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Substantial progress has been made in the understanding of anorexia nervosa (AN) and eating disorder (ED) genetics through the efforts of large-scale collaborative consortia, yielding the first genome-wide significant loci, AN-associated genes, and insights into metabo-psychiatric underpinnings of the disorders. However, the translatability, generalizability, and reach of these insights are hampered by an overly narrow focus in our research. In particular, stereotypes, myths, assumptions and misconceptions have resulted in incomplete or incorrect understandings of ED presentations and trajectories, and exclusion of certain patient groups from our studies. In this review, we aim to counteract these historical imbalances. Taking as our starting point the Academy for Eating Disorders (AED) Truth #5 “Eating disorders affect people of all genders, ages, races, ethnicities, body shapes and weights, sexual orientations, and socioeconomic statuses”, we discuss what we do and do not know about the genetic underpinnings of EDs among people in each of these groups, and suggest strategies to design more inclusive studies. In the second half of our review, we outline broad strategic goals whereby ED researchers can expand the diversity, insights, and clinical translatability of their studies.

We have previously reported repeat-induced gene silencing (RIGS) in Arabidopsis, in which transgene expression may be silenced epigenetically when repeated sequences are present. Among an allelic series of lines comprising a primary transformant and various recombinant progeny carrying different numbers of drug resistance gene copies at the same locus, silencing was found to depend strictly on repeated sequences and to correlate with an absence of steady-state mRNA. We now report characterization, in nuclei isolated from the same transgenic lines, of gene expression by nuclear run-on assay and of chromatin structure by nuclease protection assay. We find that silencing is correlated with absence of run-on transcripts, indicating that expression is silenced at the level of transcription. We find further that silencing is also correlated with increased resistance to both DNase I and micrococcal nuclease, indicating that the silenced state reflects a change in chromatin configuration. We propose that silencing results when a locally paired region of homologous repeated nucleotide sequences is flanked by unpaired heterologous DNA, which leads chromatin to adopt a local configuration that is difficult to transcribe, and possibly akin to heterochromatin.

By screening with the fluorescent stain Calcofluor, we have isolated 26 independent transposon Tn5 insertion mutants of Rhizobium meliloti that are deficient in the production of a known extracellular polysaccharide (Exo-). The mutants belonged to six distinct genetic groups based on the ability of their Exo-phenotype to be complemented by different recombinant plasmids from a R. meliloti clone bank. With few exceptions, all of the mutants formed ineffective (non-nitrogen-fixing) nodules on alfalfa. For all but one group, the complementing plasmids restored effective nodulation. These results establish a firm and extensive correlation between the ability of Rhizobium to produce a particular polysaccharide and symbiotic proficiency. The ineffective nodules appeared to contain no bacteroids and to form without shepherds' crooks or infection threads; this symbiotic phenotype matches that described for a set of independently isolated mutants that belong phenotypically and genetically to the group B exopolysaccharide mutants described previously [Finan et al. (1985) Cell 40, 869-877]. Apparently the exopolysaccharide, although not required for nodule formation, is involved in wild-type nodule invasion.

The purpose of this study was to examine students' understanding of and ability to interpret line graphs, using four tasks: two where students constructed a graph and two where students interpreted a given graph. The tasks were unique in that they did not simply involve the explanation of given data but included a language component that looked at students' cognitive processes and understanding while they were engaged in the tasks. The study is important because students are often able to define and even draw graphs yet perform poorly on graph interpretation items presented in high-stakes examinations. The sample for the study consisted of 91 fourth and fifth graders with and without learning disabilities (LD) from six schools in a major metropolitan area. Scoring rubrics were designed for each item. An analysis of variance by grade and group indicated no significant differences between fourth and fifth graders overall but revealed that typically achieving students performed at significantly higher levels than students with LD at both grade levels. Additional descriptive analyses looked at the patterns of errors evidenced and the nature of the students' constructions. These are discussed, and instructional implications are derived.

Parametric tests were conducted with an optimized 35-mm-bore-angular-contact ball bearing on a high-speed, high-temperature bearing tester. Results from both air-oil mist lubrication and oil-jet lubrication systems used to lubricate the bearing were compared to speeds of 2.5¥10 6 DN. The maximum obtainable speed with air-oil mist lubrication is 2.5¥10 6 DN. Lower bearing temperatures and higher power losses are obtained with oil-jet lubrication than with air-oil mist lubrication. Bearing power loss is a direct function of oil flow to the bearing and independent of oil delivery system. For a given oil-flow rate, bearing temperature and power loss increase with increases in speed. Bearing life is an inverse function of temperature, the difference in temperature between the individual bearing ring components, and the resultant elastohydrodynamic (EHD) film thicknesses. Bearing life is independent of the oil delivery system except as it affects temperature. Cage slip increased with increases in speed. Cage slip as high as 7 percent was measured and was generally higher with air-oil mist lubrication than with oil-jet lubrication. Presented at the 56th Annual Meeting Orlando, Florida May 20-24, 2001

Arabidopsis thaliana mutants originally isolated as hypersensitive to irradiation were screened for the ability to be transformed by Agrobacterium transferred DNA (T-DNA). One of four UV-hypersensitive mutants and one of two gamma-hypersensitive mutants tested showed a significant reduction in the frequency of stable transformants compared with radioresistant controls. In a transient assay for T-DNA transfer independent of genomic integration, both mutant lines took up and expressed T-DNA as efficiently as parental lines. These lines are therefore deficient specifically in stable T-DNA integration and thus provide direct evidence for the role of a plant function in that process. As radiation hypersensitivity suggests a deficiency in repair of DNA damage, that plant function may be one that is also involved in DNA repair, possibly, from other evidence, in repair of double-strand DNA breaks

The HO endonuclease promotes gene conversion between mating-type alleles in yeast by a DNA double-strand break at the site of conversion (the MAT-Y/Z site). As a first step toward understanding the molecular basis of homologous recombination in higher plants, we demonstrate that expression of HO in Arabidopsis enhances intrachromosomal recombination between inverted repeats of two defective beta-glucuronidase (gus) genes (GUS- test construct). One of these genes has the Y/Z site. The two genes share 2.5 kb of DNA sequence homology around the HO cut site. Somatic recombination between the two repeats was determined by using a histochemical assay of GUS activity. The frequency of Gus+ sectors in leaves of F1 plants from a cross between parents homozygous for the GUS- test construct and HO, respectively, was 10-fold higher than in F1 plants from a cross between the same plant containing the GUS- test construct and a wild-type parent. Polymerase chain reaction analysis showed restoration of the 5' end of the GUS gene in recombinant sectors. The induction of intrachromosomal gene conversion in Arabidopsis by HO reveals the general utility of site-specific DNA endonucleases in producing targeted homologous recombination in plant genomes

Infection of alfalfa with Rhizobium meliloti exo mutants deficient in exopolysaccharide results in abnormal root nodules that are devoid of bacteria and fail to fix nitrogen. Here we report further characterization of these abnormal nodules. Tightly curled root hairs or shepherd's crooks were found after inoculation with Rm 1021-derived exo mutants, but curling was delayed compared with wild-type Rm 1021. Infection threads were initiated in curled root hairs by mutants as well as by wild-type R. meliloti, but the exo mutant-induced threads aborted within the peripheral cells of the developing nodule. Also, nodules elicited by Rm 1021-derived exo mutants were more likely to develop on secondary roots than on the primary root. In contrast with wild-type R. meliloti-induced nodules, the exo mutant-induced nodules lacked a well defined apical meristem, presumably due to the abortion of the infection threads. The relationship of these findings to the physiology of nodule development is discussed

cDNA and genomic clones encoding DNA topoisomerase I were isolated from Arabidopsis thaliana λgt11 and λFix libraries by low stringency hybridization with a Saccharomyces cerevisiae TOP1 probe. The cDNA clones include a 2748-base pair open reading frame predicting an amino acid sequence that is highly homologous to sequences encoded by TOP1 from yeast and human sources. The sequence of the upstream genomic region reveals two putative TATA-like elements and a purine-rich region, but no other obvious controlling elements. Southern blot analysis shows that the gene is present as a single copy in the Arabidopsis genome. When expressed in a S. cerevisiae top1 mutant under the control of the GAL1 promoter, the gene complements the phenotype caused by loss of topoisomerase activity and directs the expression of a protein that cross-reacts with a human anti-topoisomerase I antibody.

The computer program SHABERTH was used to analyze 35-mm-bore, angular-contact ball bearings designed and manufactured for high-speed turbomachinery applications. Parametric tests of the bearings were conducted on a high-speed, high-temperature bearing tester and were compared with the computer predictions. Four bearing and cage designs were studied. The bearings were lubricated either by jet lubrication or through the split inner ring with and without outer-ring cooling. The predicted bearing life decreased with increasing speed because of increased operating contact stresses caused by changes in contact angle and centrifugal load. For thrust loads only, the differences in calculated life for the 24° and 30° contact-angle bearings was insignificant. However, for combined loading the 24° contact-angle bearing gave longer life. For split-inner-ring bearings, optimal operating conditions were obtained with a 24° contact angle and an inner-ring land-guided cage, using outer-ring cooling in conjunction with low lubricant flow rates. Lower temperature and power losses were obtained with a single-outer-ring land-guided cage for the 24° contact-angle bearing having a relieved inner ring and partially relieved outer ring. Inner-ring temperatures were independent of lubrication mode and cage design. In comparison with measured values, reasonably good engineering correlation was obtained using the computer program SHABERTH for predicted bearing power loss and for inner- and outer-ring temperatures. The Parker formula for XCAV (used in SHABERTH, a measure of oil volume in the bearing cavity) may need to be refined to reflect bearing lubrication mode, cage design, and location of cage-controlling land. Presented at the 53rd Annual Meeting in Detroit, Michigan May 17-21, 1998