cell lines provided a much better induction of PHD3 gene than HIF-1alpha. In contrast, we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF-2alpha. However, induction of PHD2 by hypoxia has HIF-1-independent and -dependent components. Short-term hypoxia (4 h) results in induction of PHD2 independent of HIF-1, while PHD2 accumulation by prolonged hypoxia (16 h) was decreased by siRNA-mediated degradation of HIF-1alpha subunit. These data further advance our understanding of the differential role of HIF factors and putative feedback loop in HIF regulation. Copyright 2004 Wiley-Liss, Inc.

  2. Cellular Oxygen Sensing: Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2)

    Energy Technology Data Exchange (ETDEWEB)

    McDonough,M.; Li, V.; Flashman, E.; Chowdhury, R.; Mohr, C.; Lienard, B.; Zondlo, J.; Oldham, N.; Clifton, I.; et al.

    2006-01-01

    Cellular and physiological responses to changes in dioxygen levels in metazoans are mediated via the posttranslational oxidation of hypoxia-inducible transcription factor (HIF). Hydroxylation of conserved prolyl residues in the HIF-{alpha} subunit, catalyzed by HIF prolyl-hydroxylases (PHDs), signals for its proteasomal degradation. The requirement of the PHDs for dioxygen links changes in dioxygen levels with the transcriptional regulation of the gene array that enables the cellular response to chronic hypoxia; the PHDs thus act as an oxygen-sensing component of the HIF system, and their inhibition mimics the hypoxic response. We describe crystal structures of the catalytic domain of human PHD2, an important prolyl-4-hydroxylase in the human hypoxic response in normal cells, in complex with Fe(II) and an inhibitor to 1.7 Angstroms resolution. PHD2 crystallizes as a homotrimer and contains a double-stranded {beta}-helix core fold common to the Fe(II) and 2-oxoglutarate-dependant dioxygenase family, the residues of which are well conserved in the three human PHD enzymes (PHD 1-3). The structure provides insights into the hypoxic response, helps to rationalize a clinically observed mutation leading to familial erythrocytosis, and will aid in the design of PHD selective inhibitors for the treatment of anemia and ischemic disease.

  3. Proteolytic activity of Escherichia coli oligopeptidase B against proline-rich antimicrobial peptides

    DEFF Research Database (Denmark)

    Mattiuzzo, Maura; De Gobba, Cristian; Runti, Giulia

    2014-01-01

    Oligopeptidase B (OpdB) is a serine peptidase widespread among bacteria and protozoa that has emerged as a virulence factor despite its function has not yet been precisely established. By using an OpdB-overexpressing Escherichia coli strain, we found that the overexpressed peptidase makes...

  4. Overexpression of hypoxia-inducible factor prolyl- hydoxylase ...

    African Journals Online (AJOL)

    Jane

    2011-08-08

    Aug 8, 2011 ... which is regulated by HIF prolyl-dydoxylase -mediated degradation. Taken together, our results ..... Chromatin immunoprecipitation analysis of gene ... phosphatidylinositol 3-kinase/Akt pathway. Endocrinology, 148(5):.

  5. Cloning, Expression, Sequence Analysis and Homology Modeling of the Prolyl Endoprotease from Eurygaster integriceps Puton

    Directory of Open Access Journals (Sweden)

    Ravi Chandra Yandamuri

    2014-10-01

    Full Text Available eurygaster integriceps Puton, commonly known as sunn pest, is a major pest of wheat in Northern Africa, the Middle East and Eastern Europe. This insect injects a prolyl endoprotease into the wheat, destroying the gluten. The purpose of this study was to clone the full length cDNA of the sunn pest prolyl endoprotease (spPEP for expression in E. coli and to compare the amino acid sequence of the enzyme to other known PEPs in both phylogeny and potential tertiary structure. Sequence analysis shows that the 5ꞌ UTR contains several putative transcription factor binding sites for transcription factors known to be expressed in Drosophila that might be useful targets for inhibition of the enzyme. The spPEP was first identified as a prolyl endoprotease by Darkoh et al., 2010. The enzyme is a unique serine protease of the S9A family by way of its substrate recognition of the gluten proteins, which are greater than 30 kD in size. At 51% maximum identity to known PEPs, homology modeling using SWISS-MODEL, the porcine brain PEP (PDB: 2XWD was selected in the database of known PEP structures, resulting in a predicted tertiary structure 99% identical to the porcine brain PEP structure. A Km for the recombinant spPEP was determined to be 210 ± 53 µM for the zGly-Pro-pNA substrate in 0.025 M ethanolamine, pH 8.5, containing 0.1 M NaCl at 37 °C with a turnover rate of 172 ± 47 µM Gly-Pro-pNA/s/µM of enzyme.

  6. Human cyclophilin B: A second cyclophilin gene encodes a peptidyl-prolyl isomerase with a signal sequence

    International Nuclear Information System (INIS)

    Price, E.R.; Zydowsky, L.D.; Jin, Mingjie; Baker, C.H.; McKeon, F.D.; Walsh, C.T.

    1991-01-01

    The authors report the cloning and characterization of a cDNA encoding a second human cyclosporin A-binding protein (hCyPB). Homology analyses reveal that hCyPB is a member of the cyclophilin B (CyPB) family, which includes yeast CyPB, Drosophila nina A, and rat cyclophilin-like protein. This family is distinguished from the cyclophilin A (CyPA) family by the presence of endoplasmic reticulum (ER)-directed signal sequences. hCyPB has a hydrophobic leader sequence not found in hCyPA, and its first 25 amino acids are removed upon expression in Escherichia coli. Moreover, they show that hCyPB is a peptidyl-prolyl cis-trans isomerase which can be inhibited by cyclosporin A. These observations suggest that other members of the CyPB family will have similar enzymatic properties. Sequence comparisons of the CyPB proteins show a central, 165-amino acid peptidyl-prolyl isomerase and cyclosprorin A-binding domain, flanked by variable N-terminal and C-terminal domains. These two variable regions may impart compartmental specificity and regulation to this family of cyclophilin proteins containing the conserved core domain. Northern blot analyses show that hCyPB mRNA is expressed in the Jurkat T-cell line, consistent with its possible target role in cyclosporin A-mediated immunosuppression

  7. Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism

    Directory of Open Access Journals (Sweden)

    Yang M

    2014-08-01

    Full Text Available Ming Yang,1 Huizhong Su,1 Tomoyoshi Soga,2 Kamil R Kranc,3 Patrick J Pollard1 1Cancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; 2Institute for Advanced Biosciences, Keio University, Mizukami, Tsuruoka, Yamagata, Japan; 3MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK Abstract: The hypoxia-inducible factor (HIF prolyl hydroxylase domain enzymes (PHDs regulate the stability of HIF protein by post-translational hydroxylation of two conserved prolyl residues in its α subunit in an oxygen-dependent manner. Trans-4-prolyl hydroxylation of HIFα under normal oxygen (O2 availability enables its association with the von Hippel-Lindau (VHL tumor suppressor pVHL E3 ligase complex, leading to the degradation of HIFα via the ubiquitin-proteasome pathway. Due to the obligatory requirement of molecular O2 as a co-substrate, the activity of PHDs is inhibited under hypoxic conditions, resulting in stabilized HIFα, which dimerizes with HIFβ and, together with transcriptional co-activators CBP/p300, activates the transcription of its target genes. As a key molecular regulator of adaptive response to hypoxia, HIF plays important roles in multiple cellular processes and its overexpression has been detected in various cancers. The HIF1α isoform in particular has a strong impact on cellular metabolism, most notably by promoting anaerobic, whilst inhibiting O2-dependent, metabolism of glucose. The PHD enzymes also seem to have HIF-independent functions and are subject to regulation by factors other than O2, such as by metabolic status, oxidative stress, and abnormal levels of endogenous metabolites (oncometabolites that have been observed in some types of cancers. In this review, we aim to summarize current understandings of the function and regulation of PHDs in cancer with an emphasis on their roles in metabolism. Keywords: prolyl hydroxylase domain (PHD

  8. Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

    Science.gov (United States)

    2017-02-01

    ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life -threatening... negative feedback loops within the pathway limit their effectiveness . For example, AKT inhibitors cause increased expression of IGF1R/ErbB3 and, as a...AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple- Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD

  9. Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.

    Directory of Open Access Journals (Sweden)

    Erica P Homan

    2014-01-01

    Full Text Available Mutations in the genes encoding cartilage associated protein (CRTAP and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1 were the first identified causes of recessive Osteogenesis Imperfecta (OI. These proteins, together with cyclophilin B (encoded by PPIB, form a complex that 3-hydroxylates a single proline residue on the α1(I chain (Pro986 and has cis/trans isomerase (PPIase activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A . This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I and α1(II collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase

  10. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

    Directory of Open Access Journals (Sweden)

    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  11. Production and characterization of two major Aspergillus oryzae secreted prolyl endopeptidases able to efficiently digest proline-rich peptides of gliadin.

    Science.gov (United States)

    Eugster, Philippe J; Salamin, Karine; Grouzmann, Eric; Monod, Michel

    2015-12-01

    Prolyl endopeptidases are key enzymes in the digestion of proline-rich proteins. Fungal extracts rich in prolyl endopeptidases produced by a species such as Aspergillus oryzae used in food fermentation would be of particular interest for the development of an oral enzyme therapy product in patients affected by intolerance to gluten. Two major A. oryzae secreted prolyl endopeptidases of the MEROPS S28 peptidase family, AoS28A and AoS28B, were identified when this fungus was grown at acidic pH in a medium containing soy meal protein or wheat gliadin as the sole source of nitrogen. AoS28B was produced by 12 reference A. oryzae strains used in food fermentation. AoS28A was secreted by six of these 12 strains. This protease is the orthologue of the previously characterized Aspergillus fumigatus (AfuS28) and Aspergillus niger (AN-PEP) prolyl endopeptidases which are encoded by genes with a similar intron-exon structure. Large amounts of secreted AoS28A and AoS28B were obtained by gene overexpression in A. oryzae. AoS28A and AoS28B are endoproteases able to cleave N-terminally blocked proline substrates. Both enzymes very efficiently digested the proline-rich 33-mer of gliadin, the most representative immunotoxic peptide deriving from gliadin, with some differences in terms of specificity and optimal pH. Digestion of the gliadin peptide in short peptides with both enzymes was found to occur from its N terminus.

  12. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires

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    Pemberton Trevor J

    2006-09-01

    Full Text Available Abstract Background The peptidyl-prolyl cis/trans isomerase (PPIase class of proteins is present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of three member families that share the ability to catalyze the cis/trans isomerisation of a prolyl bond. Some fungi have been used as model systems to investigate the role of PPIases within the cell, however how representative these repertoires are of other fungi or humans has not been fully investigated. Results PPIase numbers within these fungal repertoires appears associated with genome size and orthology between repertoires was found to be low. Phylogenetic analysis showed the single-domain FKBPs to evolve prior to the multi-domain FKBPs, whereas the multi-domain cyclophilins appear to evolve throughout cyclophilin evolution. A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. However, no such commonality was found with the FKBPs. Twelve of the 17 human cyclophilins and both human parvulins, but only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14 orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP. The repertoires of Cryptococcus neoformans, Aspergillus fumigatus, and Aspergillus nidulans were found to exhibit the highest orthology to the human repertoire, and Saccharomyces cerevisiae one of the lowest. Conclusion Given this data, we would hypothesize that: (i the evolution of the fungal PPIases is driven, at least in part, by the size of the proteome, (ii evolutionary pressures differ both between the different PPIase families and the different fungi, and (iii whilst the cyclophilins and parvulins have evolved to perform conserved

  13. Structure of the prolyl-tRNA synthetase from the eukaryotic pathogen Giardia lamblia

    Energy Technology Data Exchange (ETDEWEB)

    Larson, Eric T.; Kim, Jessica E.; Napuli, Alberto J.; Verlinde, Christophe L. M. J.; Fan, Erkang; Zucker, Frank H.; Van Voorhis, Wesley C.; Buckner, Frederick S.; Hol, Wim G. J.; Merritt, Ethan A., E-mail: merritt@u.washington.edu [Medical Structural Genomics of Pathogenic Protozoa, (United States); University of Washington, Seattle, WA 98195 (United States)

    2012-09-01

    The structure of Giardia prolyl-tRNA synthetase cocrystallized with proline and ATP shows evidence for half-of-the-sites activity, leading to a corresponding mixture of reaction substrates and product (prolyl-AMP) in the two active sites of the dimer. The genome of the human intestinal parasite Giardia lamblia contains only a single aminoacyl-tRNA synthetase gene for each amino acid. The Giardia prolyl-tRNA synthetase gene product was originally misidentified as a dual-specificity Pro/Cys enzyme, in part owing to its unexpectedly high off-target activation of cysteine, but is now believed to be a normal representative of the class of archaeal/eukaryotic prolyl-tRNA synthetases. The 2.2 Å resolution crystal structure of the G. lamblia enzyme presented here is thus the first structure determination of a prolyl-tRNA synthetase from a eukaryote. The relative occupancies of substrate (proline) and product (prolyl-AMP) in the active site are consistent with half-of-the-sites reactivity, as is the observed biphasic thermal denaturation curve for the protein in the presence of proline and MgATP. However, no corresponding induced asymmetry is evident in the structure of the protein. No thermal stabilization is observed in the presence of cysteine and ATP. The implied low affinity for the off-target activation product cysteinyl-AMP suggests that translational fidelity in Giardia is aided by the rapid release of misactivated cysteine.

  14. Prolyl 3-hydroxylase 1 and CRTAP are mutually stabilizing in the endoplasmic reticulum collagen prolyl 3-hydroxylation complex.

    Science.gov (United States)

    Chang, Weizhong; Barnes, Aileen M; Cabral, Wayne A; Bodurtha, Joann N; Marini, Joan C

    2010-01-15

    Null mutations in cartilage-associated protein (CRTAP) and prolyl 3-hydroxylase 1 (P3H1/LEPRE1) cause types VII and VIII OI, respectively, two novel recessive forms of osteogenesis imperfecta (OI) with severe to lethal bone dysplasia and overmodification of the type I collagen helical region. CRTAP and P3H1 form a complex with cyclophilin B (CyPB) in the endoplasmic reticulum (ER) which 3-hydroxylates the Pro986 residue of alpha1(I) and alpha1(II) collagen chains. We investigated the interaction of complex components in fibroblasts from types VII and VIII OI patients. Both CRTAP and P3H1 are absent or reduced on western blots and by immunofluorescence microscopy in cells containing null mutations in either gene. Levels of LEPRE1 or CRTAP transcripts, however, are normal in CRTAP- or LEPRE1-null cells, respectively. Stable transfection of a CRTAP or LEPRE1 expression construct into cells with null mutations for the transfected cDNA restored both CRTAP and P3H1 protein levels. Normalization of collagen helical modification in transfected CRTAP-null cells demonstrated that the restored proteins functioned effectively as a complex. These data indicate that CRTAP and P3H1 are mutually stabilized in the collagen prolyl 3-hydroxylation complex. CyPB levels were unaffected by mutations in either CRTAP or LEPRE1. Proteasomal inhibitors partially rescue P3H1 protein in CRTAP-null cells. In LEPRE1-null cells, secretion of CRTAP is increased compared with control cells and accounts for 15-20% of the decreased CRTAP detected in cells. Thus, mutual stabilization of P3H1 and CRTAP in the ER collagen modification complex is an underlying mechanism for the overlapping phenotype of types VII and VIII OI.

  15. A digestive prolyl carboxypeptidase in Tenebrio molitor larvae.

    Science.gov (United States)

    Goptar, Irina A; Shagin, Dmitry A; Shagina, Irina A; Mudrik, Elena S; Smirnova, Yulia A; Zhuzhikov, Dmitry P; Belozersky, Mikhail A; Dunaevsky, Yakov E; Oppert, Brenda; Filippova, Irina Yu; Elpidina, Elena N

    2013-06-01

    Prolyl carboxypeptidase (PRCP) is a lysosomal proline specific serine peptidase that also plays a vital role in the regulation of physiological processes in mammals. In this report, we isolate and characterize the first PRCP in an insect. PRCP was purified from the anterior midgut of larvae of a stored product pest, Tenebrio molitor, using a three-step chromatography strategy, and it was determined that the purified enzyme was a dimer. The cDNA of PRCP was cloned and sequenced, and the predicted protein was identical to the proteomic sequences of the purified enzyme. The substrate specificity and kinetic parameters of the enzyme were determined. The T. molitor PRCP participates in the hydrolysis of the insect's major dietary proteins, gliadins, and is the first PRCP to be ascribed a digestive function. Our collective data suggest that the evolutionary enrichment of the digestive peptidase complex in insects with an area of acidic to neutral pH in the midgut is a result of the incorporation of lysosomal peptidases, including PRCP. Published by Elsevier Ltd.

  16. Roles of Prolyl Isomerases in RNA-Mediated Gene Expression

    Directory of Open Access Journals (Sweden)

    Roopa Thapar

    2015-05-01

    Full Text Available The peptidyl-prolyl cis-trans isomerases (PPIases that include immunophilins (cyclophilins and FKBPs and parvulins (Pin1, Par14, Par17 participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer’s disease, asthma, and a number of cancers. While these PPIases are characterized as molecular chaperones, they also act in a nonchaperone manner to promote protein-protein interactions using surfaces outside their active sites. The immunosuppressive drugs act by a gain-of-function mechanism by promoting protein-protein interactions in vivo. Several immunophilins have been identified as components of the spliceosome and are essential for alternative splicing. Pin1 plays roles in transcription and RNA processing by catalyzing conformational changes in the RNA Pol II C-terminal domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of ribonucleoprotein associated PPIases are largely unknown. This review highlights PPIases that play roles in RNA-mediated gene expression, providing insight into their structures, functions and mechanisms of action in mRNP remodeling in vivo.

  17. Biochemical characterization of the prolyl 3-hydroxylase 1.cartilage-associated protein.cyclophilin B complex.

    Science.gov (United States)

    Ishikawa, Yoshihiro; Wirz, Jackie; Vranka, Janice A; Nagata, Kazuhiro; Bächinger, Hans Peter

    2009-06-26

    The rough endoplasmic reticulum-resident protein complex consisting of prolyl 3-hydroxylase 1 (P3H1), cartilage-associated protein (CRTAP), and cyclophilin B (CypB) can be isolated from chick embryos on a gelatin-Sepharose column, indicating some involvement in the biosynthesis of procollagens. Prolyl 3-hydroxylase 1 modifies a single proline residue in the alpha chains of type I, II, and III collagens to (3S)-hydroxyproline. The peptidyl-prolyl cis-trans isomerase activity of cyclophilin B was shown previously to catalyze the rate of triple helix formation. Here we show that cyclophilin B in the complex shows peptidyl-prolyl cis-trans isomerase activity and that the P3H1.CRTAP.CypB complex has another important function: it acts as a chaperone molecule when tested with two classical chaperone assays. The P3H1.CRTAP.CypB complex inhibited the thermal aggregation of citrate synthase and was active in the denatured rhodanese refolding and aggregation assay. The chaperone activity of the complex was higher than that of protein-disulfide isomerase, a well characterized chaperone. The P3H1.CRTAP.CypB complex also delayed the in vitro fibril formation of type I collagen, indicating that this complex is also able to interact with triple helical collagen and acts as a collagen chaperone.

  18. Inhibiting prolyl isomerase activity by hybrid organic-inorganic molecules containing rhodium(II) fragments.

    Science.gov (United States)

    Coughlin, Jane M; Kundu, Rituparna; Cooper, Julian C; Ball, Zachary T

    2014-11-15

    A small molecule containing a rhodium(II) tetracarboxylate fragment is shown to be a potent inhibitor of the prolyl isomerase FKBP12. The use of small molecules conjugates of rhodium(II) is presented as a general strategy for developing new protein inhibitors based on distinct structural and sequence features of the enzyme active site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. A library of fluorescent peptides for exploring the substrate specificities of prolyl isomerases

    NARCIS (Netherlands)

    Zoldak, G.; Aumuller, T.; Lucke, C.; Hritz, J.; Oostenbrink, C.; Fischer, G.; Schmid, F.X.

    2009-01-01

    To fully explore the substrate specificities of prolyl isomerases, we synthesized a library of 20 tetrapeptides that are labeled with a 2-aminobenzoyl (Abz) group at the amino terminus and a p-nitroanilide (pNA) group at the carboxy terminus. In this peptide library of the general formula

  20. Crystallization and preliminary X-ray characterization of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis

    International Nuclear Information System (INIS)

    Nakajima, Yoshitaka; Ito, Kiyoshi; Xu, Yue; Yamada, Nozomi; Onohara, Yuko; Ito, Takashi; Yoshimoto, Tadashi

    2005-01-01

    P. gingivalis prolyl tripeptidyl aminopeptidase has been crystallized by the vapour-diffusion method. Diffraction data have been collected and processed to 2.1 Å resolution. A recombinant form of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis has been crystallized by the hanging-drop vapour-diffusion method using potassium sodium tartrate as a precipitating agent. The crystals belong to the hexagonal space group P6 3 22, with unit-cell parameters a = b = 149.4, c = 159.7 Å. The crystals are most likely to contain one subunit of a dimer in the asymmetric unit, with a V M value of 3.14 Å 3 Da −1 . Diffraction data were collected to 2.1 Å resolution using synchrotron radiation at the BL5 station of the Photon Factory

  1. Crystallization and preliminary X-ray characterization of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Yoshitaka; Ito, Kiyoshi; Xu, Yue; Yamada, Nozomi; Onohara, Yuko; Ito, Takashi; Yoshimoto, Tadashi [Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2005-12-01

    P. gingivalis prolyl tripeptidyl aminopeptidase has been crystallized by the vapour-diffusion method. Diffraction data have been collected and processed to 2.1 Å resolution. A recombinant form of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis has been crystallized by the hanging-drop vapour-diffusion method using potassium sodium tartrate as a precipitating agent. The crystals belong to the hexagonal space group P6{sub 3}22, with unit-cell parameters a = b = 149.4, c = 159.7 Å. The crystals are most likely to contain one subunit of a dimer in the asymmetric unit, with a V{sub M} value of 3.14 Å{sup 3} Da{sup −1}. Diffraction data were collected to 2.1 Å resolution using synchrotron radiation at the BL5 station of the Photon Factory.

  2. A sandwich immunoassay for human prolyl 4-hydroxylase using monoclonal antibody

    International Nuclear Information System (INIS)

    Yoshida, Shinichi

    1986-01-01

    Monoclonal antibody was used in a sandwich enzyme immunoassay and in a radioimmunoassay for human serum immunoreactive prolyl 4-hydroxylase. The enzyme immunoassay utilized a monoclonal antibody as a solid phase and horseradish peroxidase-labeled rabbit antibody to human prolyl 4-hydroxylase as a conjugate. Sensitivity was 0.1 ng of enzyme per tube. With a conjugate purified by an enzyme-bound affinity column, sensitivity was increased to 0.01 ng per tube, and linearity was obtained between 0.01 to 30 ng per tube. The radioimmunoassay used a 125 I-labeled rabbit antibody (IgG) as the conjugate. Sensitivity of this technique was 0.4 ng of enzyme per tube. (Auth.)

  3. Bacillus anthracis Prolyl 4-Hydroxylase Interacts with and Modifies Elongation Factor Tu

    Energy Technology Data Exchange (ETDEWEB)

    Schnicker, Nicholas J. [Department; Razzaghi, Mortezaali [Department; Guha Thakurta, Sanjukta [Department; Chakravarthy, Srinivas [Biophysics; Dey, Mishtu [Department

    2017-10-17

    Prolyl hydroxylation is a very common post-translational modification and plays many roles in eukaryotes such as collagen stabilization, hypoxia sensing, and controlling protein transcription and translation. There is a growing body of evidence that suggests that prokaryotes contain prolyl 4-hydroxylases (P4Hs) homologous to the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes that act on elongation factor Tu (EFTu) and are likely involved in the regulation of bacterial translation. Recent biochemical and structural studies with a PHD from Pseudomonas putida (PPHD) determined that it forms a complex with EFTu and hydroxylates a prolyl residue of EFTu. Moreover, while animal, plant, and viral P4Hs act on peptidyl proline, most prokaryotic P4Hs have been known to target free l-proline; the exceptions include PPHD and a P4H from Bacillus anthracis (BaP4H) that modifies collagen-like proline-rich peptides. Here we use biophysical and mass spectrometric methods to demonstrate that BaP4H recognizes full-length BaEFTu and a BaEFTu 9-mer peptide for site-specific proline hydroxylation. Using size-exclusion chromatography coupled small-angle X-ray scattering (SEC–SAXS) and binding studies, we determined that BaP4H forms a 1:1 heterodimeric complex with BaEFTu. The SEC–SAXS studies reveal dissociation of BaP4H dimeric subunits upon interaction with BaEFTu. While BaP4H is unusual within bacteria in that it is structurally and functionally similar to the animal PHDs and collagen P4Hs, respectively, this work provides further evidence of its promiscuous substrate recognition. It is possible that the enzyme might have evolved to hydroxylate a universally conserved protein in prokaryotes, similar to the PHDs, and implies a functional role in B. anthracis.

  4. Prolyl hydroxylation regulates protein degradation, synthesis, and splicing in human induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Stoehr, Andrea; Yang, Yanqin; Patel, Sajni; Evangelista, Alicia M; Aponte, Angel; Wang, Guanghui; Liu, Poching; Boylston, Jennifer; Kloner, Philip H; Lin, Yongshun; Gucek, Marjan; Zhu, Jun; Murphy, Elizabeth

    2016-06-01

    Protein hydroxylases are oxygen- and α-ketoglutarate-dependent enzymes that catalyse hydroxylation of amino acids such as proline, thus linking oxygen and metabolism to enzymatic activity. Prolyl hydroxylation is a dynamic post-translational modification that regulates protein stability and protein-protein interactions; however, the extent of this modification is largely uncharacterized. The goals of this study are to investigate the biological consequences of prolyl hydroxylation and to identify new targets that undergo prolyl hydroxylation in human cardiomyocytes. We used human induced pluripotent stem cell-derived cardiomyocytes in combination with pulse-chase amino acid labelling and proteomics to analyse the effects of prolyl hydroxylation on protein degradation and synthesis. We identified 167 proteins that exhibit differences in degradation with inhibition of prolyl hydroxylation by dimethyloxalylglycine (DMOG); 164 were stabilized. Proteins involved in RNA splicing such as serine/arginine-rich splicing factor 2 (SRSF2) and splicing factor and proline- and glutamine-rich (SFPQ) were stabilized with DMOG. DMOG also decreased protein translation of cytoskeletal and sarcomeric proteins such as α-cardiac actin. We searched the mass spectrometry data for proline hydroxylation and identified 134 high confidence peptides mapping to 78 unique proteins. We identified SRSF2, SFPQ, α-cardiac actin, and cardiac titin as prolyl hydroxylated. We identified 29 prolyl hydroxylated proteins that showed a significant difference in either protein degradation or synthesis. Additionally, we performed next-generation RNA sequencing and showed that the observed decrease in protein synthesis was not due to changes in mRNA levels. Because RNA splicing factors were prolyl hydroxylated, we investigated splicing ± inhibition of prolyl hydroxylation and detected 369 alternative splicing events, with a preponderance of exon skipping. This study provides the first extensive

  5. Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation.

    Science.gov (United States)

    Marsolier, J; Perichon, M; DeBarry, J D; Villoutreix, B O; Chluba, J; Lopez, T; Garrido, C; Zhou, X Z; Lu, K P; Fritsch, L; Ait-Si-Ali, S; Mhadhbi, M; Medjkane, S; Weitzman, J B

    2015-04-16

    Infectious agents develop intricate mechanisms to interact with host cell pathways and hijack their genetic and epigenetic machinery to change host cell phenotypic states. Among the Apicomplexa phylum of obligate intracellular parasites, which cause veterinary and human diseases, Theileria is the only genus that transforms its mammalian host cells. Theileria infection of bovine leukocytes induces proliferative and invasive phenotypes associated with activated signalling pathways, notably JNK and AP-1 (ref. 2). The transformed phenotypes are reversed by treatment with the theilericidal drug buparvaquone. We used comparative genomics to identify a homologue of the peptidyl-prolyl isomerase PIN1 in T. annulata (TaPIN1) that is secreted into the host cell and modulates oncogenic signalling pathways. Here we show that TaPIN1 is a bona fide prolyl isomerase and that it interacts with the host ubiquitin ligase FBW7, leading to its degradation and subsequent stabilization of c-JUN, which promotes transformation. We performed in vitro and in silico analysis and in vivo zebrafish xenograft experiments to demonstrate that TaPIN1 is directly inhibited by the anti-parasite drug buparvaquone (and other known PIN1 inhibitors) and is mutated in a drug-resistant strain. Prolyl isomerization is thus a conserved mechanism that is important in cancer and is used by Theileria parasites to manipulate host oncogenic signalling.

  6. The Aminolysis Reaction of Streptomyces S9 Aminopeptidase Promotes the Synthesis of Diverse Prolyl Dipeptides▿ †

    Science.gov (United States)

    Arima, Jiro; Morimoto, Masazumi; Usuki, Hirokazu; Mori, Nobuhiro; Hatanaka, Tadashi

    2010-01-01

    Prolyl dipeptide synthesis by S9 aminopeptidase from Streptomyces thermocyaneoviolaceus (S9AP-St) has been demonstrated. In the synthesis, S9AP-St preferentially used l-Pro-OBzl as the acyl donor, yielding synthesized dipeptides having an l-Pro-Xaa structure. In addition, S9AP-St showed broad specificity toward the acyl acceptor. Furthermore, S9AP-St produced cyclo (l-Pro-l-His) with a conversion ratio of substrate to cyclo (l-Pro-l-His) higher than 40%. PMID:20418423

  7. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Torpe, Nanna; Pocock, Roger David John

    2014-01-01

    , little is known of its importance in the control of axon guidance. In a screen of prolyl 4-hydroxylase (P4H) mutants, we found that genetic removal of a specific P4H subunit, DPY-18, causes dramatic defects in C. elegans neuroanatomy. In dpy-18 mutant animals, the axons of specific ventral nerve cord......Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  8. Biochemical Characterization of the Prolyl 3-Hydroxylase 1·Cartilage-associated Protein·Cyclophilin B Complex*

    Science.gov (United States)

    Ishikawa, Yoshihiro; Wirz, Jackie; Vranka, Janice A.; Nagata, Kazuhiro; Bächinger, Hans Peter

    2009-01-01

    The rough endoplasmic reticulum-resident protein complex consisting of prolyl 3-hydroxylase 1 (P3H1), cartilage-associated protein (CRTAP), and cyclophilin B (CypB) can be isolated from chick embryos on a gelatin-Sepharose column, indicating some involvement in the biosynthesis of procollagens. Prolyl 3-hydroxylase 1 modifies a single proline residue in the α chains of type I, II, and III collagens to (3S)-hydroxyproline. The peptidyl-prolyl cis-trans isomerase activity of cyclophilin B was shown previously to catalyze the rate of triple helix formation. Here we show that cyclophilin B in the complex shows peptidyl-prolyl cis-trans isomerase activity and that the P3H1·CRTAP·CypB complex has another important function: it acts as a chaperone molecule when tested with two classical chaperone assays. The P3H1·CRTAP·CypB complex inhibited the thermal aggregation of citrate synthase and was active in the denatured rhodanese refolding and aggregation assay. The chaperone activity of the complex was higher than that of protein-disulfide isomerase, a well characterized chaperone. The P3H1·CRTAP·CypB complex also delayed the in vitro fibril formation of type I collagen, indicating that this complex is also able to interact with triple helical collagen and acts as a collagen chaperone. PMID:19419969

  9. Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    So Yeon Kim

    2015-11-01

    Full Text Available Hypoxia-inducible factor (HIF prolyl hydroxylases (PHDs are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

  10. Effects of peptidyl-prolyl isomerase 1 depletion in animal models of prion diseases.

    Science.gov (United States)

    Legname, Giuseppe; Virgilio, Tommaso; Bistaffa, Edoardo; De Luca, Chiara Maria Giulia; Catania, Marcella; Zago, Paola; Isopi, Elisa; Campagnani, Ilaria; Tagliavini, Fabrizio; Giaccone, Giorgio; Moda, Fabio

    2018-04-20

    Pin1 is a peptidyl-prolyl isomerase that induces the cis-trans conversion of specific Ser/Thr-Pro peptide bonds in phosphorylated proteins, leading to conformational changes through which Pin1 regulates protein stability and activity. Since down-regulation of Pin1 has been described in several neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Huntington's Disease (HD), we investigated its potential role in prion diseases. Animals generated on wild-type (Pin1 +/+ ), hemizygous (Pin1 +/- ) or knock-out (Pin1 -/- ) background for Pin1 were experimentally infected with RML prions. The study indicates that, neither the total depletion nor reduced levels of Pin1 significantly altered the clinical and neuropathological features of the disease.

  11. Helicobacter pylori Peptidyl Prolyl Isomerase Expression Is Associated with the Severity of Gastritis.

    Science.gov (United States)

    Oghalaie, Akbar; Saberi, Samaneh; Esmaeili, Maryam; Ebrahimzadeh, Fatemeh; Barkhordari, Farzaneh; Ghamarian, Abdolreza; Tashakoripoor, Mohammad; Abdirad, Afshin; Eshagh Hosseini, Mahmoud; Khalaj, Vahid; Mohammadi, Marjan

    2016-12-01

    Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a pro-inflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. The HP0175 gene fragment was PCR-amplified, cloned, expressed and purified by Ni-NTA affinity chromatography. Serum antigen-specific antibody responses of non-ulcer dyspeptic patients (N = 176) against recombinant HP0175 were detected by western blotting. The infection status of these subjects was determined by rapid urease test, culture, histology, and serology. The grade of inflammation and stage of atrophy were scored blindly according to the OLGA staging system. The recombinant HP0175 (rHP0175) was expressed as a ~35 kDa protein and its identity was confirmed by western blotting using anti-6X His tag antibody and pooled H. pylori-positive sera. Serum IgG antibodies against rHP0175 segregated our patients into two similar-sized groups of sero-positives (90/176, 51.1 %) and sero-negatives (86/176, 48.9 %). The former presented with higher grades of gastric inflammation (OR = 4.4, 95 % CI = 1.9-9.9, P = 0.001) and stages of gastric atrophy (OR = 18.3, 95 %CI = 1.4-246.6, P = 0.028). Our findings lend further support to the pro-inflammatory nature of H. pylori peptidyl prolyl isomerase (HP0175) and recommends this antigen as a non-invasive serum biomarker of the severity of H. pylori-associated gastritis.

  12. Optimized expression of prolyl aminopeptidase in Pichia pastoris and its characteristics after glycosylation.

    Science.gov (United States)

    Yang, Hongyu; Zhu, Qiang; Zhou, Nandi; Tian, Yaping

    2016-11-01

    Prolyl aminopeptidases are specific exopeptidases that catalyze the hydrolysis of the N-terminus proline residue of peptides and proteins. In the present study, the prolyl aminopeptidase gene (pap) from Aspergillus oryzae JN-412 was optimized through the codon usage of Pichia pastoris. Both the native and optimized pap genes were inserted into the expression vector pPIC9 K and were successfully expressed in P. pastoris. Additionally, the activity of the intracellular enzyme expressed by the recombinant optimized pap gene reached 61.26 U mL(-1), an activity that is 2.1-fold higher than that of the native gene. The recombinant enzyme was purified by one-step elution through Ni-affinity chromatography. The optimal temperature and pH of the purified PAP were 60 °C and 7.5, respectively. Additionally, the recombinant PAP was recovered at a yield greater than 65 % at an extremely broad range of pH values from 6 to 10 after treatment at 50 °C for 6 h. The molecular weight of the recombinant PAP decreased from 50 kDa to 48 kDa after treatment with a deglycosylation enzyme, indicating that the recombinant PAP was completely glycosylated. The glycosylated PAP exhibited high thermo-stability. Half of the activity remained after incubation at 50 °C for 50 h, whereas the remaining activity of PAP expressed in E. coli was only 10 % after incubation at 50 °C for 1 h. PAP could be activated by the appropriate salt concentration and exhibited salt tolerance against NaCl at a concentration up to 5 mol L(-1).

  13. Discovery, cloning and characterisation of proline specific prolyl endopeptidase, a gluten degrading thermo-stable enzyme from Sphaerobacter thermophiles

    DEFF Research Database (Denmark)

    Shetty, Radhakrishna; Vestergaard, Mike; Jessen, Flemming

    2017-01-01

    processes occur at elevated temperature. We present in this paper, the discovery, cloning and characterisation of a novel recombinant thermostable gluten degrading enzyme, a proline specific prolyl endoprotease (PEP) from Sphaerobacter thermophiles. The molecular mass of the prolyl endopeptidase......Gluten free products have emerged during the last decades, as a result of a growing public concern and technological advancements allowing gluten reduction in food products. One approach is to use gluten degrading enzymes, typically at low or ambient temperatures, whereas many food production...... was estimated to be 77 kDa by using SDS-PAGE. Enzyme activity assays with a synthetic dipeptide Z-Gly-Pro-p-nitroanilide as the substrate revealed that the enzyme had optimal activity at pH 6.6 and was most active from pH 5.0-8.0. The optimum temperature was 63 °C and residual activity after one hour incubation...

  14. Sandwich ELISA for quantitative detection of human collagen prolyl 4-hydroxylase

    Directory of Open Access Journals (Sweden)

    Myllyharju Johanna

    2010-06-01

    Full Text Available Abstract Background We describe a method for specific, quantitative and quick detection of human collagen prolyl 4-hydroxylase (C-P4H, the key enzyme for collagen prolyl-4 hydroxylation, in crude samples based on a sandwich ELISA principle. The method is relevant to active C-P4H level monitoring during recombinant C-P4H and collagen production in different expression systems. The assay proves to be specific for the active C-P4H α2β2 tetramer due to the use of antibodies against its both subunits. Thus in keeping with the method C-P4H is captured by coupled to an anti-α subunit antibody magnetic beads and an anti-β subunit antibody binds to the PDI/β subunit of the protein. Then the following holoenzyme detection is accomplished by a goat anti-rabbit IgG labeled with alkaline phosphatase which AP catalyzes the reaction of a substrate transformation with fluorescent signal generation. Results We applied an experimental design approach for the optimization of the antibody concentrations used in the sandwich ELISA. The assay sensitivity was 0.1 ng of C-P4H. The method was utilized for the analysis of C-P4H accumulation in crude cell extracts of E. coli overexpressing C-P4H. The sandwich ELISA signals obtained demonstrated a very good correlation with the detected protein activity levels measured with the standard radioactive assay. The developed assay was applied to optimize C-P4H production in E. coli Origami in a system where the C-P4H subunits expression acted under control by different promoters. The experiments performed in a shake flask fed-batch system (EnBase® verified earlier observations that cell density and oxygen supply are critical factors for the use of the inducer anhydrotetracycline and thus for the soluble C-P4H yield. Conclusions Here we show an example of sandwich ELISA usage for quantifying multimeric proteins. The method was developed for monitoring the amount of recombinant C-P4H tetramer in crude E. coli extracts. Due

  15. Prolyl carboxypeptidase in Agouti-related Peptide neurons modulates food intake and body weight

    Directory of Open Access Journals (Sweden)

    Giuseppe Bruschetta

    2018-04-01

    Full Text Available Objective: Prolyl carboxypeptidase (PRCP plays a role in the regulation of energy metabolism by inactivating hypothalamic α-melanocyte stimulating hormone (α-MSH levels. Although detected in the arcuate nucleus, limited PRCP expression has been observed in the arcuate POMC neurons, and its site of action in regulating metabolism is still ill-defined. Methods: We performed immunostaining to assess the localization of PRCP in arcuate Neuropeptide Y/Agouti-related Peptide (NPY/AgRP neurons. Hypothalamic explants were then used to assess the intracellular localization of PRCP and its release at the synaptic levels. Finally, we generated a mouse model to assess the role of PRCP in NPY/AgRP neurons of the arcuate nucleus in the regulation of metabolism. Results: Here we show that PRCP is expressed in NPY/AgRP-expressing neurons of the arcuate nucleus. In hypothalamic explants, stimulation by ghrelin increased PRCP concentration in the medium and decreased PRCP content in synaptic extract, suggesting that PRCP is released at the synaptic level. In support of this, hypothalamic explants from mice with selective deletion of PRCP in AgRP neurons (PrcpAgRPKO showed reduced ghrelin-induced PRCP concentration in the medium compared to controls mice. Furthermore, male PrcpAgRPKO mice had decreased body weight and fat mass compared to controls. However, this phenotype was sex-specific as female PrcpAgRPKO mice show metabolic differences only when challenged by high fat diet feeding. The improved metabolism of PrcpAgRPKO mice was associated with reduced food intake and increased energy expenditure, locomotor activity, and hypothalamic α-MSH levels. Administration of SHU9119, a potent melanocortin receptor antagonist, selectively in the PVN of PrcpAgRPKO male mice increased food intake to a level similar to that of control mice. Conclusions: Altogether, our data indicate that PRCP is released at the synaptic levels and that PRCP in AgRP neurons contributes to

  16. Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum.

    Science.gov (United States)

    Savale, Swapnil Anil; Pol, Chaitrali Satish; Khare, Roshni; Verma, Neeraj; Gaikwad, Subhash; Mandal, Bapi; Behera, Bhaskar C

    2016-01-01

    Lichens are source of natural bioactive compounds which are traditionally used to cure a variety of ailments. The objective of this study is to assess free radical scavenging, prolyl endopeptidase inhibitory (PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions were implemented in bioreactor to obtain high quantity of biomass for the study of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100 µg/mL, PEPI activity at 25 and 50 µg/mL, and antimicrobial activity at 5, 25, 50, and 100 µg/mL conc. All the biological activities of natural thallus extract and its derived culture extract were evaluated spectrophotometrically. Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3-butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited half inhibiting concentration (IC50) for radical scavenging activities in the range of 50-60 µg/mL, whereas the IC50 value of standard antioxidants was found to be in the range of 12-29 µg/mL. The IC50 value of lichen extract for PEPI activity was 144-288 µg/mL, whereas the IC50 value of standard prolyl endopeptidase inhibitor, Z-pro-prolinal, was 57.73 µg/mL. As far as the antimicrobial activity of MECO is concerned, minimum inhibitory concentration (MIC) value of lichen extracts against tested microorganisms was obtained in the range of 50-104 µg/mL and found to be more effective than commercially available standard erythromycin. Murashige and Skoog medium containing IBA was found to be suitable for maximum biomass production of C. olivetorum under bioreactor conditions. The cultured lichen biomass extract also showed

  17. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear.

    Science.gov (United States)

    Gumucio, J P; Flood, M D; Bedi, A; Kramer, H F; Russell, A J; Mendias, C L

    2017-01-01

    Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair. At two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons. GSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred.Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J

  18. Prolyl Endopeptidase (PREP) is Associated With Male Reproductive Functions and Gamete Physiology in Mice.

    Science.gov (United States)

    Dotolo, Raffaele; Kim, Jung Dae; Pariante, Paolo; Minucci, Sergio; Diano, Sabrina

    2016-03-01

    Prolyl endopeptidase (PREP) is a serine protease which has been implicated in many biological processes, such as the maturation and degradation of peptide hormones and neuropeptides, learning and memory, cell proliferation and differentiation, and glucose metabolism. A small number of reports have also suggested PREP participation in both male and female reproduction-associated processes. In the present work, we examined PREP distribution in male germ cells and studied the effects of its knockdown (Prep(gt/gt)) on testis and sperm in adult mice. The protein is expressed and localized in elongating spermatids and luminal spermatozoa of wild type (wt) mice, as well as Sertoli, Leydig, and peritubular cells. PREP is also expressed in the head and midpiece of epididymal spermatozoa, whereas the remaining tail region shows a weaker signal. Furthermore, testis weight, histology of seminiferous tubules, and epididymal sperm parameters were assessed in wt and Prep(gt/gt) mice: wild type testes have larger average tubule and lumen diameter; in addition, lumenal composition of seminiferous tubules is dissimilar between wt and Prep(gt/gt), as the percentage of spermiated tubules is much higher in wt. Finally, total sperm count, sperm motility, and normal morphology are also higher in wt than in Prep(gt/gt). These results show for the first time that the expression of PREP could be necessary for a correct reproductive function, and suggest that the enzyme may play a role in mouse spermatogenesis and sperm physiology. © 2015 Wiley Periodicals, Inc.

  19. High Myopia Caused by a Mutation in LEPREL1, Encoding Prolyl 3-Hydroxylase 2

    Science.gov (United States)

    Mordechai, Shikma; Gradstein, Libe; Pasanen, Annika; Ofir, Rivka; El Amour, Khalil; Levy, Jaime; Belfair, Nadav; Lifshitz, Tova; Joshua, Sara; Narkis, Ginat; Elbedour, Khalil; Myllyharju, Johanna; Birk, Ohad S.

    2011-01-01

    Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysis, the disease-associated gene was mapped to ∼1.7 Mb on chromosome 3q28 (the maximum LOD score was 11.5 at θ = 0 for marker D3S1314). Sequencing of the entire coding regions and intron-exon boundaries of the six genes within the defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1, encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The mutation affects a glycine that is conserved within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant recombinant P3H2 polypeptides expressed in insect cells showed that the mutation led to complete inactivation of P3H2. PMID:21885030

  20. Incorporation of a prolyl hydroxylase inhibitor into scaffolds: a strategy for stimulating vascularization.

    Science.gov (United States)

    Sham, Adeline; Martinez, Eliana C; Beyer, Sebastian; Trau, Dieter W; Raghunath, Michael

    2015-03-01

    Clinical applications of tissue engineering are constrained by the ability of the implanted construct to invoke vascularization in adequate extent and velocity. To overcome the current limitations presented by local delivery of single angiogenic factors, we explored the incorporation of prolyl hydroxylase inhibitors (PHIs) into scaffolds as an alternative vascularization strategy. PHIs are small molecule drugs that can stabilize the alpha subunit of hypoxia-inducible factor-1 (HIF-1), a key transcription factor that regulates a variety of angiogenic mechanisms. In this study, we conjugated the PHI pyridine-2,4-dicarboxylic acid (PDCA) through amide bonds to a gelatin sponge (Gelfoam(®)). Fibroblasts cultured on PDCA-Gelfoam were able to infiltrate and proliferate in these scaffolds while secreting significantly more vascular endothelial growth factor than cells grown on Gelfoam without PDCA. Reporter cells expressing green fluorescent protein-tagged HIF-1α exhibited dose-dependent stabilization of this angiogenic transcription factor when growing within PDCA-Gelfoam constructs. Subsequently, we implanted PDCA-Gelfoam scaffolds into the perirenal fat tissue of Sprague Dawley rats for 8 days. Immunostaining of explants revealed that the PDCA-Gelfoam scaffolds were amply infiltrated by cells and promoted vascular ingrowth in a dose-dependent manner. Thus, the incorporation of PHIs into scaffolds appears to be a feasible strategy for improving vascularization in regenerative medicine applications.

  1. Isolation of prolyl endopeptidase inhibitory peptides from a sodium caseinate hydrolysate.

    Science.gov (United States)

    Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Hsieh, You-Liang; Hsu, Kuo-Chiang

    2016-01-01

    Prolyl endopeptidase (PEP) has been associated with neurodegenerative disorders, and the PEP inhibitors can restore the memory loss caused by amnesic compounds. In this study, we investigated the PEP inhibitory activity of the enzymatic hydrolysates from various food protein sources, and isolated and identified the PEP inhibitory peptides. The hydrolysate obtained from sodium caseinate using bromelain (SC/BML) displayed the highest inhibitory activity of 86.8% at 5 mg mL(-1) in the present study, and its IC50 value against PEP was 0.77 mg mL(-1). The F-5 fraction by RP-HPLC (reversed-phase high performance liquid chromatography) from SC/BML showed the highest PEP inhibition rate of 88.4%, and 9 peptide sequences were identified. The synthetic peptides (1245.63-1787.94 Da) showed dose-dependent inhibition effects on PEP as competitive inhibitors with IC50 values between 29.8 and 650.5 μM. The results suggest that the peptides derived from sodium caseinate have the potential to be PEP inhibitors.

  2. Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

    Directory of Open Access Journals (Sweden)

    Hyeong-Jun Han

    Full Text Available Peptidyl prolyl isomerase (PIN1 regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated. Here, we report that PIN1 directly interacts with hypoxia-inducible factor (HIF-1α in human colon cancer (HCT116 cells. PIN1 binding to HIF-1α occurred in a phosphorylation-dependent manner. We also found that PIN1 interacted with HIF-1α at both exogenous and endogenous levels. Notably, PIN1 binding stabilized the HIF-1α protein, given that their levels were significantly increased under hypoxic conditions. The stabilization of HIF-1α resulted in increased transcriptional activity, consequently upregulating expression of vascular endothelial growth factor, a major contributor to angiogenesis. Silencing of PIN1 or pharmacologic inhibition of its activity abrogated the angiogenesis. By utilizing a bioluminescence imaging technique, we were able to demonstrate that PIN1 inhibition dramatically reduced the tumor volume in a subcutaneous mouse xenograft model and angiogenesis as well as hypoxia-induced transcriptional activity of HIF-1α. These results suggest that PIN1 interacting with HIF-1α is a potential cancer chemopreventive and therapeutic target.

  3. Attenuation of antagonist-induced impairment of dopamine receptors by L-prolyl-L-leucyl-glycinamide

    International Nuclear Information System (INIS)

    Saleh, M.I.M.

    1988-01-01

    The present study was undertaken in order to determine whether chronic,long-term postnatal challenge of rat pups per se, with specific dopamine D1 and D2 receptor antagonists, would modify the ontogeny of the respective receptor types. Since the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG) attenuates the effect of haloperidol on dopamine D2 receptors in adult rats it was of interest to determine whether PLG would modulate antagonists-induced alterations in the ontogeny of striatal dopamine D1 and D2 receptors. Half of the rats were treated daily for 32 days from birth with SCH-23390, a selective dopamine D1 antagonist; or spiroperidol, a selective dopamine D2 antagonists; or both SCH-23390 and spiroperidol; or saline. The other half of the litters were treated with PLG, in combination with the other treatments. Animals were decapitated at 5, 8, and 12 weeks from birth for neurochemical analysis of the striatum. Chronic SCH-23390 treatment produced a 70-80% decrease in the binding of [ 3 H] SCH-23390 to striatal homogenates. The alteration at 5 weeks was associated with a 78% decrease in the Bmax for [ 3 H] SCH-23390 binding, and no change in the K D . Similarly, at 5, 8, and 12 weeks, chronic spiroperidol treatment reduced the binding of [ 3 H] spiroperidol to striatal homogenates by 70-80%

  4. A dual inhibitor against prolyl isomerase Pin1 and cyclophilin discovered by a novel real-time fluorescence detection method

    International Nuclear Information System (INIS)

    Mori, Tadashi; Hidaka, Masafumi; Lin, Yi-Chin; Yoshizawa, Ibuki; Okabe, Takayoshi; Egashira, Shinichiro; Kojima, Hirotatsu; Nagano, Tetsuo; Koketsu, Mamoru; Takamiya, Mari; Uchida, Takafumi

    2011-01-01

    Research highlights: → A Pin1 (prolyl isomerase) inhibitor, TME-001, has been discovered by using a new established high-throughput screening method. → The TME-001 showed a cell-active inhibition with lower cytotoxic effect than known Pin1 inhibitors. → Kinetic analyses revealed that the TME-001 is the first compound that exhibits dual inhibition of Pin1 and another type of prolyl isomerase, cyclophilin. → Thus, similarities of structure and reaction mechanism between Pin1 and cyclophilin are proposed. -- Abstract: Pin1, a peptidyl prolyl cis/trans isomerase (PPIase), is a potential target molecule for cancer, infectious disease, and Alzheimer's disease. We established a high-throughput screening method for Pin1 inhibitors, which employs a real-time fluorescence detector. This screening method identified 66 compounds that inhibit Pin1 out of 9756 compounds from structurally diverse chemical libraries. Further evaluations of surface plasmon resonance methods and a cell proliferation assay were performed. We discovered a cell-active inhibitor, TME-001 (2-(3-chloro-4-fluoro-phenyl)-isothiazol-3-one). Surprisingly, kinetic analyses revealed that TME-001 is the first compound that exhibits dual inhibition of Pin1 (IC 50 = 6.1 μM) and cyclophilin, another type of PPIase, (IC 50 = 13.7 μM). This compound does not inhibit FKBP. This finding suggests the existence of similarities of structure and reaction mechanism between Pin1 and cyclophilin, and may lead to a more complete understanding of the active sites of PPIases.

  5. Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase

    Directory of Open Access Journals (Sweden)

    Soohwan Yum

    2017-12-01

    Full Text Available The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF, a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF prolyl hydroxylase-2 (PHD-2 was tested by an in vitro von Hippel–Lindau protein (VHL binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α, and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1.

  6. Minoxidil Induction of VEGF Is Mediated by Inhibition of HIF-Prolyl Hydroxylase

    Science.gov (United States)

    Yum, Soohwan; Jeong, Seongkeun; Kim, Dohoon; Lee, Sunyoung; Kim, Wooseong; Yoo, Jin-Wook; Kwon, Oh Sang; Kim, Dae-Duk; Min, Do Sik; Jung, Yunjin

    2017-01-01

    The topical application of minoxidil may achieve millimolar concentrations in the skin. We investigated whether millimolar minoxidil could induce vascular endothelial growth factor (VEGF), a possible effector for minoxidil-mediated hair growth, and how it occurred at the molecular level. Cell-based experiments were performed to investigate a molecular mechanism underlying the millimolar minoxidil induction of VEGF. The inhibitory effect of minoxidil on hypoxia-inducible factor (HIF) prolyl hydroxylase-2 (PHD-2) was tested by an in vitro von Hippel–Lindau protein (VHL) binding assay. To examine the angiogenic potential of millimolar minoxidil, a chorioallantoic membrane (CAM) assay was used. In human keratinocytes and dermal papilla cells, millimolar minoxidil increased the secretion of VEGF, which was not attenuated by a specific adenosine receptor antagonist that inhibits the micromolar minoxidil induction of VEGF. Millimolar minoxidil induced hypoxia-inducible factor-1α (HIF-1α), and the induction of VEGF was dependent on HIF-1. Moreover, minoxidil applied to the dorsal area of mice increased HIF-1α and VEGF in the skin. In an in vitro VHL binding assay, minoxidil directly inhibited PHD-2, thus preventing the hydroxylation of cellular HIF-1α and VHL-dependent proteasome degradation and resulting in the stabilization of HIF-1α protein. Minoxidil inhibition of PHD-2 was reversed by ascorbate, a cofactor of PHD-2, and the minoxidil induction of cellular HIF-1α was abrogated by the cofactor. Millimolar minoxidil promoted angiogenesis in the CAM assay, an in vivo angiogenic test, and this was nullified by the specific inhibition of VEGF. Our data demonstrate that PHD may be the molecular target for millimolar minoxidil-mediated VEGF induction via HIF-1. PMID:29295567

  7. Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Fitzpatrick, Susan F.; Fábián, Zsolt; Schaible, Bettina; Lenihan, Colin R.; Schwarzl, Thomas [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Rodriguez, Javier [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Zheng, Xingnan; Li, Zongwei [Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC (United States); Tambuwala, Murtaza M. [School of Pharmacy and Pharmaceutical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland (United Kingdom); Higgins, Desmond G.; O' Meara, Yvonne [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Slattery, Craig [School of Biomolecular and Biomedical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Manresa, Mario C. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); Fraisl, Peter; Bruning, Ulrike [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Baes, Myriam [Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven (Belgium); Carmeliet, Peter; Doherty, Glen [Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Vesalius Research Center, VIB, B-3000 (Belgium); Kriegsheim, Alex von [Systems Biology Ireland, University College Dublin, Dublin 4 (Ireland); Cummins, Eoin P. [School of Medicine and Medical Science, The Conway Institute, University College Dublin, Belfield, Dublin 4 Ireland (Ireland); and others

    2016-06-03

    Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1{sup −/−} hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease. -- Highlights: •Genetic ablation of PHD1 upregulates NF-kappaB (NF-κB) in hepatocytes. •Activation of NF-κB leads to differential DNA-binding of p50/p65 and results in differential regulation of apoptotic genes. •We identified proline 191 in the beta subunit of the I-kappaB kinase as a target for PHD1-mediated hydroxylation. •Blockade of prolyl-4-hydroxylases has been found cytoprotective in liver cells.

  8. Functional characterisation of parvulin-type peptidyl prolyl cis-trans isomerase, PinA in Dictyostelium discoideum

    International Nuclear Information System (INIS)

    Haokip, Nemneineng; Naorem, Aruna

    2017-01-01

    Pin1-type parvulins are unique among PPIases that can catalyse an otherwise slow cis-trans isomerisation of phosphorylated peptide bond preceding proline in target proteins. This prolyl isomerisation process can regulate activity, stability and localisation of target proteins and thus control cellular processes like eukaryotic cell proliferation, cell cycle progression and gene regulation. Towards understanding the function of Pin1-type prolyl isomerisation in Dictyostelium discoideum, a slime mould with distinct growth and developmental phases, we identified PinA as a novel Pin1-type parvulin by its ability to complement the temperature sensitivity phenotype associated with a mutation in ESS1 in S. cerevisiae. In D. discoideum, pinA is temporally and spatially regulated during growth and development. PinA is both nuclear as well as cytoplasmic in the growing cells. We further show that loss of pinA (pinA − ) leads to decreased growth rate, reduced spore formation and abnormal prespore-prestalk patterning. We conclude that PinA is required for normal growth as well as development in D. discoideum. - Highlights: • PinA is a bona fide homologue of S. cerevisiae Ess1. • PinA is required for normal cell proliferation of D. discoideum. • PinA is spatially localised in developmental structures. • PinA is important for cell differentiation and patterning.

  9. Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

    International Nuclear Information System (INIS)

    Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

    2009-01-01

    Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

  10. Expression and DNA methylation levels of prolyl hydroxylases PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer

    International Nuclear Information System (INIS)

    Rawluszko, Agnieszka A; Bujnicka, Katarzyna E; Horbacka, Karolina; Krokowicz, Piotr; Jagodziński, Paweł P

    2013-01-01

    Colorectal cancer (CRC) is one of the most common and comprehensively studied malignancies. Hypoxic conditions during formation of CRC may support the development of more aggressive cancers. Hypoxia inducible factor (HIF), a major player in cancerous tissue adaptation to hypoxia, is negatively regulated by the family of prolyl hydroxylase enzymes (PHD1, PHD2, PHD3) and asparaginyl hydroxylase, called factor inhibiting HIF (FIH). PHD1, PHD2, PHD3 and FIH gene expression was evaluated using quantitative RT-PCR and western blotting in primary colonic adenocarcinoma and adjacent histopathologically unchanged colonic mucosa from patients who underwent radical surgical resection of the colon (n = 90), and the same methods were used for assessment of PHD3 gene expression in HCT116 and DLD-1 CRC cell lines. DNA methylation levels of the CpG island in the promoter regulatory region of PHD1, PHD2, PHD3 and FIH were assessed using bisulfite DNA sequencing and high resolution melting analysis (HRM) for patients and HRM analysis for CRC cell lines. We found significantly lower levels of PHD1, PHD2 and PHD3 transcripts (p = 0.00026; p < 0.00001; p < 0.00001) and proteins (p = 0.004164; p = 0.0071; p < 0.00001) in primary cancerous than in histopathologically unchanged tissues. Despite this, we did not observe statistically significant differences in FIH transcript levels between cancerous and histopathologically unchanged colorectal tissue, but we found a significantly increased level of FIH protein in CRC (p = 0.0169). The reduced PHD3 expression was correlated with significantly increased DNA methylation in the CpG island of the PHD3 promoter regulatory region (p < 0.0001). We did not observe DNA methylation in the CpG island of the PHD1, PHD2 or FIH promoter in cancerous and histopathologically unchanged colorectal tissue. We also showed that 5-Aza-2’-deoxycytidine induced DNA demethylation leading to increased PHD3 transcript and protein level in HCT116 cells. We

  11. The basic tilted helix bundle domain of the prolyl isomerase FKBP25 is a novel double-stranded RNA binding module

    Science.gov (United States)

    Dilworth, David; Bonnafous, Pierre; Edoo, Amiirah Bibi; Bourbigot, Sarah; Pesek-Jardim, Francy; Gudavicius, Geoff; Serpa, Jason J.; Petrotchenko, Evgeniy V.; Borchers, Christoph H.

    2017-01-01

    Abstract Prolyl isomerases are defined by a catalytic domain that facilitates the cis–trans interconversion of proline residues. In most cases, additional domains in these enzymes add important biological function, including recruitment to a set of protein substrates. Here, we report that the N-terminal basic tilted helix bundle (BTHB) domain of the human prolyl isomerase FKBP25 confers specific binding to double-stranded RNA (dsRNA). This binding is selective over DNA as well as single-stranded oligonucleotides. We find that FKBP25 RNA-association is required for its nucleolar localization and for the vast majority of its protein interactions, including those with 60S pre-ribosome and early ribosome biogenesis factors. An independent mobility of the BTHB and FKBP catalytic domains supports a model by which the N-terminus of FKBP25 is anchored to regions of dsRNA, whereas the FKBP domain is free to interact with neighboring proteins. Apart from the identification of the BTHB as a new dsRNA-binding module, this domain adds to the growing list of auxiliary functions used by prolyl isomerases to define their primary cellular targets. PMID:29036638

  12. X-prolyl dipeptidyl aminopeptidase gene (pepX) is part of the glnRA operon in Lactobacillus rhamnosus.

    Science.gov (United States)

    Varmanen, P; Savijoki, K; Avall, S; Palva, A; Tynkkynen, S

    2000-01-01

    A peptidase gene expressing X-prolyl dipeptidyl aminopeptidase (PepX) activity was cloned from Lactobacillus rhamnosus 1/6 by using the chromogenic substrate L-glycyl-L-prolyl-beta-naphthylamide for screening of a genomic library in Escherichia coli. The nucleotide sequence of a 3.5-kb HindIII fragment expressing the peptidase activity revealed one complete open reading frame (ORF) of 2,391 nucleotides. The 797-amino-acid protein encoded by this ORF was shown to be 40, 39, and 36% identical with PepXs from Lactobacillus helveticus, Lactobacillus delbrueckii, and Lactococcus lactis, respectively. By Northern analysis with a pepX-specific probe, transcripts of 4.5 and 7.0 kb were detected, indicating that pepX is part of a polycistronic operon in L. rhamnosus. Cloning and sequencing of the upstream region of pepX revealed the presence of two ORFs of 360 and 1,338 bp that were shown to be able to encode proteins with high homology to GlnR and GlnA proteins, respectively. By multiple primer extension analyses, the only functional promoter in the pepX region was located 25 nucleotides upstream of glnR. Northern analysis with glnA- and pepX-specific probes indicated that transcription from glnR promoter results in a 2.0-kb dicistronic glnR-glnA transcript and also in a longer read-through polycistronic transcript of 7.0 kb that was detected with both probes in samples from cells in exponential growth phase. The glnA gene was disrupted by a single-crossover recombinant event using a nonreplicative plasmid carrying an internal part of glnA. In the disruption mutant, glnRA-specific transcription was derepressed 10-fold compared to the wild type, but the 7.0-kb transcript was no longer detectable with either the glnA- or pepX-specific probe, demonstrating that pepX is indeed part of glnRA operon in L. rhamnosus. Reverse transcription-PCR analysis further supported this operon structure. An extended stem-loop structure was identified immediately upstream of pepX in the gln

  13. Synthesis of protected 2-pyrrolylalanine for peptide chemistry and examination of its influence on prolyl amide isomer equilibrium.

    Science.gov (United States)

    Dörr, Aurélie A; Lubell, William D

    2012-08-03

    Protected enantiopure 2-pyrrolylalanine was synthesized for application in peptide science as an electron-rich arylalanine (histidine) analog with π-donor capability. (2S)-N-(Boc)-N'-(Phenylsulfonyl)-, (2S)-N,N'-bis-(phenylsulfonyl)-, and (2S)-N,N'-bis-(Boc)-3-(2-pyrrolyl)alanines (10, 3, and 14, respectively) were made in 13-17% overall yields and six to seven steps from oxazolidine β-methyl ester 4. Homoallylic ketone 5 was prepared by a copper-catalyzed cascade addition of vinylmagnesium bromide to ester 4 and converted to pyrrolyl amino alcohol 7 by olefin oxidation and Paal-Knorr condensation. Protecting group shuffle and oxidation of the primary alcohol enabled the synthesis of pyrrolylalanines. The bis-Boc analog 14 proved useful in peptide chemistry and was employed to make N-acetyl-pyrrolylalaninyl-proline N''-methylamide 25. A study of the influence of the pyrrole moiety on the prolyl amide isomer equilibrium of 25 using (1)H NMR spectroscopy in chloroform, DMSO, and water demonstrated that the pyrrolylalanine peptide exhibited behavior and conformations different from those of other arylalanine analogs.

  14. The Cytoplasmic Prolyl-tRNA Synthetase of the Malaria Parasite is a Dual-Stage Target for Drug Development

    Science.gov (United States)

    Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.; Ribacke, Ulf; Lukens, Amanda K.; Santos, Sofia A.; Patel, Vishal; Clish, Clary B.; Sullivan, William J.; Zhou, Huihao; Bopp, Selina E.; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M.; Keller, Tracy L.; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F.; Mazitschek, Ralph

    2015-01-01

    The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials. PMID:25995223

  15. Oral delivery of prolyl hydroxylase inhibitor: AKB-4924 promotes localized mucosal healing in a mouse model of colitis.

    Science.gov (United States)

    Marks, Ellen; Goggins, Bridie J; Cardona, Jocelle; Cole, Siobhan; Minahan, Kyra; Mateer, Sean; Walker, Marjorie M; Shalwitz, Robert; Keely, Simon

    2015-02-01

    Pharmacological induction of hypoxia-inducible factor (HIF), a global transcriptional regulator of the hypoxic response, by prolyl hydroxylase inhibitors (PHDi) is protective in murine models of colitis, and epithelial cells are critical for the observed therapeutic efficacy. Because systemic HIF activation may lead to potentially negative off-target effects, we hypothesized that targeting epithelial HIF through oral delivery of PHDi would be sufficient to protect against colitis in a mouse model. Using a chemically induced trinitrobenzene sulfonic acid murine model of colitis, we compared the efficacy of oral and intraperitoneal (i.p.) delivery of the PHDi; AKB-4924 in preventing colitis, as measured by endoscopy, histology, barrier integrity, and immune profiling. Furthermore, we measured potential off-target effects, examining HIF and HIF target genes in the heart and kidney, as well as erythropoietin and hematocrit levels. Oral administration of AKB-4924 exhibited mucosal protection comparable i.p. dosing. Oral delivery of PHDi led to reduced colonic epithelial HIF stabilization compared with i.p. delivery, but this was still sufficient to induce transcription of downstream HIF targets. Furthermore, oral delivery of PHDi led to reduced stabilization of HIF and activation of HIF targets in extraintestinal organs. Oral delivery of PHDi therapies to this intestinal mucosa protects against colitis in animal models and represents a potential therapeutic strategy for inflammatory bowel disease, which also precludes unwanted extraintestinal effects.

  16. Negative Regulation of the Stability and Tumor Suppressor Function of Fbw7 by the Pin1 Prolyl Isomerase

    Science.gov (United States)

    Min, Sang-Hyun; Lau, Alan W.; Lee, Tae Ho; Inuzuka, Hiroyuki; Wei, Shuo; Huang, Pengyu; Shaik, Shavali; Lee, Daniel Yenhong; Finn, Greg; Balastik, Martin; Chen, Chun-Hau; Luo, Manli; Tron, Adriana E.; DeCaprio, James A.; Zhou, Xiao Zhen; Wei, Wenyi; Lu, Kun Ping

    2012-01-01

    SUMMARY Fbw7 is the substrate recognition component of the SCF (Skp1-Cullin-F-box)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction. Genomic deletion or mutation of FBW7 has been frequently found in various types of human cancers, however, little is known about the upstream signaling pathway(s) governing Fbw7 stability and cellular functions. Here we report that Fbw7 protein destruction and tumor suppressor function are negatively regulated by the prolyl isomerase Pin1. Pin1 interacts with Fbw7 in a phoshorylation-dependent manner and promotes Fbw7 self-ubiquitination and protein degradation by disrupting Fbw7 dimerization. Consequently, over-expressing Pin1 reduces Fbw7 abundance and suppresses Fbw7’s ability to inhibit proliferation and transformation. By contrast, depletion of Pin1 in cancer cells leads to elevated Fbw7 expression, which subsequently reduces Mcl-1 abundance, sensitizing cancer cells to Taxol. Thus, Pin1-mediated inhibition of Fbw7 contributes to oncogenesis and Pin1 may be a promising drug target for anti-cancer therapy. PMID:22608923

  17. Characterizing the interactions between prolyl isomerase pin1 and phosphatase inhibitor-2 in living cells with FRET and FCS

    Science.gov (United States)

    Sun, Yuansheng; Wang, Lifu; Jyothikumar, Vinod; Brautigan, David L.; Periasamy, Ammasi

    2012-03-01

    Phosphatase inhibitor-2 (I2) was discovered as a regulator of protein Ser/Thr phosphatase-1 and is conserved from yeast to human. Binding between purified recombinant I2 from different species and the prolyl isomerase Pin1 has been demonstrated with pull-down assays, size exclusion chromatography and nuclear magnetic resonance spectroscopy. Despite this, questions persist as to whether these proteins associate together in living cells. In this study, we prepared fluorescent protein (FP) fusions of I2 and Pin1 and employed both Förster Resonance Energy Transfer (FRET) and Fluorescence Correlation Spectroscopy (FCS) imaging techniques to characterize their interactions in living cells. In both intensity-based and time-resolved FRET studies, we observed FRET uniformly across whole cells co-expressing I2-Cerulean and Pin1-Venus that was significantly higher than in negative controls expressing Cerulean FP (without fusing to I2) as the FRET donor and Pin1-Venus, showing a specific interaction between I2-Cerulean and Pin1-Venus in living cells. We also observed the co-diffusion of I2-Cerulean and Pin1-mCherry in Fluorescence Cross Correlation Spectroscopy (FCCS) measurements. We further showed that I2 itself as well as I2-Pin1 formed complexes in living cells (predicted from in vitro studies) via a quantitative FRET assay, and demonstrated from FCS measurements that both I2 and Pin1 (fused to Cerulean) are highly mobile in living cells.

  18. Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis.

    Science.gov (United States)

    Jain, Vitul; Yogavel, Manickam; Kikuchi, Haruhisa; Oshima, Yoshiteru; Hariguchi, Norimitsu; Matsumoto, Makoto; Goel, Preeti; Touquet, Bastien; Jumani, Rajiv S; Tacchini-Cottier, Fabienne; Harlos, Karl; Huston, Christopher D; Hakimi, Mohamed-Ali; Sharma, Amit

    2017-10-03

    Developing anti-parasitic lead compounds that act on key vulnerabilities are necessary for new anti-infectives. Malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis and coccidiosis together kill >500,000 humans annually. Their causative parasites Plasmodium, Leishmania, Toxoplasma, Cryptosporidium and Eimeria display high conservation in many housekeeping genes, suggesting that these parasites can be attacked by targeting invariant essential proteins. Here, we describe selective and potent inhibition of prolyl-tRNA synthetases (PRSs) from the above parasites using a series of quinazolinone-scaffold compounds. Our PRS-drug co-crystal structures reveal remarkable active site plasticity that accommodates diversely substituted compounds, an enzymatic feature that can be leveraged for refining drug-like properties of quinazolinones on a per parasite basis. A compound we termed In-5 exhibited a unique double conformation, enhanced drug-like properties, and cleared malaria in mice. It thus represents a new lead for optimization. Collectively, our data offer insights into the structure-guided optimization of quinazolinone-based compounds for drug development against multiple human eukaryotic pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α.

    Science.gov (United States)

    Arsenault, Patrick R; Song, Daisheng; Chung, Yu Jin; Khurana, Tejvir S; Lee, Frank S

    2016-09-15

    Prolyl hydroxylase domain protein 2 (PHD2) (also known as EGLN1) is a key oxygen sensor in mammals that posttranslationally modifies hypoxia-inducible factor α (HIF-α) and targets it for degradation. In addition to its catalytic domain, PHD2 contains an evolutionarily conserved zinc finger domain, which we have previously proposed recruits PHD2 to the HSP90 pathway to promote HIF-α hydroxylation. Here, we provide evidence that this recruitment is critical both in vitro and in vivo We show that in vitro, the zinc finger can function as an autonomous recruitment domain to facilitate interaction with HIF-α. In vivo, ablation of zinc finger function by a C36S/C42S Egln1 knock-in mutation results in upregulation of the erythropoietin gene, erythrocytosis, and augmented hypoxic ventilatory response, all hallmarks of Egln1 loss of function and HIF stabilization. Hence, the zinc finger ordinarily performs a critical positive regulatory function. Intriguingly, the function of this zinc finger is impaired in high-altitude-adapted Tibetans, suggesting that their adaptation to high altitude may, in part, be due to a loss-of-function EGLN1 allele. Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells

    International Nuclear Information System (INIS)

    Kimira, Yoshifumi; Ogura, Kana; Taniuchi, Yuri; Kataoka, Aya; Inoue, Naoki; Sugihara, Fumihito; Nakatani, Sachie; Shimizu, Jun; Wada, Masahiro; Mano, Hiroshi

    2014-01-01

    Highlights: • Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization. • Pro-Hyp significantly increased alkaline phosphatase activity. • Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. - Abstract: Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicate that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression

  1. Structure of Prolyl-tRNA Synthetase-Halofuginone Complex Provides Basis for Development of Drugs against Malaria and Toxoplasmosis.

    Science.gov (United States)

    Jain, Vitul; Yogavel, Manickam; Oshima, Yoshiteru; Kikuchi, Haruhisa; Touquet, Bastien; Hakimi, Mohamed-Ali; Sharma, Amit

    2015-05-05

    The Chinese herb Dichroa febrifuga has traditionally treated malaria-associated fever. Its active component febrifugine (FF) and derivatives such as halofuginone (HF) are potent anti-malarials. Here, we show that FF-based derivatives arrest parasite growth by direct interaction with and inhibition of the protein translation enzyme prolyl-tRNA synthetase (PRS). Dual administration of inhibitors that target different tRNA synthetases suggests high utility of these drug targets. We reveal the ternary complex structure of PRS-HF and adenosine 5'-(β,γ-imido)triphosphate where the latter facilitates HF integration into the PRS active site. Structural analyses also highlight spaces within the PRS architecture for HF derivatization of its quinazolinone, but not piperidine, moiety. We also show a remarkable ability of HF to kill the related human parasite Toxoplasma gondii, suggesting wider HF efficacy against parasitic PRSs. Hence, our cell-, enzyme-, and structure-based data on FF-based inhibitors strengthen the case for their inclusion in anti-malarial and anti-toxoplasmosis drug development efforts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Effects of UPR and ERAD pathway on the prolyl endopeptidase production in Pichia pastoris by controlling of nitrogen source.

    Science.gov (United States)

    Wang, Xiao-Dong; Jiang, Ting; Yu, Xiao-Wei; Xu, Yan

    2017-07-01

    Prolyl endopeptidase (PEP) is very useful in various industries, while the high cost of enzyme production remains a major obstacle for its industrial applications. Pichia pastoris has been used for the PEP production; however, the fermentation process has not be investigated and little is known about the impact of excessive PEP production on the host cell physiology. Here, we optimized the nitrogen source to improve the PEP expression level and further evaluated the cellular response including UPR and ERAD. During methanol induction phase the PEP activity (1583 U/L) was increased by 1.48-fold under the optimized nitrogen concentration of NH 4 + (300 mmol/L) and casamino acids [1.0% (w/v)] in a 3-L bioreactor. Evaluated by RT-PCR the UPR and ERAD pathways were confirmed to be activated. Furthermore, a strong decrease of ERAD-related gene transcription was observed with the addition of nitrogen source, which contributed to a higher PEP expression level.

  3. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    to isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) and maintenance of normal blood pressure (BP). The tripeptides IPP and VPP are sufficiently characterised. Maintenance of normal blood pressure is a beneficial physiological effect. The applicant identified a total of 20 published intervention......Following an application from Valio Ltd submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related...... relationship has not been established between the consumption of IPP and VPP and maintenance of normal blood pressure. © European Food Safety Authority, 2011...

  4. Molecular Cloning, Characterization, and Expression Analysis of a Prolyl 4-Hydroxylase from the Marine Sponge Chondrosia reniformis.

    Science.gov (United States)

    Pozzolini, Marina; Scarfì, Sonia; Mussino, Francesca; Ferrando, Sara; Gallus, Lorenzo; Giovine, Marco

    2015-08-01

    Prolyl 4-hydroxylase (P4H) catalyzes the hydroxylation of proline residues in collagen. P4H has two functional subunits, α and β. Here, we report the cDNA cloning, characterization, and expression analysis of the α and β subunits of the P4H derived from the marine sponge Chondrosia reniformis. The amino acid sequence of the α subunit is 533 residues long with an M r of 59.14 kDa, while the β subunit counts 526 residues with an M r of 58.75 kDa. Phylogenetic analyses showed that αP4H and βP4H are more related to the mammalian sequences than to known invertebrate P4Hs. Western blot analysis of sponge lysate protein cross-linking revealed a band of 240 kDa corresponding to an α2β2 tetramer structure. This result suggests that P4H from marine sponges shares the same quaternary structure with vertebrate homologous enzymes. Gene expression analyses showed that αP4H transcript is higher in the choanosome than in the ectosome, while the study of factors affecting its expression in sponge fragmorphs revealed that soluble silicates had no effect on the αP4H levels, whereas ascorbic acid strongly upregulated the αP4H mRNA. Finally, treatment with two different tumor necrosis factor (TNF)-alpha inhibitors determined a significant downregulation of αP4H gene expression in fragmorphs demonstrating, for the first time in Porifera, a positive involvement of TNF in sponge matrix biosynthesis. The molecular characterization of P4H genes involved in collagen hydroxylation, including the mechanisms that regulate their expression, is a key step for future recombinant sponge collagen production and may be pivotal to understand pathological mechanisms related to extracellular matrix deposition in higher organisms.

  5. Insights on the evolution of prolyl 3-hydroxylation sites from comparative analysis of chicken and Xenopus fibrillar collagens.

    Science.gov (United States)

    Hudson, David M; Weis, Maryann; Eyre, David R

    2011-05-03

    Recessive mutations that prevent 3-hydroxyproline formation in type I collagen have been shown to cause forms of osteogenesis imperfecta. In mammals, all A-clade collagen chains with a GPP sequence at the A1 site (P986), except α1(III), have 3Hyp at residue P986. Available avian, amphibian and reptilian type III collagen sequences from the genomic database (Ensembl) all differ in sequence motif from mammals at the A1 site. This suggests a potential evolutionary distinction in prolyl 3-hydroxylation between mammals and earlier vertebrates. Using peptide mass spectrometry, we confirmed that this 3Hyp site is fully occupied in α1(III) from an amphibian, Xenopus laevis, as it is in chicken. A thorough characterization of all predicted 3Hyp sites in collagen types I, II, III and V from chicken and xenopus revealed further differences in the pattern of occupancy of the A3 site (P707). In mammals only α2(I) and α2(V) chains had any 3Hyp at the A3 site, whereas in chicken all α-chains except α1(III) had A3 at least partially 3-hydroxylated. The A3 site was also partially 3-hydroxylated in xenopus α1(I). Minor differences in covalent cross-linking between chicken, xenopus and mammal type I and III collagens were also found as a potential index of evolving functional differences. The function of 3Hyp is still unknown but observed differences in site occupancy during vertebrate evolution are likely to give important clues.

  6. Effects of Prolyl Hydroxylase Inhibitor L-mimosine on Dental Pulp in the Presence of Advanced Glycation End Products.

    Science.gov (United States)

    Müller, Heinz-Dieter; Cvikl, Barbara; Janjić, Klara; Nürnberger, Sylvia; Moritz, Andreas; Gruber, Reinhard; Agis, Hermann

    2015-11-01

    Proangiogenic prolyl hydroxylase (PHD) inhibitors represent a novel approach to stimulate tissue regeneration. Diabetes mellitus involves the accumulation of advanced glycation end products (AGEs). Here we evaluated the impact of AGEs on the response of human pulp tissue to the PHD inhibitor L-mimosine (L-MIM) in monolayer cultures of dental pulp-derived cells (DPCs) and tooth slice organ cultures. In monolayer cultures, DPCs were incubated with L-MIM and AGEs. Viability was assessed based on formazan formation, live-dead staining, annexin V/propidium iodide, and trypan blue exclusion assay. Vascular endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 production was evaluated by quantitative polymerase chain reaction and immunoassays. Furthermore, expression levels of odontoblast markers were assessed, and alizarin red staining was performed. Tooth slice organ cultures were performed, and VEGF, IL-6, and IL8 levels in their supernatants were measured by immunoassays. Pulp tissue vitality and morphology were assessed by MTT assay and histology. In monolayer cultures of DPCs, L-MIM at nontoxic concentrations increased the production of VEGF and IL-8 in the presence of AGEs. Stimulation with L-MIM decreased alkaline phosphatase levels and matrix mineralization also in the presence of AGEs, whereas no significant changes in dentin matrix protein 1 and dentin sialophosphoprotein expression were observed. In tooth slice organ cultures, L-MIM increased VEGF but not IL-6 and IL-8 production in the presence of AGEs. The pulp tissue was vital, and no signs of apoptosis or necrosis were observed. Overall, in the presence of AGEs, L-MIM increases the proangiogenic capacity, but decreases alkaline phosphatase expression and matrix mineralization. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Peptidyl-prolyl cis/trans-isomerase A1 (Pin1) is a target for modification by lipid electrophiles.

    Science.gov (United States)

    Aluise, Christopher D; Rose, Kristie; Boiani, Mariana; Reyzer, Michelle L; Manna, Joseph D; Tallman, Keri; Porter, Ned A; Marnett, Lawrence J

    2013-02-18

    Oxidation of membrane phospholipids is associated with inflammation, neurodegenerative disease, and cancer. Oxyradical damage to phospholipids results in the production of reactive aldehydes that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His-157 and Cys-113. Time and concentration dependencies indicate that Cys-113 is the primary site of HNE modification. Pin1 was adducted in MDA-MB-231 breast cancer cells treated with 8-alkynyl-HNE as judged by click chemistry conjugation with biotin followed by streptavidin-based pulldown and Western blotting with anti-Pin1 antibody. Furthermore, orbitrap MS data support the adduction of Cys-113 in the Pin1 active site upon HNE treatment of MDA-MB-231 cells. siRNA knockdown of Pin1 in MDA-MB-231 cells partially protected the cells from HNE-induced toxicity. Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols. The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation.

  8. Insights on the evolution of prolyl 3-hydroxylation sites from comparative analysis of chicken and Xenopus fibrillar collagens.

    Directory of Open Access Journals (Sweden)

    David M Hudson

    2011-05-01

    Full Text Available Recessive mutations that prevent 3-hydroxyproline formation in type I collagen have been shown to cause forms of osteogenesis imperfecta. In mammals, all A-clade collagen chains with a GPP sequence at the A1 site (P986, except α1(III, have 3Hyp at residue P986. Available avian, amphibian and reptilian type III collagen sequences from the genomic database (Ensembl all differ in sequence motif from mammals at the A1 site. This suggests a potential evolutionary distinction in prolyl 3-hydroxylation between mammals and earlier vertebrates. Using peptide mass spectrometry, we confirmed that this 3Hyp site is fully occupied in α1(III from an amphibian, Xenopus laevis, as it is in chicken. A thorough characterization of all predicted 3Hyp sites in collagen types I, II, III and V from chicken and xenopus revealed further differences in the pattern of occupancy of the A3 site (P707. In mammals only α2(I and α2(V chains had any 3Hyp at the A3 site, whereas in chicken all α-chains except α1(III had A3 at least partially 3-hydroxylated. The A3 site was also partially 3-hydroxylated in xenopus α1(I. Minor differences in covalent cross-linking between chicken, xenopus and mammal type I and III collagens were also found as a potential index of evolving functional differences. The function of 3Hyp is still unknown but observed differences in site occupancy during vertebrate evolution are likely to give important clues.

  9. Essential roles of insulin, AMPK signaling and lysyl and prolyl hydroxylases in the biosynthesis and multimerization of adiponectin.

    Science.gov (United States)

    Zhang, Lin; Li, Ming-Ming; Corcoran, Marie; Zhang, Shaoping; Cooper, Garth J S

    2015-01-05

    Post-translational modifications (PTMs) of the adiponectin molecule are essential for its full bioactivity, and defects in PTMs leading to its defective production and multimerization have been linked to the mechanisms of insulin resistance, obesity, and type-2 diabetes. Here we observed that, in differentiated 3T3-L1 adipocytes, decreased insulin signaling caused by blocking of insulin receptors (InsR) with an anti-InsR blocking antibody, increased rates of adiponectin secretion, whereas concomitant elevations in insulin levels counteracted this effect. Adenosine monophosphate-activated protein kinase (AMPK) signaling regulated adiponectin production by modulating the expression of adiponectin receptors, the secretion of adiponectin, and eventually the expression of adiponectin itself. We found that lysyl hydroxylases (LHs) and prolyl hydroxylases (PHs) were expressed in white-adipose tissue of ob/ob mice, wherein LH3 levels were increased compared with controls. In differentiated 3T3-L1 adipocytes, both non-specific inhibition of LHs and PHs by dipyridyl, and specific inhibition of LHs by minoxidil and of P4H with ethyl-3,4-dihydroxybenzoate, caused significant suppression of adiponectin production, more particularly of the higher-order isoforms. Transient gene knock-down of LH3 (Plod3) caused a suppressive effect, especially on the high molecular-weight (HMW) isoforms. These data indicate that PHs and LHs are both required for physiological adiponectin production and in particular are essential for the formation/secretion of the HMW isoforms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Statistical optimization of cell disruption techniques for releasing intracellular X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis spp. lactis.

    Science.gov (United States)

    Üstün-Aytekin, Özlem; Arısoy, Sevda; Aytekin, Ali Özhan; Yıldız, Ece

    2016-03-01

    X-prolyl dipeptidyl aminopeptidase (PepX) is an intracellular enzyme from the Gram-positive bacterium Lactococcus lactis spp. lactis NRRL B-1821, and it has commercial importance. The objective of this study was to compare the effects of several cell disruption methods on the activity of PepX. Statistical optimization methods were performed for two cavitation methods, hydrodynamic (high-pressure homogenization) and acoustic (sonication), to determine the more appropriate disruption method. Two level factorial design (2FI), with the parameters of number of cycles and pressure, and Box-Behnken design (BBD), with the parameters of cycle, sonication time, and power, were used for the optimization of the high-pressure homogenization and sonication methods, respectively. In addition, disruption methods, consisting of lysozyme, bead milling, heat treatment, freeze-thawing, liquid nitrogen, ethylenediaminetetraacetic acid (EDTA), Triton-X, sodium dodecyl sulfate (SDS), chloroform, and antibiotics, were performed and compared with the high-pressure homogenization and sonication methods. The optimized values of high-pressure homogenization were one cycle at 130 MPa providing activity of 114.47 mU ml(-1), while sonication afforded an activity of 145.09 mU ml(-1) at 28 min with 91% power and three cycles. In conclusion, sonication was the more effective disruption method, and its optimal operation parameters were manifested for the release of intracellular enzyme from a L. lactis spp. lactis strain, which is a Gram-positive bacterium. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

    Science.gov (United States)

    Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

    2011-11-01

    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

  12. Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase.

    Science.gov (United States)

    Wright, Helena; Kiss, András L; Szeltner, Zoltán; Polgár, László; Fülöp, Vilmos

    2005-10-01

    Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris-HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 A resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 A and four molecules in the asymmetric unit.

  13. Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

    Science.gov (United States)

    Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

    2010-01-01

    Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional

  14. Peptidyl prolyl isomerase Pin1-inhibitory activity of D-glutamic and D-aspartic acid derivatives bearing a cyclic aliphatic amine moiety.

    Science.gov (United States)

    Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki

    2015-12-01

    Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain.

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    Mun Chiang Chan

    Full Text Available As part of the cellular adaptation to limiting oxygen availability in animals, the expression of a large set of genes is activated by the upregulation of the hypoxia-inducible transcription factors (HIFs. Therapeutic activation of the natural human hypoxic response can be achieved by the inhibition of the hypoxia sensors for the HIF system, i.e. the HIF prolyl-hydroxylases (PHDs. Here, we report studies on tricyclic triazole-containing compounds as potent and selective PHD inhibitors which compete with the 2-oxoglutarate co-substrate. One compound (IOX4 induces HIFα in cells and in wildtype mice with marked induction in the brain tissue, revealing that it is useful for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke.

  16. A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation.

    Science.gov (United States)

    Mori, Tadashi; Hidaka, Masafumi; Ikuji, Hiroko; Yoshizawa, Ibuki; Toyohara, Haruhiko; Okuda, Toru; Uchida, Chiyoko; Asano, Tomoichiro; Yotsu-Yamashita, Mari; Uchida, Takafumi

    2014-01-01

    The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders.

  17. How Are Substrate Binding and Catalysis Affected by Mutating Glu127 and Arg161 in Prolyl-4-hydroxylase? A QM/MM and MD Study

    Science.gov (United States)

    Timmins, Amy; de Visser, Sam P.

    2017-01-01

    Prolyl-4-hydroxylase is a vital enzyme for human physiology involved in the biosynthesis of 4-hydroxyproline, an essential component for collagen formation. The enzyme performs a unique stereo- and regioselective hydroxylation at the C4 position of proline despite the fact that the C5 hydrogen atoms should be thermodynamically easier to abstract. To gain insight into the mechanism and find the origin of this regioselectivity, we have done a quantum mechanics/molecular mechanics (QM/MM) study on wildtype and mutant structures. In a previous study (Timmins et al., 2017) we identified several active site residues critical for substrate binding and positioning. In particular, the Glu127 and Arg161 were shown to form multiple hydrogen bonding and ion-dipole interactions with substrate and could thereby affect the regio- and stereoselectivity of the reaction. In this work, we decided to test that hypothesis and report a QM/MM and molecular dynamics (MD) study on prolyl-4-hydroxylase and several active site mutants where Glu127 or Arg161 are mutated for Asp, Gln, or Lys. Thus, the R161D and R161Q mutants give very high barriers for hydrogen atom abstraction from any proline C–H bond and therefore will be inactive. The R161K mutant, by contrast, sees the regio- and stereoselectivity of the reaction change but still is expected to hydroxylate proline at room temperature. By contrast, the Glu127 mutants E127D and E127Q show possible changes in regioselectivity with the former being more probable to react compared to the latter. PMID:29170737

  18. Identification of N-glycosylation in prolyl endoprotease from Aspergillus niger and evaluation of the enzyme for its possible application in proteomics.

    Science.gov (United States)

    Sebela, Marek; Rehulka, Pavel; Kábrt, Jaromír; Rehulková, Helena; Ozdian, Tomás; Raus, Martin; Franc, Vojtech; Chmelík, Josef

    2009-11-01

    An acidic prolyl endoprotease from Aspergillus niger was isolated from the commercial product Brewers Clarex to evaluate its possible application in proteomics. The chromatographic purification yielded a single protein band in sodium dodecyl sulfate polyacrylamide gel electrophoresis providing an apparent molecular mass of 63 kDa and a broad peak (m/z 58,061) in linear matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) indicating the glycoprotein nature of the enzyme. Indeed, a colorimetric assessment with phenol and sulfuric acid showed the presence of neutral sugars (9% of weight). The subsequent treatment with N-glycosidase F released a variety of high-mannose type N-glycans, which were successfully detected using MALDI-TOF MS. MALDI-TOF/TOF tandem MS analysis of glycopeptides from a tryptic digest of prolyl endoprotease unraveled the identity of the N-glycosylation site in the primary structure. The data obtained also show that the enzyme is present in its processed form, i.e. without putative signal and propeptide parts. Spectrophotometric measurements demonstrated optimal activity at pH 4.0-4.5 and also high thermostability for the cleavage at the C-terminal part of proline residues. In-solution digestion of standard proteins (12-200 kDa) allowed to evaluate the cleavage specificity. The enzyme acts upon proline and alanine residues, but there is an additional minor cleavage at some other residues like Gly, Leu, Arg, Ser and Tyr. The digestion of a honeybee peptide comprising six proline residues (apidaecin 1A) led to the detection of specific peptides terminated by proline as it was confirmed by MALDI postsource decay analysis. Copyright 2009 John Wiley & Sons, Ltd.

  19. How Are Substrate Binding and Catalysis Affected by Mutating Glu127 and Arg161 in Prolyl-4-hydroxylase? A QM/MM and MD Study

    Directory of Open Access Journals (Sweden)

    Amy Timmins

    2017-11-01

    Full Text Available Prolyl-4-hydroxylase is a vital enzyme for human physiology involved in the biosynthesis of 4-hydroxyproline, an essential component for collagen formation. The enzyme performs a unique stereo- and regioselective hydroxylation at the C4 position of proline despite the fact that the C5 hydrogen atoms should be thermodynamically easier to abstract. To gain insight into the mechanism and find the origin of this regioselectivity, we have done a quantum mechanics/molecular mechanics (QM/MM study on wildtype and mutant structures. In a previous study (Timmins et al., 2017 we identified several active site residues critical for substrate binding and positioning. In particular, the Glu127 and Arg161 were shown to form multiple hydrogen bonding and ion-dipole interactions with substrate and could thereby affect the regio- and stereoselectivity of the reaction. In this work, we decided to test that hypothesis and report a QM/MM and molecular dynamics (MD study on prolyl-4-hydroxylase and several active site mutants where Glu127 or Arg161 are mutated for Asp, Gln, or Lys. Thus, the R161D and R161Q mutants give very high barriers for hydrogen atom abstraction from any proline C–H bond and therefore will be inactive. The R161K mutant, by contrast, sees the regio- and stereoselectivity of the reaction change but still is expected to hydroxylate proline at room temperature. By contrast, the Glu127 mutants E127D and E127Q show possible changes in regioselectivity with the former being more probable to react compared to the latter.

  20. Isolation and characterization of cyclo-(tryptophanyl-prolyl and chloramphenicol from Streptomyces sp. SUK 25 with antimethicillin-resistant Staphylococcus aureus activity

    Directory of Open Access Journals (Sweden)

    Alshaibani MM

    2016-05-01

    resonance. Results: During screening procedure, SUK 25 exhibited good antimicrobial potential against several strains of MRSA. The best biological activity was shown from fraction number VII and its subfractions F2 and F3 with minimum inhibitory concentration values at 16 µg/mL and 8 µg/mL, respectively. These two subfractions were identified as diketopiperazine cyclo-(tryptophanyl-prolyl and chloramphenicol. Conclusion: On the basis of obtained results, SUK 25 isolated from Z. spectabile can be regarded as a new valuable source to produce secondary metabolites against bacteria, especially MRSA. Keywords: Zingiber spectabile, MRSA, SUK 25, cyclo-(tryptophanyl-prolyl, chloramphenicol, HR-MS, NMR

  1. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

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    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  2. Phospho-carboxyl-terminal domain binding and the role of a prolyl isomerase in pre-mRNA 3'-End formation.

    Science.gov (United States)

    Morris, D P; Phatnani, H P; Greenleaf, A L

    1999-10-29

    A phospho-carboxyl-terminal domain (CTD) affinity column created with yeast CTD kinase I and the CTD of RNA polymerase II was used to identify Ess1/Pin1 as a phospho-CTD-binding protein. Ess1/Pin1 is a peptidyl prolyl isomerase involved in both mitotic regulation and pre-mRNA 3'-end formation. Like native Ess1, a GSTEss1 fusion protein associates specifically with the phosphorylated but not with the unphosphorylated CTD. Further, hyperphosphorylated RNA polymerase II appears to be the dominant Ess1 binding protein in total yeast extracts. We demonstrate that phospho-CTD binding is mediated by the small WW domain of Ess1 rather than the isomerase domain. These findings suggest a mechanism in which the WW domain binds the phosphorylated CTD of elongating RNA polymerase II and the isomerase domain reconfigures the CTD though isomerization of proline residues perhaps by a processive mechanism. This process may be linked to a variety of pre-mRNA maturation events that use the phosphorylated CTD, including the coupled processes of pre-mRNA 3'-end formation and transcription termination.

  3. The peptidyl prolyl cis/trans isomerase Pin1/Ess1 inhibits phosphorylation and toxicity of tau in a yeast model for Alzheimer’s disease

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    Ann De Vos

    2015-04-01

    Full Text Available Since hyperphosphorylation of protein tau is a crucial event in Alzheimer’s disease, additional mechanisms besides the interplay of kinase and phosphatase activities are investigated, such as the effect of the peptidyl prolyl cis/trans isomerase Pin1. This isomerase was shown to bind and isomerize phosphorylated protein tau, thereby restoring the microtubule associated protein function of tau as well as promoting the dephosphorylation of the protein by the trans-dependent phosphatase PP2A. In this study we used models based on Saccharomyces cerevisiae to further elucidate the influence of Pin1 and its yeast ortholog Ess1 on tau phosphorylation and self-assembly. We could demonstrate that in yeast, a lack of Pin1 isomerase activity leads to an increase in phosphorylation of tau at Thr231, comparable to AD brain and consistent with earlier findings in other model organisms. However, we could also distinguish an effect by Pin1 on other residues of tau, i.e. Ser235 and Ser198/199/202. Furthermore, depletion of Pin1 isomerase activity results in reduced growth of the yeast cells, which is enhanced upon expression of tau. This suggests that the accumulation of hyperphosphorylated and aggregation-prone tau causes cytotoxicity in yeast. This study introduces yeast as a valuable model organism to characterize in detail the effect of Pin1 on the biochemical characteristics of protein tau, more specifically its phosphorylation and aggregation.

  4. Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic-Ischemic Injury in the Neonatal Rat.

    Science.gov (United States)

    Chu, Hannah X; Jones, Nicole M

    2016-03-01

    Hypoxia leads to activation of many cellular adaptive processes which are regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 consists of HIF-1α and HIF-1ß subunits and levels of HIF-1α protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1α and PHDs at various time points after hypoxia-ischemia (HI), using a neonatal rat model of HI brain injury. Sprague-Dawley rat pups (postnatal day 7) were anaesthetized and underwent right carotid artery occlusion and were then exposed to 6 % oxygen for 2.5 h at 37 °C. HI injured animals demonstrated a significant reduction in the size of the ipsilateral hemisphere, compared to sham controls. Protein analysis using western blotting and enzyme-linked immunosorbent assay showed that 24 h after HI, there was a significant increase in PHD3 protein and an increase of HIF-1α compared to controls. At the 72 h time point, there was a reduction in PHD3 protein, which appeared to relate to cellular loss. There were no changes in PHD1 or PHD2 protein levels after HI when compared to age-matched controls. Further studies are necessary to establish roles for the HIF-1 regulatory enzyme PHD3 in brain injury processes.

  5. β-N-oxalyl-L-α, β- diaminopropionic acid induces HRE expression by inhibiting HIF-prolyl hydroxylase-2 in normoxic conditions.

    Science.gov (United States)

    Eslavath, Ravi Kumar; Sharma, Deepshikha; Bin Omar, Nabil A M; Chikati, Rajasekhar; Teli, Mahesh Kumar; Rajanikant, G K; Singh, Surya S

    2016-11-15

    Hypoxia inducible factor (HIF)-1α, a subunit of HIF transcription factor, regulates cellular response to hypoxia. In normoxic conditions, it is hydroxylated by prolyl hydroxylase (PHD)-2 and targeted for proteosomal degradation. Drugs which inhibit PHD-2 have implications in conditions arising from insufficient blood supply. β-ODAP (β-N- oxalyl-L-α, β- diaminopropionic acid), a non-protein excitatory amino acid present in Lathyrus sativus, is an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor agonist known to activate conventional protein kinase C and stabilize HIF-1α under normoxic conditions. However, the mechanism of HIF-1α stabilization by this compound is unknown. In silico approach was used to understand the mechanism of stabilization of HIF-1α which revealed β-ODAP interacts with key amino acid residues and Fe 2+ at the catalytic site of PHD-2. These results were further corroborated with luciferase HRE (hypoxia response element) reporter system in HeLa cells. Different chemical modulators of PHD-2 activity and HIF-1α levels were included in the study for comparison. Results obtained indicate that β-ODAP inhibits PHD-2 and facilitates HIF dependent HRE expression and hence, might be helpful in conditions arising from hypoxia. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Hepatitis C virus NS5A protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B.

    Science.gov (United States)

    Hanoulle, Xavier; Badillo, Aurélie; Wieruszeski, Jean-Michel; Verdegem, Dries; Landrieu, Isabelle; Bartenschlager, Ralf; Penin, François; Lippens, Guy

    2009-05-15

    We report here a biochemical and structural characterization of domain 2 of the nonstructural 5A protein (NS5A) from the JFH1 Hepatitis C virus strain and its interactions with cyclophilins A and B (CypA and CypB). Gel filtration chromatography, circular dichroism spectroscopy, and finally NMR spectroscopy all indicate the natively unfolded nature of this NS5A-D2 domain. Because mutations in this domain have been linked to cyclosporin A resistance, we used NMR spectroscopy to investigate potential interactions between NS5A-D2 and cellular CypA and CypB. We observed a direct molecular interaction between NS5A-D2 and both cyclophilins. The interaction surface on the cyclophilins corresponds to their active site, whereas on NS5A-D2, it proved to be distributed over the many proline residues of the domain. NMR heteronuclear exchange spectroscopy yielded direct evidence that many proline residues in NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl cis/trans isomerase (PPIase) activity of CypA and CypB.

  7. TAL effectors target the C-terminal domain of RNA polymerase II (CTD by inhibiting the prolyl-isomerase activity of a CTD-associated cyclophilin.

    Directory of Open Access Journals (Sweden)

    Mariane Noronha Domingues

    Full Text Available Transcriptional activator-like (TAL effectors of plant pathogenic bacteria function as transcription factors in plant cells. However, how TAL effectors control transcription in the host is presently unknown. Previously, we showed that TAL effectors of the citrus canker pathogen Xanthomonas citri, named PthAs, targeted the citrus protein complex comprising the thioredoxin CsTdx, ubiquitin-conjugating enzymes CsUev/Ubc13 and cyclophilin CsCyp. Here we show that CsCyp complements the function of Cpr1 and Ess1, two yeast cyclophilins that regulate transcription by the isomerization of proline residues of the regulatory C-terminal domain (CTD of RNA polymerase II. We also demonstrate that CsCyp, CsTdx, CsUev and four PthA variants interact with the citrus CTD and that CsCyp co-immunoprecipitate with the CTD in citrus cell extracts and with PthA2 transiently expressed in sweet orange epicotyls. The interactions of CsCyp with the CTD and PthA2 were inhibited by cyclosporin A (CsA, a cyclophilin inhibitor. Moreover, we present evidence that PthA2 inhibits the peptidyl-prolyl cis-trans isomerase (PPIase activity of CsCyp in a similar fashion as CsA, and that silencing of CsCyp, as well as treatments with CsA, enhance canker lesions in X. citri-infected leaves. Given that CsCyp appears to function as a negative regulator of cell growth and that Ess1 negatively regulates transcription elongation in yeast, we propose that PthAs activate host transcription by inhibiting the PPIase activity of CsCyp on the CTD.

  8. Identifying a novel role for X-prolyl aminopeptidase (Xpnpep) 2 in CrVI-induced adverse effects on germ cell nest breakdown and follicle development in rats.

    Science.gov (United States)

    Banu, Sakhila K; Stanley, Jone A; Sivakumar, Kirthiram K; Arosh, Joe A; Barhoumi, Rola; Burghardt, Robert C

    2015-03-01

    Environmental exposure to endocrine-disrupting chemicals (EDCs) is one cause of premature ovarian failure (POF). Hexavalent chromium (CrVI) is a heavy metal EDC widely used in more than 50 industries, including chrome plating, welding, wood processing, and tanneries. Recent data from U.S. Environmental Protection Agency indicate increased levels of Cr in drinking water from several American cities, which potentially predispose residents to various health problems. Recently, we demonstrated that gestational exposure to CrVI caused POF in F1 offspring. The current study was performed to identify the molecular mechanism behind CrVI-induced POF. Pregnant rats were treated with 25 ppm of potassium dichromate from Gestational Day (GD) 9.5 to GD 14.5 through drinking water, and the fetuses were exposed to CrVI through transplacental transfer. Ovaries were removed from the fetuses or pups on Embryonic Day (ED) 15.5, ED 17.5, Postnatal Day (PND) 1, PND 4, or PND 25, and various analyses were performed. Results showed that gestational exposure to CrVI: 1) increased germ cell/oocyte apoptosis and advanced germ cell nest (GCN) breakdown; 2) increased X-prolyl aminopeptidase (Xpnpep) 2, a POF marker in humans, during GCN breakdown; 3) decreased Xpnpep2 during postnatal follicle development; and 4) increased colocalization of Xpnpep2 with Col3 and Col4. We also found that Xpnpep2 inversely regulated the expression of Col1, Col3, and Col4 in all the developmental stages studied. Thus, CrVI advanced GCN breakdown and increased follicle atresia in F1 female progeny by targeting Xpnpep2. © 2015 by the Society for the Study of Reproduction, Inc.

  9. Proline substitutions in a Mip-like peptidyl-prolyl cis-trans isomerase severely affect its structure, stability, shape and activity

    Directory of Open Access Journals (Sweden)

    Soumitra Polley

    2015-01-01

    Full Text Available FKBP22, an Escherichia coli-specific peptidyl-prolyl cis-trans isomerase, shows substantial homology with the Mip-like virulence factors. Mip-like proteins are homodimeric and possess a V-shaped conformation. Their N-terminal domains form dimers, whereas their C-terminal domains bind protein/peptide substrates and distinct inhibitors such as rapamycin and FK506. Interestingly, the two domains of the Mip-like proteins are separated by a lengthy, protease-susceptible α-helix. To delineate the structural requirement of this domain-connecting region in Mip-like proteins, we have investigated a recombinant FKBP22 (rFKBP22 and its three point mutants I65P, V72P and A82P using different probes. Each mutant harbors a Pro substitution mutation at a distinct location in the hinge region. We report that the three mutants are not only different from each other but also different from rFKBP22 in structure and activity. Unlike rFKBP22, the three mutants were unfolded by a non-two state mechanism in the presence of urea. In addition, the stabilities of the mutants, particularly I65P and V72P, differed considerably from that of rFKBP22. Conversely, the rapamycin binding affinity of no mutant was different from that of rFKBP22. Of the mutants, I65P showed the highest levels of structural/functional loss and dissociated partly in solution. Our computational study indicated a severe collapse of the V-shape in I65P due to the anomalous movement of its C-terminal domains. The α-helical nature of the domain-connecting region is, therefore, critical for the Mip-like proteins.

  10. Therapeutic Potential of a Prolyl Hydroxylase Inhibitor FG-4592 for Parkinson’s Diseases in Vitro and in Vivo: Regulation of Redox Biology and Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Xuan Li

    2018-04-01

    Full Text Available As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α plays an important role in the pathogenesis of Parkinson’s disease (PD. HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD. Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms. In this study, we examined the therapeutic benefit of a new HIF-PHI, FG-4592, which is currently in phase 3 clinical trials to treat anemia in patients with chronic kidney diseases (CKD in PD models. FG-4592 attenuates MPP+ -induced apoptosis and loss of tyrosine hydroxylase (TH in SH-SY5Y cells. Pretreatment with FG-4592 mitigates MPP+-induced loss of mitochondrial membrane potential (MMP, mitochondrial oxygen consumption rate (OCR, production of reactive oxygen species (ROS and ATP. Furthermore, FG-4592 counterbalances the oxidative stress through up-regulating nuclear factor erythroid 2 p45-related factor 2 (Nrf-2, heme oxygenase-1 (HO-1 and superoxide dismutase 2 (SOD2. FG-4592 treatment also induces the expression of Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α through increasing the phosphorylation of AMP-activated protein kinase (AMPK. In MPTP-treated mice, FG-4592 protects against MPTP-induced loss of TH-positive neurons of substantia nigra and attenuates behavioral impairments. Collectively, our study demonstrates that FG-4592 is a promising therapeutic strategy for PD through improving the mitochondrial function under oxidative stress.

  11. Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.

    Science.gov (United States)

    Bergstrand, H; Eriksson, T; Hallberg, A; Johansson, B; Karabelas, K; Michelsen, P; Nybom, A

    1992-12-01

    To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. First-in-man-proof of concept study with molidustat: a novel selective oral HIF-prolyl hydroxylase inhibitor for the treatment of renal anaemia.

    Science.gov (United States)

    Böttcher, M; Lentini, S; Arens, E R; Kaiser, A; van der Mey, D; Thuss, U; Kubitza, D; Wensing, G

    2018-07-01

    Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and effect on EPO levels of single oral doses of molidustat in healthy male volunteers. This was a single-centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol-based solution. In total, 45 volunteers received molidustat and 14 received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma concentration and area under the concentration-time curve increased dose dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase in endogenous EPO was observed following single oral doses of molidustat of 12.5 mg and above. Geometric mean peak EPO levels were 14.8 IU l -1 (90% confidence interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l -1 (90% confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The time course of EPO levels resembled the normal diurnal variation in EPO. Maximum EPO levels were observed approximately 12 h postdose and returned to baseline after approximately 24-48 h. All doses of molidustat were well tolerated and there were no significant changes in vital signs or laboratory safety parameters. Oral administration of molidustat to healthy volunteers elicited a dose-dependent increase in endogenous EPO. These results support the ongoing development of molidustat as a potential new treatment for patients with renal anaemia. © 2018 The British Pharmacological Society.

  13. Family Therapy

    Science.gov (United States)

    Family therapy Overview Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided by a psychologist, ...

  14. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  15. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Directory of Open Access Journals (Sweden)

    Seeley TW

    2017-03-01

    Full Text Available Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu Therapeutics R&D, FibroGen, Inc., San Francisco, CA, USA Abstract: The effects of pharmacological hypoxia-inducible factor (HIF stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF, using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs, FG-4497 or roxadustat (FG-4592. In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. Keywords: cancer progression, erythropoiesis, hypoxia-inducible factor, hypoxia-inducible factor prolyl hydroxylase inhibitors, vascular endothelial growth factor, MMTV-Neu breast cancer model

  16. An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

    Science.gov (United States)

    Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

    2017-01-01

    Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently

  17. Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I.

    Science.gov (United States)

    Aro, Ellinoora; Salo, Antti M; Khatri, Richa; Finnilä, Mikko; Miinalainen, Ilkka; Sormunen, Raija; Pakkanen, Outi; Holster, Tiina; Soininen, Raija; Prein, Carina; Clausen-Schaumann, Hauke; Aszódi, Attila; Tuukkanen, Juha; Kivirikko, Kari I; Schipani, Ernestina; Myllyharju, Johanna

    2015-07-03

    Collagen prolyl 4-hydroxylases (C-P4H-I, C-P4H-II, and C-P4H-III) catalyze formation of 4-hydroxyproline residues required to form triple-helical collagen molecules. Vertebrate C-P4Hs are α2β2 tetramers differing in their catalytic α subunits. C-P4H-I is the major isoenzyme in most cells, and inactivation of its catalytic subunit (P4ha1(-/-)) leads to embryonic lethality in mouse, whereas P4ha1(+/-) mice have no abnormalities. To study the role of C-P4H-II, which predominates in chondrocytes, we generated P4ha2(-/-) mice. Surprisingly, they had no apparent phenotypic abnormalities. To assess possible functional complementarity, we established P4ha1(+/-);P4ha2(-/-) mice. They were smaller than their littermates, had moderate chondrodysplasia, and developed kyphosis. A transient inner cell death phenotype was detected in their developing growth plates. The columnar arrangement of proliferative chondrocytes was impaired, the amount of 4-hydroxyproline and the Tm of collagen II were reduced, and the extracellular matrix was softer in the growth plates of newborn P4ha1(+/-);P4ha2(-/-) mice. No signs of uncompensated ER stress were detected in the mutant growth plate chondrocytes. Some of these defects were also found in P4ha2(-/-) mice, although in a much milder form. Our data show that C-P4H-I can to a large extent compensate for the lack of C-P4H-II in proper endochondral bone development, but their combined partial and complete inactivation, respectively, leads to biomechanically impaired extracellular matrix, moderate chondrodysplasia, and kyphosis. Our mouse data suggest that inactivating mutations in human P4HA2 are not likely to lead to skeletal disorders, and a simultaneous decrease in P4HA1 function would most probably be required to generate such a disease phenotype. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3αβ involved in protection of oral squamous cell carcinoma against cadmium toxicity

    Energy Technology Data Exchange (ETDEWEB)

    So, Keum-Young [Department of Anesthesiology and Pain Medicine College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Ahn, Sang-Gun [Department of Pathology, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of); Oh, Seon-Hee, E-mail: seonh@chosun.ac.kr [Department of Premedicine, School of Medicine, College of Dentistry, Chosun University, 309 Pilmundaero, Dong-gu, Gwangju 501-759 (Korea, Republic of)

    2015-10-23

    Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose–response experiments, cleavage of procaspase-3, PARP-1, and LC3-II was induced by Cd with an IC{sub 50} of 45 μM. Expression of Pin1 was decreased at or above the Cd IC{sub 50} value and was inversely correlated with the level of phospho(p)-Ser-GSK3αβ. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3αβ; this was reversed by overexpression of Pin1. However, suppression of GSK3αβ inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3β. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3αβ and autophagy and induced apoptosis. Therefore, p-Ser-GSK3αβ can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3αβ at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. - Highlights: • Pin1 regulated autophagy to protect cells from cadmium toxicity. • Pin1 suppression inhibited cadmium-induced autophagy and induced apoptosis. • Pin1 inhibited the function of p-Ser-GSK3αβ in autophagy regulation. • p-Ser-GSK3αβ regulated autophagy independently of Pin1.

  19. Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3αβ involved in protection of oral squamous cell carcinoma against cadmium toxicity

    International Nuclear Information System (INIS)

    So, Keum-Young; Ahn, Sang-Gun; Oh, Seon-Hee

    2015-01-01

    Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose–response experiments, cleavage of procaspase-3, PARP-1, and LC3-II was induced by Cd with an IC_5_0 of 45 μM. Expression of Pin1 was decreased at or above the Cd IC_5_0 value and was inversely correlated with the level of phospho(p)-Ser-GSK3αβ. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3αβ; this was reversed by overexpression of Pin1. However, suppression of GSK3αβ inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3β. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3αβ and autophagy and induced apoptosis. Therefore, p-Ser-GSK3αβ can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3αβ at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. - Highlights: • Pin1 regulated autophagy to protect cells from cadmium toxicity. • Pin1 suppression inhibited cadmium-induced autophagy and induced apoptosis. • Pin1 inhibited the function of p-Ser-GSK3αβ in autophagy regulation. • p-Ser-GSK3αβ regulated autophagy independently of Pin1.

  20. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Guoxing [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Shi, Hui [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Li, Jiong; Yang, Zhe [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Fang, Runping; Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Zhang, Weiying, E-mail: zhwybao@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China)

    2016-04-08

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells through

  1. Hydroxylation of recombinant human collagen type I alpha 1 in transgenic maize co-expressed with a recombinant human prolyl 4-hydroxylase

    Directory of Open Access Journals (Sweden)

    Pappu Kameshwari M

    2011-06-01

    Full Text Available Abstract Background Collagens require the hydroxylation of proline (Pro residues in their triple-helical domain repeating sequence Xaa-Pro-Gly to function properly as a main structural component of the extracellular matrix in animals at physiologically relevant conditions. The regioselective proline hydroxylation is catalyzed by a specific prolyl 4-hydroxylase (P4H as a posttranslational processing step. Results A recombinant human collagen type I α-1 (rCIα1 with high percentage of hydroxylated prolines (Hyp was produced in transgenic maize seeds when co-expressed with both the α- and β- subunits of a recombinant human P4H (rP4H. Germ-specific expression of rCIα1 using maize globulin-1 gene promoter resulted in an average yield of 12 mg/kg seed for the full-length rCIα1 in seeds without co-expression of rP4H and 4 mg/kg seed for the rCIα1 (rCIα1-OH in seeds with co-expression of rP4H. High-resolution mass spectrometry (HRMS analysis revealed that nearly half of the collagenous repeating triplets in rCIα1 isolated from rP4H co-expressing maize line had the Pro residues changed to Hyp residues. The HRMS analysis determined the Hyp content of maize-derived rCIα1-OH as 18.11%, which is comparable to the Hyp level of yeast-derived rCIα1-OH (17.47% and the native human CIa1 (14.59%, respectively. The increased Hyp percentage was correlated with a markedly enhanced thermal stability of maize-derived rCIα1-OH when compared to the non-hydroxylated rCIα1. Conclusions This work shows that maize has potential to produce adequately modified exogenous proteins with mammalian-like post-translational modifications that may be require for their use as pharmaceutical and industrial products.

  2. Family Meals

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Family Meals KidsHealth / For Parents / Family Meals What's in ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  3. Family Arguments

    Science.gov (United States)

    ... 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 ...

  4. Family History

    Science.gov (United States)

    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 ...

  5. Family Issues

    Science.gov (United States)

    ... Some have two parents, while others have a single parent. Sometimes there is no parent and grandparents raise grandchildren. Some children live in foster families, adoptive families, or in stepfamilies. Families are much ...

  6. Family Disruptions

    Science.gov (United States)

    ... 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 Disruptions Page Content Article Body No matter how ...

  7. Family Privilege

    Science.gov (United States)

    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…

  8. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Science.gov (United States)

    Seeley, Todd W; Sternlicht, Mark D; Klaus, Stephen J; Neff, Thomas B; Liu, David Y

    2017-01-01

    The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. PMID:28331872

  9. Insight into a conformation of the PNA-PNA duplex with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones

    Science.gov (United States)

    Maitarad, Amphawan; Poomsuk, Nattawee; Vilaivan, Chotima; Vilaivan, Tirayut; Siriwong, Khatcharin

    2018-04-01

    Suitable conformations for peptide nucleic acid (PNA) self-hybrids with (2‧R,4‧R)- and (2‧R,4‧S)-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbones (namely, acpcPNA and epi-acpcPNA, respectively) were investigated based on molecular dynamics simulations. The results revealed that hybridization of the acpcPNA was observed only in the parallel direction, with a conformation close to the P-type structure. In contrast, self-hybrids of the epi-acpcPNA were formed in the antiparallel and parallel directions; the antiparallel duplex adopted the B-form conformation, and the parallel duplex was between B- and P-forms. The calculated binding energies and the experimental data indicate that the antiparallel epi-acpcPNA self-hybrid was more stable than the parallel duplex.

  10. Receptor type I and type II binding regions and the peptidyl-prolyl isomerase site of cyclophilin B are required for enhancement of T-lymphocyte adhesion to fibronectin.

    Science.gov (United States)

    Carpentier, Mathieu; Allain, Fabrice; Slomianny, Marie-Christine; Durieux, Sandrine; Vanpouille, Christophe; Haendler, Bernard; Spik, Geneviève

    2002-04-23

    Cyclophilin B (CyPB), a cyclosporin A (CsA) binding protein, interacts with two types of binding sites at the surface of T-lymphocytes. The type I sites correspond to functional receptors involved in endocytosis and the type II sites to sulfated glycosaminoglycans (GAGs). Mutational analysis of CyPB has revealed that W128, which is part of the CsA-binding pocket, is implicated in the binding to the functional type I receptors and that two amino acid clusters located in the N-terminus ensure the binding to GAGs. The peptidyl-prolyl isomerase activity of CyPB is not required for receptor binding. We have recently demonstrated that CyPB enhances adhesion of peripheral blood T-lymphocytes to fibronectin, a component of the extracellular matrix. We intended to identify additional amino acids involved in the binding of CyPB to its functional type I receptor and to determine regions responsible for the stimulation of peripheral blood T-lymphocyte adhesion. We determined that residues R76, G77, K132, D155, and D158 of the calcineurin (CN) interacting region were implicated in the recognition of type I receptor but not of GAGs. We also found that two different changes in the N-terminal extension that abated binding to GAGs prevented adhesion of peripheral blood T-lymphocytes to coated CyPB, whereas abbrogation of the PPIase activity had no effect. On the other hand, the adhesion of peripheral blood T-lymphocytes to coated fibronectin was not stimulated by CyPB mutants devoid of either type I receptor or GAGs binding activity or by mutants of the PPIase site. Altogether, the results demonstrate that different regions of CyPB are involved in peripheral blood T-lymphocyte activation and imply a novel important physiological function for peptidyl-prolyl isomerase activity.

  11. Family Violence and Family Physicians

    Science.gov (United States)

    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

  12. Familial gigantism

    NARCIS (Netherlands)

    W.W. de Herder (Wouter)

    2012-01-01

    textabstractFamilial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  13. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder

    2012-01-01

    Full Text Available Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  14. Family Issues

    Science.gov (United States)

    ... es Autismo? Family Issues Home / Living with Autism / Family Issues Stress Siblings A child’s autism diagnosis affects every member of the family in different ways. Parents/caregivers must now place their ... may put stress on their marriage, other children, work, finances, and ...

  15. Jamaican families.

    Science.gov (United States)

    Miner, Dianne Cooney

    2003-01-01

    The study of the family in the Caribbean originated with European scholars who assumed the universality of the patriarchal nuclear family and the primacy of this structure to the healthy functioning of society. Matrifocal Caribbean families thus were seen as chaotic and disorganized and inadequate to perform the essential tasks of the social system. This article provides a more current discussion of the Jamaican family. It argues that its structure is the result of the agency and adaptation of its members and not the root cause of the increasing marginalization of peoples in the developing world. The article focuses on families living in poverty and how the family structure supports essential family functions, adaptations, and survival.

  16. Two Paralogous Families of a Two-Gene Subtilisin Operon Are Widely Distributed in Oral Treponemes

    Science.gov (United States)

    Correia, Frederick F.; Plummer, Alvin R.; Ellen, Richard P.; Wyss, Chris; Boches, Susan K.; Galvin, Jamie L.; Paster, Bruce J.; Dewhirst, Floyd E.

    2003-01-01

    Certain oral treponemes express a highly proteolytic phenotype and have been associated with periodontal diseases. The periodontal pathogen Treponema denticola produces dentilisin, a serine protease of the subtilisin family. The two-gene operon prcA-prtP is required for expression of active dentilisin (PrtP), a putative lipoprotein attached to the treponeme's outer membrane or sheath. The purpose of this study was to examine the diversity and structure of treponemal subtilisin-like proteases in order to better understand their distribution and function. The complete sequences of five prcA-prtP operons were determined for Treponema lecithinolyticum, “Treponema vincentii,” and two canine species. Partial operon sequences were obtained for T. socranskii subsp. 04 as well as 450- to 1,000-base fragments of prtP genes from four additional treponeme strains. Phylogenetic analysis demonstrated that the sequences fall into two paralogous families. The first family includes the sequence from T. denticola. Treponemes possessing this operon family express chymotrypsin-like protease activity and can cleave the substrate N-succinyl-alanyl-alanyl-prolyl-phenylalanine-p-nitroanilide (SAAPFNA). Treponemes possessing the second paralog family do not possess chymotrypsin-like activity or cleave SAAPFNA. Despite examination of a range of protein and peptide substrates, the specificity of the second protease family remains unknown. Each of the fully sequenced prcA and prtP genes contains a 5′ hydrophobic leader sequence with a treponeme lipobox. The two paralogous families of treponeme subtilisins represent a new subgroup within the subtilisin family of proteases and are the only subtilisin lipoprotein family. The present study demonstrated that the subtilisin paralogs comprising a two-gene operon are widely distributed among treponemes. PMID:14617650

  17. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  18. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline

    2012-01-01

    I Projekt familielæsning, der er et samarbejde mellem Nationalt Videncenter for Læsning og Hillerød Bibliotek, arbejder vi med at få kontakt til de familier, som biblioteket ellers aldrig ser som brugere og dermed også de børn, der vokser op i familier, for hvem bøger og oplæsningssituationer ikk...... er en selvfølgelig del af barndommen. Det, vi vil undersøge og ønsker at være med til at udvikle hos disse familier, er det, man kan kalde family literacy....

  19. Community families

    DEFF Research Database (Denmark)

    Jensen, Lotte Groth; Lou, Stina; Aagaard, Jørgen

    2017-01-01

    : Qualitative interviews with members of volunteer families. Discussion: The families were motivated by helping a vulnerable person and to engaging in a rewarding relationship. However, the families often doubted their personal judgment and relied on mental health workers to act as safety net. Conclusion......Background: Social interventions targeted at people with severe mental illness (SMI) often include volunteers. Volunteers' perspectives are important for these interventions to work. The present paper investigates the experiences of volunteer families who befriend a person with SMI. Material...

  20. Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells.

    Science.gov (United States)

    Lin, Hung-Chih; Su, Shih-Li; Lu, Chia-Yang; Lin, Ai-Hsuan; Lin, Wan-Chun; Liu, Chin-San; Yang, Ya-Chen; Wang, Hsiu-Miao; Lii, Chong-Kuei; Chen, Haw-Wen

    2017-03-01

    Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2. We found that hypoxia stimulated the production of reactive oxygen species (ROS), the expression of HIF-1α mRNA and protein, and the expression and secretion of ET-1. These effects, however, were attenuated by co-exposure to andrographolide, bilirubin, and RuCO. Silencing Nrf2 and heme oxygenase 1 (HO-1) reversed the inhibitory effects of andrographolide on hypxoia-induced HIF-1α mRNA and protein expression. Moreover, andrographolide increased the expression of prolyl hydroxylases (PHD) 2/3, which hydroxylate HIF-1α and promotes HIF-1α proteasome degradation, with an increase in HIF-1α hydroxylation was noted under hypoxia. Inhibition of p38 MAPK abrogated the hypoxia-induced increases in HIF-1α mRNA and protein expression as well as ET-1 mRNA expression and secretion. Taken together, these results suggest that andrographolide suppresses hypoxia-induced pro-inflammatory ET-1 expression by activating Nrf2/HO-1, inhibiting p38 MAPK signaling, and promoting PHD2/3 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 918-930, 2017. © 2016 Wiley

  1. This is My Family

    OpenAIRE

    Yeğen, Hale Nur; Çetin, Merve

    2017-01-01

    Me and my family, Families poem, Mother-Father, Brother-Sister, Grandparents, Uncle-Aunt, Cousin, Family, Family handgame, My family tree, Activities (Three In a Family), Digital Games, A family poem, Quiz

  2. Family problems

    International Nuclear Information System (INIS)

    Goldman, T.

    1984-01-01

    Even Grand Unified Theories may not explain the repetitive pattern of fermions in the Standard Model. The abysmal absence of dynamical information about these ''families'' is emphasized. The evidence that family quantum numbers exist, and are not conserved, is reviewed. It is argued that rare kaon decays may be the best means to obtain more information on this important question

  3. Family problems

    International Nuclear Information System (INIS)

    Goldman, T.

    1984-01-01

    Even Grand Unified Theories may not explain the repetitive pattern of fermions in the Standard Model. The abysmal absence of dynamical information about these families is emphasized. The evidence that family quantum numbers exist, and are not conserved, is reviewed. It is argued that rare kaon decays may be the best means to obtain more information on this important question

  4. Familial hypercholesterolemia

    Science.gov (United States)

    ... and Tests A physical exam may show fatty skin growths called xanthomas and cholesterol deposits in the eye (corneal arcus). The health care provider will ask questions about your personal and family medical history. There may be: A strong family history of ...

  5. FAMILY PYRGOTIDAE.

    Science.gov (United States)

    Mello, Ramon Luciano; Lamas, Carlos José Einicker

    2016-06-14

    Pyrgotidae is a family of endoparasitics flies of beetles with worldwide distribution. The Neotropical fauna is composed by 59 valid species names disposed in 13 genera. The occurrence of Pyrgota longipes Hendel is the first record of the family in Colombia.

  6. Stimulating retinal blood vessel protection with hypoxia-inducible factor stabilization: identification of novel small-molecule hydrazones to inhibit hypoxia-inducible factor prolyl hydroxylase (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Sears, Jonathan E; Hoppe, George

    2013-09-01

    To discover novel small molecules that inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD), a key enzyme that regulates the posttranslational stability and hence activity of HIF. NIH3T3 cell line stably transfected with firefly luciferase under a HIF-1-inducible promoter was used to screen a Chembridge library of 34,000 small molecules of molecular weight 250 to 550 Da. Positive hits were considered at 4.5-fold higher luminescence than control. Selected compounds were validated in vitro. The most effective dose was then used to treat mice expressing firefly luciferase fused to the oxygen-dependent degradation domain (lucODD) in order to determine the location of the receptor for systemic treatment with small-molecule HIF PHD inhibitors. Twenty-three novel small molecules were discovered, the majority of which were hydrazones and hydrazines. Of the 23 compounds, each had different selectivity for expression of erythropoietin or vascular endothelial growth factor, two angiogenic, HIF-regulated gene products. In addition, each showed different selectivity for hepatocytes or kidney, or both or neither, when injected intraperitoneally in an in vivo reporter gene assay. The discovery of multiple small molecules that inhibit HIF PHD identifies new reagents to develop strategies to prevent the degradation of HIF by its selective PHD. These molecules are novel hypoxia mimetics that may provide new strategies to protect retinovasculature from hyperoxia.

  7. Click Chemistry-based Discovery of [3-Hydroxy-5-(1H-1,2,3-triazol-4-yl)picolinoyl]glycines as Orally Active Hypoxia Inducing Factor Prolyl Hydroxylase Inhibitors with Favorable Safety Profiles for the Treatment of Anemia.

    Science.gov (United States)

    Wu, Yue; Jiang, Zhensheng; Li, Zhihong; Gu, Jing; You, Qi-Dong; Zhang, Xiaojin

    2018-06-01

    As a gene associated with anemia, the erythropoiesis gene is physiologically expressed under hypoxia regulated by hypoxia-inducing factor-α (HIF-α). Thus, stabilizing HIF-α is a potent strategy to stimulate the expression and secretion of erythropoiesis. In this study we applied click chemistry to the discovery of HIF prolyl hydroxylase 2 (HIF-PHD2) inhibitors for the first time and a series of triazole compounds showed preferable inhibitory activity in fluorescence polarization assay. Of particular note was the orally active HIF-PHD inhibitor 15i (IC50 = 62.23 nM), which was almost ten times more active than the phase III drug FG-4592 (IC50 = 591.4 nM). Furthermore, it can upregulate the hemoglobin of cisplatin induced anemia mice (120 g/L) to normal levels (160 g/L) with no apparent toxicity observed in vivo. These results confirm that triazole compound 15i is a promising candidate for the treatment of renal anemia.

  8. Family matters

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Siersma, Volkert Dirk; Teasdale, Thomas William

    2013-01-01

    brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified...... by the parents using the Achenbach’s Child Behaviour Checklist (CBCL). RESULTS: The family stress variables relating to the healthy spouse in all six comparisons were significant (p... scores for the children. For the adjusted associations, we again found the family stress variables in the healthy spouse to be related to the risk of emotional and behavioral problems in the children. CONCLUSIONS: The present results suggest that in ABI families, the children’s emotional functioning...

  9. Small Families

    Science.gov (United States)

    ... children of larger families. The financial costs of maintaining a household are lower. It is easier for ... separated from you, hindering the development of new relationships with peers. In fact, you may have that ...

  10. Familial hypercholesterolaemia

    African Journals Online (AJOL)

    Familial hypercholesterolaemia (FH) is a monogenic disorder of low-density lipoprotein (LDL) metabolism. It is characterised .... Figure 2: Cumulative prevalence of physical signs in adult FH patients at the. GSH Lipid .... microvascular trauma.

  11. Family Life

    Science.gov (United States)

    ... family members to do your laundry, walk the dog, or update others on your progress. You may ... parenting while living with cancer . The importance of communication As demonstrated above, good communication is important in ...

  12. Familial dysautonomia

    Science.gov (United States)

    ... condition. FD occurs most often in people of Eastern European Jewish ancestry (Ashkenazi Jews). It is caused ... also be used for prenatal diagnosis. People of Eastern European Jewish background and families with a history ...

  13. Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Helena [Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Kiss, András L.; Szeltner, Zoltán; Polgár, László [Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H-1518 Budapest 112, PO Box 7 (Hungary); Fülöp, Vilmos, E-mail: vilmos@globin.bio.warwick.ac.uk [Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom)

    2005-10-01

    Acylaminoacyl peptidase from porcine liver has been crystallized. Data were collected to 3.4 Å from native crystals and a search for heavy-atom derivatives is in progress. Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris–HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl{sub 2} and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 Å resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 Å and four molecules in the asymmetric unit.

  14. Identification and characterisation of a novel acylpeptide hydrolase from Sulfolobus solfataricus: structural and functional insights.

    Directory of Open Access Journals (Sweden)

    Marta Gogliettino

    Full Text Available A novel acylpeptide hydrolase, named APEH-3(Ss, was isolated from the hypertermophilic archaeon Sulfolobus solfataricus. APEH is a member of the prolyl oligopeptidase family which catalyzes the removal of acetylated amino acid residues from the N terminus of oligopeptides. The purified enzyme shows a homotrimeric structure, unique among the associate partners of the APEH cluster and, in contrast to the archaeal APEHs which show both exo/endo peptidase activities, it appears to be a "true" aminopeptidase as exemplified by its mammalian counterparts, with which it shares a similar substrate specificity. Furthermore, a comparative study on the regulation of apeh gene expression, revealed a significant but divergent alteration in the expression pattern of apeh-3(Ss and apeh(Ss (the gene encoding the previously identified APEH(Ss from S. solfataricus, which is induced in response to various stressful growth conditions. Hence, both APEH enzymes can be defined as stress-regulated proteins which play a complementary role in enabling the survival of S. solfataricus cells under different conditions. These results provide new structural and functional insights into S. solfataricus APEH, offering a possible explanation for the multiplicity of this enzyme in Archaea.

  15. Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

    International Nuclear Information System (INIS)

    Wright, Helena; Kiss, András L.; Szeltner, Zoltán; Polgár, László; Fülöp, Vilmos

    2005-01-01

    Acylaminoacyl peptidase from porcine liver has been crystallized. Data were collected to 3.4 Å from native crystals and a search for heavy-atom derivatives is in progress. Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris–HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl 2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 Å resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 Å and four molecules in the asymmetric unit

  16. Family welfare.

    Science.gov (United States)

    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

  17. Familial macrocephaly

    International Nuclear Information System (INIS)

    Tatsuno, Masaru; Hayashi, Michiko; Iwamoto, Hiroko

    1984-01-01

    We reported 63 macrocephalic children with special emphasis on 16 cases with familial macrocephaly. Of the 16 children with familial macrocephaly, 13 were boys. Foureen parents (13 fathers and 1 mother) had head sizes above 98th percentile. Three of 5 brothers and 5 of 8 sisters also had large heads. The head circumference at birth was known for 14 of the children and it was above the 98th percentile in 7 patients. Subsequent evaluations have shown the head size of these children to be following a normal growth curve. Some of the children were hypotonic as infants, but their development was generally normal. CT scans usually clearly distinguished these children from those with hydorocephalus. The familial macrocephalic children had ventricular measurements which were within the normal range, but absolute measurements of the ventricular size may be misleading, because the CT appearance was of mildly dilated ventricles in half of them. (author)

  18. Family Structure and Family Processes in Mexican American Families

    OpenAIRE

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

    2011-01-01

    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,...

  19. Super families

    International Nuclear Information System (INIS)

    Amato, N.; Maldonado, R.H.C.

    1989-01-01

    The study on phenomena in the super high energy region, Σ E j > 1000 TeV revealed events that present a big dark spot in central region with high concentration of energy and particles, called halo. Six super families with halo were analysed by Brazil-Japan Cooperation of Cosmic Rays. For each family the lateral distribution of energy density was constructed and R c Σ E (R c ) was estimated. For studying primary composition, the energy correlation with particles released separately in hadrons and gamma rays was analysed. (M.C.K.)

  20. Family Violence.

    Science.gov (United States)

    Emery, Robert E.

    1989-01-01

    Researchers and policymakers have begun to recognize the extent and severity of family violence, particularly its effects on children. But there is much disagreement about the definition of violence, its development, the consequences for victims, and the most effective avenues for intervention. Advances recommendations for further research.…

  1. Family arizing

    NARCIS (Netherlands)

    Croes, M.J.G.; Feijs, L.M.G.; Chen, L.; Djajadingrat, T.; Feijs, L.M.G.; Hu, J.; Kufin, S.H.M.; Rampino, L.; Rodriguez, E.; Steffen, D.

    2015-01-01

    In this demo we show the two main components of the Family Arizing system which allows parents to stay in contact with their child and, in cases of distress, provide the child with a remote comforting hug. The two components to be shown are the active necklace and the active snuggle.

  2. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  3. FAMILY ASILIDAE.

    Science.gov (United States)

    Wolff, Marta; Lamas, Carlos José Einicker

    2016-06-14

    Asilidae is one of the largest Diptera families with more than 7,000 recognized species worldwide. All their species are predators on arthropods, mainly insects. This catalogue presents 71 species distributed in 26 genera, ten tribes or generic groups and four subfamilies. For each species we present the available geographical information and relevant references.

  4. Family Hypnotherapy.

    Science.gov (United States)

    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)

  5. Familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Versmissen, Jorie; Vongpromek, Ranitha; Yahya, Reyhana

    2016-01-01

    cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM). RESULTS: Seven FH patients were asymptomatic and six had...... in asymptomatic FH patients may play a role in their apparent protection from premature CHD....

  6. [Family violence].

    Science.gov (United States)

    Manoudi, F; Chagh, R; Es-soussi, M; Asri, F; Tazi, I

    2013-09-01

    Family violence is a serious public health problem, the scale of which is seriously increasing in Morocco. Although it has existed for a long time, we ignore the real characteristics of this plague in our country; our work consisted in an epidemiological approach of family violence in Marrakech during 2006. After elaborating a questionnaire, which allows the study of the demographic and social profile of the families, the study of violence exercised in the family and the evaluation of the depression in the women, we led an inquiry amongst 265 women. Analysis of the results obtained has allowed us to underline the following characteristics: 16.6% of the women in our sample had been physically beaten; the young age is a risk factor; the age range most affected by violence is in women between the ages of 30 and 40 and which represent 39% of the battered women; domestic violence touches all the social, economic and cultural classes: in our study, 63% of the women having undergone violence were housewives, 25% were managers and 3% senior executives; family problems were the most important cause of violence in our study, representing 32.32%. Requests for money was the cause in 11.3% of the cases, and imposed sexual relations were found in 6.8% of the cases; alcoholism is an aggravating factor of family violence; 27.3% of the spouses who assaulted their wives were drunk; 52% of the assaulted women were victims of violence in childhood and 36% had been witness to their father's violence; in 63.6% of the cases of violence, the children were witnesses, and in 25% of the cases the children were victims of violence at the same time as their mothers; 50% of the women victims of violence did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two percent of the assaulted woman had been traumatised by the aggression; the association of depression and violence was very high, 343% of the battered women in our study suffered from severe depression. This work

  7. FAMILY BOMBYLIIDAE.

    Science.gov (United States)

    Lamas, Carlos José Einicker; Evenhuis, Neal L

    2016-06-14

    Bombyliidae is one of the largest Diptera families with more than 4,500 recognized species worldwide. Their species vary from robust to thin, and may be small to large (2-20mm) and looks like bees or wasps. They also present great variation in color. Adults can often be seen either resting and sunning themselves on trails, rocks or twigs or feeding on flowering plants as they are nectar feeders. All reared bee flies are predators or parasitoids of arthropods. The Colombian fauna of bombyliids comprises at the moment 22 species, and 12 genera, of which, six are endemic species. Nonetheless, this number may be much higher, as Colombia is a megadiverse country and there are not many specimens of this family deposited in collections all over the world.

  8. From Drosophila to humans: Reflections on the roles of the prolyl-isomerases and chaperones, cyclophilins, in cell function and disease

    Science.gov (United States)

    Ferreira, Paulo A.; Orry, Andrew

    2013-01-01

    Despite remarkable advances in human genetics and other genetic model systems, the fruit fly, Drosophila melanogaster, remains a powerful experimental tool to probe with ease the inner workings of a myriad of biological and pathological processes, even when evolutionary forces impart apparent divergences to some of such processes. The understanding of such evolutionary differences provides mechanistic insights into genotype-phenotype correlations underpinning biological processes across metazoans. The pioneering work developed by the William Pak laboratory for the past four decades, and the work of others, epitomize the notion of how the Drosophila system breaks new fertile ground or complements research fields of high scientific and medical relevance. Among the three major genetic complementation groups produced by the Pak's laboratory and impairing distinct facets of photoreceptor neuronal function, the nina group (ninaA….J) selectively affects the biogenesis of G protein-coupled receptors (GPCR) mediating the photoconversion and transduction of light-stimuli. Among the nina genes identified, ninaA arguably assumes heightened significance for several reasons. First, it presents unique physiological selectivity toward the biogenesis of a subset of GPCRs, a standalone biological manifestation yet to be discerned for most mammalian homologues of NinaA. Second, NinaA belongs to a family of proteins, immunophilins, which are the primary targets for immunosuppressive drugs at the therapeutic forefront of a multitude of medical conditions. Third, NinaA closest homologue, cyclophilin-B (CyPB/PPIB), is an immunophilin whose loss-of-function was found recently to cause osteogenesis imperfecta in the human. This report highlights advances made by studies on some members of immunophilins, the cyclophilins. Finally, it re-examines critically data and dogmas derived from past and recent genetic, structural, biological and pathological studies on NinaA and few other

  9. Family roles as family functioning regulators

    OpenAIRE

    STEPANYAN ARMINE

    2015-01-01

    The author examines the problems of formation and functioning of family roles. Having social roots, family roles appear on individual level by performing the social function of the formation of family as a social institute.

  10. The Role of Family in Family Firms

    OpenAIRE

    Marianne Bertrand; Antoinette Schoar

    2006-01-01

    History is replete with examples of spectacular ascents of family businesses. Yet there are also numerous accounts of family businesses brought down by bitter feuds among family members, disappointed expectations between generations, and tragic sagas of later generations unable to manage their wealth. A large fraction of businesses throughout the world are organized around families. Why are family firms so prevalent? What are the implications of family control for the governance, financing an...

  11. Roles within the Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Text Size Email Print Share Roles Within the Family Page Content Article Body Families are not democracies. ...

  12. Family Psychology and Family Therapy in Japan.

    Science.gov (United States)

    Kameguchi, Kenji; Murphy-Shigematsu, Stephen

    2001-01-01

    Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family…

  13. Strengthening Family Practices for Latino Families.

    Science.gov (United States)

    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.

  14. First characterization of three cyclophilin family proteins in the oyster, Crassostrea ariakensis Gould.

    Science.gov (United States)

    Xu, Ting; Xie, Jiasong; Yang, Shoubao; Ye, Shigen; Luo, Ming; Wu, Xinzhong

    2016-08-01

    Cyclophilins (CyPs) are a family of proteins that bind the immunosuppressive agent cyclosporin A (CsA) with high-affinity and belong to one of the three superfamilies of peptidyl-prolyl cis-trans isomerases (PPIase). In this report, three cyclophilin genes (Ca-CyPs), including Ca-CyPA, Ca-CyPB and Ca-PPIL3, were identified from oyster, Crassostrea ariakensis Gould in which Ca-CyPA encodes a protein with 165 amino acid sequences, Ca-CyPB encodes a protein with 217 amino acid sequences and Ca-PPIL3 encodes a protein with 162 amino acid sequences. All of the three Ca-CyPs genes contain a typical CyP-PPIase domain with its signature sequences and Ca-CyPB contains an N-signal peptide sequences. Tissue distribution study revealed that Ca-CyPs were ubiquitously expressed in all examined tissues and the highest levels were observed in hemocytes. RLO incubation upregulated the mRNA expression levels of Ca-CyPs, indicating that three Ca-CyPs might be involved in oyster immune response against RLO infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Family Matters

    Directory of Open Access Journals (Sweden)

    Isabel de Riquer

    2011-04-01

    Full Text Available The scene is at the court of James I of Aragon in the mid-13th c., the place is the royal palace of Barcelona or any of the crown's other possessions, and the dramatis personae include the heir to the throne, prince Peire (future king Peire the Great, and the court's most famous troubadour, Cerverí de Girona (fl. 1259-85. Author of the largest corpus of any Occitan troubadour (114 poems, Cerverì distinguishes himself by the surprises and challenges he presents to his audience: an alba (the most openly erotic genre to the Virgin Mary, the Cobla in sis lengatges (Cobla in Six Languages, the apparently nonsensical Vers estrayn. Cerverì borrows equally from the folk-inspired Galician-Portuguese poetry and from the French tradition, including the chanson de malmariée, where a young woman bemoans being sold off by her family to an old man (gilos, "Jealous" and separated from her youthful doulz amis, some even praying for the death of their husband. Both within that tradition and among Cerverì's three chansons de malmariée, the Gelosesca stands out as "especially determined" to lose her husband, using every "solution" (prayer, black magic, potion or experimenta.

  16. Bequeathing Family Continuity.

    Science.gov (United States)

    Spanier, Graham B.

    1989-01-01

    Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

  17. The Reconstituted Family

    OpenAIRE

    Talbot, Yves

    1981-01-01

    The reconstituted or step-family is becoming more prevalent. The physician who cares for families should be acquainted with the different aspects of such family structure and family functioning. This will enable professionals to better understand and assist their patients, by anticipating the different stresses related to the new family formation, and supporting their adaptation.

  18. Family Capital: Implications for Interventions with Families

    Science.gov (United States)

    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…

  19. Familial Pulmonary Fibrosis

    Science.gov (United States)

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

  20. Family Activities for Fitness

    Science.gov (United States)

    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.

  1. Normal Functioning Family

    Science.gov (United States)

    ... 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 ...

  2. Improving Family Communications

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Listen Español Text Size Email Print Share Improving Family Communications Page Content Article Body How can I ...

  3. Families and family therapy in Hong Kong.

    Science.gov (United States)

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  4. Family doctors' involvement with families in Estonia

    Directory of Open Access Journals (Sweden)

    Lember Margus

    2004-10-01

    Full Text Available Abstract Background Family doctors should care for individuals in the context of their family. Family has a powerful influence on health and illness and family interventions have been shown to improve health outcomes for a variety of health problems. The aim of the study was to investigate the Estonian family doctors' (FD attitudes to the patients' family-related issues in their work: to explore the degree of FDs involvement in family matters, their preparedness for management of family-related issues and their self-assessment of the ability to manage different family-related problems. Methods A random sample (n = 236 of all FDs in Estonia was investigated using a postal questionnaire. Altogether 151 FDs responded to the questionnaire (response rate 64%, while five of them were excluded as they did not actually work as FDs. Results Of the respondents, 90% thought that in managing the health problems of patients FDs should communicate and cooperate with family members. Although most of the family doctors agreed that modifying of the health damaging risk factors (smoking, alcohol and drug abuse of their patients and families is their task, one third of them felt that dealing with these problems is ineffective, or perceived themselves as poorly prepared or having too little time for such activities. Of the respondents, 58% (n = 83 were of the opinion that they could modify also relationship problems. Conclusions Estonian family doctors are favourably disposed to involvement in family-related problems, however, they need some additional training, especially in the field of relationship management.

  5. Competitiveness of Family Businesses

    NARCIS (Netherlands)

    M.A.A.M. Leenders (Mark); E. Waarts (Eric)

    2001-01-01

    textabstractThe purpose of this study is to systematically examine the advantages and disadvantages of different types of family businesses. We distinguish four different types of family businesses based on their family and business orientation: (1) House of Business, (2) Family Money Machine, (3)

  6. Families in Transition .

    Science.gov (United States)

    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…

  7. Pure γ-families

    International Nuclear Information System (INIS)

    Dunaevskii, A.M.

    1977-01-01

    The subject of this work are pure gamma families consisting of the gamma quanta produced in the early stages of cosmic cascades. The criteria of selecting these families from the all measured families are presented. The characteristics of these families are given and some conclusions about the mechanism of the nuclear-electromagnetic cascades are extracted. (S.B.)

  8. Work-family harmony

    OpenAIRE

    Adhikari,Pralhad

    2018-01-01

    The phenomenon of positively thinking about work and organization during the family hours by a worker is called work-family harmony. On the fag opposite of work-family conflict is work-family harmony. The work extends/intrudes into the family life of the worker, but in a positive way. This kind of positive thinking about the organization helps person's subjective well-being grow and his mental health is also nourished.

  9. Family emotional expressiveness and family structure

    Directory of Open Access Journals (Sweden)

    Čotar-Konrad Sonja

    2016-01-01

    Full Text Available The present paper scrutinizes the relationship between family emotional expressiveness (i.e., the tendency to express dominant and/or submissive positive and negative emotions and components of family structure as proposed in Olson’s Circumplex model (i.e., cohesion and flexibility, family communication, and satisfaction in families with adolescents. The study was conducted on a sample of 514 Slovenian adolescents, who filled out two questionnaires: the Slovenian version of Family Emotional Expressiveness - FEQ and FACES IV. The results revealed that all four basic dimensions of family functioning were significantly associated with higher/more frequent expressions of positive submissive emotions, as well as with lower/less frequent expressions of negative dominant emotions. Moreover, expressions of negative submissive emotions explained a small, but significant amount of variance in three out of four family functioning variables (satisfaction, flexibility, and communication. The importance of particular aspects of emotional expressiveness for family cohesion, flexibility, communication, and satisfaction is discussed, and the relevance of present findings for family counselling is outlined.

  10. Nontraditional family romance.

    Science.gov (United States)

    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.

  11. Trends in family tourism

    Directory of Open Access Journals (Sweden)

    Heike A. Schänzel

    2015-03-01

    Full Text Available Purpose – Families represent a large and growing market for the tourism industry. Family tourism is driven by the increasing importance placed on promoting family togetherness, keeping family bonds alive and creating family memories. Predictions for the future of family travel are shaped by changes in demography and social structures. With global mobility families are increasingly geographically dispersed and new family markets are emerging. The purpose of this paper is to discuss the trends that shape the understanding of families and family tourism. Design/methodology/approach – This paper examines ten trends that the authors as experts in the field identify of importance and significance for the future of family tourism. Findings – What emerges is that the future of family tourism lies in capturing the increasing heterogeneity, fluidity and mobility of the family market. Originality/value – The paper contributes to the understanding about the changes taking place in family tourism and what it means to the tourism industry in the future.

  12. Strengthening Family Practices for Latino Families

    Science.gov (United States)

    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…

  13. Intra-family messaging with family circles

    NARCIS (Netherlands)

    Schatorjé, R.J.W.; Markopoulos, P.; Neustaedter, C.; Harrison, S.; Sellen, A.

    2013-01-01

    This chapter makes the argument that intra-family communication is not an issue of connectivity anytime anywhere, but of providing communication media that are flexible and expressive allowing families to appropriate them and fit their own idiosyncratic ways of communicating with each other. We

  14. Family Therapy for the "Truncated" Nuclear Family.

    Science.gov (United States)

    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)

  15. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  16. MSUD Family Support Group

    Science.gov (United States)

    ... The Treatment Of MSUD The MSUD Family Support Group has provided funds to Buck Institute for its ... of the membership of the MSUD Family Support Group, research for improved treatments and potential cure was ...

  17. National Military Family Association

    Science.gov (United States)

    ... MilitaryFamily.org © 2017 - National Military Family Association Twitter Facebook Pinterest Instagram Charity Navigator Four Star Charity GuideStar Exchange Better Business Bureau Charity Watch Independent Charity of America nonprofit ...

  18. IGSF9 Family Proteins

    DEFF Research Database (Denmark)

    Hansen, Maria; Walmod, Peter Schledermann

    2013-01-01

    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, the longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...... facilitates homophilic cell adhesion. Moreover, IGSF9 family proteins have been implicated in the outgrowth and branching of neurites, axon guidance, synapse maturation, self-avoidance, and tiling. However, despite the few published studies on IGSF9 family proteins, reports on the functions of both Turtle...

  19. Family Caregiver Alliance

    Science.gov (United States)

    ... on your schedule. Look for our launch soon! FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... AiA18 Smart Patients Caregivers Community In partnership with Family Caregiver Alliance Learn more Caregiver Research Studies show ...

  20. Resilience of refugee families

    Directory of Open Access Journals (Sweden)

    Batić Dragana

    2012-01-01

    Full Text Available This study attempted to find a correlation between the trauma of family members of war and exile, and the characteristics of family functioning and lasted from 1992-1995. The term “family resilience” refers to the processes of adaptation and coping in the family as a functional unit. This paper presents a study of refugee families from Bosnia, who lived in refugee camps in Macedonia during the war of 1992- 1995. Data were obtained by interviews, observations, and a number of psychological instruments especially for children and parents, which measured the effects of psychological stress and family relationships. Based on the results obtained by quantitative and qualitative analysis, and application of theoretical models of systemic theory and family therapy, existence for four types of refugee families has been found and described, depending on the structure and the level of functionality.

  1. Unique Family Living Situations

    Science.gov (United States)

    ... Yet, what if the family home changes for reasons of divorce, death, or economics? Factors, such as shifting between ... for a child of any age. If the reason is due to divorce, work together as a family (both parents and ...

  2. Xeroderma Pigmentosum - A Family

    Directory of Open Access Journals (Sweden)

    Garg Anush

    2000-01-01

    Full Text Available A family of xeroderma pigmentosum is reported. Four children of different ages were afflicted with varying clinical presentation. Sequential development and progression of the disease from freckling to malignancy within the family are discussed.

  3. Essays on Family Firms

    OpenAIRE

    Zhou, Haoyong

    2012-01-01

    The dissertation examines corporate performance and capital structure of family firms, contributing to the limited empirical research on family firms. Family firms are prevalent in national economies all over the world. It is the prevalence that makes family firms receive increasing attentions from academia. The dissertation consists of an introduction and three chapters. Each chapter is an independent paper. The first chapter is a joint work with Professor Morten Bennedsen and...

  4. Family Obligations in Denmark

    DEFF Research Database (Denmark)

    Koch-Nielsen, Inger

    How is the balance in obligations between the Family and the Danish Welfare State? Can we observe a trend to shift the responsibility back to the family? This booklet intends to sketch the legal framework around the division of responsibilities between the Family and the state and to analyse...... to what extent and where the unit of rights and obliagations is the individual and where it is the family or household....

  5. Identification of oxidized protein hydrolase as a potential prodrug target in prostate cancer

    International Nuclear Information System (INIS)

    McGoldrick, Christopher A; Jiang, Yu-Lin; Paromov, Victor; Brannon, Marianne; Krishnan, Koyamangalath; Stone, William L

    2014-01-01

    Esterases are often overexpressed in cancer cells and can have chiral specificities different from that of the corresponding normal tissues. For this reason, ester prodrugs could be a promising approach in chemotherapy. In this study, we focused on the identification and characterization of differentially expressed esterases between non-tumorigenic and tumorigenic prostate epithelial cells. Cellular lysates from LNCaP, DU 145, and PC3 prostate cancer cell lines, tumorigenic RWPE-2 prostate epithelial cells, and non-tumorigenic RWPE-1 prostate epithelial cells were separated by native polyacrylamide gel electrophoresis (n-PAGE) and the esterase activity bands visualized using α-naphthyl acetate or α-naphthyl-N-acetylalaninate (ANAA) chiral esters and Fast Blue RR salt. The esterases were identified using nanospray LC/MS-MS tandem mass spectrometry and confirmed by Western blotting, native electroblotting, inhibition assays, and activity towards a known specific substrate. The serine protease/esterase oxidized protein hydrolase (OPH) was overexpressed in COS-7 cells to verify our results. The major esterase observed with the ANAA substrates within the n-PAGE activity bands was identified as OPH. OPH (EC 3.4.19.1) is a serine protease/esterase and a member of the prolyl oligopeptidase family. We found that LNCaP lysates contained approximately 40% more OPH compared to RWPE-1 lysates. RWPE-2, DU145 and PC3 cell lysates had similar levels of OPH activity. OPH within all of the cell lysates tested had a chiral preference for the S-isomer of ANAA. LNCaP cells were stained more intensely with ANAA substrates than RWPE-1 cells and COS-7 cells overexpressing OPH were found to have a higher activity towards the ANAA and AcApNA than parent COS-7 cells. These data suggest that prodrug derivatives of ANAA and AcApNA could have potential as chemotherapeutic agents for the treatment of prostate cancer tumors that overexpress OPH

  6. Cross genome comparisons of serine proteases in Arabidopsis and rice

    Directory of Open Access Journals (Sweden)

    Sowdhamini R

    2006-08-01

    Full Text Available Abstract Background Serine proteases are one of the largest groups of proteolytic enzymes found across all kingdoms of life and are associated with several essential physiological pathways. The availability of Arabidopsis thaliana and rice (Oryza sativa genome sequences has permitted the identification and comparison of the repertoire of serine protease-like proteins in the two plant species. Results Despite the differences in genome sizes between Arabidopsis and rice, we identified a very similar number of serine protease-like proteins in the two plant species (206 and 222, respectively. Nearly 40% of the above sequences were identified as potential orthologues. Atypical members could be identified in the plant genomes for Deg, Clp, Lon, rhomboid proteases and species-specific members were observed for the highly populated subtilisin and serine carboxypeptidase families suggesting multiple lateral gene transfers. DegP proteases, prolyl oligopeptidases, Clp proteases and rhomboids share a significantly higher percentage orthology between the two genomes indicating substantial evolutionary divergence was set prior to speciation. Single domain architectures and paralogues for several putative subtilisins, serine carboxypeptidases and rhomboids suggest they may have been recruited for additional roles in secondary metabolism with spatial and temporal regulation. The analysis reveals some domain architectures unique to either or both of the plant species and some inactive proteases, like in rhomboids and Clp proteases, which could be involved in chaperone function. Conclusion The systematic analysis of the serine protease-like proteins in the two plant species has provided some insight into the possible functional associations of previously uncharacterised serine protease-like proteins. Further investigation of these aspects may prove beneficial in our understanding of similar processes in commercially significant crop plant species.

  7. Genome-wide identification and structure-function studies of proteases and protease inhibitors in Cicer arietinum (chickpea).

    Science.gov (United States)

    Sharma, Ranu; Suresh, C G

    2015-01-01

    Proteases are a family of enzymes present in almost all living organisms. In plants they are involved in many biological processes requiring stress response in situations such as water deficiency, pathogen attack, maintaining protein content of the cell, programmed cell death, senescence, reproduction and many more. Similarly, protease inhibitors (PIs) are involved in various important functions like suppression of invasion by pathogenic nematodes, inhibition of spores-germination and mycelium growth of Alternaria alternata and response to wounding and fungal attack. As much as we know, no genome-wide study of proteases together with proteinaceous PIs is reported in any of the sequenced genomes till now. Phylogenetic studies and domain analysis of proteases were carried out to understand the molecular evolution as well as gene and protein features. Structural analysis was carried out to explore the binding mode and affinity of PIs for cognate proteases and prolyl oligopeptidase protease with inhibitor ligand. In the study reported here, a significant number of proteases and PIs were identified in chickpea genome. The gene expression profiles of proteases and PIs in five different plant tissues revealed a differential expression pattern in more than one plant tissue. Molecular dynamics studies revealed the formation of stable complex owing to increased number of protein-ligand and inter and intramolecular protein-protein hydrogen bonds. The genome-wide identification, characterization, evolutionary understanding, gene expression, and structural analysis of proteases and PIs provide a framework for future analysis when defining their roles in stress response and developing a more stress tolerant variety of chickpea. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  9. Family Counseling Psychology.

    Science.gov (United States)

    Levant, Ronald F., ed.

    1983-01-01

    Describes programs for family counseling which use psychological-educational and skills training methods to remediate individual and family problems or enhance family life. The six articles discuss client-centered skills training, behavioral approaches, cognitive behavioral marital therapy, Adlerian parent education, and couple communication. (JAC)

  10. Year of the Family.

    Science.gov (United States)

    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,…

  11. Rethinking Family Power.

    Science.gov (United States)

    Kranichfeld, Marion L.

    1987-01-01

    Men's power is emphasized in the family power literature on marital decision making. Little attention has been paid to women's power, accrued through their deeper embeddedness in intrafamilial roles. Micro-level analysis of family power demonstrates that women's positions in the family power structure rest not on the horizontal marital tie but…

  12. Disrupted Refugee Family Life

    DEFF Research Database (Denmark)

    Shapiro, Ditte Krogh

    2017-01-01

    Fleeing civil war involves managing life threatening events and multiple disruptions of everyday life. The theoretical potentials of analysing the recreation of everyday family life among Syrian refugees in Denmark is explored based on conceptualizations that emphasize the collective agency...... of family members in social historical contexts. Studying the multiple perspectives of family members shows how social support conceptualized as care practises is conflictual in the changing everyday family practices that are transformed by policy. The purpose of studying how families manage to flee civil...... war and struggle to recreate an everyday life in exile is to contribute with contextualization and expansion of mainstream understandings of family life, suffering, and resilience in refugee family trajectories in multiple contexts....

  13. Inside the Family Firm

    DEFF Research Database (Denmark)

    Bennedsen, Morten; Nielsen, Kasper; Pérez-González, Francisco

    2005-01-01

    This paper uses a unique dataset from Denmark to investigate (1) the role of family characteristics in corporate decision making, and (2) the consequences of these decisions on firm performance. We focus on the decision to appoint either a family or an external chief executive officer (CEO). We...... show that a departing CEO's family characteristics have a strong predictive power in explaining CEO succession decisions: family CEOs are more frequently selected the larger the size of the family, the higher the ratio of male children and when the departing CEOs had only had one spouse. We...... then analyze the impact of family successions on performance. We overcome endogeneity and omitted variables problems of previous papers in the literature by using the gender of a departing CEO's first-born child as an instrumental variable (IV) for family successions. This is a plausible IV as male first...

  14. Multiplex families with epilepsy

    Science.gov (United States)

    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

  15. Family governance practices and teambuilding : Paradox of the enterprising family

    NARCIS (Netherlands)

    Berent-Braun, M.M.; Uhlaner, L.M.

    2012-01-01

    This paper explores the relationship between family governance practices and financial performance of the business and family assets of business-owning families. A business-owning family that shares a focus on preserving and growing wealth as a family is defined as the enterprising family. Results

  16. [Family therapy of encopresis].

    Science.gov (United States)

    Spitczok von Brisinski, Ingo; Lüttger, Fred

    2007-01-01

    Encopresis is a taboo symptom, which is connected with great suffering from mental pressure not only for the children concerned, but also their relatives. Family related approaches are indispensable to understand encopresis, because as a result of high symptom persistence and psychological comorbidity in many cases a purely behavior-therapeutic, symptom focused approach is not sufficient, and further psychotherapeutic interventions are necessary. There is a strong temporal correlation between family interaction and frequency of soiling and changes of interaction influence changes in soiling more than the other way round. In a literature review different family relationship patterns and approaches of family therapy are represented regarding encopresis. Meaningful differences for family therapy are represented regarding primary/secondary encopresis, encopresis with/without comorbid psychiatric disorder as well as encopresis with/without dysfunctional family interaction. Distinctions are made between symptom focused, not-symptom focused and combined family therapeutic approaches, which are illustrated with case examples of outpatient and inpatient treatment. Symptom focused family therapy like e.g. externalizing of the soiling is helpful also if no dysfunctional family interaction patterns are present, because all family members can contribute to treatment success according to their own resources.

  17. Extended family medicine training

    Science.gov (United States)

    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

  18. Internationalization of Family Businesses

    DEFF Research Database (Denmark)

    Boyd, Britta; Hollensen, Svend; Goto, Toshio

    2010-01-01

    This article focuses on the international joint venture formation process of family businesses. The reasoning behind Danfoss’ decision to cooperate with two competing family businesses in Japan and China as well as two nonfamily businesses in Canada and Britain will be analysed. In......-depth qualitative interviews reveal the driving forces on both sides and show how the psychic distance can be reduced between the different parent firms including the joint venture (JV) child. The purpose of this study is to compare equal split or equity joint ventures of non-family and family firms regarding...... the formation process including competences and cultures. The study indicates what core competences of a family business matter when cooperating in equal split joint ventures. Implications for family business owners and ideas for future research are discussed....

  19. Advancing family psychology.

    Science.gov (United States)

    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. (c) 2016 APA, all rights reserved).

  20. Sharing family and household:

    DEFF Research Database (Denmark)

    Winther, Ida Wentzel

    Keynote: Family relationships are normatively assumed to be characterized by ‘sharing’, such as living together in the same home, occupying the same place, sharing stuff, blood and biology, spending special and ordinary time together, and consequently creating shared biographical experiences....... In that way, families are thrown into togetherness. At the same time, we see families in varying forms where 'sharing' is lived and contested differently. In Denmark, many children live in nuclear families, and many live in different variations of more than one household. For those who share household...... and family, 'sharing' will be a basic condition. No matter what, they should share life circumstances, more stories, more places and spaces, more households families with both kin and non-kin. This keynote addresses the particular of children’s experiences of living apart and/or living together in sharing...

  1. Familial Transient Global Amnesia

    Directory of Open Access Journals (Sweden)

    R.Rhys Davies

    2012-12-01

    Full Text Available Following an episode of typical transient global amnesia (TGA, a female patient reported similar clinical attacks in 2 maternal aunts. Prior reports of familial TGA are few, and no previous account of affected relatives more distant than siblings or parents was discovered in a literature survey. The aetiology of familial TGA is unknown. A pathophysiological mechanism akin to that in migraine attacks, comorbidity reported in a number of the examples of familial TGA, is one possibility. The study of familial TGA cases might facilitate the understanding of TGA aetiology.

  2. The DLGAP family

    DEFF Research Database (Denmark)

    Rasmussen, Andreas H; Rasmussen, Hanne B; Silahtaroglu, Asli

    2017-01-01

    downstream signalling in the neuron. The postsynaptic density, a highly specialized matrix, which is attached to the postsynaptic membrane, controls this downstream signalling. The postsynaptic density also resets the synapse after each synaptic firing. It is composed of numerous proteins including a family...... in the postsynapse, the DLGAP family seems to play a vital role in synaptic scaling by regulating the turnover of both ionotropic and metabotropic glutamate receptors in response to synaptic activity. DLGAP family has been directly linked to a variety of psychological and neurological disorders. In this review we...... focus on the direct and indirect role of DLGAP family on schizophrenia as well as other brain diseases....

  3. Life in Remarriage Families.

    Science.gov (United States)

    Dahl, Ann Sale; And Others

    1987-01-01

    In preliminary findings from research interviews with nonclinical remarriage families who were not receiving treatment, both marital satisfaction and children's adjustment were described in primarily positive terms, especially after the first few years. Families reported that the process of managing complexities, uncertainties, and mixed feelings…

  4. Family Open House

    Science.gov (United States)

    Search Family Open House Join us for an afternoon of science fun. The Fermilab Family Open House is a party for children of all ages to learn about the world of physics. The Open House is supported by Open House? Check out our YouTube video to learn more! Explore physics concepts with hands-on

  5. Family Support and Education

    Science.gov (United States)

    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. Changing Families, Changing Workplaces

    Science.gov (United States)

    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…

  7. Family Perspectives on Prematurity

    Science.gov (United States)

    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…

  8. Families Falling Apart.

    Science.gov (United States)

    Moynihan, Daniel Patrick

    1990-01-01

    Reviews trends in Black male unemployment, out-of-wedlock births, and the number of Aid to Families with Dependent Children cases over the past 25 years. Argues that family breakdown is creating a state of urban social chaos that could lead to martial law. (FMW)

  9. Family and household demography

    NARCIS (Netherlands)

    Willekens, F.J.C.; Zeng, Yi

    2009-01-01

    Households are groups of people that co-reside and share some resources. Families are households of related individuals. Household and family demography is the study of these primary social groups or social units, and in particular of group membership and the relationships between members of the

  10. Family intervention for schizophrenia.

    Science.gov (United States)

    Pharoah, F M; Mari, J J; Streiner, D

    2000-01-01

    It has been showed that 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 their emotions. Psychosocial interventions designed to reduce these levels of expressed emotions within families now exist for mental health workers. These interventions are proposed as adjuncts rather than alternatives to drug treatments, and their main purpose is to decrease the stress within the family and also the rate of relapse. To estimate the effects of family psychosocial interventions in community settings for the care of those with schizophrenia or schizophrenia-like conditions compared to standard care. Electronic searches of the Cochrane Library (Issue 2, 1998), the Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1981-1995) and MEDLINE (1966-1995) were undertaken and supplemented with reference searching of the identified literature. Randomised or quasi-randomised studies were selected if they focused on families of people with schizophrenia or schizoaffective disorder and compared community-orientated family-based psychosocial intervention of more than five sessions to standard care. Data were reliably extracted, and, where appropriate and possible, summated. Peto odds ratios (OR), their 95% confidence intervals (CI) and number needed to treat (NNT) were estimated. The reviewers assume that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Family intervention may decrease the frequency of relapse (one year OR 0.57 CI 0.4-0.8, NNT 6.5 CI 4-14). The trend over time of this main finding is towards the null and some small but negative studies may not have been identified by the search. Family intervention may decrease hospitalisation and encourage compliance with medication but data are few and equivocal. Family intervention does not

  11. Fighting for the family

    DEFF Research Database (Denmark)

    Heiselberg, Maj Hedegaard

    2016-01-01

    ‘relational spaces’ that allow them to preserve intimate relationships despite geographical distances. Besides dealing with the practical responsibilities of everyday life, soldiers’ partners also fight to maintain the sense of closeness associated with normative ideals about family relations and a ‘good......The article explores how military deployment affects the everyday lives of Danish soldiers’ families. By approaching the challenges faced by soldiers and their partners from an anthropological perspective of the family, the article provides new insights into the social consequences of military...... deployment and the processes of militarization at home. Drawing on ethnographic examples from recent fieldwork among women, children, and soldiers at different stages of deployment, the article demonstrates how soldiers and their families attempt to live up to ideals about parenthood and family by creating...

  12. Maintenance of family networks

    DEFF Research Database (Denmark)

    marsico, giuseppina; Chaudhary, N; Valsiner, Jaan

    2015-01-01

    Families are social units that expand in time (across generations) and space (as a geographically distributed sub-structures of wider kinship networks). Understanding of intergenerational family relations thus requires conceptualization of communication processes that take place within a small...... collective of persons linked with one another by a flexible social network. Within such networks, Peripheral Communication Patterns set the stage for direct everyday life activities within the family context. Peripheral Communication Patterns are conditions where one family network member (A) communicates...... manifestly with another member (B) with the aim of bringing the communicative message to the third member (C) who is present but is not explicitly designated as the manifest addressee of the intended message. Inclusion of physically non-present members of the family network (elders living elsewhere, deceased...

  13. Negotiating Family Tracking

    DEFF Research Database (Denmark)

    Albrechtslund, Anders; Bøge, Ask Risom; Sonne Damkjær, Maja

    This presentation explores the question: What motivates the use of tracking technologies in families, and how does the use transform the relations between parent and child? The purpose is to investigate why tracking technologies are used in families and how these technologies potentially change...... the relation between parents and children. The use of tracking technologies in families implicate negotiations about the boundaries of trust and intimacy in parent-child relations which can lead to strategies of resistance or modification (Fotel and Thomsen, 2004; Rooney, 2010; Steeves and Jones, 2010......). In the presentation, we report from a qualitative study that focuses on intergenerational relations. The study draws on empirical data from workshops with Danish families as well as individual and group interviews. We aim to gain insights about the sharing habits and negotiations in intimate family relations...

  14. Family Functioning and Child Psychopathology: Individual Versus Composite Family Scores.

    Science.gov (United States)

    Mathijssen, Jolanda J. J. P.; Koot, Hans M.; Verhulst, Frank C.; De Bruyn, Eric E. J.; Oud, Johan H. L.

    1997-01-01

    Examines the relationship of individual family members' perceptions and family mean and discrepancy scores of cohesion and adaptability with child psychopathology in a sample of 138 families. Results indicate that family mean scores, contrary to family discrepancy scores, explain more of the variance in parent-reported child psychopathology than…

  15. 75 FR 17946 - Family Report, MTW Family Report

    Science.gov (United States)

    2010-04-08

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-25] Family Report, MTW Family... comments on the subject proposal. Tenant data is collected to understand demographic, family profile.... This Notice Also Lists the Following Information Title of Proposal: Family Report, MTW Family Report...

  16. Family planning education.

    Science.gov (United States)

    Hamburg, M V

    1983-02-01

    17 days were spent devoted to the effort of learning about China's educational approach to family planning in the hope of discovering how they are achieving their remarkable success in reducing population growth. As a member of the 1981 New York University/SIECUS Colloquim in China, it was necessary to rely on the translation provided by the excellent guides. Discussions were focused on questions prepared in advance about the topics that concerned the group. These observations, based on a short and limited exposure, cover the following areas: marriage and family planning policies; the family planning program; school programs; adult education; family planning workers; and unique aspects of the program. China has an official position on marriage and family planning that continues to undergo revisions. The new marriage law sets the minimum ages of marriage at 22 for men and 20 for women. Almost everyone marries, and an unmarried person over age 28 is a rarity. The family planning program in China is carried out by an extensive organizational network at national, provincial, and local government levels. Officials termed it a "propaganda campaign." Hospitals, clinics, and factories invariably displayed posters; a popular set of four presents the advantages of the 1 child family as follows: late marriage is best, for it allows more time to work and study; 1 child is best for the health of the mother; one gets free medical care for his/her child if a family has only 1 child; and there is more time to teach 1 child. The state operated television regularly explains the 1 child policy utilizing special films. According to 1 family planning official, "before marriage there is little sex." There are few abortions for unmarried women. Education about sex is for adults, for those persons who are about to be married. There is little if any sex education in schools. Sexual teaching is not generally acceptable, especially in the rural areas. By contrast, in Shanghai the physiology

  17. Gender and family stability

    Directory of Open Access Journals (Sweden)

    2001-02-01

    Full Text Available The increasing trend of partnership disruption among families with children in recent decades has been accompanied by substantial changes in traditional gender roles in industrialized countries. Yet, relatively little is known about the effects of changing gender relations on family stability in the European context. In this paper, we study such gender influences at the familial and societal level in Sweden and Hungary between the mid-1960s and the early 1990s. We focus on the disruption of the first parental union (i.e. the union in which a couple's first child was born. Our analysis is based on data extracted from the Swedish and Hungarian Fertility and Family Surveys of 1992/93. We use the method of hazard regression. The results suggest (i that the establishment of the dual-earner family model influences family stability only if it is accompanied by some changes in traditional gender relations within the family, and (ii that women's and men's labor-market behavior have different effects in spite of the relatively long history of women's (also mothers' labor-force participation in both Sweden and Hungary.

  18. Working with Chronically Dysfunctional Families.

    Science.gov (United States)

    Younger, Robert; And Others

    This paper reviews family therapy with chronically dysfunctional families including the development of family therapy and current trends which appear to give little guidance toward working with severely dysfunctional families. A theoretical stance based upon the systems approach to family functioning and pathology is presented which suggests: (1)…

  19. Family Structure and Social Influence.

    Science.gov (United States)

    Olson, Dawn R.

    Regardless of family form, there is a universal belief that one's family is the most powerful agent of socialization. A sample of 38 junior high school students from single parent and nuclear families completed a questionnaire in order to examine the relative effects of peer influence and family influence in single parent and nuclear families.…

  20. IDEA and Family Involvement

    Directory of Open Access Journals (Sweden)

    Mehmet Emin Öztürk

    2017-01-01

    Full Text Available Individuals with Disabilities Education Act (IDEA gives many rights to parents with special needs in terms of involvement and participation. Given the importance of family involvement in the special education process, and federal legislation that increasingly mandated and supported such involvement over time, considerable research has focused on the multiple ways that relationships between schools and families in the special education decision making process have played out. Educational professionals should create a positive climate for CLD families so that they feel more comfortable and therefore are able to participate more authentically and meaningfully.

  1. Families of vicious walkers

    International Nuclear Information System (INIS)

    Cardy, John; Katori, Makoto

    2003-01-01

    We consider a generalization of the vicious walker problem in which N random walkers in R d are grouped into p families. Using field-theoretic renormalization group methods we calculate the asymptotic behaviour of the probability that no pairs of walkers from different families have met up to time t. For d > 2, this is constant, but for d -α , which we compute to O(ε 2 ) in an expansion in ε = 2 - d. The second-order term depends on the ratios of the diffusivities of the different families. In two dimensions, we find a logarithmic decay (ln t) -α-bar and compute α-bar exactly

  2. Family and non-family business differences in Estonia

    Directory of Open Access Journals (Sweden)

    Maret Kirsipuu

    2014-01-01

    Full Text Available This paper seeks to identify differences between family enterprises and non-family enterprises. The concepts of entrepreneurship, entrepreneur and enterprise/business are clarified. The paper contains the results of research conducted by the author among family entrepreneurs in 2007–2012 that can be compared to the research results reached by Wahl (2011. This research demonstrates that there are differences between family entrepreneurs and non-family entrepreneurs, which are primarily caused by that family entrepreneurs value first of all their family members, family traditions and only then profit earning.

  3. Family medical leave as a resilience resource for family caregivers.

    Science.gov (United States)

    Swanke, Jayme; Zeman, Laura Dreuth

    2009-01-01

    Case managers mobilize family networks to care for patients. Family medical leave can be a resource for case managers who seek to enhance resilience among family caregivers. The Family Medical Leave Act, passed in 1993, was the first U.S. policy to regulate employee leaves from work for family care purposes (29 CFR 825.102). This policy offers family caregivers increased flexibility and equality. Current and emerging policies also can reduce financial strain. The discussion examines how case managers can integrate family medical leave into best-practice models to support patients and family caregivers.

  4. Madspild i familier

    DEFF Research Database (Denmark)

    Winkel, Thomas Dyrmann

    særligt henblik på forholdet mellem familiens sociale dynamikker, praksisser og hverdagens organisering. Et misforhold mellem hverdagens organisering og familiemedlemmernes madpraksisser er en væsentlig årsag til madspild. Teorien, der forklarer, hvorfor familiers praksis forårsager madspild, ligger til...... forskningsspørgsmål, forskningsdesign analyse og konklusioner. I afhandlingen omhandler et studie af familiers praksis, der forårsager madspild. Resultatet er en teori herom og en metode til at reducere madspildet gennem ændring af familiers praksisser. Jeg undersøger i familiestudiet seks børnefamiliers praksis med...... grund for en metode til at reducere madspildet. Metoden bygger primært på praksisteori og tager højde for etiske implikationer i ændringen af familiers praksis. Den udviklede metode er tilpasset anvendelse i organisatorisk praksis og indeholder et konkret redskab til brug før, under og efter...

  5. Familial polycystic ovarian disease.

    Science.gov (United States)

    Givens, J R

    1988-12-01

    Emphasis is placed on the heterogeneity of the phenotypic presentation of PCOD. It is the common expression of an unknown number of disorders and thus is a sign and not a specific diagnosis. Two essential features are arrested follicular maturation and atresia of follicles. Normal folliculogenesis is described, emphasizing that a large number of areas could be subject to derangement causing PCOD. Any interference of the finely balanced sequence of events can lead to PCOD. The genetic defect causing familial PCOD is unknown and the initiating event remains undefined. Three families are described that illustrate four features of familial PCOD. A number of associated disorders such as diabetes, hyperinsulinemia, obesity, and hypertension are described. The potential importance of agents that modulate the LH and FSH activity that may cause PCOD is emphasized. The theoretic means by which similar male and female gonadal abnormalities may be coupled in families through growth factors EGF and alpha TGF are presented.

  6. VIRUS FAMILIES – contd

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. VIRUS FAMILIES – contd. Minus strand RNA viruses. Rhabdovirus e.g. rabies. Paramyxovirus e.g. measles, mumps. Orthomyxovirus e.g. influenza. Retroviruses. RSV, HTLV, MMTV, HIV. Notes:

  7. Asbestos: Protect Your Family

    Science.gov (United States)

    ... Related Topics: Asbestos Contact Us Share 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 ...

  8. Family Weight School treatment

    DEFF Research Database (Denmark)

    Nowicka, Paulina; Höglund, Peter; Pietrobelli, Angelo

    2008-01-01

    OBJECTIVE: The aim was to evaluate the efficacy of a Family Weight School treatment based on family therapy in group meetings with adolescents with a high degree of obesity. METHODS: Seventy-two obese adolescents aged 12-19 years old were referred to a childhood obesity center by pediatricians...... and school nurses and offered a Family Weight School therapy program in group meetings given by a multidisciplinary team. Intervention was compared with an untreated waiting list control group. Body mass index (BMI) and BMI z-scores were calculated before and after intervention. RESULTS: Ninety percent...... group with initial BMI z-score 3.5. CONCLUSIONS: Family Weight School treatment model might be suitable for adolescents with BMI z...

  9. Families talen en algebra

    NARCIS (Netherlands)

    Asveld, P.R.J.

    1976-01-01

    Operaties op formele talen geven aanleiding tot bijbehorende operatoren op families talen. Bepaalde onderwerpen uit de algebra (universele algebra, tralies, partieel geordende monoiden) kunnen behulpzaam zijn in de studie van verzamelingen van dergelijke operatoren.

  10. The Family Startup Program

    DEFF Research Database (Denmark)

    Trillingsgaard, Tea; Maimburg, Rikke Damkjær; Simonsen, Marianne

    2015-01-01

    Background: Inadequate parenting is an important public health problem with possible severe and long-term consequences related to child development. We have solid theoretical and political arguments in favor of efforts enhancing the quality of the early family environment in the population at large....../design: Participants will be approximately 2500 pregnant women and partners. Inclusion criteria are parental age above 18 and the mother expecting first child. Families are recruited when attending routine pregnancy scans provided as a part of the publicly available prenatal care program at Aarhus University Hospital...... and community resources. The program consists of twelve group sessions, with nine families in each group, continuing from pregnancy until the child is 15 months old. TAU is the publicly available pre- and postnatal care available to families in both conditions. Analyses will employ survey data, administrative...

  11. The family Cyclobacteriaceae

    Digital Repository Service at National Institute of Oceanography (India)

    AnilKumar, P.; Srinivas, T.N.R.

    , carotenoid biosynthesis, antibiotic resistance, and quorum-sensing regulation were found Pathogenicity is not reported among the Cyclobacteriaceae members This contribution is a modified and updated version of previous family descriptions (Nedashkovskaya OI...

  12. A randomised, double-blind, cross-over trial to evaluate bread, in which gluten has been pre-digested by prolyl endoprotease treatment, in subjects self-reporting benefits of adopting a gluten-free or low-gluten diet.

    Science.gov (United States)

    Rees, Dinka; Holtrop, Grietje; Chope, Gemma; Moar, Kim M; Cruickshank, Morven; Hoggard, Nigel

    2018-03-01

    The aim of the present study was to determine if the enzyme Aspergillus niger prolyl endoprotease (ANPEP), which degrades the immunogenic proline-rich residues in gluten peptides, can be used in the development of new wheat products, suitable for gluten-sensitive (GS) individuals. We have carried out a double-blind, randomised, cross-over trial with two groups of adults; subjects, self-reporting benefits of adopting a gluten-free or low-gluten diet (GS, n 16) and a control non-GS group (n 12). For the trial, volunteers consumed four wheat breads: normal bread, bread treated with 0·8 or 1 % ANPEP and low-protein bread made from biscuit flour. Compared with controls, GS subjects had a favourable cardiovascular lipid profile - lower LDL (4·0 (sem 0·3) v. 2·8 (sem 0·2) mmol/l; P=0·008) and LDL:HDL ratio (3·2 (sem 0·4) v. 1·8 (sem 0·2); P=0·005) and modified haematological profile. The majority of the GS subjects followed a low-gluten lifestyle, which helps to reduce the gastrointestinal (GI) symptoms severity. The low-gluten lifestyle does not have any effect on the quality of life, fatigue or mental state of this population. Consumption of normal wheat bread increased GI symptoms in GS subjects compared with their habitual diet. ANPEP lowered the immunogenic gluten in the treated bread by approximately 40 %. However, when compared with the control bread for inducing GI symptoms, no treatment effects were apparent. ANPEP can be applied in the production of bread with taste, texture and appearance comparable with standard bread.

  13. Family Demands, Social Support and Family Functioning in Taiwanese Families Rearing Children with Down Syndrome

    Science.gov (United States)

    Hsiao, C-Y.

    2014-01-01

    Background: Down syndrome (DS) affects not only children but also their families. Much remains to be learned about factors that influence how families of children with DS function, especially families in non-Western populations. The purpose of this cross-sectional, correlational study was to examine how family demographics, family demands and…

  14. WOMEN IN FAMILY BUSINESS

    OpenAIRE

    Mr Anshu

    2012-01-01

    The role of women in family businesses is explored in the paper. Although recognized as generally very important players, the role of women is often defined as invisible in business decision-making, supportive in men’s traditional business domains and only rarelyadequately recognized and rewarded. The paper explores possible differences in the views of men and women who manage small family firms. Their attitudes opposing the traditional business roles ofwomen, different views on managerial, o...

  15. Family employees and absenteeism

    OpenAIRE

    Laszlo Goerke; Jörn Block; Jose Maria Millan; Concepcion Roman

    2014-01-01

    Work effort varies greatly across employees, as evidenced by substantial differences in absence rates. Moreover, absenteeism causes sizeable output losses. Using data from the European Community Household Panel (ECHP), this paper investigates absence behavior of family employees, i.e. workers who are employed in enterprises owned by a relative. Our estimates indicate that being a family employee instead of a regular employee in the private sector significantly reduces both the probability and...

  16. The tubby family proteins

    OpenAIRE

    Mukhopadhyay, Saikat; Jackson, Peter K

    2011-01-01

    The tubby mouse shows a tripartite syndrome characterized by maturity-onset obesity, blindness and deafness. The causative gene Tub is the founding member of a family of related proteins present throughout the animal and plant kingdoms, each characterized by a signature carboxy-terminal tubby domain. This domain consists of a β barrel enclosing a central α helix and binds selectively to specific membrane phosphoinositides. The vertebrate family of tubby-like proteins (TULPs) includes the foun...

  17. Genetics Home Reference: familial candidiasis

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Familial candidiasis Familial candidiasis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Familial candidiasis is an inherited tendency to develop infections caused ...

  18. Creating a family health history

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000947.htm Creating a family health history To use the sharing ... Many health problems tend to run in families. Creating a family history can help you and your ...

  19. [Family, Suicide and Mourning].

    Science.gov (United States)

    Garciandía Imaz, José Antonio

    2013-01-01

    Death is an event that always breaks into family life in a surprising way. Of all the deaths, suicide is the one which more strongly questions the functionality of a family and increases the risk of difficulties in the mourning process. Families in which a suicide has occurred are exposed to a greater possibility of disintegration, disorganization and pathological expressions in their members. To present a reduced and circumscribed narrative revision, restricted to examine the relationship between suicide and the mourning process in the family. The suicide of a loved one is an event that may contribute to pathological grief and mental dysfunctions in surviving relatives. Death in the family is a natural phenomenon. However, death by suicide is one of the phenomena that can generate more alterations in the structure and organization of the family, due to the difficulty related to the mourning process. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  20. Mandolin Family Instruments

    Science.gov (United States)

    Cohen, David J.; Rossing, Thomas D.

    The mandolin family of instruments consists of plucked chordophones, each having eight strings in four double courses. With the exception of the mandobass, the courses are tuned in intervals of fifths, as are the strings in violin family instruments. The soprano member of the family is the mandolin, tuned G3-D4-A4-E5. The alto member of the family is the mandola, tuned C3-G3-D4-A4. The mandola is usually referred to simply as the mandola in the USA, but is called the tenor mandola in Europe. The tenor member of the family is the octave mandolin, tuned G2-D3-A3-E4. It is referred to as the octave mandolin in the USA, and as the octave mandola in Europe. The baritone member of the family is the mandocello, or mandoloncello, tuned C2-G2-D3-A3. A variant of the mandocello not common in the USA is the five-course liuto moderno, or simply liuto, designed for solo repertoire. Its courses are tuned C2-G2-D3-A3-E4. A mandobass was also made by more than one manufacturer during the early twentieth century, though none are manufactured today. They were fretted instruments with single string courses tuned E1-A1-D2-G2. There are currently a few luthiers making piccolo mandolins, tuned C4-G4-D5-A5.

  1. "Not a Real Family": Microaggressions Directed toward LGBTQ Families.

    Science.gov (United States)

    Haines, Kari M; Boyer, C Reyn; Giovanazzi, Casey; Galupo, M Paz

    2018-01-01

    The present study investigates microaggressions toward individuals in lesbian, gay, bisexual, transgender, and queer (LGBTQ) families. Microaggressions are subtle forms of discrimination experienced on a daily basis as verbal or behavioral slights against individuals in oppressed groups. LGBTQ microaggressions are often studied at an individual level and understood as being directed toward an individual based on perceived identity. The present study allows for an understanding of bias directed at the family system level. Participants included 46 adults who identified as being part of an LGBTQ family. Participants completed an online questionnaire and described their experiences of LGBTQ family microaggressions. Thematic analysis revealed that LGBTQ family microaggressions were salient to individuals across multiple family roles. Three specific themes emerged: family legitimacy, conflicts with family values, and gender violation within family. These findings highlight the way LGBTQ microaggressions are influenced by cultural notions of family and impact the family system.

  2. Smooth School Transitions: Tips for Military Families

    Science.gov (United States)

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

  3. The intersubjectivity of family consumption

    DEFF Research Database (Denmark)

    Linnet, Jeppe Trolle

    identity and family scape, I analyze how family members negotiate purchase decisions, and relate to each other’s preferences and desires, as well as those of other families. I consider how family members' interrelations as consumers and long-term negotiations over symbolic meanings of consumption......This study of everyday consumption is based on an ethnographic fieldwork conducted among four Danish middle-class families in Copenhagen, from which an illustrative example of family car purchase is drawn. By introducing two new concepts to the study of family consumption; intra-family consumer...

  4. Changing families, changing workplaces.

    Science.gov (United States)

    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 distribution. Between 1975 and 2009, the labor force rate of mothers with children under age eighteen increased from 47.4 percent to 71.6 percent. Mothers today also return to work much sooner after the birth of a child than did mothers half a century ago. High divorce rates and a sharp rise in the share of births to unmarried mothers mean that more children are being raised by a single parent, usually their mother. Workplaces too have changed, observes Bianchi. Today's employees increasingly work nonstandard hours. The well-being of highly skilled workers and less-skilled workers has been diverging. For the former, work hours may be long, but income has soared. For lower-skill workers, the lack of "good jobs" disconnects fathers from family obligations. Men who cannot find work or have low earnings potential are much less likely to marry. For low-income women, many of whom are single parents, the work-family dilemma is how to care adequately for children and work enough hours to support them financially. Jobs for working-class and lower middle-class workers are relatively stable, except in economic downturns, but pay is low, and both parents must work full time to make ends meet. Family income is too high to qualify for government subsidized child care, but too low to afford high-quality care in the private market. These families struggle to have a reasonable family life and provide for their family's economic well-being. Bianchi concludes that the "work and family" problem has no one solution because it is not one problem. Some workers need more work and more money. Some need to take time off around the birth of a child

  5. Family First? The Costs and Benefits of Family Centrality for Adolescents with High-Conflict Families.

    Science.gov (United States)

    Yuen, Cynthia X; Fuligni, Andrew J; Gonzales, Nancy; Telzer, Eva H

    2018-02-01

    Youth who do not identify with or value their families (i.e., low family centrality) are considered to be at risk for maladjustment. However, the current study investigated whether low family centrality may be adaptive in negative family contexts (i.e., high family conflict) because youth's self-worth should be less tied to the quality of their family relationships. Multilevel models using daily diaries and latent variable interactions using longitudinal questionnaires indicated that, among a sample of 428 Mexican American adolescents (49.8% male, M age  = 15.02 years), lower family centrality was generally detrimental to youth's well-being. However, for youth in adverse family environments, low family centrality ceased to function as a risk factor. The present findings suggest that family centrality values play a more nuanced role in youth well-being than previously believed, such that low family centrality may be an adaptive response to significant family challenges.

  6. Use of family management styles in family intervention research.

    Science.gov (United States)

    Alderfer, Melissa A

    2006-01-01

    Family management styles (FMSs) explain some of the complexities embedded in a family with a child who has chronic illness. The FMS typologies provide descriptions of family adjustment and management of care. These 5 distinct patterns may be valuable in tailoring and evaluating family interventions in research.

  7. Engaging Families in In-Home Family Intervention

    Science.gov (United States)

    Thompson, Ronald W.; Koley, Sarah

    2014-01-01

    Boys Town has created a program called In-Home Family Services to deliver help to families in stress. In-home family intervention programs have become widely used to help more families who are at risk and experiencing difficulties with a wide range of problems including domestic violence, child behavior problems, parent-child and family…

  8. Opportunity NYC--Family Rewards: Qualitative Study of Family Communication

    Science.gov (United States)

    Fraker, Carolyn A.; Greenberg, David

    2011-01-01

    Aimed at low-income families in six of New York City's highest-poverty communities, the Family Rewards program ties cash rewards to a pre-specified set of activities. This paper presents the qualitative findings from interviews with 77 families. It examines how families incorporated the program into their households, and specifically the…

  9. 24 CFR 982.515 - Family share: Family responsibility.

    Science.gov (United States)

    2010-04-01

    ... URBAN DEVELOPMENT SECTION 8 TENANT BASED ASSISTANCE: HOUSING CHOICE VOUCHER PROGRAM Rent and Housing 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 is...

  10. Anxiety Disorders and the Family: How families affect psychiatric disorders

    OpenAIRE

    Hunsley, John

    1991-01-01

    Family functioning and anxiety disorders, the most prevalent forms of psychiatric disorder, influence one another. The empirical literature on family studies of anxiety disorder (ie, aggregration of disorders within families), on parent-child relationships and anxiety disorders, and on marriage and anxiety disorders is reviewed. Finally, the challenges for patients and their families of post-traumatic stress disorder are discussed.

  11. Education, Parenting and Family: The Social Geographies of Family Learning

    Science.gov (United States)

    Wainwright, Emma; Marandet, Elodie

    2017-01-01

    This paper explores the relationship between education, parenting and family through the prism and particularities of family learning. Family learning is an example of an educational initiative, primarily aimed at parents and linked to wider policy concerns, which can be explored through a mapping of its social geographies; family learning is…

  12. Adoptive Family Adjustment and Its Relation to Perceived Family Environment.

    Science.gov (United States)

    Martin, Betty; Kelly, Mary Margaret; Towner-Thyrum, Elizabeth

    1999-01-01

    Interviewed adopted college students regarding perceptions of adoptive family life. Found that overall satisfaction with adoptive status and family life was the strongest predictor of perceived general family environment. Perception of adoptive parents' communication styles predicted different aspects of family environment. Acknowledgment of life…

  13. Who counts as family? Family typologies, family support, and family undermining among young adult gay and bisexual men.

    Science.gov (United States)

    Soler, Jorge H; Caldwell, Cleopatra H; Córdova, David; Harper, Gary; Bauermeister, José A

    2018-06-01

    Gay and bisexual men may form chosen families in addition to or in place of families of origin. However, the characteristics of these diverse families remain largely unexamined in the quantitative literature. The purpose of this study was to develop a family typology based on responses from a racially and ethnically diverse sample of young adult gay and bisexual men (YGBM) recruited from the Detroit Metropolitan Area (N=350; 18-29 years old). To explore the role of family, we then examined family social support and social undermining in relation to YGBM psychological distress within different family types. A series of multivariate regressions were used to examine associations between family social support and social undermining with depression and anxiety outcomes. The majority (88%) of YGBM included family of origin in their definitions of family and 63% indicated having chosen families. Associations between family social processes and psychological outcomes varied by type of family, suggesting that family composition shapes how perceptions of support and undermining relate to experiencing symptoms of depression and anxiety. Chosen families play a prominent role in the lives of YGBM and should not be overlooked in family research. Findings also highlight the importance of examining co-occurring family social support and social stress processes to further address psychological distress symptoms among YGBM.

  14. Family functioning in the families of psychiatric patients: a comparison with nonclinical families.

    Science.gov (United States)

    Trangkasombat, Umaporn

    2006-11-01

    To examine family functioning in the families of psychiatric patients. Families of psychiatric patients and nonclinical families were compared. There were 60 families in each group. The instrument included a semistructured interview of family functioning and the Chulalongkorn Family Inventory (CFI), a self-report questionnaire designed to assess the perception of one's family. From the assessment by semistructured interview, 83.3% of psychiatric families and 45.0% of nonclinical families were found to be dysfunctional in at least one dimension. The difference was statistically significant (p dysfunctional dimensions in the psychiatric families was significantly higher than in the nonclinical control group, 3.5 +/- 1.9 and 0.98 +/- 1.5 respectively, p families were significantly lower than the control group, reflecting poor family functioning. The dysfunctions were mostly in the following dimensions: problem-solving, communication, affective responsiveness, affective involvement, and behavior control. Psychiatric families faced more psychosocial stressors and the average number of stressors was higher than the control families, 88.3% vs. 56.7% and 4.2 +/- 2.7 vs. 1.3 +/- 1.47 stressors respectively, p < 0.0001. Family functioning of psychiatric patients was less healthy than the nonclinical control. The present study underlined the significance of family assessment and family intervention in the comprehensive care of psychiatric patients.

  15. Attitudes toward family planning.

    Science.gov (United States)

    Gille, H

    1984-06-01

    Many of the 135 countries participating in the 1974 UN World Population Conference were far from accepting the basic human right to decide freely and responsibly the number and spacing of their children and to have the information, education, and means to do so. Considerable progress has been made since then, and the number of developing countries that provide direct government support for family planning has increased to over 60%. Many have liberalized laws and regulations which restricted access to modern contraceptive methods, and a growing number provide family planning services within their health care programs. A few have recognized the practice of family planning as a constitutional right. In late 1983 at the Second African Population Conference, recognition of family as a human right was strongly contested by several governments, particularly those of West Africa. in developed countries most of the women at risk of unwanted pregnancy are using contraceptives. Of the major developing regions the highest use level is in Latin America, wherein most countries 1/3 to 1/2 of married women are users. Levels in Asian countries range from up to 10% in Afghanistan, Nepal, and Pakistan to up to 40% in the southeastern countries. China, a special case, now probably exceeds an overall use level of 2/3 of married women. Contraceptive use is lowest in Africa. There is room for improvement even among many of the successful family planning programs, as access to contraceptives usually is not sufficient to overcome limiting factors. To ensure the individual's free choice and strengthen the acceptability and practice of family planning, all available methods should be provided in service programs and inluded in information and education activities. Family planning programs should engage local community groups, including voluntary organizations, in all aspects of planning, management, and allocation of resources. At the government level a clear political commitment to family

  16. Gender Stereotyping in Family

    Directory of Open Access Journals (Sweden)

    Muhammad Hussain

    2015-07-01

    Full Text Available Gender stereotyping and gender role development is one of the debatable concerns to sociologists especially those who are interested in sociology of gender. This study attempts to investigate the role of family inculcating gender stereotyping in Pakhtun culture and its impact on gender role development conducted in public-sector universities of Malakand Division, Khyber Pakhtunkhwa province of Pakistan. The data were collected through in-depth interview method using interview guide as a tool of data collection. A sample size of 24 respondents consisting male and female students and teachers (8 samples from each university through purposive sampling technique was selected from three universities in the region, that is, University of Malakand, University of Swat, and Shaheed Benazir Bhutto University Sharingal (main campus. The collected information has been analyzed qualitatively where primary information has been linked with secondary data for further elaboration and attainment of grounded facts. The study reveals that gender stereotyping and gender role formation are sociocultural and relational constructs, which are developed and inculcated in the institutional network, social interaction, and social relationships especially in family. The study indicated that in family sphere, gender stereotyping and gender role formation are the outcome of gender socialization, differential familial environment, and parents’ differential role with children. The study recommends that gender-balanced familial environment, adopting the strategy of gender mainstreaming and positive role of media, can overcome gender stereotyping and reduce its impacts on gender and social role formation.

  17. Egypt boosts family planning.

    Science.gov (United States)

    1977-10-27

    A $4 million Agency for International Development (AID) agreement was signed in Cairo September 30 which will help the Egyptian government increase family planning services. The project is in response to a request for up to $17 million of AID funds for family planning programs during the next 3 years. The funds will pay for: contract advisors to provide short-term in-country training of physicians, architectural and engineering services to renovate a hospital for family planning and obstetrics/gynecology training, and a field training site for family planning service providers. Some Egyptians will receive training in specialized areas in the U.S. and other countries. More than $1.5 million of the $4 million will finance local costs of goods and services required. In addition, it is anticipated that U.S.-owned local currencies will be obligated for direct support of U.S. technical personnel. Over the 3-year life of the project the $17 million from AID plus $664,000 of U.S.-owned local currency will cover 44% of the total costs of selected Egyptian family planning activities. The Egyptian government will contribute at least $18.4 million and the U.N. Fund for Population Activities and the International Bank for Reconstruction and Development will contribute $4.3 million.

  18. Family focused nursing education

    Directory of Open Access Journals (Sweden)

    R. A. E. Thompson

    1993-03-01

    Full Text Available At the present time the majority of nurse education programmes are firmly tied to the perspectives of curative medicine within hospitals - they are disease and hospital oriented. This model, which indicates a 'sickness’ concept of nursing is entirely inappropriate if contemporary and future health care needs are to be met. The shift in education should be towards a health, family and whole person centered approach. The family is the most fundamental and dynamic unit in society with a profound influence upon its members. Besides performing a variety of other functions, the family has a central role in promoting and maintaining the health of its members. Because the family unit is the microcosm of society and accurately reflects the needs of society at large it is appropriate that this should be a key area of experience. Family attachments during training provide opportunities for close and committed contact with people in their everyday world and for learning what is really important to them.

  19. Conferences and Family Reunions

    Directory of Open Access Journals (Sweden)

    Sarah Sutherland

    2012-12-01

    Full Text Available Professional associations and conferences have similarities with and differences from families and family reunions. This comparison can illustrate some ways professional associations can approach the integration of new members and the planning of conferences in order to facilitate membership development and leadership renewal. Unlike family reunions, professional conferences are not closed events that require a shared culture in order to fully participate; they are events that should show the constant change and development of practice that is representative of the profession – for both members and non-members. Some of the topics explored in the article are: making it easy for outsiders to contribute, considering the tastes of new members, making it easy to volunteer in a meaningful way, and remembering who the future of the organization is. These simple considerations will assist in opening professional associations to new participants and help them to maintain their relevance and vitality over time.

  20. Everyday Family Life

    DEFF Research Database (Denmark)

    Westerling, Allan

    2010-01-01

    and methods and it illustrates this by presenting a research design which comprises a multi-methodological approach combining quantitative and qualitative methods in the study of the relationship between the individual and the social (the individual/social), thus enabling analysis of both meaning...... project takes a social psychological approach, combining quantitative and qualitative methods in a longitudinal study of family life. The knowledge interest of the project is the constitution of communality and individuality in everyday family life. This article presents the theoretical framework......What are the implications of ongoing processes of modernization and individualization for social relations in everyday life? This overall research question is the pivotal point in empirical studies at the Centre of Childhood-, Youth- and Family Life Research at Roskilde University. One research...

  1. Familial gigantiform cementoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Won Jeong; Kim, Eun Kyung [Dankook Univ. School of Dentistry, Seoul (Korea, Republic of)

    2006-09-15

    Familial gigantiform cementoma is a rate fibro-cemento-osseous disease of the jaws which appears to be transmitted as an autosomal dominant trait with variable expressivity of the phenotype. A 7-year-old girl visited DKUDH complaining of the painless facial deformity. Clinically, significant facie-lingual expansion was observed at the left maxilla, left mandibular body and symphysis portion. Malposition of lower anterior teeth was found. Panoramic radiograph and CT scan showed the extensive expandile mixed lesion at maxilla and mandible. Bone scan revealed hot spot at the maxilla and left side of mandible. Histologic examination revealed moderately dense fibrous connective tissue with scattered masses resembling cementum. The patient's mother had a history of the mandibular resection due to benign tumor. Her younger brother had buccal expansion of right mandible. We report our finding of a family that has exhibited clinical, radiographic and histologic findings consistent with the familial gigantiform dementoma.

  2. Familial gigantiform cementoma

    International Nuclear Information System (INIS)

    Han, Won Jeong; Kim, Eun Kyung

    2006-01-01

    Familial gigantiform cementoma is a rate fibro-cemento-osseous disease of the jaws which appears to be transmitted as an autosomal dominant trait with variable expressivity of the phenotype. A 7-year-old girl visited DKUDH complaining of the painless facial deformity. Clinically, significant facie-lingual expansion was observed at the left maxilla, left mandibular body and symphysis portion. Malposition of lower anterior teeth was found. Panoramic radiograph and CT scan showed the extensive expandile mixed lesion at maxilla and mandible. Bone scan revealed hot spot at the maxilla and left side of mandible. Histologic examination revealed moderately dense fibrous connective tissue with scattered masses resembling cementum. The patient's mother had a history of the mandibular resection due to benign tumor. Her younger brother had buccal expansion of right mandible. We report our finding of a family that has exhibited clinical, radiographic and histologic findings consistent with the familial gigantiform dementoma

  3. Family environment patterns in families with bipolar children.

    Science.gov (United States)

    Belardinelli, Cecilia; Hatch, John P; Olvera, Rene L; Fonseca, Manoela; Caetano, Sheila C; Nicoletti, Mark; Pliszka, Steven; Soares, Jair C

    2008-04-01

    We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Parents of bipolar children reported lower levels of family cohesion (pfamilies where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder.

  4. Substance Abuse and the Family.

    Science.gov (United States)

    Murphy, John P.

    1984-01-01

    Examines the effect that a substance abuser may have on the family system and the maladaptive roles sometimes assumed by family members. Discusses dysfunctional family phases and therapeutic issues and presents 11 guidelines for counselors working with chemically dependent families. (JAC)

  5. 75 FR 63753 - Family Offices

    Science.gov (United States)

    2010-10-18

    ... interpreted the term, because, among the variety of services provided, family offices are in the business of...: Private Wealth Management in the Family Context, Wharton Global Family Alliance (Apr. 1, 2008), available..., management, and employment structures and arrangements employed by family offices.'' \\14\\ We have taken this...

  6. 76 FR 37983 - Family Offices

    Science.gov (United States)

    2011-06-29

    ... term family member undefined could allow typical commercial investment advisory businesses to rely on... experience and client base and on studies of family businesses, would comfortably accommodate most family... have a management role in the entity.\\77\\ Others believed that non- family clients more broadly should...

  7. Gendered Discourse about Family Business

    Science.gov (United States)

    Danes, Sharon M.; Haberman, Heather R.; McTavish, Donald

    2005-01-01

    Language patterns of family business owners were explored by identifying discourse styles and emphasized ideas in four presenting contexts: business, family, intersection of family and business, and business success. The content analysis supports the existence of a general discourse style within family businesses and of similarities and…

  8. Family ties and residential locations

    NARCIS (Netherlands)

    Mulder, C.H.; Cooke, T.J.

    2009-01-01

    In this paper, and in the Special Issue it introduces, the focus is on the role of family ties in residential location choice and, conversely, the role of residential locations in maintaining family ties. Not only do events in the nuclear family trigger residential relocations, but nearby family

  9. Characteristics of a Healthy Family.

    Science.gov (United States)

    Lin, Phylis Lan

    The reason for studying the characteristics of a healthy family is to encourage and strengthen the family and to move toward an enriched family life by using the characteristics as bench marks. Six characteristics are discussed as the essence of a healthy family: (1) commitment; (2) togetherness; (3) appreciation; (4) good communication; (5)…

  10. Work and Family. Special Focus.

    Science.gov (United States)

    Goetz, Kathy, Ed.

    1992-01-01

    This newsletter issue focuses on issues concerning families with both parents employed outside the home and describes several employer programs designed to help employees balance their work and family life. The newsletter includes the following articles: (1) "Work and Family: 1992"; (2) "Levi Strauss and Co.--A Work/Family Program…

  11. Incarceration in fragile families.

    Science.gov (United States)

    Wildeman, Christopher; Western, Bruce

    2010-01-01

    Since the mid-1970s the U.S. imprisonment rate has increased roughly fivefold. As Christopher Wildeman and Bruce Western explain, the effects of this sea change in the imprisonment rate--commonly called mass imprisonment or the prison boom--have been concentrated among those most likely to form fragile families: poor and minority men with little schooling. Imprisonment diminishes the earnings of adult men, compromises their health, reduces familial resources, and contributes to family breakup. It also adds to the deficits of poor children, thus ensuring that the effects of imprisonment on inequality are transferred intergenerationally. Perversely, incarceration has its most corrosive effects on families whose fathers were involved in neither domestic violence nor violent crime before being imprisoned. Because having a parent go to prison is now so common for poor, minority children and so negatively affects them, the authors argue that mass imprisonment may increase future racial and class inequality--and may even lead to more crime in the long-term, thereby undoing any benefits of the prison boom. U.S. crime policy has thus, in the name of public safety, produced more vulnerable families and reduced the life chances of their children. Wildeman and Western advocate several policy reforms, such as limiting prison time for drug offenders and for parolees who violate the technical conditions of their parole, reconsidering sentence enhancements for repeat offenders, and expanding supports for prisoners and ex-prisoners. But Wildeman and Western argue that criminal justice reform alone will not solve the problems of school failure, joblessness, untreated addiction, and mental illness that pave the way to prison. In fact, focusing solely on criminal justice reforms would repeat the mistakes the nation made during the prison boom: trying to solve deep social problems with criminal justice policies. Addressing those broad problems, they say, requires a greater social

  12. Family Resilience in the Military

    Science.gov (United States)

    Meadows, Sarah O.; Beckett, Megan K.; Bowling, Kirby; Golinelli, Daniela; Fisher, Michael P.; Martin, Laurie T.; Meredith, Lisa S.; Osilla, Karen Chan

    2016-01-01

    Abstract Military life presents a variety of challenges to military families, including frequent separations and relocations as well as the risks that service members face during deployment; however, many families successfully navigate these challenges. Despite a recent emphasis on family resilience, the U.S. Department of Defense (DoD) does not have a standard and universally accepted definition of family resilience. A standard definition is a necessary for DoD to more effectively assess its efforts to sustain and improve family resilience. RAND authors reviewed the literature on family resilience and, in this study, recommend a definition that could be used DoD-wide. The authors also reviewed DoD policies related to family resilience, reviewed models that describe family resilience and identified key family resilience factors, and developed several recommendations for how family-resilience programs and policies could be managed across DoD. PMID:28083409

  13. What is a Family Business?

    OpenAIRE

    Fernández-Roca, Francisco Javier; Gutiérrez Hidalgo, Fernando

    2017-01-01

    Defining the concept of family business is an ongoing challenge. The debate around it is here discussed from the point of view of business history and family business theories as developed in the last fifteen years. Historians are interested in reflecting changes in family businesses at different periods and within different societies, and focus their research work on ownership and control within family firms. For their part, family business theorists still understand the concept as a ...

  14. Another way to teach family: family nursing game

    Directory of Open Access Journals (Sweden)

    Carla Sílvia Neves da Nova Fernandes

    2014-10-01

    Full Text Available Current paper describes the application of an innovative strategy to teach family, within a hospital context, by sensitizing nurses on the family subject through the use of a game. Given the hospitalization of a relative, the family faces changes in its dynamics caused by the crisis it is exposed to. It is the relevance for including the family within the care process. Since nurses are expected to assume a key role for which they need specific competence to intervene in families when experiencing an eventual crisis. The in-service education becomes a strategy of generating new skills and enhances human capital to improve the quality of nursing care. Considering the importance of including family in the care context, a playful tool called Family Nursing Game has been invented for teaching the family, especially by passing a model of family intervention. The strategy is based on the belief of the existence of relationship between game and learning.

  15. Family interactions in adoptive compared to nonadoptive families.

    Science.gov (United States)

    Rueter, Martha A; Keyes, Margaret A; Iacono, William G; McGue, Matt

    2009-02-01

    Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents' increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior. Copyright 2009 APA, all rights reserved.

  16. Family caring strategies in neutropenia.

    Science.gov (United States)

    Eggenberger, Sandra K; Krumwiede, Norma; Meiers, Sonja J; Bliesmer, Mary; Earle, Patricia

    2004-12-01

    Aggressive chemotherapy protocols result in neutropenia in approximately half of all patients receiving chemotherapy. Thus, neutropenia continues to be a significant and potentially life-threatening side effect of treatment, even with use of colony-stimulating factors. Families of patients with neutropenia often provide the primary healing environment because most chemotherapy protocols are managed on an outpatient basis. To learn about the family's experience of managing chemotherapy-induced neutropenia (CIN), a grounded-theory methodology was used to analyze data from seven families. The central theme revealed by these families was "turbulent waiting with intensified connections." This meant that when families had a sense of greater vulnerability in response to the waiting after diagnosis of CIN, they connected intensely with each other and healthcare providers. Families reported that connections with nurses became more significant when neutropenia interrupted chemotherapy. Families also developed family caring strategies to manage this period of waiting for the chemotherapy to resume. These strategies included family inquiry, family vigilance, and family balancing. Nurses need to be aware of approaches to support the family's ability to manage CIN. Interventions and approaches constructed from the perspective of a family-professional partnership will enhance the family cancer experience as well as ongoing family growth and function.

  17. Getting a High-Speed Family Connection: Associations between Family Media Use and Family Connection

    Science.gov (United States)

    Padilla-Walker, Laura M.; Coyne, Sarah M.; Fraser, Ashley M.

    2012-01-01

    The way families have used the media has substantially changed over the past decade. Within the framework of family systems theory, this paper examines the relations between family media use and family connection in a sample of 453 adolescents (mean age of child = 14.32 years, SD = 0.98, 52% female) and their parents. Results revealed that cell…

  18. South African Family Practice

    African Journals Online (AJOL)

    South African Family Practice(SAFP) is a peer-reviewed scientific journal, which strives to ... The content of SAFP is designed to reflect and support further development of the broad ... Vol 60, No 2 (2018) ... of doctors and physiotherapists in the rehabilitation of people living with HIV · EMAIL ... AJOL African Journals Online.

  19. Family First Considerations

    Science.gov (United States)

    LaFee, Scott

    2012-01-01

    The typical superintendent these days is male (though the percentage of female superintendents is steadily rising, now accounting for one in four, according to AASA's 2010 decennial study of the superintendency), in his 40s and almost always married with children. When educators become superintendents, the issues of family dynamics and related…

  20. Choosing a Family Doctor

    Science.gov (United States)

    ... age or sex. This includes care for your physical, mental, and emotional health. Family doctors get to know their patients. They ... and Wellness Staying Healthy Healthy Living Travel Occupational Health First Aid and ... Pets and Animals myhealthfinder Food and Nutrition Healthy Food ...

  1. The Pycnogonid family Austrodecidae

    NARCIS (Netherlands)

    Stock, J.H.

    1957-01-01

    DE PYCNOGONIDEN- FAMILIE AUSTRODECIDAE Toen mij, in 1954, uit Oslo een verzameling Pycnogonida van de „Norwegian Scientific Expedition to Tristan da Cunda 1937—1938“ ter bewerking werd opgezonden, kon ik niet vermoeden dat deze kleine collectie aanleiding zou geven tot een uitgebreide revisie van

  2. The African Family Physician

    African Journals Online (AJOL)

    North America and Europe, and these serve us well up to a point. When a colleague ... Maybe we need a different set of principles to work by in the Afri- ... base the balance. ... The African Family Physician is dedicated to life-long learning and.

  3. Software product family evaluation

    NARCIS (Netherlands)

    van der Linden, F; Bosch, J; Kamsties, E; Kansala, K; Krzanik, L; Obbink, H; VanDerLinden, F

    2004-01-01

    This paper proposes a 4-dimensional software product family engineering evaluation model. The 4 dimensions relate to the software engineering concerns of business, architecture, organisation and process. The evaluation model is meant to be used within organisations to determine the status of their

  4. The family Planococcaceae

    Digital Repository Service at National Institute of Oceanography (India)

    Shivaji, S.; Srinivas, T.N.R.; Reddy, G.S.N.

    rods in case of other genera Diagnostic amino acid in the peptidoglycan is l-lysine with a peptidoglycan variation of A4alfa type Most dominating fatty acids of the family are iso-C15:0 or anteiso-C15:0 or iso-C16:0 or C...

  5. Familial primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Iqbal, P.; Javed, R.

    2007-01-01

    A case of primary hyperparathyroidism in a 17 years old female is described. Patient presented with severe abdominal and pelvic pains associate with discomfort. Diagnostic testing revealed multiple upper and lower limb fractures and renal stones. Case was self limiting. Patient's condition resolved on parathyroidectomy for adenoma and partial thyroidectomy. Follow-up showed familial links. (author)

  6. Families at Work

    Science.gov (United States)

    Schomaker, Peggy K.

    1988-01-01

    Today, school age and preschool children are more likely to have a working mother and to be living with one parent than in the past. Many families headed by women are living in poverty. Much of the teaching in public schools and many work force benefits are geared to the traditional models of the past. (JOW)

  7. Dignifying families at risk

    DEFF Research Database (Denmark)

    Villumsen, Anne Marie Anker

    for a family of two parents and two children to be assigned ten different professionals from the municipality. In addition, the coordination between these different sectors is weak, leaving the collaboration between the different professionals almost non-exiting. However, in one Danish municipality a new...

  8. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood. Risk factors include a family history of lipoprotein lipase deficiency. The condition is usually ...

  9. The colpitts oscillator family

    DEFF Research Database (Denmark)

    Lindberg, Erik; Murali, K.; Tamasevicius, A.

    A tutorial study of the Colpitts oscillator family defined as all oscillators based on a nonlinear amplifier and a three- terminal linear resonance circuit with one coil and two capacitors. The original patents are investigated. The eigenvalues of the linearized Jacobian for oscillators based...

  10. Understanding family support

    DEFF Research Database (Denmark)

    Jensen, Niels Rosendal

    2018-01-01

    I anmeldelsen understreges, at fremstillingen henvender sig til praktikere og viser de komplekse samspil mellem politik, teori og praksis og indeholder en stor mængde relevant diskussion af betydning for grundlaget i arbejdet med familier (resilience, social kapital, social hjælp m.v.) og hvordan...

  11. Family Fitness Fun

    Science.gov (United States)

    Being active with your family can be a fun way to get everybody moving. All of you will get the health benefits that come from being active. Plus, you’ll be a positive role model, helping your children develop good habits for an active lifetime.

  12. 5. Natural Family Planning

    African Journals Online (AJOL)

    Sitwala

    Medical Journal of Zambia, Vol. 37, No. 4 (2010) ... Methods: A cross sectional study was done in five health posts of ... Data was collected using a structured interview schedule ... This means they did not know what impact large families will ...

  13. Family Constellations in Europe

    NARCIS (Netherlands)

    A. Puur; L. Sakkeus; N. Schenk (Niels); A. Põldma

    2010-01-01

    textabstractThe importance of one’s family in times of need is unquestionable. Young children rely on their parents for proper living conditions, who in turn receive help from their aging parents in raising and caring for their children. There also comes a time when elderly parents themselves

  14. Centering of quadrupole family

    International Nuclear Information System (INIS)

    Pinayev, Igor

    2007-01-01

    A procedure for finding the individual centers for a family of quadrupoles fed with a single power supply is described. The method is generalized for using the correctors adjacent to the quadrupoles. Theoretical background is presented as well as experimental data for the NSLS rings. The method accuracy is also discussed

  15. It Takes a Family

    Centers for Disease Control (CDC) Podcasts

    2007-11-01

    This podcast follows an African American man with diabetes and his family as they discuss living healthfully with diabetes.  Created: 11/1/2007 by National Diabetes Education Program (NDEP), a joint program of the Centers for Disease Control and Prevention and the National Institutes of Health.   Date Released: 11/12/2007.

  16. Families in the Military

    Science.gov (United States)

    ... family that loses the active presence of a parent through separation faces significant challenges and stress. During the parent's ... children can and do adjust successfully to the separation and stress involved when a parent in the military is deployed. Visit AACAP's Military ...

  17. Regional identity and family

    Directory of Open Access Journals (Sweden)

    Tripković Gordana D.

    2003-01-01

    Full Text Available This paper is a continuation of a study on regionalisation and family, within the project named Sociological Aspects of Multiculturality and Regionalisation and their influence on the development of AP Vojvodina and the Republic of Serbia. The author focuses her attention to operationalisation of the theoretical and methodological premises that were developed in the previous paper (Tripković, 2002: 111-127, which means that it represents the results of the second phase of the research plan. This phase includes adjusting of theoretical concepts to the fieldwork displaying the results of the research and the analysis of the findings that put a family in the context of confronting different identities, above all national and regional. As possible "identity difference" was emphasized in the research, theoretical and methodological apparatus was adjusted to this goal. That is why in this paper the replies of interviewees that can suggest or reject the assumption that their national identity can influence significantly the evaluation of identity specificities are presented and analyzed, concerning more or less visible aspects of family life, like welfare status, relations between spouses, respect to the elder, family harmony, number of children, connections with relatives, etc.

  18. Improving Family Communication.

    Science.gov (United States)

    Medrano, Vilma; Bonilla, Gladys; Hernández, Ericka; Romanjek, Mariana Harnecker; Gómez, Adriana; Hernández, Jasón; Reyes, Marcela Ríos; Lindenberg, Cathy Strachan

    2017-03-01

    TeenSmart International harnesses the power and flexibility of technology to empower youth to take personal responsibility for their health and lifestyle choices. Access to the Internet via mobile phones is often cheaper than paying to connect to a wired broadband service, and in rural areas, mobile networks may be the only means of accessing the Internet. This study assessed the feasibility, acceptability, and impact of "cues to action" or brief motivating cell phone text messages to improve adolescent family communication and relationships. A quasi-experimental design using a voluntary sample of 100 Nicaraguan youth at high risk for poor family communication participated. Pre- and posttest quantitative measures using Student t statistical analysis, a focus group, and a participant testimony provided the evaluation evidence. Findings suggest that there are economic and motivational barriers to the use of text messages, but when barriers are eliminated, the behavioral results are positive. Youth who received two weekly text messages over a 6-month period demonstrated statistically significant improvements in family communication perceptions, attitudes, and behaviors, strengthening their family communications and relationships. Brief and personalized text messaging "cues to action" may be a cost-effective intervention to improve adolescent healthy lifestyle behaviors.

  19. India's misconceived family plan.

    Science.gov (United States)

    Jacobson, J L

    1991-01-01

    India's goal of reducing the national birth rate by 50% by the year 2000 is destined to failure in the absence of attention to poverty, social inequality, and women's subordination--the factors that serve to perpetuate high fertility. There is a need to shift the emphasis of the population control effort from the obligation of individual women to curtail childbearing to the provision of the resources required for poor women to meet their basic needs. Female children are less likely to be educated or taken for medical care than their male counterparts and receive a lower proportion of the family's food supply. This discrimination stems, in large part, from parents' view that daughters will not be able to remunerate their families in later life for such investments. The myth of female nonproductivity that leads to the biased allocation of family resources overlooks the contribution of adult women's unpaid domestic labor and household production. Although government statistics state that women comprise 46% of India's agricultural labor force (and up to 90% of rural women participate in this sector on some basis), women have been excluded systematically from agricultural development schemes such as irrigation projects, credit, and mechanization. In the field of family planning, the Government's virtually exclusive focus on sterilization has excluded younger women who are not ready to terminate childbearing but would like methods such as condoms, diaphragms, IUDs, and oral contraceptives to space births. More general maternal-child health services are out of reach of the majority of poor rural women due to long distances that must be travelled to clinics India's birth rate could be reduced by 25% by 2000 just by filling the demand for quality voluntary family planning services. Without a sustained political commitment to improve the status of women in India, however, such gains will not be sustainable.

  20. Maternity and family leave policies in rural family practices.

    Science.gov (United States)

    Mainguy, S; Crouse, B J

    1998-09-01

    To help recruit and retain physicians, especially women, rural family practice groups need to establish policies regarding maternity and other family leaves. Also important are policies regarding paternity leave, adoptive leave, and leave to care for elderly parents. We surveyed members of the American Academy of Family Physicians in rural practice in 1995 to assess the prevalence of leave policies, the degree to which physicians are taking family leave, and the characteristics of ideal policies. Currently, both men and women physicians are taking family leaves of absence, which indicates a need for leave policies. Furthermore, a lack of family leave policies may deter women from entering rural practice.

  1. Family Patterns Associated with Anorexia Nervosa.

    Science.gov (United States)

    Grigg, Darryl N.; And Others

    1989-01-01

    Used family systems perspective to explore familial transactional patterns related to anorexia nervosa among 22 families with an anorexic child and 22 matched control families. Identified 7 family groups with unique family dynamics differentiating one from another. With no single family pattern characterizing families of anorexics, results…

  2. Oral features of a family with benign familial neutropenia.

    Science.gov (United States)

    Porter, S R; Luker, J; Scully, C; Oakhill, A

    1994-05-01

    The oral features of three members of a family with familial benign neutropenia (a mother and two children) are detailed. Prepubertal periodontitis, oral ulceration, and angular stomatitis were the principal features.

  3. Study of a family that overcomes poverty issues: family resilience?

    Directory of Open Access Journals (Sweden)

    María Ángela Mattar Yunes

    2015-09-01

    Full Text Available Generally, researches with families focus the difficulties and the negative aspects of family life by bringing up their maladjustments and failures. The interest in family resilience contributes to change this logic by demonstrating the healthy aspects of the family world. Nevertheless, the term resilience presents ideological controversies which are more severe when the discussion is about families and poverty. In order to diminish these contradictions this study adopted a systemic concept of resilience which refers to “those processes that make possible to overcome adversities”. A case study was realized with a low income family who lived in a “very poor” neighborhood in the deep south of Brazil. The methodological strategies to the formal investigation of the family were: life history of the family using the principles of reflexive interview, genograms and data analyses through the approach of the grounded theory. The results showed that the family lived a number of risk experiences such as adoption, privation of basic needs, migration and diseases. Among the indicators of their abilities of “overcoming adversities”, emerged the belief system as the core of the discourses. The family showed that they value the interpersonal relationships through intra and extra familiar interactions based in the patterns of help, learning, affection and solidarity. During the crisis the family gives meaning to the difficulties in order to maintaining the situation controlled through cohesion, open communication, mutual respect and getting support of the extended family/ social network. The pos-adversity period is perceived as benefic and transforming as the family feels stronger and with feelings of solidarity, which is a mark of this family. Their attitude in relation to the neighborhood is active in the sense of promoting the welfare of other families who live in the same social address. Would those above identified processes be adequate to

  4. FRANCHISE FROM FAMILY BUSINESS?

    Directory of Open Access Journals (Sweden)

    Adrián NAGY

    2016-06-01

    Full Text Available The purpose of this study was to examine the franchise as a form of enterprise in perspective to existing family businesses and how can they operate this way. Why is this form better for them, what advantages it has? In this case an ice cream shop’s economic inidicators were examined ,one which is owned by a hungarian family in Jász-Nagykun-Szolnok county who runs several shops like this. That is why this study was made, to find out if it is possible to run it sucsessfully and what costs does the newcomers in the franchise business network have to pay and how much is the time on the return of investments.

  5. Product Family Assessment

    DEFF Research Database (Denmark)

    Kvist, Morten

    their focus from single products to entire product families and try to incorporate the development of product variety into a future product family. The key is to create fit between the product design and production setup. The challenge of understanding this fit and modelling dispositional relations between...... and on the ideas of lean production, plus experiences from the industrial collaboration. The idea of waste from the lean philosophy is brought into a product variety context, and discussed in relation to product development. Verification of the model has been carried out in an industrial setting at Danfoss......This thesis reports the results of a PhD project from the Technical University of Denmark. The research has been carried out in a collaborative project with the Danish company Danfoss Automatic Controls. In the global market companies are struggling to meet customers’ expectation of products...

  6. Balancing Family and Career

    Science.gov (United States)

    Andam, Aba Bentil; Dawson, Silvina Ponce; Horton, K. Renee; Sandow, Barbara

    2005-10-01

    In essentially all countries, responsibilities for child care, cooking, cleaning, and other homemaking tasks fall predominantly on the wife and mother. In addition, the childbearing years come during the period when a physicist must study hard, work long hours on research, and take temporary positions, often abroad. Thus, balancing family and career has long been one of the major barriers to women's participation in science and engineering fields, including physics. While many young women believe that they must choose between having children and having a science career, the fact is that the majority of women physicists in both developing and developed countries have successfully done both. This paper summarizes some ideas and recommendations raised in discussions, especially focused on easing the challenges of having children while in temporary jobs, returning to physics after a career break, the need for "family-friendly" working conditions, and the dual-career problem facing couples where both are scientists.

  7. Marriage and Family Therapy

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    About the author: Chen Yiyun graduated from the Russian Language and Literature Departraent at Beijing University in 1964. She then enrolled at the Sociology Institute of the China Academy of Social Sciences in 1978. Upon graduation, she remained at the Institute as a research fellow. She later became editor-in-chief of the magazine Sociology Abroad. She translated and edited dozens of sociology books. In 1988, after she returned from the United States, she devoted herself to the research of sociology and marriage consultation. In 1993, Chen set up the Jinglun Family Science Center, a non-governmental organization which is a combination of scientific research and social practice. She organized scholars, social workers and volunteers from sectors of public health, education and legislation to conduct useful activities to promote democracy in the family, equality, health and civilization.

  8. The Family Album

    DEFF Research Database (Denmark)

    Albrechtslund, Anders

    in family relations can be seen as a result of the dynamics of a participatory surveillance culture shaped by digital media. References: Albrechtslund, A. (2008). Online Social Networking as Participatory Surveillance. First Monday, 13(3). Fotel, T., & Thomsen, T. U. (2002). The Surveillance of Children...... that parents do not generally plan to store or organize their photos, and even less their children’s photos. This seems to indicate a shift from a pre-digital perception of photos as objects to be packaged, accumulated, framed etc. which can age and disappear (see Sontag, 1977) to something perceived less...... as images to archive and preserve and more as social artefacts serving more immediate communicative purposes (Lobinger, 2016). The use of digital technologies in families also implicate negotiations about the boundaries of trust and intimacy in parent-child relations which can lead to strategies...

  9. Familial Mediterranean Fever

    Directory of Open Access Journals (Sweden)

    Adem Kucuk

    2014-01-01

    Full Text Available Familial Mediterranean Fever is an autosomal recessive inherited disease with a course of autoinflammation, which is characterized by the episodes of fever and serositis. It affects the populations from Mediterranean basin. Genetic mutation of the disease is on MEFV gene located on short arm of Chromosome 16. The disease is diagnosed based on clinical evaluation. Amyloidosis is the most important complication. The only agent that decreases the development of amyloidosis and the frequency and severity of the episodes is colchicine, which has been used for about 40 years. In this review, we aimed to discuss especially the most recent advances about Familial Mediterranean Fever which is commonly seen in our population.

  10. Family resources study: part 1: family resources, family function and caregiver strain in childhood cancer.

    Science.gov (United States)

    Panganiban-Corales, Avegeille T; Medina, Manuel F

    2011-10-31

    Severe illness can disrupt family life, cause family dysfunction, strain resources, and cause caregiver burden. The family's ability to cope with crises depends on their resources. This study sought to assess families of children with cancer in terms of family function-dysfunction, family caregiver strain and the adequacy of family resources using a new family resources assessment instrument. This is a cross-sectional study involving 90 Filipino family caregivers of children undergoing cancer treatment. This used a self-administered questionnaire composed of a new 12-item family resources questionnaire (SCREEM-RES) based on the SCREEM method of analysis, Family APGAR to assess family function-dysfunction; and Modified Caregiver Strain Index to assess strain in caring for the patient. More than half of families were either moderately or severely dysfunctional. Close to half of caregivers were either predisposed to strain or experienced severe strain, majority disclosed that their families have inadequate economic resources; many also report inaccessibility to medical help in the community and insufficient educational resources to understand and care for their patients. Resources most often reported as adequate were: family's faith and religion; help from within the family and from health providers. SCREEM-RES showed to be reliable with Cronbach's alpha of 0.80. There is good inter-item correlation between items in each domain: 0.24-0.70. Internal consistency reliability for each domain was also good: 0.40-0.92. Using 2-point scoring system, Cronbach's alpha were slightly lower: full scale (0.70) and for each domain 0.26-.82. Results showed evidence of association between family resources and family function based on the family APGAR but none between family resources and caregiver strain and between family function and caregiver strain. Many Filipino families of children with cancer have inadequate resources, especially economic; and are moderately or severely

  11. Family resources study: part 1: family resources, family function and caregiver strain in childhood cancer

    Directory of Open Access Journals (Sweden)

    Panganiban-Corales Avegeille T

    2011-10-01

    Full Text Available Abstract Background Severe illness can disrupt family life, cause family dysfunction, strain resources, and cause caregiver burden. The family's ability to cope with crises depends on their resources. This study sought to assess families of children with cancer in terms of family function-dysfunction, family caregiver strain and the adequacy of family resources using a new family resources assessment instrument. Methods This is a cross-sectional study involving 90 Filipino family caregivers of children undergoing cancer treatment. This used a self-administered questionnaire composed of a new 12-item family resources questionnaire (SCREEM-RES based on the SCREEM method of analysis, Family APGAR to assess family function-dysfunction; and Modified Caregiver Strain Index to assess strain in caring for the patient. Results More than half of families were either moderately or severely dysfunctional. Close to half of caregivers were either predisposed to strain or experienced severe strain, majority disclosed that their families have inadequate economic resources; many also report inaccessibility to medical help in the community and insufficient educational resources to understand and care for their patients. Resources most often reported as adequate were: family's faith and religion; help from within the family and from health providers. SCREEM-RES showed to be reliable with Cronbach's alpha of 0.80. There is good inter-item correlation between items in each domain: 0.24-0.70. Internal consistency reliability for each domain was also good: 0.40-0.92. Using 2-point scoring system, Cronbach's alpha were slightly lower: full scale (0.70 and for each domain 0.26-.82. Results showed evidence of association between family resources and family function based on the family APGAR but none between family resources and caregiver strain and between family function and caregiver strain. Conclusion Many Filipino families of children with cancer have inadequate

  12. Nuclear Industry Family Study

    International Nuclear Information System (INIS)

    1993-01-01

    This is a copy of the U.K.A.E.A. Question and Answer brief concerning an epidemiological study entitled the Nuclear Industry Family Study, to investigate the health of children of AEA, AWE, and BNFL Workers. The study is being carried out by an independent team of medical research workers from the London School of Hygiene and Tropical Medicine, and the Imperial Cancer Research Fund. (UK)

  13. Origin of family symmetries

    International Nuclear Information System (INIS)

    Nilles, Hans Peter

    2012-04-01

    Discrete (family) symmetries might play an important role in models of elementary particle physics. We discuss the origin of such symmetries in the framework of consistent ultraviolet completions of the standard model in field and string theory. The symmetries can arise due to special geometrical properties of extra compact dimensions and the localization of fields in this geometrical landscape. We also comment on anomaly constraints for discrete symmetries.

  14. Innovation in Family Firms

    DEFF Research Database (Denmark)

    Filser, Matthias; Brem, Alexander; Gast, Johanna

    2016-01-01

    , organizational culture and behaviour, resources, and innovation and strategy. Second, based on a thorough literature review the major research avenues are reflected. The comparison of the results of both analyses showed the following areas for future research on family firm innovation: members‘ individual human...... capital and their leadership behaviour, openness to externals, cross-country comparisons, and finally the family‘s functional integrity on innovation performance....

  15. Origin of family symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Nilles, Hans Peter [Bonn Univ. (Germany). Bethe Center for Theoretical Physics; Bonn Univ. (Germany). Physikalisches Inst.; Ratz, Michael [Technische Univ. Muenchen, Garching (Germany). Physik-Department; Vaudrevange, Patrick K.S. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2012-04-15

    Discrete (family) symmetries might play an important role in models of elementary particle physics. We discuss the origin of such symmetries in the framework of consistent ultraviolet completions of the standard model in field and string theory. The symmetries can arise due to special geometrical properties of extra compact dimensions and the localization of fields in this geometrical landscape. We also comment on anomaly constraints for discrete symmetries.

  16. Familial Aggregation of Insomnia.

    Science.gov (United States)

    Jarrin, Denise C; Morin, Charles M; Rochefort, Amélie; Ivers, Hans; Dauvilliers, Yves A; Savard, Josée; LeBlanc, Mélanie; Merette, Chantal

    2017-02-01

    There is little information about familial aggregation of insomnia; however, this type of information is important to (1) improve our understanding of insomnia risk factors and (2) to design more effective treatment and prevention programs. This study aimed to investigate evidence of familial aggregation of insomnia among first-degree relatives of probands with and without insomnia. Cases (n = 134) and controls (n = 145) enrolled in a larger epidemiological study were solicited to invite their first-degree relatives and spouses to complete a standardized sleep/insomnia survey. In total, 371 first-degree relatives (Mage = 51.9 years, SD = 18.0; 34.3% male) and 138 spouses (Mage = 55.5 years, SD = 12.2; 68.1% male) completed the survey assessing the nature, severity, and frequency of sleep disturbances. The dependent variable was insomnia in first-degree relatives and spouses. Familial aggregation was claimed if the risk of insomnia was significantly higher in the exposed (relatives of cases) compared to the unexposed cohort (relatives of controls). The risk of insomnia was also compared between spouses in the exposed (spouses of cases) and unexposed cohort (spouses of controls). The risk of insomnia in exposed and unexposed biological relatives was 18.6% and 10.4%, respectively, yielding a relative risk (RR) of 1.80 (p = .04) after controlling for age and sex. The risk of insomnia in exposed and unexposed spouses was 9.1% and 4.2%, respectively; however, corresponding RR of 2.13 (p = .28) did not differ significantly. Results demonstrate evidence of strong familial aggregation of insomnia. Additional research is warranted to further clarify and disentangle the relative contribution of genetic and environmental factors in insomnia. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  17. A Family Affair : Explaining Co-Working By Family Members

    NARCIS (Netherlands)

    Ruijter, Esther de; Lippe, Tanja van der; Raub, Werner; Weessie, Jeroen

    2008-01-01

    This study focuses on co-working by intimate partners and other family members in entrepreneurs’ businesses. We hypothesize that co-working by family is beneficial because it reduces trust problems associated with employment relations. On the other hand, co-working is risky because co-working family

  18. Family and Family Change in Ireland: An Overview

    Science.gov (United States)

    Canavan, John

    2012-01-01

    In Ireland, historically and in the current era, family has been a central concern for society and the State. This article provides a descriptive overview of family life in Ireland and of major family-related changes over the past 40 years. It presents a general framework of analysis within which these changes can be understood, considers the…

  19. 75 FR 9247 - Single Family Mortgage Insurance Premium, Single Family

    Science.gov (United States)

    2010-03-01

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5376-N-13] Single Family Mortgage Insurance Premium, Single Family AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice... is soliciting public comments on the subject proposal. Lenders use the Single Family Premium...

  20. Families as Partners: Supporting Family Resiliency through Early Intervention

    Science.gov (United States)

    Frantz, Rebecca; Hansen, Sarah Grace; Squires, Jane; Machalicek, Wendy

    2018-01-01

    Child development occurs within the context of the child's family, neighborhood, and community environment. Early childhood providers support positive outcomes, not only for the children with whom they directly work with but also for their families. Families of children with developmental delays often experience unique challenges. A family…

  1. Parental Ethnotheories and Family Language Policy in Transnational Adoptive Families

    Science.gov (United States)

    Fogle, Lyn Wright

    2013-01-01

    Family language policy refers to explicit and overt decisions parents make about language use and language learning as well as implicit processes that legitimize certain language and literacy practices over others in the home. Studies in family language policy have emphasized the ways in which family-internal processes are shaped by and shape…

  2. The netrin protein family.

    Science.gov (United States)

    Rajasekharan, Sathyanath; Kennedy, Timothy E

    2009-01-01

    The name netrin is derived from the Sanskrit Netr, meaning 'guide'. Netrins are a family of extracellular proteins that direct cell and axon migration during embryogenesis. Three secreted netrins (netrins 1, 3 and 4), and two glycosylphosphatidylinositol (GPI)-anchored membrane proteins, netrins G1 and G2, have been identified in mammals. The secreted netrins are bifunctional, acting as attractants for some cell types and repellents for others. Receptors for the secreted netrins include the Deleted in Colorectal Cancer (DCC) family, the Down's syndrome cell adhesion molecule (DSCAM), and the UNC-5 homolog family: Unc5A, B, C and D in mammals. Netrin Gs do not appear to interact with these receptors, but regulate synaptic interactions between neurons by binding to the transmembrane netrin G ligands NGL1 and 2. The chemotropic function of secreted netrins has been best characterized with regard to axon guidance during the development of the nervous system. Extending axons are tipped by a flattened, membranous structure called the growth cone. Multiple extracellular guidance cues direct axonal growth cones to their ultimate targets where synapses form. Such cues can be locally derived (short-range), or can be secreted diffusible cues that allow target cells to signal axons from a distance (long-range). The secreted netrins function as short-range and long-range guidance cues in different circumstances. In addition to directing cell migration, functional roles for netrins have been identified in the regulation of cell adhesion, the maturation of cell morphology, cell survival and tumorigenesis.

  3. Homozygous familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Cuchel, Marina; Bruckert, Eric; Ginsberg, Henry N

    2014-01-01

    AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the......AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights...... into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance...... 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and...

  4. Undefined familial colorectal cancer.

    Science.gov (United States)

    Zambirinis, Constantinos Pantelis; Theodoropoulos, George; Gazouli, Maria

    2009-10-15

    Colorectal cancer (CRC), one of the most common cancers of the world, is actually a spectrum of several subtypes, with different molecular profiles, clinico-pathological characteristics and possibly separate pathways of progression. It is estimated that in approximately 25%-35% of cases, a familial component exists, so they are classified as familial CRC (fCRC). However the known hereditary CRC syndromes justify only up to 5%. The rest are attributed to some inherited genetic predisposition passed to offspring through low-penetrance genes, which in the proper environmental setting can bring on tumorigenesis. Furthermore, part of the familial clustering may be attributed to chance. Because of the complexity regarding the etiology of CRC, the clinician is sometimes faced with obscure patient data, and cannot be sure if they are dealing with fCRC or sporadic CRC. The elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis, classification and treatment of CRC, but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.

  5. [Familial Wolfram syndrome].

    Science.gov (United States)

    Bessahraoui, M; Paquis, V; Rouzier, C; Bouziane-Nedjadi, K; Naceur, M; Niar, S; Zennaki, A; Boudraa, G; Touhami, M

    2014-11-01

    Wolfram syndrome (WS) is a rare autosomal recessive progressive neurodegenerative disorder, and it is mainly characterized by the presence of diabetes mellitus and optic atrophy. Other symptoms such as diabetes insipidus, deafness, and psychiatric disorders are less frequent. The WFS1 gene, responsible for the disease and encoding for a transmembrane protein called wolframin, was localized in 1998 on chromosome 4p16. In this report, we present a familial observation of Wolfram syndrome (parents and three children). The propositus was a 6-year-old girl with diabetes mellitus and progressive visual loss. Her family history showed a brother with diabetes mellitus, optic atrophy, and deafness since childhood and a sister with diabetes mellitus, optic atrophy, and bilateral hydronephrosis. Thus, association of these familial and personal symptoms is highly suggestive of Wolfram syndrome. The diagnosis was confirmed by molecular analysis (biology), which showed the presence of WFS1 homozygous mutations c.1113G>A (p.Trp371*) in the three siblings and a heterozygote mutation in the parents. Our observation has demonstrated that pediatricians should be aware of the possibility of Wolfram syndrome when diagnosing optic atrophy in diabetic children. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Family Process - Autism Spectrum Disorders

    OpenAIRE

    Benson, Mark

    2012-01-01

    Slides for a talk about family process and the importance of parenting dimensions in adolescent development. The slides list findings to date, and propose research into the influence of family on outcomes for those diagnosed with an autism spectrum disorder.

  7. Cybernetics of Brief Family Therapy.

    Science.gov (United States)

    Keeney, Bradford P.; Ross, Jeffrey M.

    1983-01-01

    Presents a cybernetic view of brief family therapy. Includes a historical discussion of the key ideas underlying brief family therapy, a cybernetic model of therapeutic change, and a clinical case for exemplification. (Author/JAC)

  8. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  9. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... Tos Ferina AAP CME ask your doctor brochure family stories faq meet dr. gary freed meet keri ... media video/audio pneumonia tb overview links & resources families advocacy about civil rights kids' rights sample school ...

  10. Effects of PTSD on Family

    Science.gov (United States)

    ... for PTSD » Public » Effects of PTSD on Family PTSD: National Center for PTSD Menu Menu PTSD PTSD Home For the Public ... code here Enter ZIP code here Effects of PTSD on Family Public This section is for Veterans, ...

  11. Myth of the Perfect Family

    Science.gov (United States)

    ... a family group made up of only a father, mother, and children. Although most people tend to think that this particular family structure has always been the dominant one, that is not the case. The nuclear ...

  12. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  13. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Chickenpox (Varicella) One family's struggles with chickenpox We ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  14. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Rotavirus One family's struggles with rotavirus We provide ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  15. Axions from chiral family symmetry

    International Nuclear Information System (INIS)

    Chang, D.; Pal, P.B.; Maryland Univ., College Park; Senjanovic, G.

    1985-01-01

    We investigate the possibility that family symmetry, Gsub(F), is spontaneously broken chiral global symmetry. We classify the interesting cases when family symmetry can result in an automatic Peccei-Quinn symmetry U(1)sub(PQ) and thus provide a solution to the strong CP problem. The result disfavors having two or four families. For more than four families, U(1)sub(PQ) is in general automatic. In the case of three families, a unique Higgs sector allows U(1)sub(PQ) in the simplest case of Gsub(F)=[SU(3)] 3 . Cosmological consideration also puts strong constraint on the number of families. For Gsub(F)=[SU(N)] 3 cosmology singles out the three-family (N=3) case as a unique solution if there are three light neutrinos. Possible implication of decoupling theorem as applied to family symmetry breaking is also discussed. (orig.)

  16. National Survey of Family Growth

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Survey of Family Growth (NSFG) gathers information on family life, marriage and divorce, pregnancy, infertility, use of contraception, and men's and...

  17. Canada's family violence initiative: partnerships

    OpenAIRE

    Scott,Elaine

    1994-01-01

    Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior) abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and developmen...

  18. Roadmap for Navy Family Research.

    Science.gov (United States)

    1980-08-01

    09 NAVY FAMIILIES *11* I.- Study *conosical, psychological , and social " rank * duŕ military "areer " employment status . extent of of spouse family...Study ha o. thmfpeect of relocation o familis series with: I I a frequency and t iming of SBANCE *, acconpanied vs. umaccompaiad URE tours alevel of...UNDERSTANDING IMPACT OF RELOCATION ON NAVY FAMILIES AREA 1: STUDY ECONOMICAL, PSYCHOLOGICAL , AND SOCIAL IMPACT ON DIFFERENT FAMILY MEMBERS, FOR

  19. Family networks and income hiding

    NARCIS (Netherlands)

    Beekman, Gonne; Gatto, Marcel; Nillesen, Eleonora

    2015-01-01

    This study investigates the relationship between family network density and income hiding in rural Liberia. We link people's behaviour in a modified lottery experiment and a time preference game to detailed information about their family networks. We find that individuals with a dense family

  20. Family members' experiences of autopsy

    NARCIS (Netherlands)

    Oppewal, F; Meyboom-de Jong, B

    Background. The experiences of family members will teach us how to handle an autopsy, the ultimate quality assessment tool. Objective. The aim of this study was to determine surviving family members' experience of autopsy. Method. Seven GPs were asked to approach surviving family members of

  1. Molecular basis of familial hypercholesterolemia

    NARCIS (Netherlands)

    Bruikman, Caroline S.; Hovingh, Gerard K.; Kastelein, John J. P.

    2017-01-01

    Purpose of review To provide an overview about the molecular basis of familial hypercholesterolemia. Recent findings Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial

  2. Family Values in American Drama.

    Science.gov (United States)

    Brown, Joanne

    When an educator was invited by a Chinese university to teach a seminar in American drama, she used "family drama" as the organizing theme of her course because she was (and is) convinced that from Eugene O'Neill on, American playwrights have been obsessed with family disintegration and the failure of family harmony. This paper is an…

  3. Children's Impressions of Television Families.

    Science.gov (United States)

    Wartella, Ellen

    This research study examines the types of social behaviors portrayed by families in various television series and explores children's impressions of the TV family members. Content analysis of nine family-oriented TV series was employed to describe the ranges of behaviors of fathers, mothers and children on television. Eleven shows from each series…

  4. Quick Assessment of Family Functioning.

    Science.gov (United States)

    Golden, Larry B.

    1988-01-01

    Describes five criteria (parental resources, chronicity communication between family members, parental authority, and rapport with professional helpers) of family functioning of an assessment model which can be used to determine which families could benefit from brief interventions by a school counselor. Provides results of 20 case studies with…

  5. A Feminist Family Therapy Scale.

    Science.gov (United States)

    Black, Leora; Piercy, Fred P.

    1991-01-01

    Reports on development and psychometric properties of Feminist Family Therapy Scale (FFTS), a 17-item instrument intended to reflect degree to which family therapists conceptualize process of family therapy from feminist-informed perspective. Found that the instrument discriminated between self-identified feminists and nonfeminists, women and men,…

  6. Family Issues in Multigenerational Households.

    Science.gov (United States)

    Feinauer, Leslie L; And Others

    1987-01-01

    Studied issues faced by multigenerational families and their implications for family therapy. Major factors in multigenerational households included dependency, sibling relationships, depression, and demanding and egocentric behavior. Factors to consider during family therapy include respite care, age, interdependence, dignity, provision of care,…

  7. Housing and family: an introduction

    NARCIS (Netherlands)

    Mulder, C.H.; Lauster, N.T.

    2010-01-01

    This paper introduces the Housing Studies special issue 'Housing and Family'. The issue consists of a collection of papers in which a number of connections between housing and family issues are highlighted. Three themes are addressed: the influence of the family of origin on housing characteristics

  8. Family Dinners. For Parents Particularly.

    Science.gov (United States)

    Klein, Helen Altman

    2001-01-01

    Asserts that family dinners deserve attention as a positive contributor to children's well-being. Maintains that family dinners give stability to a potentially confusing day, present a place for children to express themselves, and provide children's first community. Includes ideas for helping families identify their own dinner patterns and…

  9. NASA Science Served Family Style

    Science.gov (United States)

    Noel-Storr, Jacob; Mitchell, S.; Drobnes, E.

    2010-01-01

    Family oriented innovative programs extend the reach of many traditional out-of-school venues to involve the entire family in learning in comfortable and fun environments. Research shows that parental involvement is key to increasing student achievement outcomes, and family-oriented programs have a direct impact on student performance. Because families have the greatest influence on children's attitudes towards education and career choices, we have developed a Family Science program that provides families a venue where they can explore the importance of science and technology in our daily lives by engaging in learning activities that change their perception and understanding of science. NASA Family Science Night strives to change the way that students and their families participate in science, within the program and beyond. After three years of pilot implementation and assessment, our evaluation data shows that Family Science Night participants have positive change in their attitudes and involvement in science.  Even after a single session, families are more likely to engage in external science-related activities and are increasingly excited about science in their everyday lives.  As we enter our dissemination phase, NASA Family Science Night will be compiling and releasing initial evaluation results, and providing facilitator training and online support resources. Support for NASA Family Science Nights is provided in part through NASA ROSES grant NNH06ZDA001N.

  10. Family control and financing decisions

    NARCIS (Netherlands)

    Croci, Ettore; Doukas, John A.; Gonenc, Halit

    2011-01-01

    This study uses a comprehensive European dataset to investigate the role of family control in corporate financing decisions during the period 1998-2008. We find that family firms have a preference for debt financing, a non-control-diluting security, and are more reluctant than non-family firms to

  11. Family identity: black-white interracial family health experience.

    Science.gov (United States)

    Byrd, Marcia Marie; Garwick, Ann Williams

    2006-02-01

    The purpose of this interpretive descriptive study was to describe how eight Black-White couples with school-aged children constructed their interracial family identity through developmental transitions and interpreted race to their children. Within and across-case data analytic strategies were used to identify commonalities and variations in how Black men and White women in couple relationships formed their family identities over time. Coming together was the core theme described by the Black-White couples as they negotiated the process of forming a family identity. Four major tasks in the construction of interracial family identity emerged: (a) understanding and resolving family of origin chaos and turmoil, (b) transcending Black-White racial history, (c) articulating the interracial family's racial standpoint, and (d) explaining race to biracial children across the developmental stages. The findings guide family nurses in promoting family identity formation as a component of family health within the nurse-family partnership with Black-White mixed-race families.

  12. Dual-career family as an exampleof egalitarian family

    Directory of Open Access Journals (Sweden)

    Joanna Ostrouch-Kamińska

    2011-11-01

    Full Text Available The economic, cultural, and social transformation, growth of women's economic strength as well as the level of their education, and development of ideas of equal rights of women and men on the labour market and in social life cause changes in gender relation in the family. Poles more and more often declare and support egalitarian family, and a new model of a family appears among existing ones – dual-career family.The main aim of the article is to consider the sources of its rise, description of gender positions in marital relation, the division of tasks and responsibilities, possible dilemmas and conflicts, but also emotional, intellectual and social advantages. The analysis were put into context of changes in defining and describing family, and also in context of different family discourses. One of them was underlined the most – egalitarian one as the most approximate to the way of defining and understanding dual-career family model.

  13. Family dynamics and infant temperament in Danish families

    DEFF Research Database (Denmark)

    Wilson, M.E.; Hall, Elisabeth O.C.; White, M.A.

    1994-01-01

    , although always in a negative direction, in family dynamics over this transition. The largest change was an increase in perceived role conflict reported by both mothers and fathers. Mothers reported more role conflict than fathers. Positive family dynamics were related to infant rhythmicity.......Transition to parenthood involves the fine balance of family dynamics which both affect, and are affected by, the infant's temperament. The purpose of this study was to investigate changes in family dynamics over the transition to parenthood and the relationship of family dynamics to infant...... temperament. A sample of 99 families in Odense, Denmark, completed the Family Dynamics Measure in the third trimester of pregnancy and again when the infant was 8-9 months old. At this second time, the mothers also completed the Revised Infant Temperament Questionnaire. Overall we found small changes...

  14. Family dynamics and infant temperament in Danish families

    DEFF Research Database (Denmark)

    Wilson, M.E.; Hall, Elisabeth O.C.; White, M.A.

    1994-01-01

    temperament. A sample of 99 families in Odense, Denmark, completed the Family Dynamics Measure in the third trimester of pregnancy and again when the infant was 8-9 months old. At this second time, the mothers also completed the Revised Infant Temperament Questionnaire. Overall we found small changes......Transition to parenthood involves the fine balance of family dynamics which both affect, and are affected by, the infant's temperament. The purpose of this study was to investigate changes in family dynamics over the transition to parenthood and the relationship of family dynamics to infant......, although always in a negative direction, in family dynamics over this transition. The largest change was an increase in perceived role conflict reported by both mothers and fathers. Mothers reported more role conflict than fathers. Positive family dynamics were related to infant rhythmicity....

  15. The 15-minute family interview: a family health strategy tool

    Directory of Open Access Journals (Sweden)

    Mariana Cristina Lobato dos Santos Ribeiro Silva

    2013-06-01

    Full Text Available The 15-minute family interview is a condensed form of the Calgary Family Assessment and Intervention Models (CFAM and CFIM that aims to contribute to the establishment of a therapeutic relationship between nurses and family and to implement interventions to promote health and suffering relief, even during brief interactions. This study investigated the experience of nurses from the Family Health Strategy (FHS who used the 15-minute interview on postpartum home. The qualitative research was conducted in three stages: participants' training program, utilization of the 15-minute family interview by participants, and interviews with nurses. The data were collected through semi-structured interviews with eight nurses. The thematic analysis revealed two main themes: dealing with the challenge of a new practice and evaluating the assignment. This work shows that this tool can be used to deepen relationships between nurses and families in the Family Health Strategy.

  16. The Family in Us: Family History, Family Identity and Self-Reproductive Adaptive Behavior.

    Science.gov (United States)

    Ferring, Dieter

    2017-06-01

    This contribution is an essay about the notion of family identity reflecting shared significant experiences within a family system originating a set of signs used in social communication within and between families. Significant experiences are considered as experiences of events that have an immediate impact on the adaptation of the family in a given socio-ecological and cultural context at a given historical time. It is assumed that family history is stored in a shared "family memory" holding both implicit and explicit knowledge and exerting an influence on the behavior of each family member. This is described as transgenerational family memory being constituted of a system of meaningful signs. The crucial dimension underlying the logic of this essay are the ideas of adaptation as well as self-reproduction of systems.

  17. Small family, smart family? : family size and the IQ scores of young men

    OpenAIRE

    Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell Gunnar

    2007-01-01

    How do families influence the ability of children? Cognitive skills have been shown to be a strong predictor of educational attainment and future labor market success; as a result, understanding the determinants of cognitive skills can lead to a better understanding of children's long run outcomes. This paper uses a large dataset on the male population of Norway and focuses on one family characteristic: the effect of family size on IQ. Because of the endogeneity of family size, we instrument ...

  18. The Family Saprospiraceae

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Nielsen, Per Halkjær

    2014-01-01

    associated with predation of other bacteria and algae. Family members are likely important in the breakdown of complex organic compounds in the environment. Such a role is at least demonstrated in situ for activated sludge wastewater treatment systems where these organisms are frequently observed...... by 16S rRNA gene phylogeny. Most are isolated from aquatic environments, predominantly marine associated but also freshwater and activated sludge. Isolates and in situ strains have a demonstrated ability for the hydrolysis and utilization of complex carbon sources, with the helical gliding strains also...

  19. QUAD FAMILY CENTERING

    International Nuclear Information System (INIS)

    PINAYEV, I.

    2005-01-01

    It is well known that beam position monitors (BPM) utilizing signals from pickup electrodes (PUE) provide good resolution and relative accuracy. The absolute accuracy (i.e. position of the orbit in the vacuum chamber) is not very good due to the various reasons. To overcome the limitation it was suggested to use magnetic centers of quadrupoles for the calibration of the BPM [1]. The proposed method provides accuracy better then 200 microns for centering of the beam position monitors using modulation of the whole quadrupole family

  20. Familial neurohypophyseal diabetes insipidus

    DEFF Research Database (Denmark)

    Kvistgaard, Helene

    2011-01-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is characterized by severe low-solute polyuria and polydipisa. The disease is caused by a deficient neurosecretion of the antidiuretic hormone arginine vasopressin (AVP). The hormone is normally synthesized by the magnocellular neurons...... as one sporadic case of early-onset diabetes insipidus. Genetic testing of the sporadic case of diabetes insipidus revealed a highly unusual mosaicism for a variation in the gene encoding the AVP receptor (AVPR2). This mosaicism had resulted in a partial phenotype and initial diagnostic difficulties...

  1. Family Background and Entrepreneurship

    DEFF Research Database (Denmark)

    Lindquist, Matthew J.; Sol, Joeri; Van Praag, Mirjam

    Vast amounts of money are currently being spent on policies aimed at promoting entrepreneurship. The success of such policies, however, rests in part on the assumption that individuals are not ‘born entrepreneurs’. In this paper, we assess the importance of family background and neighborhood...... effects as determinants of entrepreneurship. We start by estimating sibling correlations in entrepreneurship. We find that between 20 and 50 percent of the variance in different entrepreneurial outcomes is explained by factors that siblings share. The average is 28 percent. Allowing for differential...... entrepreneurship does play a large role, as do shared genes....

  2. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  3. Familial adenomatous polyposis.

    OpenAIRE

    Burn, J; Chapman, P D; Eastham, E J

    1994-01-01

    Abstract Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rect...

  4. Balancing family and work

    Science.gov (United States)

    Showstack, Randy

    2011-08-01

    More than 45% of women scientists at top universities in the United States have indicated that their careers have kept them from having as many children as they want, according to an 8 August study, “Scientists want more children,” which appears in the journal PLoS ONE. The study, by sociologists Elaine Howard Ecklund of Rice University and Anne Lincoln of Southern Methodist University, indicates that 24.5% of male scientists surveyed indicated the same concerns. The study also found that among junior scientists, 29% of women indicated concern that a science career would prevent them from having a family; 7% of men indicated the same concern.

  5. Familial Gastric Cancers.

    Science.gov (United States)

    Setia, Namrata; Clark, Jeffrey W; Duda, Dan G; Hong, Theodore S; Kwak, Eunice L; Mullen, John T; Lauwers, Gregory Y

    2015-12-01

    Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. ©AlphaMed Press.

  6. Family Ties and Civic Virtues

    DEFF Research Database (Denmark)

    Ljunge, Jan Martin

    I establish a positive relationship between family ties and civic virtues, as captured by disapproval of tax and benefit cheating, corruption, and a range of other dimensions of exploiting others for personal gain. I find that family ties are a complement to social capital, using within country...... evidence from 83 nations and data on second generation immigrants in 29 countries with ancestry in 85 nations. Strong families cultivate universalist values and produce more civic and altruistic individuals. The results provide a constructive role for families in promoting family values that support...

  7. Small Family, Smart Family? Family Size and the IQ Scores of Young Men

    Science.gov (United States)

    Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

    2010-01-01

    This paper uses Norwegian data to estimate the effect of family size on IQ scores of men. Instrumental variables (IV) estimates using sex composition as an instrument show no significant negative effect of family size; however, IV estimates using twins imply that family size has a negative effect on IQ scores. Our results suggest that the effect…

  8. Family support in cancer survivorship.

    Science.gov (United States)

    Muhamad, Mazanah; Afshari, Mojgan; Kazilan, Fitrisehara

    2011-01-01

    This paper raises issues about the role of family members in providing support for breast cancer survivors. Data were collected from 400 breast cancer survivors in Peninsular Malaysia through a custom-designed questionnaire fielded at hospitals and support group meetings. The data were analyzed using descriptive statistics. The analyses show that all family members could be supportive, especially in decision making and help with emotional issues. The spouse was the main support provider among the family members (others were children, parents, siblings and more distant relatives). The results also indicated that a significant percentage practiced collaborative decision-making. Breast cancer survivors needed their family members' support for information on survivorship strategies such as managing emotions, health, life style and dietary practice. The family members' supportive role may be linked to the Malaysian strong family relationship culture. For family members to contribute more adequately to cancer survivorship, it is suggested that appropriate educational intervention also be provided to them.

  9. NASA's Astronant Family Support Office

    Science.gov (United States)

    Beven, Gary; Curtis, Kelly D.; Holland, Al W.; Sipes, Walter; VanderArk, Steve

    2014-01-01

    During the NASA-Mir program of the 1990s and due to the challenges inherent in the International Space Station training schedule and operations tempo, it was clear that a special focus on supporting families was a key to overall mission success for the ISS crewmembers pre-, in- and post-flight. To that end, in January 2001 the first Family Services Coordinator was hired by the Behavioral Health and Performance group at NASA JSC and matrixed from Medical Operations into the Astronaut Office's organization. The initial roles and responsibilities were driven by critical needs, including facilitating family communication during training deployments, providing mission-specific and other relevant trainings for spouses, serving as liaison for families with NASA organizations such as Medical Operations, NASA management and the Astronaut Office, and providing assistance to ensure success of an Astronaut Spouses Group. The role of the Family Support Office (FSO) has modified as the ISS Program matured and the needs of families changed. The FSO is currently an integral part of the Astronaut Office's ISS Operations Branch. It still serves the critical function of providing information to families, as well as being the primary contact for US and international partner families with resources at JSC. Since crews launch and return on Russian vehicles, the FSO has the added responsibility for coordinating with Flight Crew Operations, the families, and their guests for Soyuz launches, landings, and Direct Return to Houston post-flight. This presentation will provide a summary of the family support services provided for astronauts, and how they have changed with the Program and families the FSO serves. Considerations for future FSO services will be discussed briefly as NASA proposes one year missions and beyond ISS missions. Learning Objective: 1) Obtain an understanding of the reasons a Family Support Office was important for NASA. 2) Become familiar with the services provided for

  10. Familial hypercholesterolemia: A review

    International Nuclear Information System (INIS)

    Varghese, Mithun J

    2014-01-01

    Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH

  11. Familial Exudative Vitreoretinopathy.

    Science.gov (United States)

    Sızmaz, Selçuk; Yonekawa, Yoshihiro; T Trese, Michael

    2015-08-01

    Familial exudative vitreoretinopathy (FEVR) is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats' disease.

  12. Singing about family planning.

    Science.gov (United States)

    Emah, E

    1993-01-01

    The Nigerian Family Health services project teamed up with the Johns Hopkins University's Population Communication Services to produce songs called "Choices" and "Wait for Me." The songs, which were about sexual responsibility, were performed by popular music stars King Sunny Ade and Onyeka Onwenu and appeared under King Sonny Ade's long playing albums in 1989. Teaching sexual responsibility through song was suggested in focus group discussions. Findings indicated that young people were responsive to messages about sexual responsibility, postponing sex or saying "no," male sexual responsibility, and children by informed choice and not chance among married couples. An impact assessment of the songs was conducted in February, 1991. Survey findings revealed that 64% of urban and 22% of rural respondents recalled having heard the songs and seen the videos. 48% of urban youth discussed the songs with friends, and 27% discussed the songs with sexual partners. 90% of respondents reported agreement with the message that couples should have only the number of children that they can care for, and that couples should practice family planning. The target population that was affected most by the songs was aged less than 35 years. The strategy of using songs to teach youth responsible parenting appears to be a reliable strategy for mass education and mobilization. There is mass support from among members of the National Council for Women's Societies, the Planned Parenthood Federation of Nigeria, and Coca Cola Corporation, as well as the public at large.

  13. Family life education.

    Science.gov (United States)

    Maniar, N

    1968-01-01

    Family life education is not just instruction of sex and reproduction, but an attitude of love and values that starts from infancy. A child who comes into the world wanted is already loved. Later on, he himself will give love because his 1st contact in the world was a happy one. Most children will go through thumb sucking and masturbation, which is normal and innocent behavior. Toilet training is another important factor in sex education. According to our attitude the child will learn that this part of his body is good or bad. By the age of 3 or 6, children learn to discover the difference in sex from our attitude to each other, and when parents practice double standards, the child is confused and worried. Children's curiousity for knowledge is insatiable. If parents find they are embarressed by their children's questions about sex, it is better to put off answering than to convey the impression that something is not quite nice. 11-year old females should be prepared for menarche with knowledge, and fathers should explain to their sons about voice changes, night emissions and fantasy dreams. Masturbation is normal during adolescence, and the only harm comes from wrong anxiety about it. If 2 young people wish to have premarital intercourse, we must have the courage to tell them that chastity remains a value whether they accept it or not. Education for family life means taking account of the child's attitudes and sex values as a future marriage partner and parent.

  14. Familial Exudative Vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Selçuk Sızmaz

    2015-08-01

    Full Text Available Familial exudative vitreoretinopathy (FEVR is a hereditary disease associated with visual loss, particularly in the pediatric group. Mutations in the NDP, FZD4, LRP5, and TSPAN12 genes have been shown to contribute to FEVR. FEVR has been reported to have X-linked recessive, autosomal dominant, and autosomal recessive inheritances. However, both the genotypic and phenotypic features are variable. Novel mutations contributing to the disease have been reported. The earliest and the most prominent finding of the disease is avascularity in the peripheral retina. As the disease progresses, retinal neovascularization, subretinal exudation, partial and total retinal detachment may occur, which may be associated with certain mutations. With early diagnosis and prompt management visual loss can be prevented with laser photocoagulation and anti-VEGF injections. In case of retinal detachment, pars plana vitrectomy alone or combined with scleral buckling should be considered. Identifying asymptomatic family members with various degrees of insidious findings is of certain importance. Wide-field imaging with fluorescein angiography is crucial in the management of this disease. The differential diagnosis includes other pediatric vitreoretinopathies such as Norrie disease, retinopathy of prematurity, and Coats’ disease. (Turk J Ophthalmol 2015; 45: 164-168

  15. Familial adenomatous polyposis

    Directory of Open Access Journals (Sweden)

    Rozen Paul

    2009-10-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE, desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system. A less aggressive variant of FAP, attenuated FAP (AFAP, is characterized by fewer colorectal adenomatous polyps (usually 10 to 100, later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC gene. Most patients (~70% have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP, which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a

  16. Family pediatrics: report of the Task Force on the Family.

    Science.gov (United States)

    Schor, Edward L

    2003-06-01

    WHY A TASK FORCE ON THE FAMILY? The practice of pediatrics is unique among medical specialties in many ways, among which is the nearly certain presence of a parent when health care services are provided for the patient. Regardless of whether parents or other family members are physically present, their influence is pervasive. Families are the most central and enduring influence in children's lives. Parents are also central in pediatric care. The health and well-being of children are inextricably linked to their parents' physical, emotional and social health, social circumstances, and child-rearing practices. The rising incidence of behavior problems among children attests to some families' inability to cope with the increasing stresses they are experiencing and their need for assistance. When a family's distress finds its voice in a child's symptoms, pediatricians are often parents' first source for help. There is enormous diversity among families-diversity in the composition of families, in their ethnic and racial heritage, in their religious and spiritual orientation, in how they communicate, in the time they spend together, in their commitment to individual family members, in their connections to their community, in their experiences, and in their ability to adapt to stress. Within families, individuals are different from one another as well. Pediatricians are especially sensitive to differences among children-in their temperaments and personalities, in their innate and learned abilities, and in how they view themselves and respond to the world around them. It is remarkable and a testament to the effort of parents and to the resilience of children that most families function well and most children succeed in life. Family life in the United States has been subjected to extensive scrutiny and frequent commentary, yet even when those activities have been informed by research, they tend to be influenced by personal experience within families and by individual and

  17. A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

    Science.gov (United States)

    Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

    2017-03-17

    Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

  18. Family Ties: The Role of Family Context in Family Health History Communication about Cancer

    Science.gov (United States)

    Rodríguez, Vivian M.; Corona, Rosalie; Bodurtha, Joann N.; Quillin, John M.

    2016-01-01

    Family health history about cancer is an important prevention and health promotion tool. Yet, few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. Average age was 34 years, 59% identified as Black, 31% graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that, in turn, inform cancer prevention interventions. PMID:26735646

  19. Family Ties: The Role of Family Context in Family Health History Communication About Cancer.

    Science.gov (United States)

    Rodríguez, Vivian M; Corona, Rosalie; Bodurtha, Joann N; Quillin, John M

    2016-01-01

    Family health history about cancer is an important prevention and health promotion tool. Yet few studies have identified family context factors that promote such discussions. We explored relations among family context (cohesion, flexibility, and openness), self-efficacy, and cancer communication (gathering family history, sharing cancer risk information, and frequency) in a diverse group of women enrolled in a randomized control trial. Baseline survey data for 472 women were analyzed. The women's average age was 34 years, 59% identified as Black, 31% had graduated high school, and 75% reported a family history of any cancer. Results showed that greater family cohesion and flexibility were related to higher communication frequency and sharing cancer information. Women who reported greater self-efficacy were more likely to have gathered family history, shared cancer risk information, and communicated more frequently with relatives. Openness was not associated with communication but was related to greater family cohesion and flexibility. Adjusting for demographic variables, self-efficacy, and family cohesion significantly predicted communication frequency. Women with higher self-efficacy were also more likely to have gathered family health history about cancer and shared cancer risk information. Future research may benefit from considering family organization and self-efficacy when developing psychosocial theories that in turn inform cancer prevention interventions.

  20. Hospitalized elders and family caregivers: a typology of family worry.

    Science.gov (United States)

    Li, Hong

    2005-01-01

    This qualitative study explored the kinds of worry that family caregivers experience when their older relatives are hospitalized. Little is known about what kinds of worries family caregivers may have in association with the hospitalizations of older relatives. An understanding of the different patterns of family worry may help health care teams intervene more effectively to meet family caregiver's needs by reducing their anxiety. A qualitative descriptive design with Loftland and Loftland (1984) approach for the study of a phenomenon occurring in a social setting was used. A purposeful sample of 10 participants was obtained that included six family caregivers and four nurses. Participants were recruited from two hospitals in the northwest US. Intensive interviews and participant observations were used for data collection, and Loftland and Loftland's (1984) qualitative approach was used for data analysis. Family worry was defined as family caregivers' felt difficulty in fulfilling their roles because of worry. Four categories of family worry were identified as a result of this study: (i) worry about the patient's condition; (ii) worry about the patient's care received from the health care team; (iii) worry about future care for the patient provided by the family caregiver; and (iv) worry about finances. The findings of this pilot study provide nurses with the initial knowledge of the typology of family worry associated with elderly relatives' hospitalizations. The findings of this study may sensitize the nurses to more precisely evaluate family caregivers' worry about their hospitalized elders and provide more effective nursing interventions to improve outcomes of both patients and their family caregivers.

  1. CADASIL and A Family

    Directory of Open Access Journals (Sweden)

    Figen Varlıbaş

    2008-04-01

    Full Text Available OBJECTIVE: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a systemic vasculopathy that causes various clinical pictures as recurrent ischemic attacks, migrainous headache, pseudo bulbar palsy, epileptic seizures and dementia. Mutations of notch3 gene on chromosome 19 are responsible for the disease. METHODS: The aim of this study is to draw attention to the family history and neuroradiological investigations of a genetically diagnosed CADASIL case. RESULTS: A forty-seven-years-old woman who presented with left hemiparesis was investigated for the cause of stroke as well as her family history. Her mother was reported to have chronic headache. Then inappropriate crying and laughing attacks, behavioral disturbances, urinary incontinency had contributed and she had died at the age of 51 following sudden loss of consciousness. Her father had had four stroke attacks after 45 and before he died at the age of 73 he was unresponsive for the last 10 years. First sibling, 58 years-old female had a history of three stroke attacks and reported forgetfulness. Second sibling, a female, suffered from headache and had died at the age of 37 succeeding two epileptic seizures. Third sibling, 53 years-old female was said to be living bedridden for the last 5 years. Fourth sibling was 51 years-old male and had had a stroke attack at the age of 38. Fifth sibling was 48 years-old female whose speech disorder started 10 years ago. Laughing and crying attacks, incontinency, childish behavior and forgetfulness were also added. Sixth sibling was our patient. Seventh sibling was 45 years-old, male and had no complaints. First, fourth, sixth and seventh siblings were evaluated in systematic, neurological, neuropsychological and neuroradiological perspectives. CONCLUSION: In addition to family history, hyperintensities in temporal polar region and external capsule on flair and T2-weighted MRI supported the diagnosis of

  2. Familial nevus of ota

    Directory of Open Access Journals (Sweden)

    Kumari Rashmi

    2006-01-01

    Full Text Available A 23-year-old pregnant woman with an asymptomatic unilateral, bluish, pigmented lesion on her left periocular skin was referred from the obstetrics department for dermatological evaluation. Dermatologic examination revealed unilateral, blue-gray, poorly defined macule on the periorbital skin of the left side of the face mainly over the malar prominence and left temple not crossing the midline, conforming to the maxillary division of trigeminal nerve distribution. The pigmentation was speckled with interspersed dark-brownish elements. Her father, a 47 - year- old man had a similar pigmentation at the same site over the malar prominence of face not extending onto the forehead. Here we report two cases of nevus of Ota occurring in 2 generations of the same family for its rarity.

  3. Religion and family planning.

    Science.gov (United States)

    Pinter, Bojana; Hakim, Marwan; Seidman, Daniel S; Kubba, Ali; Kishen, Meera; Di Carlo, Costantino

    2016-12-01

    Religion is embedded in the culture of all societies. It influences matters of morality, ideology and decision making, which concern every human being at some point in their life. Although the different religions often lack a united view on matters such contraception and abortion, there is sometimes some dogmatic overlap when general religious principles are subject to the influence of local customs. Immigration and population flow add further complexities to societal views on reproductive issues. For example, present day Europe has recently faced a dramatic increase in refugee influx, which raises questions about the health care of immigrants and the effects of cultural and religious differences on reproductive health. Religious beliefs on family planning in, for example, Christianity, Judaism, Islam and Hinduism have grown from different backgrounds and perspectives. Understanding these differences may result in more culturally competent delivery of care by health care providers. This paper presents the teachings of the most widespread religions in Europe with regard to contraception and reproduction.

  4. The palm family (Arecaceae)

    DEFF Research Database (Denmark)

    Nadot, Sophie; Alapetite, Elodie; Baker, William J.

    2016-01-01

    Among the 416 angiosperm families, palms (Arecaceae) are striking in possessing almost all possible combinations of hermaphroditic and/or unisexual flowers, making them a particularly interesting subject for studies of the evolution of plant sexuality. The purpose of this review is to highlight...... the amazing diversity of sexual expression in palms with a view to proposing scenarios to explain the evolution of this character, drawing on the numerous advances that have been made over the last 20 years in palm systematics, ecology, developmental biology, phylogenetics and genomics. We provide an overview...... of the variability of sexual expression in palms, with illustrations of the associated morphological diversity and its significance to reproduction. We discuss the evolution of sexual systems using the most recent phylogenetic framework available for palms. Finally, we review advances made towards unravelling...

  5. Supersymmetric family unification

    International Nuclear Information System (INIS)

    Frampton, P.H.; Kephart, T.W.

    1983-01-01

    The superheavy symmetry breaking of the gauge group in supersymmetrized unified theories is studied. The requirement that supersymmetry be unbroken strongly constrains the possible gauge group breaking, and we systematize such constraints group theoretically. In model building, one issue is whether to permit an adjoint matter superfield with concomitant color exotic fermions. A second issue is that of naturalness which is complicated by the well-known supersymmetry non-renormalization theorems. Both with and without an adjoint matter superfield, the most promising group appears to be SU(9) where three families can be naturally accommodated, at least for low-energy gauge group SU(3) x SU(2) x U(1). With an extra U(1) factor, as advocated by Fayet, the non-renormalization theorem must be exploited. (orig.)

  6. Familial Granuloma Annulare

    Directory of Open Access Journals (Sweden)

    Zennure Takci

    2015-09-01

    Full Text Available Granuloma annulare is a benign, asymptomatic, relatively common, often self-limited chronic granulomatos disorder of the skin that can affect both children and adults. The primary skin lesion usually is grouped papules in an enlarging annular shape, with color ranging from flesh-colored to erythematous. The two most common types of granuloma annulare are localized, which typically is found on the lateral or dorsal surfaces of the hands and feet; and disseminated, which is widespread. Rarely, familial cases of granuloma annulare has been reported. Herein, we report two sisters with annular papules and plaques diagnosed as granuloma annulare with the clinical and pathological findings. [J Contemp Med 2015; 5(3.000: 189-191

  7. Family Farming Goods Distribution

    Directory of Open Access Journals (Sweden)

    Guilherme Soares Loiola

    2015-11-01

    Full Text Available Farmers need interaction mechanisms closer to customers interested in purchasing their products. The lack of communication between producer and potential buyers impacts on producers financial performance (that could have losses in sales volume, and buyers, which ultimately acquire lower-quality products. Thus, this paper aims to provide a technological solution proposal, the Buscagro: a software application that can be used on mobile devices and towards to enable a better interaction between family farmers and buyers, allowing a greater display of products from the farmer and disclosure of interests of potential buyers. The features of this technology are based on farmers goods data and information products demanded by potential buyers. In this way, the software application performs combinations based on supply and demand data, generating results for producers to have access in how to find buyers and for consumers to find products a greater agility.

  8. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  9. Contemporary family life

    DEFF Research Database (Denmark)

    Viala, Eva Silberschmidt

    2011-01-01

    to parents’ daily practices with their child. Contrary to the paradox in existing research between the ideal of gender equality on the one hand, and the differentiated and gender-based division of housework and care on the other, it is argued that changes are accruing even though parents still appear...... to adopt gender-based models when it comes to the day-to-day care and the distribution of domestic chores. Through empirical analyses it is demonstrated how the advent of the child becomes a fulcrum, and also how female and male parents’ expectations, beliefs and practises are rooted in traditional notions...... of complementary gender roles as well as in new understandings of gender equality based on ideals of mutual trust, respect and support. As a result, it is important to investigate how parenthood, family life and parental roles are constantly reflected upon and reproduced, negotiated and transformed through...

  10. Family characteristics of stuttering children

    Directory of Open Access Journals (Sweden)

    Simić-Ružić Budimirka

    2008-01-01

    Full Text Available INTRODUCTION Stuttering is a functional impairment of speech, which is manifested by conscious, but nonintentionally interrupted, disharmonic and disrhythmic fluctuation of sound varying in frequency and intensity. Aetiology of this disorder has been conceived within the frame of theoretical models, which tend to connect genetic and epigenetic factors. OBJECTIVE The goal of the paper was to study the characteristics of the family functioning of stuttering children in comparison to the family functioning of children without speech disorder, which confirmed the justification of the introduction of family orientated therapeutic interventions into the therapy spectrum of child stuttering. METHOD Seventy-nine nucleus families of 3 to 6 year-old children were examined; of these, 39 families had stuttering children and 40 had children without speech disorder. The assessment of family characteristics was made using the Family Health Scale, an observer-rating scale which according to semistructured interview and operational criteria, measures 6 basic dimensions of family functioning: Emotional State, Communication, Borders, Alliances, Adaptability & Stability, Family Skills. A total score calculated from the basic dimensions, is considered as a global index of family health. RESULTS Families with stuttering children compared to families with children without speech disorder showed significantly lower scores in all the basic dimension of family functioning, as well as in the total score on the Family Health Scale. CONCLUSION Our research results have shown that stuttering children in comparison with children without speech disorder live in families with unfavorable emotional atmosphere, impaired communication and worse control over situational and developmental difficulties, which affect children's development and well-being. In the light of previous research, the application of family therapy modified according to the child's needs is now considered

  11. Epigenetic Control of Prolyl and Asparaginyl Hydroxylases in Prostate Cancer

    Science.gov (United States)

    2011-07-01

    melanoma, renal carcinoma and breast cancer cell lines. Furthermore, we show that neither HIF-1a protein levels nor hypoxic response through an HRE ...constitutively expressed gene to control for equivalent DNase digestion between the cell lines examined. HRE -Luciferase assay Cell lines ,85% confluent in 60...mm dishes were transfected with an HRE -luciferase reporter vector [19] (2.5 mg) and Renilla luciferase (1.5 mg) according to Lipofectamine 2000

  12. Complex Regulation of Prolyl-4-Hydroxylases Impacts Root Hair Expansion

    DEFF Research Database (Denmark)

    Velasquez, Silvia M; Ricardi, Martiniano M; Poulsen, Christian Peter

    2015-01-01

    Root hairs are single cells that develop by tip growth, a process shared with pollen tubes, axons, and fungal hyphae. However, structural plant cell walls impose constraints to accomplish tip growth. In addition to polysaccharides, plant cell walls are composed of hydroxyproline-rich glycoproteins......5, and to a lesser extent P4H2 and P4H13, are pivotal for root hair tip growth. Second, we demonstrate that P4H5 has in vitro preferred specificity for EXT substrates rather than for other HRGPs. Third, by P4H promoter and protein swapping approaches, we show that P4H2 and P4H13 have interchangeable...... peptidyl-proline hydroxylation on EXTs, and possibly in other HRGPs, is required for proper cell wall self-assembly and hence root hair elongation in Arabidopsis thaliana....

  13. The family and leisure time

    Directory of Open Access Journals (Sweden)

    GRAŻYNA DURKA

    2017-10-01

    Full Text Available Family is the most important educational environment. It is in the family that a child discovers the world of values. The opinions and attitude are shaped, traditions are recognized. A properly functioning family fulfils the basic needs for safety, love, security, and trust. Family shapes one's interests as well as securing and organising leisure time for children. The research conducted was to find an answer to the question: How does a family organize the leisure time of its children? The acquired data confirms the hypothesis that family organises the leisure time of its children and allows for the development of interests that foster the development of personality and introduce one to the world of values. Furthermore, a proper organisation of leisure time prevents the demoralisation of children and youth

  14. Reconciling Work and Family Life

    DEFF Research Database (Denmark)

    Holt, Helle

    The problems of balancing work and family life have within the last years been heavily debated in the countries of the European Union. This anthology deals with the question of how to obtain a better balance between work and family life. Focus is set on the role of companies. The anthology tries...... to shed some light on questions such as: How can compagnies become more family friendly? What are the barriers and how can they be overcome? What is the social outcome when companies are playing an active role in employees’ possiblities for combining family life and work life? How are the solutions...... on work/ family unbalance/ problems related to the growing social problems related to unemployment? The anthology is the result of a reseach-network on ”Work-place Contributions ro Reconcile Work and Family Life” funded by the European Commission, DG V, and co-coordinated by the editors....

  15. Today's Changing Families and their Needs.

    Science.gov (United States)

    Thierman, Susan B.

    This paper discusses the changing concept of the American family, identifying four major trends in family structure: (1) a dramatic increase in two-wage-earner families; (2) more working women; (3) more single-parent families; and (4) restructuring of families through divorces and remarriages. The family has been losing many of its traditional…

  16. Family Maths and Complexity Theory

    OpenAIRE

    Webb, Paul; Austin, Pam

    2012-01-01

    The importance of family involvement is highlighted by findings that parents’ behaviours, beliefs and attitudes affect children’s behaviour in a major way. The Family Maths programme, which is the focus of this study, provides support for the transformative education practices targeted by the South African Department of Education by offering an intervention which includes teachers, learners and their families in an affirming learning community. In this study participating parents were intervi...

  17. Neutrino masses and family symmetry

    International Nuclear Information System (INIS)

    Grinstein, B.; Preskill, J.; Wise, M.B.

    1985-01-01

    Neutrino masses in the 100 eV-1 MeV range are permitted if there is a spontaneously broken global family symmetry that allows the heavy neutrinos to decay by Goldstone boson emission with a cosmologically acceptable lifetime. The family symmetry may be either abelian or nonabelian; we present models illustrating both possibilities. If the family symmetry is nonabelian, then the decay tau -> μ + Goldstone boson or tau -> e + Goldstone may have an observable rate. (orig.)

  18. Lie families: theory and applications

    International Nuclear Information System (INIS)

    Carinena, Jose F; Grabowski, Janusz; De Lucas, Javier

    2010-01-01

    We analyze the families of non-autonomous systems of first-order ordinary differential equations admitting a common time-dependent superposition rule, i.e. a time-dependent map expressing any solution of each of these systems in terms of a generic set of particular solutions of the system and some constants. We next study the relations of these families, called Lie families, with the theory of Lie and quasi-Lie systems and apply our theory to provide common time-dependent superposition rules for certain Lie families.

  19. Canada's family violence initiative: partnerships

    Directory of Open Access Journals (Sweden)

    Elaine Scott

    1994-01-01

    Full Text Available Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and development of projects. Activities funded by the seven federal departments and agencies involved in the Initiative emphasize partnerships with the professional, voluntary, corporate, non-government and government sectors.

  20. The Family Therapist as Intermediary

    Science.gov (United States)

    Hurvitz, Nathan

    1974-01-01

    The family therapist performs specific activities associated with his functions as a therapist, consultant, and intermediary. The intermediary function is based upon concepts associated with symbolic interactionism. (Author)

  1. Policy implications for familial searching.

    Science.gov (United States)

    Kim, Joyce; Mammo, Danny; Siegel, Marni B; Katsanis, Sara H

    2011-11-01

    In the United States, several states have made policy decisions regarding whether and how to use familial searching of the Combined DNA Index System (CODIS) database in criminal investigations. Familial searching pushes DNA typing beyond merely identifying individuals to detecting genetic relatedness, an application previously reserved for missing persons identifications and custody battles. The intentional search of CODIS for partial matches to an item of evidence offers law enforcement agencies a powerful tool for developing investigative leads, apprehending criminals, revitalizing cold cases and exonerating wrongfully convicted individuals. As familial searching involves a range of logistical, social, ethical and legal considerations, states are now grappling with policy options for implementing familial searching to balance crime fighting with its potential impact on society. When developing policies for familial searching, legislators should take into account the impact of familial searching on select populations and the need to minimize personal intrusion on relatives of individuals in the DNA database. This review describes the approaches used to narrow a suspect pool from a partial match search of CODIS and summarizes the economic, ethical, logistical and political challenges of implementing familial searching. We examine particular US state policies and the policy options adopted to address these issues. The aim of this review is to provide objective background information on the controversial approach of familial searching to inform policy decisions in this area. Herein we highlight key policy options and recommendations regarding effective utilization of familial searching that minimize harm to and afford maximum protection of US citizens.

  2. THE CHALLENGES OF FAMILY BUSINESS

    Directory of Open Access Journals (Sweden)

    Stoilkovska Aleksandra

    2011-12-01

    Full Text Available Small businesses give a lot of possibilities for realization of your own creativity and inventivity. Employment of new family members creates work atmosphere that cannot be felt in other companies. Organizational culture results from the employee cohesion and from their devotion to the organization and to the work, and therefore cannot be achieved in other organizations and with any other motivational techniques. These excellent working conditions are a great base for fulfilling the organizational aims, as well as for united and satisfied family. The work in the family organizations is specific from two aspects: from the advantages that it offers and from the problems that arise from this kind of business. Knowing the conditions in the family business, i.e. knowing the factors that influence the effectiveness and efficiency of family business enables more efficient work. Family business development with change of generation or with the increase in the number of family members brings new moments. In addition, one good story can be transformed in an unpleasant conflict and can get to disunion in the family as well in the business. Knowing the possibilities and threats in connection to the factors that influence the family business enables preventive actions in order to avoid undesirable situations.

  3. Understanding familial and non-familial renal cell cancer

    NARCIS (Netherlands)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  4. Understanding familial and non-familial renal cell cancer.

    NARCIS (Netherlands)

    Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

    2002-01-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

  5. Family Therapy with Reconstituted Families: A Crisis-Induction Approach.

    Science.gov (United States)

    Baptiste, David A.

    1983-01-01

    Describes a crisis-based therapeutic approach for overcoming resistance in reconstituted families. Presents therapeutically induced crisis as a means through which therapists might purposefully disequilibrate families in which resistance is high and subsequently redirect them to meaningful change. Reviews implications and contraindications for the…

  6. Family profiles in eating disorders: family functioning and psychopathology

    Directory of Open Access Journals (Sweden)

    Cerniglia L

    2017-10-01

    Full Text Available Luca Cerniglia,1 Silvia Cimino,2 Mimma Tafà,2 Eleonora Marzilli,2 Giulia Ballarotto,2 Fabrizia Bracaglia2 1Faculty of Psychology, International Telematic University UNINETTUNO, 2Department of Dynamic and Clinical Psychology, University of Rome “La Sapienza”, Rome, Italy Abstract: Research has studied family functioning in families of patients suffering from eating disorders (EDs, particularly investigating the associations between mothers’ and daughters’ psychopathological symptoms, but limited studies have examined whether there are specific maladaptive psychological profiles characterizing the family as a whole when it includes adolescents with anorexia nervosa (AN, bulimia nervosa (BN, and binge eating disorder (BED. Through the collaboration of a network of public and private consultants, we recruited n=181 adolescents diagnosed for EDs (n=61 with AN, n=60 with BN, and n=60 with BEDs and their parents. Mothers, fathers, and youths were assessed through a self-report measure evaluating family functioning, and adolescents completed a self-report questionnaire assessing psychopathological symptoms. Results showed specific family functioning and psychopathological profiles based on adolescents’ diagnosis. Regression analyses also showed that family functioning characterized by rigidity predicted higher psychopathological symptoms. Our study underlines the importance of involving all members of the family in assessment and intervention programs when adolescent offspring suffer from EDs. Keywords: family functioning, eating disorders, adolescents, psychopathological risk

  7. Families Hardest Hit: Effects of Welfare Reform on Homeless Families.

    Science.gov (United States)

    Dworkin, Julie

    This report presents data from 1999 surveys of people living in Chicago shelters and warming centers for families with children. The surveys asked about the impacts of welfare reform on respondents' lives. Researchers also surveyed housing and food assistance agencies, shelters, and other social service agencies. Of 481 families surveyed, 44…

  8. Children's Views on Family Communications in Families with their ...

    African Journals Online (AJOL)

    Mrs Afam

    perceived a low extent of adjustment in the families. It was therefore ... that adoptive parents should make personal efforts to improve their family communication in order to ... styles become laden with pride, lack of guilt, and lack of fearful inhibitions, resulting ..... Impact of open adoption and contact with biological mothers on.

  9. Patterns of family management of childhood chronic conditions and their relationship to child and family functioning.

    Science.gov (United States)

    Knafl, Kathleen A; Deatrick, Janet A; Knafl, George J; Gallo, Agatha M; Grey, Margaret; Dixon, Jane

    2013-01-01

    Understanding patterns of family response to childhood chronic conditions provides a more comprehensive understanding of their influence on family and child functioning. In this paper, we report the results of a cluster analysis based on the six scales comprising the Family Management Measure (FaMM) and the resulting typology of family management. The sample of 575 parents (414 families) of children with diverse chronic conditions fell into four patterns of response (Family Focused, Somewhat Family Focused, Somewhat Condition Focused, Condition Focused) that differed in the extent family life was focused on usual family routines or the demands of condition management. Most (57%) families were in either the Family Focused or Somewhat Family Focused pattern. Patterns of family management were related significantly to family and child functioning, with families in the Family Focused and Somewhat Family Focused patterns demonstrating significantly better family and child functioning than families in the other two patterns. Copyright © 2013. Published by Elsevier Inc.

  10. Familial risks of glomerulonephritis - a nationwide family study in Sweden.

    Science.gov (United States)

    Akrawi, Delshad Saleh; Li, Xinjun; Sundquist, Jan; Fjellstedt, Erik; Sundquist, Kristina; Zöller, Bengt

    2016-08-01

    Familial risks of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been studied. This study aims to determine the familial risks of glomerulonephritis. Individuals born from1932 onwards diagnosed with glomerulonephritis (acute [n = 7011], chronic [n = 10,242] and unspecified glomerulonephritis [n = 5762]) were included. The familial risk (Standardized incidence ratio = SIR) was calculated for individuals whose parents/full-siblings were diagnosed with glomerulonephritis compared to those whose parents/full-siblings were not. The procedure was repeated for spouses. Familial concordant risk (same disease in proband and exposed relative) and discordant risk (different disease in proband and exposed relative) of glomerulonephritis were determined. Familial concordant risks (parents/full-sibling history) were: SIR = 3.57 (95% confidence interval, 2.77-4.53) for acute glomerulonephritis, SIR = 3.84 (3.37-4.36) for chronic glomerulonephritis and SIR = 3.75 (2.85-4.83) for unspecified glomerulonephritis. High familial risks were observed if two or more relatives were affected; the SIR was 209.83 (150.51-284.87) in individuals with at least one affected parent as well as one full-sibling. The spouse risk was only moderately increased (SIR = 1.53, 1.33-1.75). Family history of glomerulonephritis is a strong predictor for glomerulonephritis, and is a potentially useful tool in clinical risk assessment. Our data emphasize the contribution of familial factors to the glomerulonephritis burden in the community. Key Messages The familial risks (full-sibling/parent history) of glomerulonephritis (acute, chronic and unspecified glomerulonephritis) have not been determined previously. The familial risks of glomerulonephritis were increased among individuals with family history of acute, chronic or unspecified glomerulonephritis. The familial risks of glomerulonephritis were slightly increased among spouses indicating a

  11. Type Families with Class, Type Classes with Family

    DEFF Research Database (Denmark)

    Serrano, Alejandro; Hage, Jurriaan; Bahr, Patrick

    2015-01-01

    Type classes and type families are key ingredients in Haskell programming. Type classes were introduced to deal with ad-hoc polymorphism, although with the introduction of functional dependencies, their use expanded to type-level programming. Type families also allow encoding type-level functions......, now as rewrite rules. This paper looks at the interplay of type classes and type families, and how to deal with shortcomings in both of them. Furthermore, we show how to use families to simulate classes at the type level. However, type families alone are not enough for simulating a central feature...... of type classes: elaboration, that is, generating code from the derivation of a rewriting. We look at ways to solve this problem in current Haskell, and propose an extension to allow elaboration during the rewriting phase....

  12. Family culture and adolescent sexuality.

    Science.gov (United States)

    Ferreira, Manuela; Nelas, Paula; Duarte, João; Albuquerque, Carlos; Grilo, Célia; Nave, Filipe

    2013-05-01

    Adolescence is characterized by an increase in autonomy and the transformation of family relationships. Their experience has different meanings in future quality of life. To analyze the relationship between the sociodemographic variables, of Sexual context and attitudes adopted by teenagers facing sexuality with the organizational culture of the family. Observational descriptive and correlational, transversal study. The non-probabilistic convenience sample consists of 1216 adolescents attending the 9th year of study in Portuguese Public Schools and is part of the project PTDC/CPE-CED/103313/2008, the questionnaire applied was family organizational culture of Nave (2007) and attitudes towards sexuality of Nelas et al (2010). The majority lives in a village (47.5% of boys and 50.0% girls) .12.9%of boys do not use condoms in all relationships, and the same applies to 17.8% of girls. They belong mostly (55.8% boys and 49.5% girls) to a family with poor interpersonal relationships culture. The majority (51.8%) males and (58.9%) females have a family with moderate heuristic culture. Boys and girls (33.6% and 36.9%) both demonstrate a predominantly moderate hierarchy family culture and a moderate social goals family culture as well. Adolescents who have a bad attitude towards sexuality, mostly (43.2%) present a weak interpersonal relationships family culture with statistical significance (χ(2)=32,092, p=0.000) and have moderate hierarchy family culture and also moderate social goals family culture, without statistical significance. The family that loves, welcomes and cares is the same that educates and informs about sexuality, promoting youth empowerment making them safer, healthier and happier. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  14. The Caenorhabditis chemoreceptor gene families.

    Science.gov (United States)

    Thomas, James H; Robertson, Hugh M

    2008-10-06

    Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  15. Natural family planning.

    Science.gov (United States)

    Brown, J B; Blackwell, L F; Billings, J J; Conway, B; Cox, R I; Garrett, G; Holmes, J; Smith, M A

    1987-10-01

    It is now well accepted that a woman can conceive from an act of intercourse for a maximum of only about 7 days of her menstrual cycle. The reliability of natural family planning depends on identifying this window of fertility without ambiguity. Several symptomatic markers, cervical mucus and basal body temperature, have been used extensively and with considerable success in most women but failures occur. Ovarian and pituitary hormone production show characteristic patterns during the cycle. Urinary estrogen and pregnanediol measurements yield reliable information concerning the beginning, peak, and end of the fertile period, provided that the assays are accurate and performed on timed specimens of urine. We have developed such enzyme immunoassays for urinary estrogen and pregnanediol glucuronides that can be performed at home. In the early versions of the assays, enzyme reaction rates were measured by eye, but more recently, a simple photoelectronic rate meter has been used. The final problem to be solved is not technologic but whether women are sufficiently motivated to expend the same time and effort each day for 10 days a month, with less cost, on fertility awareness as they spend on making a cup of tea.

  16. A growing family

    CERN Multimedia

    2012-01-01

    Increasing membership of the CERN family featured strongly at the CERN Council meetings this week, with Serbia’s ratification documents being received along with an application for Associate Membership from Ukraine. We also learned that an official application is on its way from Brazil and I can report that discussions are ongoing with several other countries around the world.   Serbia joins Israel as an Associate Member in the pre-stage to Membership, and since Yugoslavia was a founder member of CERN in 1954, it was good to welcome Belgrade back. Looking forward, the Council has agreed to set up fast fact finding missions to other applicant countries, so I think it’s fair to say that 2012 will be a year of growth for CERN, fulfilling our mission of science bringing nations together. In a similar vein, it was a pleasure for me to be able to report to the Council an important development at SESAME, the light source for the Middle East established in Jordan on the CERN mode...

  17. Family transitions and juvenile delinquency.

    Science.gov (United States)

    Schroeder, Ryan D; Osgood, Aurea K; Oghia, Michael J

    2010-01-01

    There is a large body of research that shows children from non-intact homes show higher rates of juvenile delinquency than children from intact homes, partially due to weaker parental control and supervision in non-intact homes. What has not been adequately addressed in the research is the influence of changes in family structure among individual adolescents over time on delinquent offending. Using the first and third waves of the National Youth Study, we assess the effect of family structure changes on changes in delinquent offending between waves through the intermediate process of changes in family time and parental attachment. Although prior research has documented adolescents in broken homes are more delinquent than youth in intact homes, the process of family dissolution is not associated with concurrent increases in offending. In contrast, family formation through marriage or cohabitation is associated with simultaneous increases in offending. Changes in family time and parental attachment account for a portion of the family formation effect on delinquency, and prior parental attachment and juvenile offending significantly condition the effect of family formation on offending.

  18. Military Families: A Selected Bibliography

    Science.gov (United States)

    2011-08-01

    CTC_depression_family_sheet.pdf U.S. Army War College. Basics from the Barracks: Military Etiquette and Protocol ; A Spouse’s Quick Reference to Its Unique Customs...http://youtu.be/zfTknLkDPTY U.S. Army War College. Military Family Program. Customs & Courtesies/ Protocol . Carlisle Barracks: U.S. Army War College

  19. The Black Family as Educator.

    Science.gov (United States)

    Wallace, Joan

    The black family is the primary socializing agent of the black child and, thus, the primary educator. The culture of blacks in America, in which the child is steeped, is unique, complex and rich-the result of a convergence and fusion of African, American, and European influences. In its education of the black child, the black family must deal,…

  20. Family Ties and Bottom Lines.

    Science.gov (United States)

    Michaels, Bonnie; McCarty, Elizabeth

    1993-01-01

    The conflict between family and work is not going to go away by itself. Many companies offer programs, benefits, and services that support workers and their families. Tracking results of the programs on such issues as productivity, turnover, absenteeism, and tardiness will help organizations modify or supplement their training and education…

  1. Definability and almost disjoint families

    DEFF Research Database (Denmark)

    Törnquist, Asger Dag

    2018-01-01

    We show that there are no infinite maximal almost disjoint ("mad") families in Solovay's model, thus solving a long-standing problem posed by A.D.R. Mathias in 1967. We also give a new proof of Mathias' theorem that no analytic infinite almost disjoint family can be maximal, and show more generally...

  2. Parenting in Planned Lesbian Families

    NARCIS (Netherlands)

    Bos, Henny

    2004-01-01

    This thesis reports on a study on lesbian families in which the children were born to the lesbian relationship (planned lesbian families). How strong is the desire of lesbian mothers to have a child, and what are their motivations? How do lesbian mothers experience parenthood? What do they strive

  3. The semiosis of family conflict

    DEFF Research Database (Denmark)

    Musaeus, Peter; Brinkmann, Svend

    2011-01-01

    by family members in attempts to break a cycle of conflict—violence but they also exacerbate negative emotions, which we see in the case of conflict. The article develops a critique of the practice of punishment and reward. By analyzing psychotherapy as signs and technologies of the self impacting family...

  4. On Family Size and Intelligence.

    Science.gov (United States)

    Armor, David J.

    2001-01-01

    Critiques research by Rodgers, et al. (June 2000) on the impact of family size on intelligence, explaining that it applied very simple analytic techniques to a very complex question, leading to unwarranted conclusions about family size and intelligence. Loss of cases, omission of an important ability test, and failure to apply multivariate…

  5. Family Medicine's Waltz with Systems

    Science.gov (United States)

    Downing, Raymond

    2012-01-01

    Family Medicine first formally confronted systems thinking with the adoption of the biopsychosocial model for understanding disease in a holistic manner; this is a description of a natural system. More recently, Family Medicine has been consciously engaged in developing itself as a system for delivering health care, an artificial system. We make…

  6. Comprehensive Treatment of Addictive Families.

    Science.gov (United States)

    Schlesinger, Stephen E.; Horberg, Lawrence K.

    This article describes a practical approach to treating addictive families, designed to help them repair the damage, create more satisfying lives, and prevent long-lasting deleterious effects, commonly associated with "co-dependency" and "children of addicts." This approach is grounded in a developmental model of family recovery which was devised…

  7. Counselling Intervention for Family Security

    Science.gov (United States)

    Fareo, Dorcas Oluremi

    2015-01-01

    All couples look forward to having normal healthy babies. The issues of disabilities in their children shake the families and serve as sources of severe psychological disruption to family adjustment. The parents of such children live with many difficult issues and frequently experience trauma, grief and stress. This article deals with counselling…

  8. BRCA Families in Western Denmark

    DEFF Research Database (Denmark)

    Nielsen, Henriette Roed

    2015-01-01

    Formålet med ph.d. afhandlingen BRCA-familier i Vestdanmark; cancer risiko og genetiske profiler var at bidrage til at optimere den genetiske rådgivning af familier med mutationer i BRCA1 og BRCA2 generne ved at præcisere risikoestimater og identificere sammenhænge mellem mutation og sygdomsforek...

  9. Power Politics of Family Psychotherapy.

    Science.gov (United States)

    Whitaker, Carl A.

    It is postulated that the standard framework for psychotherapy, a cooperative transference neurosis, does not validly carry over to the successful psychotherapy of a two-generation family group. In many disturbed families, the necessary and sufficient dynamics for change must be initiated, controlled, and augmented by a group dynamic power-play,…

  10. The Family in Value Orientations

    Science.gov (United States)

    Lezhnina, Iu. P.

    2011-01-01

    Russia's declining birth rate is linked to a delay in a family's decision to have children and to uncertainty about the place of children in a couple's relationship. Despite the rise of individualism and the importance of career and self-realization, however, the family retains a very important place in Russian society. (Contains 1 table, 1…

  11. Familial Risk and Child Competence.

    Science.gov (United States)

    Sameroff, Arnold J.; Seifer, Ronald

    1983-01-01

    Examines components of familial risk in the context of a four-year longitudinal study of children with mentally ill mothers. Risk factors examined were parental mental health, social status, parental perspectives, and family stress. Interactions among risk factors were found to be complex and different for cognitive and social-emotional…

  12. Families Facing the Nuclear Taboo.

    Science.gov (United States)

    Jacobs, Judith Bula

    1988-01-01

    Discusses attitudes of 12 families participating in group which was formed to focus on issues related to the possibility of a nuclear disaster. Why and how these families are facing the nuclear taboo plus various outcomes of doing so are discussed as well as the role of the professional in encouraging such openness about these difficult issues.…

  13. Books that Focus on Family.

    Science.gov (United States)

    Winfield, Evelyn T.

    1989-01-01

    Twelve books which touch upon family relationships are reviewed in this article. These books show how families can build positive relationships among their members in a variety of situations. Issues include self-concept, health, sibling rivalry, the generation gap, divorce, and death. (IAH)

  14. Analysis of USAREUR Family Housing.

    Science.gov (United States)

    1985-04-01

    Standard Installation/Division Personnel System SJA ................ Staff Judge Advocate SPSS ............... Statistical Package for the...for Projecting Family Housing Requirements. a. Attempts to define USAREUR’s programmable family housing deficit Sbased on the FHS have caused anguish ...responses using the Statistical Package for the Social Sciences ( SPSS ) computer program. E-2 ANNEX E RESPONSE TO ESC HOUSING QUESTIONNAIRE Section Page I

  15. Helping Families: To Help Themselves.

    Science.gov (United States)

    International Journal of Family Therapy, 1981

    1981-01-01

    Considers various social changes affecting the American family including: the rise in single-person households; growing percentage of older adults; the increase in single-parent families; and the increase in working married women. Discusses various needs of children and older adults, as well as the role of community organizations. Prepared by The…

  16. Family needs after brain injury

    DEFF Research Database (Denmark)

    Norup, Anne; Perrin, Paul B; Cuberos-Urbano, Gustavo

    2015-01-01

    OBJECTIVE: The objective of this study was to explore differences by country in the importance of family needs after traumatic brain injury (TBI), as well as differences in met/unmet needs. METHOD: Two hundred and seventy-one family members of an individual with TBI in Mexico, Colombia, Spain...

  17. Intergenerational Learning in the Family

    Science.gov (United States)

    Jelenc Krašovec, Sabina; Kump, Sonja

    2012-01-01

    Intergenerational learning in the family is today often hindered due to the family changes and changes in society. We start from the supposition, that social transitions between generations are still important for transmission of heritage and knowledge. In the paper we discuss the connectedness of intergenerational learning, socialization, and…

  18. Family therapy, conflicts and change

    DEFF Research Database (Denmark)

    Musaeus, Peter

    2007-01-01

    Given the relative lack of sociocultural approaches to therapy, this presentation aims to contribute to a sociocultural understanding of motivation and socio-emotional problems in children and families undergoing family therapy. The study was designed as a case study using semi structured...... will be sketched pertaining to the area of family therapy. The study argues for the importance of a holistic, non-mechanical (Valsiner) approach to motivation for change in understanding how "at risk" or "problematic" children and youth (who are for instance experiencing school absenteeism, domestic violence...... interviews with 15 families undergoing family therapy delivered by a communal agency in Denmark.   Using notions of crisis interlinked with institutions and everyday lives (Hedegaard) framed by historical, contentious struggles (Holland and Lave), a model of conflict, violence, learning and motivation...

  19. FAMily-Oriented Support (FAMOS)

    DEFF Research Database (Denmark)

    Salem, Hanin; Johansen, Christoffer; Schmiegelow, Kjeld

    2017-01-01

    BACKGROUND: We developed and tested the feasibility of a manualized psychosocial intervention, FAMily-Oriented Support (FAMOS), a home-based psychosocial intervention for families of childhood cancer survivors. The aim of the intervention is to support families in adopting healthy strategies...... to cope with the psychological consequences of childhood cancer. The intervention is now being evaluated in a nationwide randomized controlled trial (RCT). METHODS AND DESIGN: FAMOS is based on principles of family systems therapy and cognitive behavioral therapy, and is delivered in six sessions at home...... satisfaction with the format, timing, and content of the intervention. CONCLUSION: The results indicate that the FAMOS intervention is feasible in terms of recruitment, retention, and acceptability. The effects of the intervention on post-traumatic stress, depression, anxiety, family functioning, and quality...

  20. X-Y Converter Family

    DEFF Research Database (Denmark)

    Bhaskar, Mahajan Sagar; Sanjeevikumar, Padmanaban; Wheeler, Patrick

    2016-01-01

    A New breed of a buck boost converter, named as the XY converter family is proposed in this article. In the XY family, 16 topologies are presented which are highly suitable for renewable energy applications which require a high ratio of DC-DC converter; such as a photovoltaic multilevel inverter...... system, high voltage automotive applications and industrial drives. Compared to the traditional boost converter and existing recent converters, the proposed XY converter family has the ability to provide a higher output voltage by using less number of power devices and reactive components. Other distinct...... features of the XY converter family are i) Single control switch ii) Provide negative output voltage iii) Non-isolated topologies iv) High conversion ratio without making the use of high duty cycle and v) modular structure. XY family is compared with the recent high step-up converters and the detailed...

  1. Understanding familial and non-familial renal cell cancer.

    Science.gov (United States)

    Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J M; Eleveld, Marc J; Martens, Gerard J M; Weterman, Marian A J; van Kessel, Ad Geurts

    2002-10-01

    Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is still pending. Additionally, a novel role for constitutional chromosome 3 translocations as risk factors for conventional RCC development is rapidly emerging. Also, several candidate loci have been mapped to other chromosomes in both familial and non-familial RCCs of distinct histologic subtypes. The MET gene on chromosome 7, for example, was found to be involved in both forms of papillary RCC. A PRCC-TFE3 fusion gene is typically encountered in t(X;1)-positive non-familial papillary RCCs and results in abrogation of the cell cycle mitotic spindle checkpoint in a dominant-negative fashion, thus leading to RCC. Together, these data turn human RCC into a model system in which different aspects of both familial and non-familial syndromes may act as novel paradigms for cancer development.

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

    Science.gov (United States)

    Starkweather, Kathrine E

    2017-06-01

    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.

  3. Tau anomaly and vectorlike families

    International Nuclear Information System (INIS)

    Babu, K.S.; Pati, J.C.; Zhang, X.

    1992-01-01

    The implications of a recently indicated increase in τ lifetime are discussed. It is stressed that the available experimental constraints (from δρ,ε 3 , and N ν , etc.) are satisfied most naturally if the indicated τ anomaly is attributed to the mixing of the τ family with a heavy vectorlike family Q L, R ' with masses ∼200 GeV to 2 TeV, which is a doublet of SU(2) R and singlet of SU(2) L , rather than with a heavy fourth family with standard chiral couplings. L↔R symmetry would imply that Q L, R ' is accompanied by the parity-conjugate family Q L, R which is a doublet of SU(2) L and singlet of SU(2) R . Two such vectorlike families, together with an increase in τ τ , are, in fact, crucial predictions of a recently proposed supersymmetric composite model that possesses many attractive features, in particular, explanations of the origin of diverse scales and family replication. In the context of such a model, it is noted that 3 an increase in τ τ due to mixing involving vectorlike families will necessarily imply a correlated decrease in neutrino counting N ν from the CERN e + e- collider LEP from 3. Such a decrease in N ν would be absent, however, if the τ anomaly is attributed to a mixing involving a standard fourth family with chiral couplings. Because of the seesaw nature of the mass matrix of the three chiral and two vectorlike families, that arises naturally in the model, departures from universality in the first two families as well as in bar bb and τ + τ - channels (linked to down flavors) are strongly suppressed, in accord with observations

  4. Families, children, migration and AIDS.

    Science.gov (United States)

    Haour-Knipe, Mary

    2009-01-01

    Migration is very often a family affair, and often involves children, directly or indirectly. It may give rise to better quality of life for an entire family, or to bitter disappointment, and may also increase vulnerability to HIV and AIDS. This review, carried out for the Joint Learning Initiative on Children and AIDS, links the literature on "migration", on "HIV and AIDS" and on "families". Three themes are sketched: (1) As both HIV prevalence and circular migration increase, former migrant workers affected by AIDS may return to their families for care and support, especially at the end of life, often under crisis conditions. Families thus lose promising members, as well as sources of support. However, very little is known about the children of such migrants. (2) Following patterns of migration established for far different reasons, children may have to relocate to different places, sometimes over long distances, if their AIDS-affected parents can no longer care for them. They face the same adaptation challenges as other children who move, but complicated by loss of parent(s), AIDS stigma, and often poverty. (3) The issue of migrant families living with HIV has been studied to some extent, but mainly in developed countries with a long history of migration, and with little attention paid to the children in such families. Difficulties include involuntary separation from family members, isolation and lack of support, disclosure and planning for children's care should the parent(s) die and differences in treatment access within the same family. Numerous research and policy gaps are defined regarding the three themes, and a call is made for thinking about migration, families and AIDS to go beyond description to include resilience theory, and to go beyond prevention to include care.

  5. Prenatal family support, postnatal family support and postpartum depression.

    Science.gov (United States)

    Xie, Ri-Hua; Yang, Jianzhou; Liao, Shunping; Xie, Haiyan; Walker, Mark; Wen, Shi Wu

    2010-08-01

    Inadequate social support is an important determinant of postpartum depression (PPD). Social support for pregnant women consists of supports from various sources and can be measured at different gestation periods. Differentiating the effects of social support from different sources and measured at different gestation periods may have important implications in the prevention of PPD. In the family centred Chinese culture, family support is likely to be one of the most important components in social support. The aim of this study was to assess the association of prenatal family support and postnatal family support with PPD. A prospective cohort study was conducted between February and September 2007 in Hunan, China. Family support was measured with social support rating scale at 30-32 weeks of gestation (prenatal support) and again at 2 weeks of postpartum visit (postnatal support). PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) score > or =13. A total of 534 pregnant women were included, and among them, 103 (19.3%) scored 13 or more on the EPDS. PPD was 19.4% in the lowest tertile versus 18.4% in the highest quartile (adjusted odds ratio: 1.04, 95% confidence interval 0.60, 1.80) for prenatal support from all family members, and PPD was 39.8% in the lowest tertile versus 9.6% in the highest tertile (adjusted odds ratio: 4.4, 95% confidence interval 2.3, 8.4) for postnatal support from all family members. Among family members, support from husband had the largest impact on the risk of developing PPD. Lack of postnatal family support, especially the support from husband, is an important risk factor of PPD.

  6. Family Change and Implications for Family Solidarity and Social Cohesion

    Directory of Open Access Journals (Sweden)

    Ravanera, Zenaida

    2008-01-01

    Full Text Available EnglishSocial cohesion can be viewed in terms of common projects and networks of social relations that characterize families, communities and society. In the past decades, the basis for family cohesion has shifted from organic to mechanical or from breadwinner to collaborative model. As in many Western countries, data on family change in Canada point to a greater flexibility in the entry and exit from relationships, a delay in the timing of family events, and a diversity of family forms. After looking at changes in families and in the family setting of individuals, the paper considers both intra-family cohesion and families as basis for social cohesion. Implications are raised for adults, children and publicp olicy.FrenchLa cohésion sociale peut se voir à travers les projets communs et les réseaux desrelations sociales qui caractérisent les familles, les communautés et les sociétés.La base de cohésion familiale est passée d’organique à mécanique, pour utiliserles termes de Durkheim, ou vers un modèle de collaboration plutôt qu’unepartage asymétrique de tâches. Comme dans d’autres sociétés orientales, lafamille au Canada est devenue plus flexible par rapport aux entrées et sortiesd’unions, il y a un délais dans les événements familiaux, et une variété deformes de familles. Après un regard sur les changements dans les familles etdans la situation familiale des individus, nous considérons la cohésion intrafamilialeet la famille comme base de cohésion sociale. Nous discutons desimpacts sur les adultes, les enfants et la politique publique.

  7. South African Families Raising Children with Autism Spectrum Disorders: Relationship between Family Routines, Cognitive Appraisal and Family Quality of Life

    Science.gov (United States)

    Schlebusch, L.; Samuels, A. E.; Dada, S.

    2016-01-01

    Background: The purpose of this study was to investigate the relationship between family routines, cognitive appraisal of the impact of autism spectrum disorders (ASD) on the family and family quality of life (FQOL) in families raising children with ASD in South Africa. Methods: A sample of 180 families of young children with ASD who were…

  8. Lepton family number violation

    International Nuclear Information System (INIS)

    Herczeg, P.

    1999-01-01

    At present there is evidence from neutrino oscillation searches that the neutrinos are in fact massive particles and that they mix. If confirmed, this would imply that the conservation of LFN is not exact. Lepton family number violation (LFNV) has been searched for with impressive sensitivities in many processes involving charged leptons. The present experimental limits on some of them (those which the author shall consider here) are shown in Table 1. These stringent limits are not inconsistent with the neutrino oscillation results since, given the experimental bounds on the masses of the known neutrinos and the neutrino mass squared differences required by the oscillation results, the effects of LFNV from neutrino mixing would be too small to be seen elsewhere (see Section 2). The purpose of experiments searching for LFNV involving the charged leptons is to probe the existence of other sources of LFNV. Such sources are present in many extensions of the SM. In this lecture the author shall discuss some of the possibilities, focusing on processes that require muon beams. Other LFNV processes, such as the decays of the kaons and of the τ, provide complementary information. In the next Section he shall consider some sources of LFNV that do not require an extension of the gauge group of the SM (the added leptons or Higgs bosons may of course originate from models with extended gauge groups). In Section 3 he discusses LFNV in left-right symmetric models. In Section 4 he considers LFNV in supersymmetric models, first in R-parity conserving supersymmetric grand unified models, and then in the minimal supersymmetric standard model with R-parity violation. The last section is a brief summary of the author's conclusions

  9. Matching career and family related factors for families with children

    OpenAIRE

    Rutkienė, Aušra; Trepulė, Elena

    2015-01-01

    Work-family conflict is a complex, multi-dimensional construct. When families decide to continue their professional career, work and family role matching demands efforts and causes strain. Results of a qualitative research show that having and taking care of pre-school and primary-school age children is one of main conflict reasons. Child-care arrangements have an important impact on parents’ experiences of work and their career paths. Job tenure and involvement into work-team are lower stres...

  10. Observing relationships in Finnish adoptive families: Oulu Family Rating Scale.

    Science.gov (United States)

    Tienari, Pekka; Wynne, Lyman C; Sorri, Anneli; Lahti, Ilpo; Moring, Juha; Nieminen, Pentti; Joukamaa, Matti; Naarala, Mikko; Seitamaa, Markku; Wahlberg, Karl-Erik; Miettunen, Jouko

    2005-01-01

    Adoption studies were intended to separate genetic from environmental "causal" factors. In earlier adoption studies, psychiatric diagnostic labels for the adoptive parents were used as a proxy for the multiple dimensions of the family rearing environment. In the Finnish Adoption Study, research design provided the opportunity to study directly the adoptive family rearing environment. For this purpose 33 sub-scales were selected creating what we call Oulu Family Rating Scale (OPAS, Oulun PerheArviointiSkaala). In this paper, the manual for scoring of these sub-scales is presented.

  11. Queer Youth in Family Therapy.

    Science.gov (United States)

    Harvey, Rebecca G; Stone Fish, Linda

    2015-09-01

    Trends in popular belief about same-sex relationships have undergone noteworthy change in the United States over the last decade. Yet this change has been marked by stark polarizations and has occurred at varying rates depending upon regional, community, racial, religious, and individual family context. For queer youth and their families, this cultural transformation has broadened opportunities and created a new set of risks and vulnerabilities. At the same time, youth's increasingly open and playful gender fluidity and sexual identity is complicated by unique intersections of class, race, religion, and immigration. Effective family therapy with queer youth requires practitioner's and treatment models that are sensitive to those who bear the burden of multiple oppressions and the hidden resilience embedded in their layered identities. We present case examples of our model of family therapy which addresses refuge, supports difficult dialogs, and nurtures queerness by looking for hidden resilience in the unique intersections of queer youths' lives. These intersections provide transformational potential for youth, their families and even for family therapists as we are all nurtured and challenged to think more complexly about intersectionality, sexuality, and gender. © 2015 Family Process Institute.

  12. Family planning: the unfinished agenda.

    Science.gov (United States)

    Cleland, John; Bernstein, Stan; Ezeh, Alex; Faundes, Anibal; Glasier, Anna; Innis, Jolene

    2006-11-18

    Promotion of family planning in countries with high birth rates has the potential to reduce poverty and hunger and avert 32% of all maternal deaths and nearly 10% of childhood deaths. It would also contribute substantially to women's empowerment, achievement of universal primary schooling, and long-term environmental sustainability. In the past 40 years, family-planning programmes have played a major part in raising the prevalence of contraceptive practice from less than 10% to 60% and reducing fertility in developing countries from six to about three births per woman. However, in half the 75 larger low-income and lower-middle income countries (mainly in Africa), contraceptive practice remains low and fertility, population growth, and unmet need for family planning are high. The cross-cutting contribution to the achievement of the Millennium Development Goals makes greater investment in family planning in these countries compelling. Despite the size of this unfinished agenda, international funding and promotion of family planning has waned in the past decade. A revitalisation of the agenda is urgently needed. Historically, the USA has taken the lead but other governments or agencies are now needed as champions. Based on the sizeable experience of past decades, the key features of effective programmes are clearly established. Most governments of poor countries already have appropriate population and family-planning policies but are receiving too little international encouragement and funding to implement them with vigour. What is currently missing is political willingness to incorporate family planning into the development arena.

  13. [Comparison among families of Mutong].

    Science.gov (United States)

    Ma, Hong-mei; Zhang, Bo-li

    2002-06-01

    To distinguish families of Mutong correctly and direct effective and safe clinical administration. Comparison among families of Mutong on Herbs, Taxology, Clinic, Pharmacology and Toxicology. 1. There are mainly three families of Mutong: Lardizabalaceae, Ranunculaceae, Aristolochiaceae, which were all included in China Pharmacopeia in 1963. However only Mutong of Ranunculaceae and Aristolochiaceae family have been included in China Pharmacopeia since 1977, but Mutong of Lardizabalaceae family has not been included in China Pharmacopeia ever since. 2. It was Mutong of Lardizabalaceae family that was used mainly through the ages without toxic records, and Mutong of Aristolochiaceae e.g. Caulis Aristolochia manshuriensis (CAM) was not put down in writing of past ages but is mainly used today with toxicity repeatedly. 3. CAM contain aristolochic acid and aristololactam with high toxicity, which plays an uncertain role in diuresis with poor bactericidal power. Mutong of Lardizabalaceae family e.g. Akebia trifoliata (Thunb.) Koidz. var. australis (Diels) Rehd (ATKV) don't contain aristolochic acid and aristololactam, which has low toxicity and plays a certain role in diuresis with high bactericidal power. It may be quite safe to use ATKV instead of CAM in clinics. So we suggest that ATKV should be reused as first Mutong in China Pharmacopeia revised edition in order to ensure a correct understanding of the facts and reveal Mutong in its true colors, and CAM should be used as second Mutong strictly according to the rules in China Pharmacopeia revised edition.

  14. FAMILIAL AMYLOID POLYNEUROPATHY——CLINICAL REPORT OF A FAMILY

    Institute of Scientific and Technical Information of China (English)

    李延峰; 郭玉璞; 池田修一; 方定华

    1996-01-01

    This paper reports a familial amyloid polyneumpathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset was about 3 to 5 decades. The initial symptoms were autonomic nerve symptcans, such as impotence, dyspepaia and diarrhoea, associated with the sensory loss of lower extremities. As the disease progressed. the upper extremities and motor ability were also involved. The duration of disease course wasabout 8-10 years, most patients died of infection and cacbexia. Sural biopsy in 3 patients had showed positive Congo red staining. From the clinical view, this FAP family is similar to FAP I found in Japan. Thetrue classification, however, should be confirmed by further genetic analysis.

  15. Familial Idiopathic Cranial Neuropathy in a Chinese Family.

    Science.gov (United States)

    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.

  16. Same sex families and children

    Directory of Open Access Journals (Sweden)

    Mršević Zorica

    2009-01-01

    Full Text Available Introduction comprises the information on two main forms of same sex families, civic partnership (same sex partnership and same sex marriage. Countries and various status modalities of legal regulations are mentioned. The main part of the text is dedicated to presentation of the findings of the most recent research on various aspects regarding children of same sex partnerships. It comprises presentations grouped in four main chapters: acceptance of same sex partnerships, acceptance of legal recognition of the same sex partnerships, family plans of homosexual teenagers, and raising children within and by the same sex partners. Also the real life cases mirroring legal changes through their life destinies are presented, such is e.g. the Irish way to legalization of the same sex partnerships. In addition, a love story of two women crowned by giving birth of their four children is mentioned. Reasons against and negative reactions the author puts under the title Homophobia. In the Concluding remarks, the author presents the most recent examples of legal changes happened in Norway, Ecuador, and in the American states of California and Connecticut. It was also stated that in European countries of low birth rate, the same sex families are inevitably identified as one of demographically valuable source of creating and raising children, which is worthy to be supported, rather than being hindered without reason and discriminated. Although different than a model of heterosexual family, same sex partnerships neither are harrowing to traditional family values, nor reflex of any kind of promiscuous, antisocial behavior, avoidance of parenthood, and negation of family. Quite opposite, these families are an outcome of endeavors of homosexuals not to be deprived of family, parenthood and all of other values of stabile, monogamous, emotional/sexual socially accepted and legally recognized and regulated conventional family. .

  17. Associations between family characteristics and parental empowerment in the family, family service situations and the family service system.

    Science.gov (United States)

    Vuorenmaa, M; Perälä, M-L; Halme, N; Kaunonen, M; Åstedt-Kurki, P

    2016-01-01

    Parental empowerment signifies parents' sense of confidence in managing their children, interacting with services that their children use and improving child care services. High empowerment is associated with parents' resilience to demands and their confidence to make decisions and take actions that positively affect their families. Most families with children access various healthcare and education services. Professionals working in these services are therefore ideally placed to reinforce parental empowerment. However, little is known about the characteristics associated with parental empowerment within a generic sample of parents or in the context of basic child care services. The aim of this study was to assess how family characteristics are associated with maternal and paternal empowerment in the family, in service situations and in the service system. Parental empowerment was measured among 955 parents (mothers = 571; fathers = 384) of children aged 0-9 years using the Generic Family Empowerment Scale. Family characteristics were assessed through questions on children, parents and the life situation. Associations between empowerment and family characteristics were evaluated using one-way analysis of variance and t-test. Parental empowerment was predicted by multiple linear regression analysis. Parents' concerns related to their parenting, such as whether they possessed sufficient skills as a parent or losing their temper with children, as well as experiences of stress in everyday life, were negatively associated with all dimensions of maternal and paternal empowerment. Both determinants were more common and more significant in empowerment than child-related problems. Promoting parental self-confidence and providing appropriate emotional and concrete support for everyday functioning may reinforce parental empowerment, thereby enhancing families' well-being and coping, as well as improving their access to required services and timely support. Finally

  18. Working to End Family Homelessness. Annual Report

    Science.gov (United States)

    National Center on Family Homelessness (NJ1), 2012

    2012-01-01

    The National Center on Family Homelessness is determined to end family homelessness. Sheltering families provides a temporary safe haven. Connecting families to permanent housing, essential services, and critical supports can change their lives forever. Through research the Center learns what families need to rebound from the housing, economic,…

  19. Alternative Families and Children: Implications for Education.

    Science.gov (United States)

    Alexander, Jannette; Eiduson, Bernice T.

    1980-01-01

    Since 1973, the UCLA Family Styles Project has studied a sample of nontraditional Caucasian families (single mothers, social contract families, communal families) plus a comparison group of conventional nuclear families. Findings are reported on parents' personal/social values and changes in childrearing practices. Implications for education are…

  20. Family Adjustment to Geographic Mobility: Military Families on the Move

    Science.gov (United States)

    1981-08-11

    military are the related topics of father absence and transcultural experiences. MOBILITY AND ITS EFFECTS ON CHILDREN Children in military families...c-ild experi- ences added stress due to geographic mobility, transcultural experi- ences, transient father absences, and early retirement of the...family, and that short-term crisis therapy was the ideal psychotherapeutic modality for treatment of military children. CONCLUSION In summary, there are

  1. Research Agenda on Families and Family Wellbeing for Europe

    OpenAIRE

    Beier, Loreen; Dechant, Anna; Haag, Christian; Rupp, Marina

    2011-01-01

    This report is the final outcome of FAMILYPLATFORM and the result of the encounter between more than 170 experts and stakeholders from all over Europe and beyond, creating a lively think tank on family issues. It summarises important policy questions, research gaps and research issues that were highlighted during the 18 months of working together closely within FAMILYPLATFORM. A series of societal challenges for families, family‐related policy and research have been identified through the wor...

  2. MCH promotes family planning.

    Science.gov (United States)

    Duan, Y

    1992-06-01

    Family planning (FP) has been promoted in China through improvements in maternal and child health (MCH) which have affected people's attitude toward childbearing. A case study of FP in Taicang County of Jiangsu Province, China is given. Total population is 446,620; natural increase is 10/1000. 99% of births have been planned in recent years. Contraceptive prevalence has reached 92.71%. Contraceptive awareness has opened people up to health education in general. The community participates in management of human wastes, improvement of water supplies, and parasite control in rural areas. MCH was begun in the early 1980s with premarital examinations, prenatal examinations, postnatal visits, and physical checkups. A systematic program has established in 1983. A pilot program integrating FP, MCH, and parasite control operated between 1984 and 1986, in 7 townships was established and MCH was institutionalized. Increases occurred in comprehensive care for women from 49.1% in 1984 to 78.3% in 1986. Children's coverage rose from 78.2% to 85.9%. Perinatal mortality dropped from 30.2/1000 to 20.8/1000. Neonatal mortality declined from 21.3/1000 to 17.3/1000. Infant mortality also decreased from 31.6/1000 to 21.5/1000. Integration of programs throughout the county was achieved after 1987. 99% of women used the MCH handbook. Between 1987 and 1990, the perinatal, neonatal, and infant mortality rate dropped to 12.9/1000, 9.5/1000, and 14.7/1000, respectively. MCH achievements are attributed to a strengthening of the MCH network to improve access and improve MCH workers' level of professional skill, to the availability of premarriage and couples of reproductive age services and child care, and to the contribution of research. Careful monitoring during pregnancy helped reduce the incidence of difficult labors for high risk women from 17.55 in 1984 to 11-15% in recent years. 99.9% deliver in hospitals. There were no maternal deaths in 1989 or 1990. Neonatal tetanus has been

  3. Mediation for resolving family disputes

    Directory of Open Access Journals (Sweden)

    Kamenecka-Usova M.

    2016-01-01

    Full Text Available Nowadays the understanding of the institute of marriage and its importance in the society has changed. Marriage is no longer assumed to be a commitment for a lifetime. As the principle of equality has replaced hierarchy as the guiding principle of family law it gave more grounds for family disputes and it became socially acceptable to leave marriages that are intolerable or merely unfulfilling. The aim of this article is to suggest an alternative dispute resolution method-mediation as a worthy option for resolving family conflicts.

  4. Family skills for overcoming adversity

    Directory of Open Access Journals (Sweden)

    Mónica Patricia Ardila Hernández

    2013-12-01

    Full Text Available This section draws on research four families in displacement in Tunja Boyacá step of this research is to present the problem of displacement from another different look that has embargoed regarding this topic. Critical reflection was raised from resilient approach Parsons theory in order to understand families immersed in this conflict as change agents capable of adapting to a new system and overcome adversity. Within this scheme is used to obtain qualitative research of the following categories : adaptation to the new social context risk factors present in families and protective factors.

  5. Family unification within SO(15)

    International Nuclear Information System (INIS)

    Enqvist, K.; Maalampi, J.

    1981-01-01

    We present a model for the unification of fermion families based on the gauge symmetry SO(15). It is a minimal SO(n) model which can accommodate the known fermions within a single irreducible representation. The model predicts four ordinary fermion families and four families of mirror fermions. The latter have V + A weak interactions, and their mass scale is predicted to be 10 2 GeV/c 2 . We argue that radiative corrections to the fermion masses can cause non-negligible mixing between ordinary and mirror fermions. The implications of these mixings for the weak interaction phenomenology and solar neutrinos are discussed. (orig.)

  6. Family therapy and clinical psychology

    OpenAIRE

    Carr, Alan

    1995-01-01

    The results of a survey of 111 clinical psychologists in the Republic of Ireland along with some comparable data from US and UK surveys were used to address a series of questions about the link between family therapy and clinical psychology. Family therapy was not a clearly identifiable sub-specialty within clinical psychology in Ireland. Family therapy theoretical models were used by more than a quarter of the Irish sample to conceptualize their work but by less than a tenth of US and UK res...

  7. Who benefits from family support? Work schedule and family differences.

    Science.gov (United States)

    Jennings, Kristen S; Sinclair, Robert R; Mohr, Cynthia D

    2016-01-01

    Prior research has demonstrated the benefits of family-supportive organization perceptions (FSOP) for reducing stress, increasing satisfaction, and increasing worker commitment; however, less research has studied health outcomes or possible differences in the effects of FSOP based on worker characteristics. The present study examined relationships between FSOP and health outcomes, as well as how those relationships may depend on work schedule and family differences. Using a sample of 330 acute care nurses, the findings indicated that FSOP predicted several health and well-being outcomes obtained 9 months later. Further, the relationships between FSOP and the outcome variables depended on some work schedule and family differences. In terms of family differences, FSOP was most strongly related to life satisfaction for those who cared for dependent adults. The relationship between FSOP and health outcomes of depression, musculoskeletal pain, and physical health symptoms were generally significant for workers with dependent children, but not significant for workers with no children. Regarding schedule differences, the relationship between FSOP and life satisfaction was significant for those on nonstandard (evening/night) shifts but not significant for standard day shift workers; however, there were no differences in FSOP relationships by number of hours worked per week. The findings demonstrate that FSOP may benefit some employees more than others. Such differences need to be incorporated into both future work-family theory development and into efforts to document the effectiveness of family-supportive policies, programs, and practices. (c) 2016 APA, all rights reserved).

  8. Family Economic Security Policies and Child and Family Health.

    Science.gov (United States)

    Spencer, Rachael A; Komro, Kelli A

    2017-03-01

    In this review, we examine the effects of family economic security policies (i.e., minimum wage, earned income tax credit, unemployment insurance, Temporary Assistance to Needy Families) on child and family health outcomes, summarize policy generosity across states in the USA, and discuss directions and possibilities for future research. This manuscript is an update to a review article that was published in 2014. Millions of Americans are affected by family economic security policies each year, many of whom are the most vulnerable in society. There is increasing evidence that these policies impact health outcomes and behaviors of adults and children. Further, research indicates that, overall, policies which are more restrictive are associated with poorer health behaviors and outcomes; however, the strength of the evidence differs across each of the four policies. There is significant diversity in state-level policies, and it is plausible that these policy variations are contributing to health disparities across and within states. Despite increasing evidence of the relationship between economic policies and health, there continues to be limited attention to this issue. State policy variations offer a valuable opportunity for scientists to conduct natural experiments and contribute to evidence linking social policy effects to family and child well-being. The mounting evidence will help to guide future research and policy making for evolving toward a more nurturing society for family and child health and well-being.

  9. Family Caregivers in Cancer (PDQ)

    Science.gov (United States)

    ... Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... For Parents Survivorship A New Normal Follow-Up Medical Care Late Side Effects Family Issues Survivorship Care ...

  10. EAMJ-March Family Plan

    African Journals Online (AJOL)

    iMac User

    2008-03-03

    Mar 3, 2008 ... Shisana, Human Sciences Research Council, P. Dana, Human Sciences Research Council and K. Zuma, Human Sciences .... The aim of this study was to investigate family ..... World Health Organization WHO, United Nations.

  11. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... tb overview links & resources families advocacy about civil rights kids' rights sample school policies school letter someone you know ... organizations wishing to create their own end slates. Right-click any link to download to your computer. ...

  12. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... tb overview links & resources families advocacy about civil rights kids' rights sample school policies school letter someone you know ... organizations wishing to create their own end slates. Right-click any link to download to your computer. ...

  13. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... getvaxed about GETVAXED print ads go to GETVAXED.ORG cme Immunizations Rotavirus One family's struggles with rotavirus ... free-of-charge. Branded videos contain the "PKIDs.ORG" end slate; unbranded videos are provided for organizations ...

  14. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... getvaxed about GETVAXED print ads go to GETVAXED.ORG cme Immunizations Chickenpox (Varicella) One family's struggles with ... free-of-charge. Branded videos contain the "PKIDs.ORG" end slate; unbranded videos are provided for organizations ...

  15. Kaiser Family Foundation - Content Search

    Data.gov (United States)

    U.S. Department of Health & Human Services — Chartpacks, chartbooks, factsheets, reports, and slide presentations bring Kaiser Family Foundation information to life, and can be easily incorporated into your...

  16. One Family's Struggle with Chickenpox

    Medline Plus

    Full Text Available ... find a doctor find health information helpful articles antibiotics colds fevers injection tips sports travel in health ... your family doctor to see if you could benefit. Copyright 1996 - by PKIDs. All rights reserved. home ...

  17. One Family's Struggles with Rotavirus

    Medline Plus

    Full Text Available ... find a doctor find health information helpful articles antibiotics colds fevers injection tips sports travel in health ... your family doctor to see if you could benefit. Copyright 1996 - by PKIDs. All rights reserved. home ...

  18. Collective health and family medicine

    Directory of Open Access Journals (Sweden)

    Donovan Casas Patiño

    2013-05-01

    Full Text Available In Mexico, the arrangement of clinical practice has been influenced by a decision-making process that seeks to improve health indicators, thus transforming the patient into a number. Family medicine has been practiced within the limits of an institutional biomedical model where the health-disease process is approached from a biologist perspective. On the other hand, collective health understands this process as stemming from the collective sphere and includes social and biological perspectives, giving an important standing to society. Likewise, it puts policy as a determinant in bettering social health bringing together public policy with health matters. Family medicine must become the axis around which health needs are catered to, together with social conditioning factors that affect families and individuals. This leads to a trans-disciplinary approach to communities set free from a mere biomedical profile. In this context, collective health provides theoretical support to the upcoming debate on family medicine.

  19. Administration for Children and Families

    Science.gov (United States)

    ... 9 (San Francisco) Region 10 (Seattle) Social sharing Administration for Children and Families Search form Search Main navigation Home About Expand What We Do Vision, Mission & Values Leadership Offices Budget Freedom of Information Act (FOIA) ...

  20. A Family Finds Its Way

    Science.gov (United States)

    ... conditions as a family. Photo courtesy of Stefan Radtke, www.stefanradtke.com The Woodruffs deal with Bob's ... be as she matures. Photo courtesy of Stefan Radtke, www.stefanradtke.com Do you talk with her ...