Crystal structure of Pseudomonas aeruginosa catabolic ornithine transcarbamoylase at 3.0-A resolution: a different oligomeric organization in the transcarbamoylase family.

The crystal structure of the Glu-105-->Gly mutant of catabolic ornithine transcarbamoylase (OTCase; carbamoyl phosphate + L-ornithine = orthophosphate + L-citrulline, EC 2.1.3.3) from Pseudomonas aeruginosa has been determined at 3.0-A resolution. This mutant is blocked in the active R (relaxed) state. The structure was solved by the molecular replacement method, starting from a crude molecular model built from a trimer of the catalytic subunit of another transcarbamoylase, the extensively studied aspartate transcarbamoylase (ATCase) from Escherichia coli. This model was used to generate initial low-resolution phases at 8-A resolution, which were extended to 3-A by noncrystallographic symmetry averaging. Four phase extensions were required to obtain an electron density map of very high quality from which the final model was built. The structure, including 4020 residues, has been refined to 3-A, and the current crystallographic R value is 0.216. No solvent molecules have been added to the model. The catabolic OTCase is a dodecamer composed of four trimers organized in a tetrahedral manner. Each monomer is composed of two domains. The carbamoyl phosphate binding domain shows a strong structural homology with the equivalent ATCase part. In contrast, the other domain, mainly implicated in the binding of the second substrate (ornithine for OTCase and aspartate for ATCase) is poorly conserved. The quaternary structures of these two allosteric transcarbamoylases are quite divergent: the E. coli ATCase has pseudo-32 point-group symmetry, with six catalytic and six regulatory chains; the catabolic OTCase has 23 point-group symmetry and only catalytic chains. However, both enzymes display homotropic and heterotropic cooperativity.

Isolation and characterization of a MAGE gene family in the Xp21.3 region.

A human gene with strong homology to the MAGE gene family located in Xq27-qter has been isolated by using exon-trapping of cosmids in the Xp21.3 region. We have mapped and sequenced cDNA and genomic clones corresponding to this gene, MAGE-Xp, and shown that the last exon contains the open reading frame and is present in a minimum of five copies in a 30-kb interval. MAGE-Xp is expressed only in testis and, unlike the Xq27-qter MAGE genes, it is not expressed in any of 12 different tumor tissues tested. However, the gene and predicted protein structure are conserved, suggesting a similar function. MAGE-Xp is located in the 160-kb critical interval defined for the locus involved in sex determination within Xp21 and is 50 kb distal to the DAX-1 gene, which is responsible for X-chromosome-linked adrenal hypoplasia congenita.

Family firms and the great crisis: evidence from the italian case

Few studies have analyzed how family firms have acted during the global great crisis in comparison to their nonfamily counterparts. This paper tries to fill this gap on the basis of the Italian experience using a sample of almost 4,500 for 2007 and 2010. We study whether family control affects labour productivity, labour costs and competitiveness and if the adoption of performance related pay (PRP) reveals an efficacious strategy to mitigate the effects of the crisis and reduce the gap in competitiveness with respect to nonfamily firms. We use quantile regression techniques to test the heterogeneous role of PRP and pay attention for its possible endogeneity. We have observed that after the outburst of the crisis, the distance in terms of competitiveness of family firms with respect to their nonfamily counterparts has been amplified. We also find that family firms may take advantage from the adoption of incentive schemes, such as PRP, to encourage commitment and motivation from their employees more than nonfamily firms. The positive role of PRP on labour productivity, coupled with a moderate influence of these schemes on wage premiums, enable them to regain competitiveness also under hostile pressures, as those featuring the strong global crisis.

How does family intervention improve the outcome of people with schizophrenia?

Background: There is strong evidence of the efficacy of family psychosocial interventions for schizophrenia, but evidence of the role played by the attitudes of relatives in the therapeutic process is lacking. Method: To study the effect of a family intervention on family attitudes and to analyse their mediating role in the therapeutic process 50 patients with schizophrenia and their key relatives undergoing a trial on the efficacy of a family psychosocial intervention were studied by means of the Affective Style Coding System, the Scale of Empathy, and the Relational Control Coding System. Specific statistical methods were used to determine the nature of the relationship of the relatives’ attitudes to the outcome of family intervention. Results: Family psychosocial intervention was associated with a reduction in relatives’ guilt induction and dominance and an improvement in empathy. Empathy and lack of dominance were identified as independent mediators of the effect of family psychosocial intervention. The change in empathy and dominance during the first 9 months of the intervention predicted the outcome in the following 15 months. Conclusion: Relatives’ empathy and lack of dominance are mediators of the beneficial effect of family psychosocial intervention on patient’s outcome.

A national case-control study of Ewing's sarcoma family of tumours in Australia

Limited population-based epidemiologic information is available on Ewing's sarcoma family of tumours (ESFT), a rare group of neoplasms. Several associations have been noted on a few studies but results were not consistent, except for exposure to farming among cases and their parents. Here we present the non-farm findings of a nationwide case-control study of ESFT in children and young adults in Australia. The analysis included 106 persons with confirmed ESFT and 344 population-based controls selected randomly via telephone. Information was collected by interview (84% face to face). We found a strong and significant association of ESFT with hernias, in particular hernia repaired in hospital (OR = 5.6, 95% Cl 1.3-6.4). Among other factors, there was a near doubling of risk for males, and male cases had their pubertal signs earlier (started shaving earlier) than male controls. There was also an increased risk of ESFT at higher levels of self-assessed exercise, but no other factor really stood out. For pregnancy-related factors, there was a tripling of risk for glandular fever, a doubling of risk for urinary tract infection and a near doubling of risk for X-rays during or just before pregnancy, but these estimates were not significant. In addition, there was a large number of inverse associations with medical conditions (specifically bone disorders), case exposure to medications, vaccinations and X-rays, with ultrasound during the pregnancy having the most certain effects. We conclude that, although the aetiology of ESFT remains obscure, overall there is strong evidence of an association with inguinal hernia; this can now be added to the farm-associated risk reported by others and us. The other associations reported here await replication and refinement in future studies. (C) 2003 Wiley-Liss, Inc.

Probing the S100 protein family through genomic and functional analysis

The EF-hand superfamily of calcium binding proteins includes the S100, calcium binding protein, and troponin subfamilies. This study represents a genome, structure, and expression analysis of the S100 protein family, in mouse, human, and rat. We confirm the high level of conservation between mammalian sequences but show that four members, including S100A12, are present only in the human genome. We describe three new members of the S100 family in the three species and their locations within the S100 genomic clusters and propose a revised nomenclature and phylogenetic relationship between members of the EF-hand superfamily. Two of the three new genes were induced in bone-marrow-derived macrophages activated with bacterial lipopolysaccharide, suggesting a role in inflammation. Normal human and murine tissue distribution profiles indicate that some members of the family are expressed in a specific manner, whereas others are more ubiquitous. Structure-function analysis of the chemotactic properties of murine S100A8 and human S100A12, particularly within the active hinge domain, suggests that the human protein is the functional homolog of the murine protein. Strong similarities between the promoter regions of human S100A12 and murine S100A8 support this possibility. This study provides insights into the possible processes of evolution of the EF-hand protein superfamily. Evolution of the S100 proteins appears to have occurred in a modular fashion, also seen in other protein families such as the C2H2-type zinc-finger family. (C) 2004 Elsevier Inc. All rights reserved.

GP130/OSMR is the only LIF/IL-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors

Leukemia inhibitory factor (LIF) and its receptor (LIFR) are "twins" of Oncostatin M (OSM) and OSMR, respectively, likely having arisen through gene duplications. We compared their effects in a bone nodule-forming model of in vitro osteogenesis, rat calvaria (RC) cell cultures. Using a dominant-negative LIF mutant (hLIF-05), we showed that in RC cell cultures mouse OSM (mOSM) activates exclusively glycoprotein 130 (gp130)/OSMR. In treatments starting at early nodule formation stage, LIF, mOSM, IL-11, and IL-6 + sIL-6R inhibit bone nodule formation, that is, osteoprogenitor differentiation. Treatment with mOSM, and no other cytokine of the family, in early cultures (day 1-3 or 1-4) increases bone colony numbers. hLIF-05 also dose dependently stimulates bone nodule formation, confirming the inhibitory action of gp130/LIFR on osteogenesis. In pulse treatments at successive stages of bone nodule formation and maturation, LIF blocks osteocalcin (OCN) expression by differentiated osteoblasts, but has no effect on bonesialoprotein (BSP) expression. Mouse OSM inhibits OCN and BSP expression in preconfluent cultures with no or progressively reduced effects at later stages, reflecting the disruption of early nodules, possibly due to the strong apoptotic action of mOSM in RC cell cultures. In summary, LIFR and OSMR display differential effects on differentiation and phenotypic expression of osteogenic cells, most likely through different signal transduction pathways. In particular, gp130/OSMR is the only receptor complex of the family to stimulate osteoprogenitor differentiation in the RC cell culture model. © 2005 Wiley-Liss, Inc.

The impact of migration and intergenerational changes on the Cuban family in the United States

This study examines changes in the Cuban family in the United States produced by time, migration, and the rise of new generations. The thesis will use a data set extracted from the 5% Public Use Microdata Series (PUMS) of the U.S. Decennial Census of Population for the years 1970, 1980 and 1990. Contingency table analysis and comparison of means were used to examine various family-related variables. The analysis points to changes in the traditional Cuban family towards less traditional family arrangements. The multigenerational feature of the Cuban household has diminished as the elderly have become independent and are more likely to be living on their own. Although female labor participation remains high, the occupational patterns of the first generation of Cuban women have diversified and a new trend has emerged for the second generation. The second generation of Cuban women demonstrates a strong inclination for white-collar occupations. Fertility rates remain low.

Prognostic value of the diagnostic criteria distinguishing endometrial stromal sarcoma, low grade from undifferentiated endometrial sarcoma, 2 entities within the invasive endometrial stromal neoplasia family

The World Health Organization (WHO 2003) recognizes 3 endometrial stromal neoplasms: noninvasive endometrial stromal nodule and the 2 invasive neoplasms, endometrial stromal sarcoma (ESS), low grade and undifferentiated endometrial sarcoma (UES). It is important to note that the WHO 2003 does not define moderate atypia (an important differentiating diagnostic criterion for ESS, low grade and UES), nor does it discuss its significance. Moreover, studies on reproducibility and additional prognostic value of other diagnostic features in large are lacking. Using strict definitions, we analyzed the agreement between routine and expert-review necrosis and nuclear atypia in 91 invasive endometrial stromal neoplasias (IESN). The overall 5-year and 10-year recurrence-free survival rate estimates of the 91 IESN patients were 82% and 75%, respectively. Necrosis was well reproducible, and nuclear atypia was reasonably well reproducible. The 10-year recurrence-free survival rates for necrosis absent/inconspicuous versus prominent were 89% and 45% (P<0.001) and those for review-confirmed none/mild, moderate, severe atypia were 90%, 30%, and <20% (P<0.00001). Therefore, cases with moderate/severe atypia should be grouped together. Nuclear atypia and necrosis had independent prognostic values (Cox regression). Once these features were taken into account, no other feature had an independent additional prognostic value, including mitotic count. Using "none/mild atypia, necrosis absent/inconspicuous" as ESS, low grade versus "moderate/severe atypia present or necrosis present" as UES resulted in 68 ESS, low grade and 23 UES cases with disease-specific overall mortality-free survival of 99% versus 48% (P<0.00001, hazard ratio=45.4). When strictly defined microscopic criteria are used, the WHO 2003 diagnoses of ESS, low grade and UES are well reproducible and prognostically strong. © 2012 International Society of Gynecological Pathologists.

Impact of Genetic Testing and Family Health History Based Risk Counseling on Behavior Change and Cognitive Precursors for Type 2 Diabetes.

Family health history (FHH) in the context of risk assessment has been shown to positively impact risk perception and behavior change. The added value of genetic risk testing is less certain. The aim of this study was to determine the impact of Type 2 Diabetes (T2D) FHH and genetic risk counseling on behavior and its cognitive precursors. Subjects were non-diabetic patients randomized to counseling that included FHH +/- T2D genetic testing. Measurements included weight, BMI, fasting glucose at baseline and 12 months and behavioral and cognitive precursor (T2D risk perception and control over disease development) surveys at baseline, 3, and 12 months. 391 subjects enrolled of which 312 completed the study. Behavioral and clinical outcomes did not differ across FHH or genetic risk but cognitive precursors did. Higher FHH risk was associated with a stronger perceived T2D risk (pKendall < 0.001) and with a perception of "serious" risk (pKendall < 0.001). Genetic risk did not influence risk perception, but was correlated with an increase in perception of "serious" risk for moderate (pKendall = 0.04) and average FHH risk subjects (pKendall = 0.01), though not for the high FHH risk group. Perceived control over T2D risk was high and not affected by FHH or genetic risk. FHH appears to have a strong impact on cognitive precursors of behavior change, suggesting it could be leveraged to enhance risk counseling, particularly when lifestyle change is desirable. Genetic risk was able to alter perceptions about the seriousness of T2D risk in those with moderate and average FHH risk, suggesting that FHH could be used to selectively identify individuals who may benefit from genetic risk testing.

Family Background and Access to Post-Secondary Education: What Happened in the 1990's (Woking Paper 34)

This paper presents new evidence on the relationships between access to post-secondary education and family background. More specifically, we use the School Leavers Survey (SLS) and the Youth in Transition Survey (YITS)to analyze participation rates first in 1991, and then almost a decade later in 2000. Overall, post-secondary education participation rates rose over this period. However, participation is strongly related to parent’s education, and whereas participation increased for individuals with more highly educated parents (especially those who went to university), they increased rather less, or in some cases (especially for males) declined for those from lower parental education families. The already strong “effect” of parents’ education on post-secondary access became even greater in the 1990’s. Participation rates are also strongly related to family type, but whereas those from two parent families continue to have an advantage over single mother families, the gap generally shrunk in the 1990’s, especially where the mother had university level schooling. We also find a number of interesting trends by province.

Adolescent substance use in the context of the family: a qualitative study of young people’s views on parent-child attachments, parenting style and parental substance use

Background: Adolescent substance use can place youth at risk of a range of poor outcomes. Few studies have attempted to explore in-depth young people’s perceptions of how familial processes and dynamics influence adolescent substance use.
Objectives: This paper aimed to explore risk and protective factors for youth substance use within the context of the family with a view to informing family based interventions.
Methods: Nine focus groups supplemented with participatory techniques were facilitated with a purposive sample of sixty-two young people (age 13-17 years) from post-primary schools across Northern Ireland. The data were transcribed verbatim and analysed using thematic analysis.
Results: Three themes emerged from the data: 1) parent-child attachments, 2) parenting style and 3) parental and sibling substance misuse. Parent-child attachment was identified as an important factor in protecting adolescents from substance use in addition to effective parenting particularly an authoritative style supplemented with parental monitoring and strong parent-child communication to encourage child disclosure. Family substance use was considered to impact on children’s substance use if exposed at an early age and the harms associated with parental substance misuse were discussed in detail. Both parent and child gender differences were cross-cutting themes.
Conclusion: Parenting programmes (tailored to mothers and fathers) may benefit young people via components on authoritative styles, parental monitoring, communication, nurturing attachments and parent-child conflict. Youth living with more complex issues, e.g. parental substance misuse, may benefit from programmes delivered beyond the family environment e.g. school based settings.

Big bang bifurcations in von Bertalanffy’s dynamics with strong and weak Allee effects

The main purpose of this work was to study population dynamic discrete models in which the growth of the population is described by generalized von Bertalanffy's functions, with an adjustment or correction factor of polynomial type. The consideration of this correction factor is made with the aim to introduce the Allee effect. To the class of generalized von Bertalanffy's functions is identified and characterized subclasses of strong and weak Allee's functions and functions with no Allee effect. This classification is founded on the concepts of strong and weak Allee's effects to population growth rates associated. A complete description of the dynamic behavior is given, where we provide necessary conditions for the occurrence of unconditional and essential extinction types. The bifurcation structures of the parameter plane are analyzed regarding the evolution of the Allee limit with the aim to understand how the transition from strong Allee effect to no Allee effect, passing through the weak Allee effect, is realized. To generalized von Bertalanffy's functions with strong and weak Allee effects is identified an Allee's effect region, to which is associated the concepts of chaotic semistability curve and Allee's bifurcation point. We verified that under some sufficient conditions, generalized von Bertalanffy's functions have a particular bifurcation structure: the big bang bifurcations of the so-called box-within-a-box type. To this family of maps, the Allee bifurcation points and the big bang bifurcation points are characterized by the symmetric of Allee's limit and by a null intrinsic growth rate. The present paper is also a significant contribution in the framework of the big bang bifurcation analysis for continuous 1D maps and unveil their relationship with the explosion birth and the extinction phenomena.

Running in the Family – Paternalism and Familiness in the Development of Family Businesses

The study focuses on two features of family businesses (FBs), namely familiness and paternalism. These two concepts are inseparable in two ways: inseparable from family businesses and also from each other. Family businesses differ from one another in the degree of family involvement, leadership and management in the business. Paternalism as a leadership attitude is naturally present in FBs, especially in the founding stage of development. This feature provides the solid bases for establishing a strong and proud culture built around the personality and success of the founder. This characteristic however can become a major hindering factor upon succession. Through a review of the literature and the INSIST studies for Central Europe this study aims to identify the supportive and limiting factors of both phenomena and examine the case studies of the INSIST research project for signs of the existence of these supportive and limiting factors. It is found that the degree of familiness in these firms is a sliding scale and a lack of familiness is not a precursor for failure. Paternalism is found to be broken down into authoritarian, benevolent, moral and enlightened. After discovering studies claiming that paternalism is a stage in the process of leadership style changing from participative to autocratic (or vice versa) and that Central Europe and the current era of instability and uncertainty lead to employees preferring a more autocratic or paternalistic style, our findings suggest that there are more driving than restraining forces for family firms adopting a paternalistic style. Furthermore many cases appear to be on the path from an authoritative towards a more enlightened paternalistic leadership style either out of choice in the search to shake off the drawbacks of other types of paternalism or as part of a natural evolution of this particular leadership style within the context of this study.