Evolution by the birth-and-death process in multigene families of the vertebrate immune system

Concerted evolution is often invoked to explain the diversity and evolution of the multigene families of major histocompatibility complex (MHC) genes and immunoglobulin (Ig) genes. However, this hypothesis has been controversial because the member genes of these families from the same species are not necessarily more closely related to one another than to the genes from different species. To resolve this controversy, we conducted phylogenetic analyses of several multigene families of the MHC and Ig systems. The results show that the evolutionary pattern of these families is quite different from that of concerted evolution but is in agreement with the birth-and-death model of evolution in which new genes are created by repeated gene duplication and some duplicate genes are maintained in the genome for a long time but others are deleted or become nonfunctional by deleterious mutations. We found little evidence that interlocus gene conversion plays an important role in the evolution of MHC and Ig multigene families.

Evolution of alcohol dehydrogenase genes in the palm and grass families.

The alcohol dehydrogenase (Adh; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family has two or three loci in a broad array of angiosperm species. The relative stability in the number of Adh loci led Gottlieb [Gottlieb, L. D. (1982) Science 216, 373-380] to propose that the Adh gene family arose from an ancient gene duplication. In this study, the isolation of three loci from the California fan palm (Washingtonia robusta) is reported. The three loci from palm are highly diverged. One palm Adh gene, referred to here as adhB, has been completely sequenced, including 950 nucleotides of the upstream regulatory region. For the second locus, adhA, 81% of the exon sequence is complete. Both show the same basic structure as grass Adh genes in terms of intron number and intron location. The third locus, adhC, for which only a small amount of sequence is available (12% of exon sequence) appears to be more highly diverged. Comparison of the Adh gene families from palms and grasses shows that the adh1 and adh2 genes of grasses, and the adhA and adhB genes of palms, arose by duplication following the divergence of the two families. This finding suggests that the multiple Adh loci in different monocot lineages are not the result of a single ancestral duplication but, rather, of multiple duplication events.

The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families.

Thyrotropin is the primary hormone that, via one heptahelical receptor, regulates thyroid cell functions such as secretion, specific gene expression, and growth. In human thyroid, thyrotropin receptor activation leads to stimulation of the adenylyl cyclase and phospholipase C cascades. However, the G proteins involved in thyrotropin receptor action have been only partially defined. In membranes of human thyroid gland, we immunologically identified alpha subunits of the G proteins Gs short, Gs long, Gi1, Gi2, Gi3, G(o) (Go2 and another form of Go, presumably Go1), Gq, G11, G12, and G13. Activation of the thyrotropin (TSH) receptor by bovine TSH led to increased incorporation of the photoreactive GTP analogue [alpha-32P]GTP azidoanilide into immunoprecipitated alpha subunits of all G proteins detected in thyroid membranes. This effect was receptor-dependent and not due to direct G protein stimulation because it was mimicked by TSH receptor-stimulating antibodies of patients suffering from Grave disease and was abolished by a receptor-blocking antiserum from a patient with autoimmune hypothyroidism. The TSH-induced activation of individual G proteins occurred with EC50 values of 5-50 milliunits/ml, indicating that the activated TSH receptor coupled with similar potency to different G proteins. When human thyroid slices were pretreated with pertussis toxin, the TSH receptor-mediated accumulation of cAMP increased by approximately 35% with TSH at 1 milliunits/ml, indicating that the TSH receptor coupled to Gs and G(i). Taken together, these findings show that, at least in human thyroid membranes, in which the protein is expressed at its physiological levels, the TSH receptor resembles a naturally occurring example of a general G protein-activating receptor.

Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease.

Mutations in the human phosphofructokinase muscle subunit gene (PFKM) are known to cause myopathy classified as glycogenosis type VII (Tarui disease). Previously described molecular defects include base substitutions altering encoded amino acids or resulting in abnormal splicing. We report a mutation resulting in phosphofructokinase deficiency in three patients from an Ashkenazi Jewish family. Using a reverse transcription PCR assay, PFKM subunit transcripts differing by length were detected in skeletal muscle tissue of all three affected subjects. In the longer transcript, an insertion of 252 nucleotides totally homologous to the structure of the 10th intron of the PFKM gene was found separating exon 10 from exon 11. In addition, two single base transitions were identified by direct sequencing: [exon 6; codon 95; CGA (Arg) to TGA (stop)] and [exon 7; codon 172; ACC (Thr) to ACT (Thr)] in either transcript. Single-stranded conformational polymorphism and restriction enzyme analyses confirmed the presence of these point substitutions in genomic DNA and strongly suggested homozygosity for the pathogenic allele. The nonsense mutation at codon 95 appeared solely responsible for the phenotype in these patients, further expanding genetic heterogeneity of Tarui disease. Transcripts with and without intron 10 arising from identical mutant alleles probably resulted from differential pre-mRNA processing and may represent a novel message from the PFKM gene.

Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases.

The regions surrounding the catalytic amino acids previously identified in a few "retaining" O-glycosyl hydrolases (EC 3.2.1) have been analyzed by hydrophobic cluster analysis and have been used to define sequence motifs. These motifs have been found in more than 150 glycosyl hydrolase sequences representing at least eight established protein families that act on a large variety of substrates. This allows the localization and the precise role of the catalytic residues (nucleophile and acid catalyst) to be predicted for each of these enzymes, including several lysosomal glycosidases. An identical arrangement of the catalytic nucleophile was also found for S-glycosyl hydrolases (myrosinases; EC 3.2.3.1) for which the acid catalyst is lacking. A (beta/alpha)8 barrel structure has been reported for two of the eight families of proteins that have been grouped. It is suggested that the six other families also share this fold at their catalytic domain. These enzymes illustrate how evolutionary events led to a wide diversification of substrate specificity with a similar disposition of identical catalytic residues onto the same ancestral (beta/alpha)8 barrel structure.

Restriction fragment length polymorphism-coupled domain-directed differential display: a highly efficient technique for expression analysis of multigene families.

In this paper, a reverse-transcriptase PCR-based protocol suitable for efficient expression analysis of multigene families is presented. The method combines restriction fragment length polymorphism (RFLP) technology with a gene family-specific version of mRNA differential display and hence is called "RFLP-coupled domain-directed differential display. "With this method, expression of all members of a multigene family at many different developmental stages, in diverse tissues and even in different organisms, can be displayed on one gel. Moreover, bands of interest, representing gene family members, are directly accessible to sequence analysis, without the need for subcloning. The method thus enables a detailed, high-resolution expression analysis of known gene family members as well as the identification and characterization of new ones. Here the technique was used to analyze differential expression of MADS-box genes in male and female inflorescences of maize (Zea mays ssp. mays). Six different MADS-box genes could be identified, being either specifically expressed in the female sex or preferentially expressed in male or female inflorescences, respectively. Other possible applications of the method are discussed.

Post-Conflict Maternal Communication, Children's Understandings, and Child Functioning in Violent and Non-Violent Families

The last two decades have been marked by a growing public awareness of family violence. Research by social scientists has suggested that family violence is widespread (Gelles and Straus, 1988). It is estimated that every year 1.8 to 4 million women are physically abused by their partners (Novello, 1992). In fact, more women are abused by their husbands or boyfriends than are injured in car accidents, muggings, or rapes (Jaffe, Wolfe, and Wilson, 1990). A recent prevalence study by Fantuzzo, Boruch, Beriama, Atkins, and Marcus (1997) found that children were disproportionately present in households where there was a substantial incident of adult female assault. Experts estimate that 3.3 to 10 million children are exposed to marital violence each year (Carlson, 1984; Straus, 1991). Until recently, most researchers did not consider the impact of parental conflict on the children who witness this violence. The early literature in this field primarily focused on the incidence of violence against women and the inadequate response of community agencies (Jaffe et al, 1990). The needs of children were rarely considered. However, researchers have become increasingly aware that children exposed to marital violence are victims of a range of psychological maltreatment (e.g., terrorizing, isolation;Hart, Brassared & Karlson, 1996) and are at serious risk for the development of psychological problems (Fantuzzo, DePaola, Lambert, Martino, Anderson, and Sutton, 1991). Jouriles, Murphy and O'Leary (1989) found that children of battered women were four times more likely to exhibit psychopathology as were children living in non-violent homes. Further, researchers have found associations between childhood exposure to parental violence and the expression of violence in adulthood (Carlson, 1990). Existing research suggests that children who have witnessed marital violence manifest numerous emotional, social, and behavioral problems (Sternberg et al., 1993; Fantuzzo et al., 1991; Jaffe et al, 1990). Studies have found that children of battered women exhibit more internalizing and externalizing behavior problems than non-witnesschildren (Hughes and Fantuzzo, 1994; McCloskey, Figueredo, and Koss, 1995). In addition, children exposed to marital violence have been found to exhibit difficulties with social problem-solving, and have lower levels of social competence than nonwitnesses (Rosenberg, 1987; Moore, Pepler, Weinberg, Hammond, Waddell, & Weiser, 1990). Other reported difficulties include low self esteem (Hughes, 1988), poor school performance (Moore et al., 1990) and problems with aggression (Holden & Ritchie, 1991; Jaffe, Wolfe, Wilson, & Zak, 1986). Further, within the last decade, researchers have found that some children are traumatized by the witnessing experience, showing elevated levels of posttraumatic stress symptoms (Devoe & Graham-Bermann, 1997; Rossman, Bingham, & Emde, 1996; Kilpatrick, Litt, & Williams, 1997). These findings corroborate clinical reports that describe many exposed children as experiencing trauma reactions. It appears that the negative effects of witnessing marital violence are numerous and varied, ranging from mild emotional and behavioral problems to clinically significant levels of posttraumatic stress symptoms. These incidence figures and research findings indicate that children's exposure to violence is a significant problem in our nation today and has serious implications for the future.

Using Emotion to Foster Acceptance: A Treatment Approach for Family Therapists Working with Transgender Adolescents and their Families

Currently, there is limited research and clinical focus on family therapy with transgender adolescents. When an adolescent discloses his/her transgender identity to his/her family, the family can experience an array of emotions, such as fear, distrust, anger, and sadness, along with confusion and invalidating behavior that can threaten secure attachment among family members. The purpose of this paper is to present a family therapy treatment approach for therapists working with transgender adolescents that is both culturally sensitive to the needs of these families as well as based on a systemic family therapy model. Emotionally Focused Family Therapy (EFFT) is a systemic model that is grounded in attachment theory and focuses on using emotion as a key tool in restructuring problematic relational patterns and fostering more secure family bonds. Through the use of a hypothetical case study, this paper aims at illustrating how EFFT can help family members process feelings related to the transgender identity of an adolescent family member and restore their attachment in a manner that strengthens family relationships and bonds.

Early Career Teachers' Efficacy in Working with Families

Partnering effectively with families is an important skill for teachers to have to support student achievement, and one that is especially important for early career teachers in order to protect them from burnout and attrition. However, research has demonstrated that teachers do not feel prepared to work with families, and further research is needed to see what difficulties are specific to early career teachers. The following research questions were addressed in the study: 1) What current situation and prior training factors affect early career teachers’ perceptions of efficacy in working with families? 2) Which family-school partnering topics do teachers report the most experience in their prior preparation programs and in their current daily practice? 3) Is there a relationship between number of years reported teaching and overall efficacy scores? 4) What family-school partnering training do early career teachers believe would have been or would be beneficial to receive in their teacher preparation programs versus during their first five years of practice? A survey was created which included a pre-existing self-efficacy scale adapted to reflect family partnering language. This survey was disseminated to 76 first through fifth year Colorado teachers. Results indicate that age of current school placement had a significant effect on overall self-efficacy scale scores, while several other variables had an effect on subscales of the efficacy scale. Recommendations are presented for future research, teacher preparation programs, and school district mentoring.

Examining the Complex Relationships of Early Intervention on Language and Psychosocial Development in Families Facing Multiple Risks with a Focus on Children of Hispanic Immigrants

Abundant research has shown that poverty has negative influences on young child academic and psychosocial development, and unfortunately, disparities in school readiness between low and high income children can be seen as early the first year of life. The largest federal early care and education intervention for these vulnerable children is Early Head Start (EHS). To diminish these disparate child outcomes, EHS seeks to provide community based flexible programming for infants and toddlers and their families. Given how relatively recent these programs have been offered, little is known about the nuances of how EHS impacts infant and toddler language and psychosocial development. Using a framework of Community Based Participatory Research (CBPR) this paper had 5 goals: 1) to characterize the associations between domain specific and cumulative risk and child outcomes 2) to validate and explore these risk-outcome associations separately for Children of Hispanic immigrants (COHIs), 3) to explore relationships among family characteristics, multiple environmental factors, and dosage patterns in different EHS program types, 4) to examine the relationship between EHS dosage and child outcomes, and 5) to examine how EHS compliance impacts child internalizing and externalizing behaviors and emerging language abilities. Results of the current study showed that risks were differentially related to child outcomes. Poor maternal mental health was related to child internalizing and externalizing behaviors, but not related to emerging child language skills. Although child language skills were not related to maternal mental health, they were related to economic hardship. Additionally, parent level Spanish use and heritage orientation were associated with positive child outcomes. Results also showed that these relationships differed when COHIs and children with native-born parents were examined separately. Further, unique patterns emerged for EHS program use, for example families who participated in home-based care were less likely to comply with EHS attendance requirements. These findings provide tangible suggestions for EHS stakeholders: namely, the need to develop effective programming that targets engagement for diverse families enrolled in EHS programs.

The Jewish Law Firm: Past and Present

The rise and growth of large Jewish law firms in New York City during the second half of the twentieth century was nothing short of an astounding success story. As late as 1950, there was not a single large Jewish law firm in town. By the mid-1960s, six of the largest twenty law firms were Jewish, and by 1980, four of the largest ten prestigious law firms were Jewish firms. Moreover, the accomplishment of the Jewish firms is especially striking because, while the traditional large White Anglo-Saxon Protestant law firms grew at a fast rate during this period, the Jewish firms grew twice as fast, and they did so in spite of experiencing explicit discrimination. What happened? This book chapter is a revised, updated study of the rise and growth of large New York City Jewish law firms. It is based on the public record, with respect to both the law firms themselves and trends in the legal profession generally, and on over twenty in-depth interviews with lawyers who either founded and practiced at these successful Jewish firms, attempted and failed to establish such firms, or were in a position to join these firms but decided instead to join WASP firms. According to the informants interviewed in this chapter, while Jewish law firms benefited from general decline in anti-Semitism and increased demand for corporate legal services, a unique combination of factors explains the incredible rise of the Jewish firms. First, white-shoe ethos caused large WASP firms to stay out of undignified practice areas and effectively created pockets of Jewish practice areas, where the Jewish firms encountered little competition for their services. Second, hiring and promotion discriminatory practices by the large WASP firms helped create a large pool of talented Jewish lawyers from which the Jewish firms could easily recruit. Finally, the Jewish firms benefited from a flip side of bias phenomenon, that is, they benefited from the positive consequences of stereotyping. Paradoxically, the very success of the Jewish firms is reflected in their demise by the early twenty-first century: because systematic large law firm ethno-religious discrimination against Jewish lawyers has become a thing of the past, the very reason for the existence of Jewish law firms has been nullified. As other minority groups, however, continue to struggle for equality within the senior ranks of Big Law, can the experience of the Jewish firms serve as a “separate-but-equal” blueprint for overcoming contemporary forms of discrimination for women, racial, and other minority attorneys? Perhaps not. As this chapter establishes, the success of large Jewish law firms was the result of unique conditions and circumstances between 1945 and 1980, which are unlikely to be replicated. For example, large law firms have become hyper-competitive and are not likely to allow any newcomers the benefit of protected pockets of practice. While smaller “separate-but-equal” specialized firms, for instance, ones exclusively hiring lawyer-mothers occasionally appear, the rise of large “separate-but-equal” firms is improbable.