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Precise star positions near the Sun were measured during the 21 August 2017 total solar eclipse in order to measure their gravitational deflections. The equipment, procedures, and analysis are described in detail. A portable refractor, a CCD camera, and a computerized mount were set up in Wyoming. Detailed calibrations were necessary to improve accuracy and precision. Nighttime measurements taken just before the eclipse provided cubic optical distortion corrections. Calibrations based on star field images 7.4° on both sides of the Sun taken during totality gave linear and quadratic plate constants. A total of 45 images of the sky surrounding the Sun were acquired during the middle part of totality, with an integrated exposure of 22 s. The deflection analysis depended on accurate star positions from the USNO’s UCAC5 star catalog. The final result was a deflection coefficient L  =  1.7512 arcsec, in perfect agreement with the theoretical value, with an uncertainty of only 3%. [ABSTRACT FROM AUTHOR]

A statement of the professional umbrella society DGPT is presented that was formulated in cooperation with the various professional societies and with the German Society of Psychosomatic Medicine and Psychotherapy and the Society of Child and Adolescent Therapy. The statement is a reaction to the public claim for effective evidence of psychotherapy and takes the opportunity for a comprehensive presentation of this field. In the introduction Alf Gerlach, as chairman of the umbrella society at the time of the formulation of this statement and now executive chairman responsible for coordinating research, describes the history of the development of the statement. There were two particular moments prompting this statement. On the one hand the Scientific Advisory Board for Psychotherapy as an advisory committee based on the law of psychotherapy, has presented demands for effective evidence that are incompatible with psychoanalysis. Thus, the recognition of psychoanalysis as a treatment method for illnesses was put in doubt. On the other hand, a suggestion was put forward to the Board to recognize psychodynamic psychotherapy as an independent entity. This questioned the unity of the psychotherapeutic field. The statement was passed onto the Scientific Advisory Board last autumn. It is intended for a professional audience and includes answers to important issues of this field. It will have an important role to play in future discussions about professional politics. For this reason, we have decided to begin the present issue of our journal with this statement and thus to open a wide discussion forum. [ABSTRACT FROM AUTHOR]

While numerous studies on verbal working memory have investigated the capacity of the phonological loop and the effectiveness of rehearsal as one core process for maintaining the memory trace, the reconstruction of the memory trace from long-term memory, called redintegration, has been studied less thoroughly. This holds particularly for the population of students with special educational learning needs and mild and borderline intellectual disabilities (MBID). In a previous study, we found a differential developmental relation between the effectiveness of redintegration and vocabulary size, counter-intuitively suggesting that students with MBID tend to show less effective redintegration with higher vocabulary size. However, differential item functioning (DIF) in the picture naming task may have biased the result. Therefore, the current study is a re-analysis of this interaction controlling for DIF in the vocabulary measure. To this end, the items of the picture naming task ( k  = 95) were analyzed through a Rasch model, and k  = 29 biased items were excluded. The resulting corrected vocabulary score was used to predict the redintegration effectiveness, comparing students with and without MBID. The interaction remains significant, supporting the original finding that students with MBID have a differential developmental pattern and are less able to make adequate use of a growing vocabulary when reconstructing traces in their working memory. Implications of this result for the understanding of MBID and further research directions are discussed., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bruns.)

This text compares four essays dealing with war, state terror in dictatorships, social violence such as racism, mourning and the avoidance of mourning. It shows that dictatorships share similarities in their techniques of manipulation, linguistic style and reference to history. They seek to exploit national myths through manipulative alienation. Myths are a central element of cultural memory, and their effect can be understood through a model of internal dialogue. This dialogue determines whether the regime's attempts at manipulation are successful.

Introduction: While maintaining or restoring work ability after a cancer diagnosis is an essential aim of the rehabilitation process for working-age patients, problems can arise during the return to work (RTW) or when retaining work. Counselling could provide support for patients with or after cancer with employment-related questions (eg, questions related to RTW and work retention). Outpatient psychosocial cancer counselling centres in Germany offer counselling on work-related questions; however, resources for this are limited. This protocol presents a feasibility study of an intensified needs-based counselling intervention that supports those seeking employment-related advice., Methods and Analysis: The CARES (cancer rehabilitation support by cancer counselling centres) project is a feasibility study for a newly developed counselling intervention. The intervention is being developed as part of the project and piloted in about 20 outpatient cancer counselling centres. The CARES study has a quasi-experimental pre-post design with a control cohort. First, patients who undergo regular counselling are recruited. Second, after the counsellors have been trained for the newly developed intervention, participants for the intervention group are recruited from the cancer counselling centres. Quantitative and formative evaluations will be performed in accordance with the existing guidelines. The quantitative evaluation comprises three patient surveys (at the beginning of the counselling process, 3 months into the counselling process and, for the intervention group, at the end of the counselling process) and routine data of the counselling process. The formative evaluation includes interviews with patients, counsellors and other stakeholders, as well as participatory observations of counselling sessions., Ethics and Dissemination: Approval has been obtained from the ethics committee of the Medical Faculty of the University Bonn (061/22; 09.04.2022). A data protection concept ensures adherence to data protection regulations for the handled data. The dissemination strategies include discussing the results with the cancer counselling centres., Trial Registration Number: German Clinical Trials Register (DRKS00028121); Pre-results., Competing Interests: Competing interests: CB and CK are employed by the German Cancer Society (Deutsche Krebsgesellschaft). The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of the study is to look at the specific contribution of outpatient cancer counselling centers (OCCC) from the perspective of both the person seeking advice and the referring health care professionals., Methods: Qualitative design by means of guideline-based face-to-face interviews with cancer patients/relatives and individual telephone interviews with referring health care professionals., Results: A total of 43 persons seeking advice and 30 referring health care professionals were interviewed. With regard to the contents of counselling, psycho-oncological support and help for self-help in combination with social-legal information about additional support services are perceived as central features. In the group of referring physicians, however, there seems to be some uncertainty about what OCCCs (can) provide., Conclusion: On the one hand, the results point to a specific core of the services offered by OCCCs, and on the other hand to ambiguous perceptions on the part of the respondents. They may contribute to further sharpening the profile of OCCC and to clarifying their place in the health care system., Competing Interests: Susanne Singer erhielt Vortrags- bzw. Juryhonorare von Pfizer, Lilly, Boehringer-Ingelheim und BMS, alle außerhalb der hier vorgestellten Studie. Andreas Ihrig, Evelyn Flohr-Schmitt, Markus Besseler, Gudrun Bruns, Norbert Gelse und Alexander Wünsch sind selbst Mitarbeiter/innen einer Krebsberatungsstelle. Alle anderen Autor/innen (Margret Xyländer, Oliver Bayer, Melanie Schranz, Thorsten Meyer) geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Aim: The aim of the present survey was to describe and evaluate experiences of German psychosocial cancer counselling centers with user surveys as a quality management measure., Methods: Representatives of various psychosocial cancer counselling centers were asked to prepare an experience report on user surveys. Nine field reports were presented and discussed in summary by the working group "Cancer Counselling Centers" of the Working Group Psychooncology of the German Cancer Society (PSO). Special attention was paid to the short questionnaire KBS-N (Cancer Counselling Centre Questionnaire) recommended by the working group., Results: All psychosocial cancer counselling centers reported positive experiences with user surveys, which, however, represent an effort in terms of personnel and logistics. In addition to the KBS-N, more detailed questionnaires were also used. The surveys were conducted either continuously or on a random basis over a limited period of time. Those seeking advice were usually asked at a defined time directly after the initial interviews or after the end of the counselling sequence. The response rate was higher (85-95%) when the questionnaire was handed out personally after the initial consultation than for postal delivery and return (47-89%). All counselling centers reported positive feedback on the counselling services provided. Isolated points of criticism were related in particular to organizational framework conditions., Conclusion: After weighing up the costs and benefits, an active follow-up survey of those seeking advice using the short questionnaire KBS-N appears to be a practicable quality assurance measure, at least over a limited period of time. More detailed user surveys require more effort and are therefore more suitable for use in research that go beyond quality assurance., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

In verbal working memory, two processes serve to retain a fading memory trace: subvocal rehearsal and lexical redintegration. While recent studies on students with mild and borderline intellectual disabilities (MBID) have yielded mixed results on rehearsal, redintegration has not been researched in MBID, yet. Furthermore, most studies have used a group-matched design which, due to methodological constraints, can only distinguish between two different development patterns. Thus, we study both rehearsal and redintegration in students with MBID using developmental trajectories that have greater potential for identifying differential developmental patterns than traditional group-matching approaches. We investigate whether three aspects in working memory develop differently in students with MBID in comparison to typically developing students: (a) the general capacity of the phonological loop, and the effectiveness of (b) rehearsal, and (c) redintegration. We use three different developmental indicators to compare trajectories: chronological age, cognitive capacity, and vocabulary size. N = 210 students (87 students with MBID, 123 typically developing students) completed working memory span tasks with short and long (1- vs. 3-syllable) real words and pseudowords. The effect for word length (short vs. long) measures rehearsal, and the lexicality effect (real words vs. pseudowords) measures redintegration. Results show that developmental trajectories reveal an intercept difference but no slowed rate in rehearsal, and no impairment in redintegration. However, concerning the developmental relation between redintegration and vocabulary size, students with MBID reveal a differential pattern as redintegration appears higher for students with small vocabulary size, but unexpectedly decreases as vocabulary size increases. We conclude that students with MBID show a delayed onset in the development of capacity of the phonological loop and rehearsal and that they do not catch up in their development. Redintegration does not seem to be impaired in relation to age and cognitive capacity. However, the differential relation of redintegration with vocabulary size calls for further research. While impaired subvocal rehearsal appears to be connected to the developmental problems of students with MBID, lexical redintegration seems to be intact in relation to chronological age and cognitive capacity, making it a possible area of strength.

SILVA (lat. forest) is a comprehensive web resource, providing services around up to date, high-quality datasets of aligned ribosomal RNA gene (rDNA) sequences from the Bacteria, Archaea, and Eukaryota domains. SILVA dates back to the year 1991 when Dr. Wolfgang Ludwig from the Technical University Munich started the integrated software workbench ARB (lat. tree) to support high-quality phylogenetic inference and taxonomy based on the SSU and LSU rDNA marker genes. At that time, the ARB project maintained both, the sequence reference datasets and the software package for data analysis. In 2005, with the massive increase of DNA sequence data, the maintenance of the software system ARB and the corresponding rRNA databases SILVA was split between Munich and the Microbial Genomics and Bioinformatics Research Group in Bremen. ARB has been continuously developed to include new features and improve the usability of the workbench. Thousands of users worldwide appreciate the seamless integration of common analysis tools under a central graphical user interface, in combination with its versatility. The first SILVA release was deployed in February 2007 based on the EMBL-EBI/ENA release 89. Since then, full SILVA releases offering the database content in various flavours are published at least annually, complemented by intermediate web-releases where only the SILVA web dataset is updated. SILVA is the only rDNA database project worldwide where special emphasis is given to the consistent naming of clades of uncultivated (environmental) sequences, where no validly described cultivated representatives are available. Also exclusive for SILVA is the maintenance of both comprehensive aligned 16S/18S rDNA and 23S/28S rDNA sequence datasets. Furthermore, the SILVA alignments and trees were designed to include Eukaryota, another unique feature among rDNA databases. With the termination of the European Ribosomal RNA Database Project in 2007, the SILVA database has become the authoritative rDNA database project for Europe. The application spectrum of ARB and SILVA ranges from biodiversity analysis, medical diagnostics, to biotechnology and quality control for academia and industry., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)

During the last years two studies for the investigation of the etiology of porcine ear necrosis were carried out at the Clinic for Swine of the University of Veterinary Medicine Vienna. In study 1, parameters, which are discussed in this context, were collected by veterinary practitioners by completing specially designed questionnaires in farms with symptoms of the porcine ear necrosis syndrome. In study 2, samples of piglets and feed were collected for laboratory analysis of the most important infectious agents as well as mycotoxins. In the present manuscript, the results of both projects were compared. Even if the selection criteria of both studies differed, the affected age class was comparable (5.5 to ten weeks of life in study 1 and six to ten weeks of life in study 2). The herd-specific prevalence of the porcine ear necrosis syndrome varied considerably with percentages between 2 and 10, respectively, to 100%. The evaluation of questionnaires in study 1 showed that 51% of the farms had problems with cannibalism. Particles of plant material, which were frequently seen on the histologic slides of study 2, could have got into the tissue by chewing the ears of the pen mates or cannibalism. Whereas in study 1 the negative effect of parameters as high pig density, suboptimal climate, missing enrichment material and bad quality of feed and water were considered, in study 2 all these factors were checked at sample collection and ruled out as precursor for cannibalism. In both studies bacterial agents proved to be a crucial co-factor for the expansion of the necroses to deeper tissue layers, whereas viral pathogens were classified less important. In both projects it was not possible to estimate the direct impact of infectious agents and mycotoxins as direct trigger of the necroses as well as their participation as co-factors or precursor in the sense of an immunosuppression or previous damage of blood vessels or tissue.

The aim of this study was to identify the causative factors of porcine ear necrosis syndrome (PENS) in 72 pigs, 5.5-10 weeks in age housed on nine farms. Biopsy samples of ear pinnae were collected from all piglets for bacteriology, histopathology and in situ hybridization for porcine circovirus type 2 (PCV2). At the same time, serum samples were taken for serological analysis and viral PCR, and feed was sampled for mycotoxin analysis. The initial lesion of PENS seemed to be a focal epidermal necrosis. Streptococci were isolated from 44 and staphylococci from 36 pinnae. PCV2 could not be detected by in situ hybridization or qPCR. Seven piglets were positive for porcine reproductive and respiratory syndrome virus, and one for Mycoplasma suis. One piglet had antibodies against Sarcoptes scabiei var. suis. No infectious agents were found in 15 samples. Positive virology and parasitology were often found alongside positive bacteriology. Deoxynivalenol, zearalenone and ergot alkaloids were detected in feed. The findings suggest that PENS is multifactorial in origin and that although infectious agents can be involved in the development of the syndrome they are not the exclusive triggering factor., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

One of the counterarguments against empirical research in psychoanalysis is that research negatively influences the treatment situation. In this paper, the impact of a neurobiological study on psychoanalytically oriented treatments is presented from three different perspectives: patients' views, a study group of participating psychoanalysts and a clinical case example. Twenty chronically depressed patients, 20 healthy controls and 16 psychoanalysts participated in the project on research. Results show a clear influence of the neurobiological study on the course of treatments. Patients consistently reported that study participation had a positive impact on their treatment experiences. However, study participation was conflictual for the psychoanalysts and forced them to carefully reflect on their unconscious and conscious involvement to establish a psychoanalytic stance independent from empirical research.

Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

The aim of the study was to investigate the whole-body protein turnover, either before or after continuous, moderate ethanol-induced oxidative stress by red wine consumption over a relatively short period in healthy volunteers. Ten healthy adults received an individual regular diet over 20 days. After 10 days, the subjects consumed 0.4 ml ethanol kg(-1) day(-1) as red wine together with dinner over a 10-day period. After 8 and 18 days, respectively, a (15)N-labelled yeast protein was administered in a dosage of 4.2 mg kg(-1) body weight. Urine and faeces were collected over 48 h, respectively. The (15)N-enrichment was measured by isotope ratio mass spectrometry, whereas the protein flux rates were calculated by a three-compartment model. The whole-body protein turnover without/with red wine consumption amounted to 3.73±0.6 and 3.49±0.6 g kg(-1) day(-1) (not significant), respectively. Moderate alcohol consumption does not induce significant short-term changes in the whole-body protein turnover of healthy adults.

The elimination of a hydrogen bond in imidazolium based ionic liquids which results in an increased melting point is investigated by means of static quantum chemical and molecular dynamics simulations.

Genetic screening has opened up new paths for progress in preventive and curative medicine, and will probably progressively increase its positive contribution in the future. Rules and regulations have been established attempting to protect the donors' rights and to avoid damage to the donor and to others. Present day regulations seem unable to prevent the occurrence of serious problems and possible dangers. These are: 1. Ownership of genetic information and right to determine to whom it is divulged. 2. Direct emotional damage to individuals (mainly young persons expecting late-onset catastrophes) by having the information. 3. Damage caused by unsought for findings. 4. Restriction of transfer of information to the stated aim. 5. Right to release information important for public safety. The aim of this article is to propose that the donor's ownership of the information be abolished and that a board should decide to whom the genetic information should be given. An alternative solution is to leave the decisions regarding to whom genetic information should be divulged in the hands of the donor and his physician, controlled by an institutional review board.

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was thought to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending approximately 3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located approximately 40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected mate shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3.

We report the mapping of the human and mouse genes encoding SEK1 (SAPK/ERK kinase-1), a newly identified protein kinase that is a potent physiological activator of the stress-activated protein kinases. The human SERK1 gene was assigned to human chromosome 17 using genomic DNAs from human-rodent somatic cell hybrid lines. A specific human PCR product was observed solely in the somatic cell line containing human chromosome 17. The mouse Serk1 gene was mapped to chromosome 11, closely linked to D11Mit4, using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x M. spretus backcross.

The Ikaros gene is an essential regulator in the development and homeostasis of the mouse lymphopoietic system. To study the role of the Ikaros gene in the human lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the human, as in the mouse, differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues. Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes. The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr). The high degree of conservation of the Ikaros gene at the genetic and expression levels strongly suggests that it plays a fundamental role in the ontogeny of the lymphopoietic system across species.

The WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) deletion region on chromosome 11p13 has been extensively characterized by deletion analysis and long-range restriction mapping. A dense probe set is available for this genomic region, which harbors a number of disease gene loci, some of which still are not cloned. The identification of candidates for these genes would be greatly facilitated by a complete gene map for this chromosomal segment. As an initial step toward this goal, we have isolated the entire region in 58 overlapping YAC clones. The contig spanning 8 Mb from RAG1 to KCNA4 has been assembled by STS and probe content mapping for 76 loci with an average spacing of about 100 kb. A subset of clones has been analyzed by PFG analysis to position these within the known physical map. Common microsatellite markers permit an alignment of the YAC contig with the genetic and radiation hybrid maps of chromosome 11. Ten known genes, some with much more refined map positions, are placed in the contig. The severalfold coverage of 11p13-p14.1 provides a reliable resource for the future development of a complete gene map of this region.

A new gene (239FB) with predominant and differential expression in fetal brain has recently been isolated from a chromosome 11p13-p14 boundary area near FSHB. The corresponding mRNA has an open reading frame of 294 amino acids, a 3' untranslated region of 1247 nucleotides, and a highly GC-rich 5' untranslated region. The coding and 3' UT sequence is specified by 6 exons within nearly 87 kb of isolated genomic locus. The 5' end region of the transcript maps adjacent to the only genomically defined CpG island in a chromosomal subregion that may be associated with part of the mental retardation of some WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome patients. In addition to nucleotide and amino acid similarity to an EST from a normalized infant brain cDNA library, the predicted protein has extensive similarity to two Caenorhabditis elegans polypeptides of, as yet, unknown function. The 239FB locus is, therefore, likely part of a family of genes with two members expressed in human brain. The extensive conservation of the predicted protein suggests a fundamental function of the gene product and will enable evaluation of the role of the 239FB gene in neurogenesis in model organisms.

Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11p13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as well as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.

Actin-binding protein-280 (ABP-280) is a dimeric actin filament crosslinking protein that promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. We have mapped the ABP-280 filamin gene (FLN) to Xq28 by Southern blot analysis of somatic cell hybrid lines, by fluorescence in situ hybridization, and through identification of portions of the FLN gene within cosmids and YACs mapped to Xq28. The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus.

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate 11p13 Wilms' tumor gene, WT1, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WT1 gene. Analysis of the remaining WT1 allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WT1 polypeptide as a transcriptional regulator.

The combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in the family: an insertion of brand 11p13-p14 carrying the genes for predisposition to Wilms' tumor, WT1, and for aniridia, AN2, into the long arm of chromosome 11 in 11q13-q14. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 11, most likely resulting from the loss of the 11p13 band inserted in 11q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide variation in clinical expression. One child, with the karyotype 46,XY, del(11)(p13p14), presented the full-blown WAGR syndrome with aniridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WT1 gene can result in similar genital and kidney abnormalities.

Norrie disease is a human X-linked recessive disorder of unknown etiology characterized by congenital blindness, sensory neural deafness and mental retardation. This disease gene was previously linked to the DXS7 (L1.28) locus and the MAO genes in band Xp11.3. We report here fine physical mapping of the obligate region containing the Norrie disease gene (NDP) defined by a recombination and by the smallest submicroscopic chromosomal deletion associated with Norrie disease identified to date. Analysis, using in addition two overlapping YAC clones from this region, allowed orientation of the MAOA and MAOB genes in a 5'-3'-3'-5' configuration. A recombination event between a (GT)n polymorphism in intron 2 of the MAOB gene and the NDP locus, in a family previously reported to have a recombination between DXS7 and NDP, delineates a flanking marker telomeric to this disease gene. An anonymous DNA probe, dc12, present in one of the YACs and in a patient with a submicroscopic deletion which includes MAOA and MAOB but not L1.28, serves as a flanking marker centromeric to the disease gene. An Alu-PCR fragment from the right arm of the MAO YAC (YMAO.AluR) is not deleted in this patient and also delineates the centromeric extent of the obligate disease region. The apparent order of these loci is telomere ... DXS7-MAOA-MAOB-NDP-dc12-YMAO.AluR ... centromere. Together these data define the obligate region containing the NDP gene to a chromosomal segment less than 150 kb.

Recombinant phages that carry the human smooth muscle (enteric type) gamma-actin gene were isolated from human genomic DNA libraries. The amino acid sequence deduced from the nucleotide sequence matches those of cDNAs but differs from the protein sequence previously reported at one amino acid position, codon 359. The gene containing one 5' untranslated exon and eight coding exons extends for 27 kb on human chromosome 2. The intron between codons 84 and 85 (site 3) is unique to the two smooth muscle actin genes. In the 5' flanking region, there are several CArG boxes and E boxes, which are regulatory elements in some muscle-specific genes. Hybridization with the 3' untranslated region, which is specific for the human smooth muscle gamma-actin gene, suggests the single gene in the human genome and specific expressions in enteric and aortic tissues. From characterized molecular structures of the six human actin isoform genes, we propose a hypothesis of evolutionary pathway of the actin gene family. A presumed ancestral actin gene had introns at least sites 1, 2, and 4 through 8. Cytoplasmic actin genes may have directly evolved from it through loss of introns at sites 5 and 6. However, through duplication of the ancestral actin gene with substitutions of many amino acids, a prototype of muscle actin genes had been created. Subsequently, striated muscle actin and smooth muscle actin genes may have evolved from this prototype by loss of an intron at site 4 and acquisition of a new intron at site 3, respectively.