bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical mapping of the gene for juvenile nephronophthisis (NPH1) by construction of a complete YAC contig of 7 Mb on chromosome 2q13
Authors: Hildebrandt F. , Cybulla M. , Strahm B. , Nothwang H.G. , Singh-Sawhney I. , Berz K. , Nicklin M. , Reiner O. , Brandis M.
Published: May 2008

Familial juvenile nephronophthisis (NPH) is an autosomal recessive cystic disease of the kidney that leads to end-stage renal failure in adolescence. NPH is the most common genetic cause of end-stage renal disease in children. A gene locus for nephronophthisis (NPH1) has been mapped by linkage analysis to chromosome 2ql 3. We report here the construction of a complete YAC contig in the minimum genetic region for NPH1 by STS content mapping using clones of the CEPH YAC libraries. A physical map of maximum distances between 32 STS markers was constructed, thereby defining the order of a total of 27 STS markers. Since D2S340 and D2S121 have previously been identified as flanking markers to the NPH1 gene, the new contig defines on a physical map the NPH1 minimum genetic region to a 6.4-Mb interval. As a novel assignment, expressed genes, some of which may be candidates for the disease, were localized to the NPH1 region. In addition, the known interstitial telomeric repeat on chromosome 2 was physically mapped to this region. This contig assembly provides the basis for closer definition of the NPH 1 critical region through identification of more narrow flanking markers and for the construction of a transcriptional map of the region towards isolation of the NPH1 gene.
Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22
Authors: Demetrick D.J. , Zhang H. , Beach D.H.
Published: May 2008

The human cdk2/cyclin A kinase complex is a key regulator of the events of S phase. This complex contains several proteins involved in regulating its catalytic activity, including one or more of the CKS proteins, which have recently been shown to inhibit the activation of the cdk2 kinase. To investigate whether the CKS genes may be altered in human neoplasia, we mapped the chromosome locations of CKS 1 and CKS2 by fluorescence in situ hybridization (FISH). CKS1 was localized to 8q21, a locus that is seldom grossly altered in cancer. The localization of CKS2to 9q22 places it very near to a putative tumour suppressor locus suggested to be responsible for susceptibility to the Basal Cell Nevus Syndrome (BCNS or Gorlin’s syndrome) familial cancer disorder. Six fibroblast cell lines isolated from patients with BCNS were demonstrated by FISH to have both copies of CKS2 present. Partial sequencing of a genomic clone of CKS2 revealed that the open reading frame lies over three exons. Examination of the six cell lines by SSCP and PCR-based sequencing of the parts of the three exons coding for the full length protein demonstrated no consistent divergence from the reported cDNA sequence in any exon. It is unlikely that CKS2 is the BCNS tumour suppressor gene.
The RNA polymerase I transcription factor UBF and rDNA are located at the same major sites in both interphase and mitotic pig embryonic kidney (PK) cells
Authors: Zatsepina O.V. , Schöfer C. , Weipoltshammer K. , Mosgoeller W. , Almeder M. , Stefanova V.N. , Jordan E.G. , Wachtler F.
Published: May 2008

Indirect immunolabeling with anti-UBF antibodies, in situ hybridization with an rDNA probe, and confocal scanning laser microscopy were used to study nucleolar organizer regions (NORs) during the cell cycle in pig embryonic kidney (PK) cells. The chromosomal distribution of the polymerase I transcription factor UBF and rDNA was compared with the number of silver-stained NORs (Ag-NORs) present and nucleolar size. It was shown, both at interphase and mitosis, that the majority of UBF and rDNA signals were located at the same foci and that the amounts of UBF and rDNA at any given site were in a striking positive correlation. At mitosis, only the NORs were labeled; at interphase, the signals for both UBF and rDNA were arranged in necklace-like structures around the nucleoli. No chromosomal NORs without Ag-proteins or UBF were present, indicating that all NORs in PK cells are active at interphase. It was concluded that (1) UBF and rDNA co-localize throughout the cell cycle in PK cells; (2) their association with mitotic NORs is determined by the number of rDNA repeats, rather than by any differential ability of NORs to recruit the transcription factor; and (3) the amount of UBF can be correlated with the size and activity of the nucleoli at interphase.
Localization of the human gene encoding the 13.3-kDa subunit of mitochondrial complex III (UQCRB) to 8q22 by in situ hybridization
Authors: Malaney S. , Heng H.H.Q. , Tsui L.C. , Shi X.M. , Robinson B.H.
Published: May 2008

We have localized the human gene encoding the 13.3-kDa subunit of mitochondrial complex III (UQCRB) to chromosome 8 using both radioactive in situ hybridization and fluorescence in situ hybridization. The additional peak obtained with the former method is attributed to the higher sensitivity of this technique, which results in hybridization of the probe to the less conserved pseudogene. We therefore conclude that the functional gene is most likely located at 8q22.
Double and triple in situ chromosomal labeling of human spermatozoa by PRINS
Authors: Coignet L. , Girardet A. , Andréo B. , Charlieu J.P. , Pellestor F.
Published: May 2008

The PRimed IN Situ (PRINS) labeling method allows rapid, specific detection of human chromosomes in situ. We have adapted the PRINS protocol to mature human sperm in combination with a 3 M NaOH protocol for simultaneous in situ decondensation and denaturation of sperm nuclei. Using fluorochrome-labeled dNTPs in a sequential PRINS reaction, the direct detection of two or three distinct chromosomes must be performed within a timespan of 3 h. The method was tested with primers specific for chromosomes 8, 9, 12, 13, 16, 18, and 21 and the X. The frequencies of disomy ranged from 0.11 % to 0.34%. Chromosome-specific primers have been defined for most of the human chromosomes, including some that are indistinguishable by fluorescence in situ hybridization (FISH) with centromeric probes. Consequently, this new strategy constitutes a rapid and efficient alternative to FISH for detecting nondisjunction in human sperm.
Fluorescent in situ hybridization on archival G-banded slides
Authors: EI-Rifai W. , Knuutila S.
Published: May 2008

We report a simple procedure that allows the application of chromosomal in situ suppression hybridization to standard G-banded and Entellan-mounted archival preparations that had been stored for 4–8 y. The procedure includes removing the cover slips in xylene, refixation in buffered formaldehyde-acetone mixture, and washing in 2 × SSC, Tween 20.
Structural aberrations of metaphase derivative chromosomes from reciprocal translocations as revealed by scanning electron microscopy
Authors: Uehara S. , Sasaki H. , Takabayashi T. , Yajima A.
Published: May 2008

Metaphase chromosomes from three reciprocal translocation carriers were examined by scanning electron microscopy. A gap was detected in one of the two derivative chromosomes in each carrier. The position of each gap was identical with that of the respective breakpoint of the derivative chromosome to which the longer chromosome fragment was translocated. The gap length resembled a midsize G-band. Our observations suggest that derivative chromosomes of reciprocal translocations involve aberrations of a high-ordered structure of chromatid fibers at the translocation sites.
Identification of complex chromosome rearrangements in the gibbon by fluorescent in situ hybridization (FISH) of a human chromosome 2q specific microlibrary, yeast artificial chromosomes, and reciprocal chromosome painting
Authors: Arnold N. , Stanyon R. , Jauch A. , O’Brien P. , Wienberg J.
Published: May 2008

Chromosome painting has revealed that the human chromosome homologs in lesser apes are often fragmented and translocated to a number of different hylobatid chromosomes. We investigated the fragmented human chromosome 2 homologs in gibbons to illustrate a new strategy in mapping regional and band-specific chromosomal homologies between species. Previous research showed that the DNA library specific to human chromosome 2 paints parts of four gibbon (lar species group) chromosomes (viz., 1, 10, 12, and 16) and yields five distinct hybridization signals (including two on gibbon chromosome 16). However, the exact segments of human chromosome 2 that were translocated to the various gibbon chromosomes could not be distinguished. To determine the origin of the human chromosome 2 signals, we hybridized a microlibrary for the long arm of human chromosome 2, as well as YACs specific for most of the major bands on this chromosome, to metaphases of the gibbon. For reciprocal chromosome ainting, we hybridized flow-sorted gibbon chromosome probes to human chromosome 2. Each method added additional insights that helped clarify the shuffling of human chromosome 2 material in the highly reorganized gibbon genome. There was an excellent correspondence between these complementary techniques. YAC 958d2 identified the breakpoint between human chromosome 2 material present on gibbon chromosomes 10 and 16. The reciprocal chromosome painting permitted a more complete and regional assignment of homology between segments on various gibbon chromosomes to human chromosome 2. The results show that a combination of reciprocal chromosome painting, subregional microlibraries, and band-specific probes (such as YACs) can be used to identify homologies between species and to rapidly construct detailed comparative chromosome maps, especially when the karyo-types are highly rearranged.
Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a human cDNA highly homologous to human erythrocyte adducin
Authors: Katagiri T. , Ozaki K. , Fujiwara T. , Shimizu F. , Kawai A. , Okuno S. , Suzuki M. , Nakamura Y. , Takahashi E. , Hirai Y.
Published: May 2008

From a human fetal-brain cDNA library we isolated a novel human cDNA, termed human adducin-like 70 (gene symbol ADDL), whose predicted amino acid sequence showed a high degree of homology to adducins. This cDNA clone (ADDL), which contained an open reading frame of 2,022 nucleotides encoding 674 amino acids, revealed 54%, 53%, and 59 % identity in predicted amino acid sequence with alpha and beta components of human adducin and rat adducin 63, respectively. Human adducin-like 70 is likely to play an important role in the skeletal organization of the cell membrane. Northern blot analysis indicated ubiquitous expression of this gene in adult human tissues. We localized the gene to chromosome bands 10q24.2→q24.3 by fluorescence in situ hybridization (FISH).
Subregional mapping of the human lymphocyte prolyl oligopeptidase gene (PREP) to human chromosome 6q22
Authors: Goossens F.J. , Wauters J.G. , Vanhoof G.C. , Bossuyt P.J. , Schatteman K.A. , Loens K. , Scharpé S.L.
Published: May 2008

Prolyl oligopeptidase is a large monomeric proline specific serine endopeptidase, the activity of which correlates well with different stages of depression. We have subregionally mapped human lymphocytic prolyl oligopeptidase (PREP) by FISH using a cosmid probe. The probe mapped to the long arm of chromosome 6, and the signal clustered in band q22.
The Brn-3a transcription factor gene (POU4F1) maps close to the locus for the variant late infantile form of neuronal ceroid-lipofuscinosis
Authors: Still I.H. , Cowell J.
Published: May 2008

We have refined the location of the Brn-3a genomic locus (POU4F1), using somatic cell hybrid analysis, to 13q21.1→q22. Furthermore, we have shown that two YACs, known to contain the closest marker linked to neuronal ceroidlipofuscinosis (CLN5), also contains the Brn-3a gene. As one of these YACs is only 320 kb long, this localises POU4F1 within the critical region defining the CLN5 locus, and raises the possibility that POU4F1 is a candidate gene for CLN5.
Genetic and physical mapping of the ovine cystic fibrosis gene
Authors: Tebbutt S.J. , Broom M.F. , van Stijn T.C. , Montgomery G.W. , Hill D.F.
Published: May 2008

Two yeast artificial chromosomes (YACs 48B6 and 88F7) that span the ovine cystic fibrosis transmembrane conductance regulator (CFTR) gene locus have been isolated. These YAC clones have been physically assigned to the interval 4q23→q25 on sheep chromosome 4, using fluorescence in situ hybridization. A sequence polymorphism in exon 7 of the CFTR gene was identified in Merino sheep and present at a low frequency. This polymorphism segregated in several flocks. Linkage analysis confirmed the location of CFTR on sheep chromosome 4. The most likely location is within a 13.7-cM region close to markers MAF70 and TGLA116.
High-resolution FISH mapping of β-defensin genes to river buffalo and sheep chromosomes suggests a chromosome discrepancy in cattle standard karyotypes
Authors: lannuzzi L. , Gallagher D.S. , Di Meo G.P. , Diamond G. , Bevins C.L. , Womack J.E.
Published: May 2008

High-resolution chromosomal fluorescence in situ hybridization (FISH) and R-banding allowed the chromosomal localization of the β-defensin gene cluster (DEFB@) to chromosome band 1p12 in the river buffalo (Bubalus bubalis, 2n = 50) and to band 24q13 in sheep (Ovis aries, 2n = 54), according to standard nomenclatures. The localizations permitted the tentative assignment of the entire bovine syntenic group U25 to these chromosomes. A FISH mapping control on cattle chromosomes confirmed the localization of DEFB@ in the homoeologous chromosome and chromosome band. Comparisons were made between river buffalo chromosome 1p and the homoeologous cattle chromosome on standard karyotypes; the results are discussed in light of gene assignments, extensive chromosome band conservation among the Bovidae, and inconsistencies in domestic cattle chromosome nomenclatures.
Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization
Authors: Bentz M. , Bergerheim U.S.R. , Li C. , Joos S. , Werner C.A. , Baudis M. , Gnarra J. , Merino M.J. , Zbar B. , Linehan W.M. , Lichter P.
Published: May 2008

We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.
Cloning of the bovine activin receptor type II gene (ACVR2) and mapping to chromosome 2 (BTA2)
Authors: Flavin N. , Heriz A. , Monteagudo L.V. , Ennis S. , Martin F. , Barendse W. , Arruga M.V. , Rogers M.
Published: May 2008

The cDNA for the bovine activin receptor type II (ACVR2) gene has been cloned and sequenced. It encodes a protein of 513 amino acids which is highly homologous (∼98 % identity) to the human, mouse, and rat proteins. Using PCR analysis of bovine × hamster somatic cell lines, the ACVR2 gene was mapped to syntenic group U17, which has been localised to bovine chromosome 2. Comparative mapping has shown that the genes within U17 are also in a syntenic group on the long arm of human and sheep chromosome 2, as well as on mouse chromosome 1. This group of genes represents an evolutionarily conserved mammalian chromosomal segment. Genotyping a highly polymorphic microsatellite locus, (AT)4(GT)9(AT)11, found within an intron of this gene confirmed the localisation by linking the ACVR2-associated microsatellite to the region of chromosome 2 flanked by CSSM42 and TGLA226. This gene locus, which has the characteristics of a type I and type II mapping locus, represents the first localisation of this gene in any species to date.
Identification and chromosome mapping of the mouse homologue of the human gene (DDX6) that encodes a putative RNA helicase of the DEAD box protein family
Authors: Akao Y. , Matsuda Y.
Published: May 2008

The human DDX6 gene (alias RCK) at chromosome 11 band q23 was identified through the study of the breakpoint of t(11;14)(q23;q32) translocation in a B-cell lymphoma cell line, RC-K8. DDX6 encodes a DEAD box protein/ RNA helicase. Positive mouse genomic and cDNA recombinant clones were obtained by screening mouse B-cell genomic and cDNA libraries with a human DDX6 cDNA probe. The deduced amino acid sequence of an open reading frame from a cDNA clone revealed a protein with 92.5% identity to human ddx6/p54. All positive mouse genomic recombinant clones, and cDNA clones containing mouse Ddx6 (previous gene symbol: Rck), were localized by fluorescent in situ hybridization to band B of mouse Chromosome 9, a region showing conserved linkage homology to human chromosome 11 band q23. Mouse Ddx6 was localized to the region between Ncam and D9MM5 by molecular linkage analysis. A 7.5-kb mRNA and a 54-kDa protein were identified as mouse Ddx6 gene products which are similar in size to products of the human DDX6 gene, as shown by Northern and Western blot analyses.
Spontaneous and aphidicolin-sensitive fragile site 3cen co-localizes with the (TTAGGG)n telomeric sequence in Chinese hamster cells
Authors: Musio A. , Rainaldi G. , Sbrana I.
Published: May 2008

Aphidicolin-sensitive fragile sites were analyzed in immortalized Chinese hamster embryonal fibroblast cells (CHEF 18) at three different passages along their spontaneous progression toward tumorigenicity. Five fragile sites (viz., 1q22, 3cen, 3p21, 3q31, and Xq21) were detected. Three of these sites carry spontaneous aberrations and are thus regions of chromosomal instability; however, they were not involved in the formation of the clonal rearrangements that are characteristic of CHEF 18 cells. The presence of the (TTAGGG)n telomeric sequence in chromosome bands associated with fragile sites was investigated using fluorescence in situ hybridization and primed in situ labeling. A common location of fragile sites and telomeric sequence was found at the centromere of chromosome 3.
Mapping of 29 YAC clones and identification of 3 YACs spanning the translocation t(3;8)(p14.2;q24.1) breakpoint at 8q24.1 in hereditary renal cell carcinoma
Authors: Shi G. , Cannizzaro L.A.
Published: May 2008

The constitutional balanced translocation t(3;8)(p14.2;q24.1) has been described in a family in which a large number of individuals developed renal cell carcinoma (RCC) at an early age. The translocation event in which genes from the 3p14.2 and the 8q24.1 sites are brought in close proximity is considered a critical, initial step for the development and progression of RCC. Even though the 3p14.2 breakpoint region has been cloned, a gene has not yet been identified, which may be responsible for either the initiation or progression of hereditary RCC. As a crucial step toward cloning the 3;8 breakpoint at the 8q24.1 site, we have mapped a series of YACs which surround this region by fluorescence in situ hybridization (FISH). Three YACs have been identified that span the 8q24.1 breakpoint region. One of these YACs is approximately 180 kb in length, and has been used to initiate construction of a high resolution cosmid contig. Several cosmids have been isolated which have been positioned in relation to the 8q24.1 breakpoint region. In addition, we have positioned 26 other YACs in relation to the 3;8 translocation breakpoint. These results provide a basis for the isolation of genes surrounding the 3;8 RCC translocation breakpoint region at 8q24.1.
Complex chromosomal mechanisms lead to APRT loss of heterozygosity in heteroploid cells
Authors: Shao C. , Gupta P.K. , Sun Y. , Sahota A. , Tischfield J.A.
Published: May 2008

Loss of the wild-type allele of a tumor suppressor gene, or loss of heterozygosity (LOH), is one of the most important mechanisms of carcinogenesis. Adenine phosphoribosyl-transferase (APRT) has been used as a surrogate marker for tumor suppressor genes. We have previously shown that APRT deficiency in an APRT heterozygous human cell line, MR12-1, was predominantly caused by the loss of the remaining wild-type allele. Here we report the characterization of the chromosomal pathways leading to LOH in four clones derived from this heteroploid cell line. We performed karyotype analysis, chromosome 16-specifïc painting, and fluorescence in situ hybridization with an APRT-containing cosmid on these clones and their heteroploid parental cells. Our findings suggest that LOH occurs in tetraploid as well as diploid cells, and that diploid cells with LOH may undergo endoreduplication to attain tetraploidy. Our results also suggest that, in addition to LOH being caused by a single event (such as mitotic recombination or deletion), LOH may be caused by a combination of sequential events, such as mitotic recombination or translocation followed by chromosome loss. The instability of the genomes of the parental cells may have provided a greater diversity of options for genetic evolution. Similar karyotypic evolution may occur at late stages of carcinogenesis in vivo.
Characterization of an atypical NOR site polymorphism in brown trout (Salmo trutta) with Ag- and CMA3-staining, and fluorescent in situ hybridization
Authors: Castro J. , Viñas A. , Sánchez L. , Martínez P.
Published: May 2008

We have analyzed by Ag- and CMA3-staining, and rDNA fluorescent in situ hybridization an unusual NOR site polymorphism in a population of Salmo trutta from Miño basin (Northwestern Spain). A multichromosomal Ag-NOR distribution largely different from standard individuals both in the number and position of Ag-NORs, as well as in the pattern of activity, was revealed. Atypical Ag-NORs consist of rDNA genes, as evidenced by rDNA FISH, and are capable of constituting their own nucleolus. In spite of the large number of available NORs per individual, the mean number of Ag-NOR per cell was less than 3 in most individuals, which suggests a regulation mechanism to adjust the ribosomal production. The new rDNA clusters detected seem to be stably integrated, however, some characteristics of the NOR pattern observed suggest that this polymorphism is an unstable phenomenon.
Novel strategies for eutherian x marsupial somatic cell hybrids: mapping the genome of Monodelphis domestica
Authors: Nesterova T.B. , Isaenko A.A. , Matveeva N.M. , Shilov A.G. , Rubtsov N.B. , Vorobieva N.V. , Rubtsova N.V. , VandeBerg J.L , Zakian S.M.
Published: May 2008

Two hundred thirty-seven independent somatic cell hybrids have been obtained between opossum (Monodelphis domestica) splenocytes, bone marrow cells, or primary fibroblasts, and HPRT-deficient or TK-deficient Chinese hamster, mouse, American mink, or common vole fibroblast lines. Because extreme segregation and fragmentation of marsupial chromosomes commonly occurs in eutherian × marsupial somatic cell hybrids, we developed a rapid primary screening method that enables the identification of primary clones containing a large amount of opossum DNA 20–25 d after fusion. This method, which depends on in situ hybridization of biotin-labeled total opossum DNA on interphase nuclei of hybrid cells fixed on the bottom of microwell plates, was used to screen the 237 hybrid clones; 52 of them had a substantial amount of opossum DNA. G-banding and in situ hybridization of biotin labeled total opossum DNA on metaphase spreads of the clones enabled identification of 17 hybrid clones containing from two to seven intact chromosomes of M. domestica on the background of Chinese hamster or vole chromosomes. The hybrid clones with intact opossum chromosomes are used in a panel constructed for mapping the opossum genome. Initial mapping results from these clones have led to the tentative assignment of GPI and GOT1 to chromosome 1; 6PGD to chromosome 4; LDHA to chromosome 5; LDHB to chromosome 8; and PGK and G6PD to the X chromosome. On the basis of indirect evidence we also tentatively assigned HPRT to the X chromosome and TK to chromosome 5 of M. domestica. These are the first tentative chromosomal assignments by any technique for this species.
Evolution of the black muntjac (Muntiacus crinifrons) karyotype revealed by comparative chromosome painting
Authors: Yang F. , O’Brien P.C.M. , Wienberg J. , Ferguson-Smith M.A.
Published: May 2008

The black muntjac (Muntiacus crinifrons) has an unusual karyotype of 2n = 8 in females and 2n = 9 in males. We have studied the evolution of this karyotype by hybridising chromosome-specific paints derived from flow-sorted chromosomes of the Chinese muntjac (M. reevesi, 2n = 46) to chromosomes of the black muntjac. The hybridisation pattern allowed us to infer chromosomal homologies between these two species. Tandem and centromeric fusions, reciprocal translocations, and insertions are involved in the reduction of the diploid number from 2n = 46 to 2n = 8, 9. The painting patterns further show complex chromosomal rearrangements in the male black muntjac which involve more than half the karyotype, including both sex chromosomes. Since early meiosis is reported to be normal without any visible inversion loops of the synaptonemal complex, the observed chromosomal rearrangements would lead to heterosynapsis and, therefore, leave a large fraction of the male black muntjac karyotype balanced between the two sexes.
Genome composition in Venezuelan spiny-rats of the genus Proechimys (Rodentia, Echimyidae). I. Genome size, C-heterochromatin and repetitive DNAs in situ hybridization patterns
Authors: Garagna S. , Pérez-Zapata A. , Zuccotti M. , Mascheretti S. , Marziliano N. , Redi C.A. , Aguilera M. , Capanna E.
Published: May 2008

The genome sizes of the Venezuelan spiny-rats Proechimys guairae guairae (2n = 48) and P. trinitatis (2n = 62) were evaluated and proved to be 12.5 ± 0.5pg and 12.6 ± 0.3pg respectively, the highest so far recorded among mammals; also the C-heterochromatin (32.7 %, Coefficient of Variation [CV] 3.8 and 35.8%, CV4.4) and GC (44.2%, CV2.7 and 43.6%, CV 2.9) contents are very high. Highly repetitive (rep) DNAs were isolated from restriction enzyme digested genomic DNAs of both species. The intra- and inter-specific chromosomal allocations of these rep DNAs were analyzed by direct and cross-hybridizations. Results show that the two genomes harbour several rep DNA families which show both species-specificity and interspecific relatedness in their in situ hybridization patterns. The rep DNA families show an equilocal distribution at both the pericentromeric areas of all chromosomes and in the whole arms of two pairs of the uniarmed group, suggesting co-evolution of the rep DNAs. P. g. guairae BamHI digested DNA, when cloned and sequenced, proved to consist of a long “composite” unit (1,239 bp) containing two copies of each of 75-bp and 110-bp internal subrepeats. Karyotype restructuring between P. g. guairae and P. trinitatis, mainly due to Robertsonian changes, was accompanied by slight intra- and intergenomic movements of the putative satellite DNA families within stable genome sizes and C-heterochromatin contents. We discuss the findings obtained in Proechimys in the light of those regarding the kangaroo rat, the pocket gopher and the house mouse; they support the idea that karyotype restructuring could be the expression of molecular driven events of rep DNA amplification and homogenisation through non-homologous chromosomes.
Genomic structure of the human PLCD1 (phospholipase C delta 1) locus on 3p22→p21.3
Authors: Ishikawa S. , Takahashi T. , Ogawa M. , Nakamura Y.
Published: May 2008

A large-scale sequencing analysis of genomic DNA in the vicinity of a homozygous deletion on chromosome 3p found in a lung cancer cell line disclosed that the gene encoding phospholipase Cδ1 (PLCD1) is located just distal to the region removed by the deletion. We report the genomic structure of this gene, which consists of 15 exons and spans about 22 kb, and its precise localization to chromosome 3p22→p21.3.
Experimental assessment of the detection limit of genomic amplification by comparative genomic hybridization CGH
Authors: Parente F. , Gaudray P. , Carle G.F. , Turc-Carel C.
Published: May 2008

Artificial amplicons of known size, constructed by use of YACs featuring human 8p12 and 12q13, were analyzed by comparative genomic hybridization (CGH). A minimum of 15 Mb of overrepresented DNA sequences could be detected. The sensitivity is (1) not dependent on the chromosome site and (2) related to the size of the amplicon, decreasing with decreasing size.
Paternal age effect of YY aneuploidy in human sperm, as assessed by fluorescence in situ hybridization
Authors: Kinakin B. , Rademaker A. , Martin R.
Published: May 2008

Sperm samples were collected from 18 healthy men of various ages. Multicolor FISH was performed on each sample, using probes for the sex chromosomes and chromosome 1. A minimum of 10,000 sperm per donor was analyzed. The Pearson correlation coefficient was used to determine if there was an association between donor age and disomy frequency for the sex chromosomes.
Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1→q22.3: exclusion of GAS1 and XPA
Authors: Blair I.P. , Dawkins J.L , Nicholson G.A.
Published: May 2008

The peripheral neuropathy, hereditary sensory neuropathy type I (HSN-I) is an autosomal dominant degenerative disorder of sensory and motor neurons. The disease leads to distal sensory loss, distal muscle wasting and weakness, and variable neural deafness. The HSN-I locus was recently mapped to a large genetic interval on chromosome 9q22 that includes the candidate genes GASl and XPA. XPA mutations have been shown to cause peripheral neuropathy, and GAS 1 is related to the PMP22 gene, which is critical in the pathogenesis of two other peripheral neuropathies. By undertaking extensive genetic linkage analysis within the candidate region, we have refined the HSN-I locus to a critical interval of 3–4 cM. GASl, XPA, and several other genes that map within the interval initially identified for the disease locus have been investigated and excluded from playing a pathogenic role in HSN-I.
The SH3D1A gene maps to human chromosome 21q22.1→q22.2
Authors: Chen H. , Antonarakis S.E.
Published: May 2008

Exon trapping was used to identify portions of genes on human chromosome 21. BLAST search of databases revealed that the trapped sequence hmc02a08 (one of 559 different trapped exons) was identical to a region of GenBank entry U61166 for an SH3 (Src-homology) domain-containing gene SH3D1A (formerly called SH3P17; Sparks et al., 1996). We subsequently mapped this gene to YACs and cosmids within 21q22.1→q22.2 between DNA markers D21S319 and D21S65 using hybridization and PCR amplification.
Molecular studies of an ependymoma-associated constitutional t(1;22)(p22;q11.2)
Authors: Rhodes C.H. , Call K.M. , Budarf M.L , Barnoski B.L , Bell C.J. , Emanuel B.S. , Bigner S.H. , Park J.P. , Mohandas T.K.
Published: May 2008

We previously described a patient with a de novo constitutional translocation, t(l;22)(p22;ql 1.2), who developed a malignant ependymoma at age 5, and we proposed that the translocation predisposed the child to the development of the tumor. As a step toward isolation of a putative cancer gene, we have characterized the breakpoints of the (1;22) translocation at the molecular level. The chromosome 22 breakpoint has been narrowed to a region between ARVCF and D22S264. The chromosome 1 breakpoint has been mapped onto a doubly-linked Whitehead YAC contig by PCR analysis of the STS contents of the patient’s derivative chromosomes isolated in somatic cell hybrids. Loss-of-heterozygosity (LOH) studies of the patient’s ependymoma and of sporadic ependymomas showed no evidence of consistent loss in the breakpoint regions, suggesting that activation of an oncogene, rather than inactivation of a tumor suppressor gene, is the more likefv molecular mechanism involved in this case. The gene xor Edg-1, a neurally expressed, seven-segment transmembrane receptor, maps to the region of the chromosome 1 breakpoint but does not appear to be interrupted by the translocation. Molecular characterization of the breakpoint regions reported here represents an important step in the identification of the gene(s) affected by this translocation.
Isolation and sequence analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase (aminopeptidase P)
Authors: Vanhoof G. , Goossens F. , Juliano M.A. , Juliano L. , Hendriks D. , Schatteman K. , Lin A.H. , Scharpé S.
Published: May 2008

A novel human cDNA (XPNPEPL) encoding a protein of 623 amino acids exhibiting 44% sequence identity and 62 % sequence similarity to pig kidney X-prolyl aminopeptidase (aminopeptidase P; EC 3.4.11.9) was obtained by reverse transcription/polymerase chain reaction of phytohemagglutin-in-stimulated lymphocyte mRNA. Conserved sequences were found with the prokaryotic X-prolyl aminopeptidase encoding gene (pepP). The human gene translation product exhibits a high sequence homology to the Schizosaccharomyces pombe chromosome I hypothetical protein C22G7.01c and to the S. cerevisiae ORF yll029w. Northern blot analysis indicates an ubiquitous expression of the human XPNPEPL sequence.
Mapping FRA11A, a folate-sensitive fragile site in human chromosome band 11q13.3
Authors: Perucca-Lostanlen D. , Hecht B.K. , Courseaux A. , Grosgeorge J. , Hecht F. , Gaudray P.
Published: May 2008

FRA11A, a rare folate-sensitive fragile site assigned to 11q13.3, lies in an area of genomic instability associated with several diseases and amplification events. To map FRA11 A, we used fluorescence in situ hybridization with yeast artificial chromosome and cosmid probes on metaphase chromosomes of patients expressing the fragile site. FRA11A was found situated centromeric to ACTN3 and telomeric to D11S913, these markers being within an interval of ∼1 Mb in the 11q13.3 region.
Chromosomal assignment of human endogenous retrovirus K (HERV-K) env open reading frames
Authors: Mayer J. , Meese E. , Mueller-Lantzsch N.
Published: May 2008

The haploid human genome contains at least one human endogenous retrovirus K (HERV-K) env gene displaying an open reading frame, as evidenced by the high antibody titers against HERV-K Env in germ cell tumor patients at the time of tumor detection. However, the chromosomal assignment of an intact HERV-K env sequence is complicated by the existence of 25–30 HERV-K copies per haploid human genome. Recently, we reported the application of the protein truncation test (PTT) to chromosomally assign HERV-K gag open reading frames. Here, we set out to determine the chromosomal distribution of full-length HERV-K env genes. As demonstrated by somatic hybrid mapping and the PTT, HERV-K env open reading frames were found on human chromosomes 7, 19, and Y. By sequencing chromosome-specific HERV-K env subregions, we assigned two recently reported intact HERV-K sequences on human chromosomes 7 and 19, respectively. Chromosomes 7 and 19 and the Y are furthermore candidates for harboring a putative completely intact HERV-K locus.
Models of Randomness and Complexity, from Turbulence to Stock Markets
Authors: Bouchaud Jean-Philippe
Published: May 2008

Inspired by the increasing complexity of statistical models for turbulence and stock markets, the author presents some reflections on the very notion of a model and illustrates some relations between physics and aesthetics. He argues that aesthetic emotions arise from a delicate balance between regularity and surprise.
Nanotechnology: The Endgame of Materialism
Authors: Gimzewski James K.
Published: May 2008

Imagine that one could arrange atoms in any form one wanted: What would one create? What kind of mind would it take to change the world through this metamorphosis of rearrangement and design? The ultimate endgame of our current technological capability to make material things is determined by our own creativity. The author examines how technological interfaces join the human mind to objects of experience from the nanometric to the planetary scale and theorizes the impact this perceptual condition will have on the personal and collective psyche.
Civil Society and Peace Negotiations: Confronting Exclusion
Authors: Kew Darren , Wanis-St. John Anthony
Published: May 2008

The fact that civil society groups play important roles in post-conflict peacebuilding has entered the mainstream of international conflict resolution dogma. Rarely do local civil society groups get a seat at the negotiation table for peace accords. Although the exclusion of civil society from peace negotiations may streamline the process, the absence of civil society voices and interests at the negotiating table can negatively impact the sustainability of a peace agreement during peacebuilding. Surveying a wide variety of different peace processes, a strong correlation was found between active civil society participation in peace negotiations and the durability of peace during the peacebuilding phase. Cases in which civil society groups actively engaged in peace negotiations seemed to enjoy more sustained peace in the peacebuilding phase. This holds true also for cases in which civil society groups did not have a direct seat at the table, but did exercise significant influence with the negotiators because they were democratic actors. War resumed in many cases not characterized by direct or indirect civil society involvement in the peace negotiations. No claim of causality is made; the sustainability of peace surely rests on causes as complex and dynamic as the initiation of war does. However, these findings do call attention to the need for further research to understand the special impact that civil society inclusion at the peace table may have.
A Diagnostic Model of the Nordic Seas and Arctic Ocean Circulation: Quantifying the Effects of a Variable Bottom Density along a Sloping Topography
Authors: Aaboe Signe , Nøst Ole Anders
Published: May 2008

A linear diagnostic model, solving for the time-mean large-scale circulation in the Nordic seas and Arctic Ocean, is presented. Solutions on depth contours that close within the Nordic seas and Arctic Ocean are found from vorticity balances integrated over the areas enclosed by the contours. Climatological data for wind stress and hydrography are used as input to the model, and the bottom geostrophic flow is assumed to follow depth contours. Comparison against velocity observations shows that the simplified dynamics in the model capture many aspects of the large-scale circulation.

Special attention is given to the dynamical effects of an along-isobath varying bottom density, which leads to a transformation between barotropic and baroclinic transport. Along the continental slope, enclosing both the Nordic seas and Arctic Ocean, the along-slope barotropic transport has a maximum in the Nordic seas and a minimum in the Canadian Basin with a difference of 9 Sv (1 Sv ≡ 106 m3 s−1) between the two. This is caused by the relatively lower bottom densities in the Canadian Basin compared to the Nordic seas and suggests that most of the barotropic transport entering the Arctic Ocean through the Fram Strait is transformed to baroclinic transport. A conversion from barotropic to baroclinic flow may be highly important for the slope–basin exchange in the Nordic seas and Arctic Ocean.

The model has obvious shortcomings due to its simplicity. However, the simplified physics and the agreement with observations make this model an excellent framework for understanding the large-scale circulation in the Nordic seas and Arctic Ocean.
Optimal Surface Salinity Perturbations of the Meridional Overturning and Heat Transport in a Global Ocean General Circulation Model
Authors: Sévellec Florian , Huck Thierry , Ben Jelloul Mahdi , Grima Nicolas , Vialard Jérôme , Weaver Anthony
Published: May 2008

Recent observations and modeling studies have stressed the influence of surface salinity perturbations on the North Atlantic circulation over the past few decades. As a step toward the estimation of the sensitivity of the thermohaline circulation to salinity anomalies, optimal initial surface salinity perturbations are computed and described for a realistic mean state of a global ocean general circulation model [Océan Parallélisé (OPA)]; optimality is defined successively with respect to the meridional overturning circulation intensity and the meridional heat transport maximum. Although the system is asymptotically stable, the nonnormality of the dynamics is able to produce a transient growth through an initial stimulation. Optimal perturbations are calculated subject to three constraints: the perturbation applies to surface salinity; the perturbation conserves the global salt content; and the perturbation is normalized, to remove the degeneracy in the linear maximization problem. Maximization using Lagrangian multipliers leads to explicit solutions (rather than eigenvalue problems), involving the integration of the model adjoint for each value to maximize.

The most efficient transient growth for the intensity of the meridional overturning circulation appears for a delay of 10.5 yr after the perturbation by the optimal surface salinity anomaly. This optimal growth is induced by an initial anomaly located north of 50°N. In the same way, the most efficient transient growth for the intensity of the meridional heat transport appears for a shorter delay of 2.2 yr after the perturbation by the optimal surface salinity anomaly. This initial optimal perturbation corresponds to a zonal salinity gradient around 24°N. The optimal surface salinity perturbations studied herein yield upper bounds on the intensity of the response in meridional overturning circulation and meridional heat transport. Using typical amplitudes of the Great Salinity Anomalies, the upper bounds for the associated variability are 0.8 Sv (1 Sv ≡ 106 m3 s−1) (11% of the mean circulation) and 0.03 PW (5% of the mean circulation), respectively.
The Variability of Adjoint Sensitivity with Respect to Model Physics and Basic-State Trajectory
Authors: Ancell Brian C. , Mass Clifford F.
Published: May 2008

Adjoint sensitivity fields have generally been viewed deterministically in the atmospheric science literature. However, uncertainty exists in the components of the adjoint model, such as the physics and the basic-state trajectories used to calculate the sensitivity fields. In this paper, the variability of adjoint sensitivity fields is examined for two collections of trajectories, each valid over a single time window: one supplied by three global operational models, and the other from a regional, operational ensemble Kalman filter system. Adjoint sensitivities are also compared using a dry adjoint and dry basic state, a moist adjoint and moist basic state, and a moist basic state and dry adjoint. The goal of these latter experiments is to explore the differences in mesoscale sensitivity fields with and without moisture, and to examine how sensitivities degrade when adjoint models utilize simplified physics. In all cases, 24-h sensitivities are produced with a low-level pressure response function over the coastal lowlands of the Pacific Northwest. Furthermore, this study examines these adjoint sensitivities at higher resolution than in previous studies. It is found that adjoint sensitivity can vary significantly in structure, magnitude, and location when different, but equally likely, basic-state trajectories are considered. Since the predicted response function shows large variance when using different basic-state trajectories, adjoint sensitivity should be viewed probabilistically. It is also found that the inclusion of moisture in both the forward and adjoint model produces significantly different sensitivity fields from the fully dry run. Furthermore, a large degradation occurs when removing moisture from the adjoint model but retaining moisture in the basic state, causing sensitivity fields to resemble that of a fully dry adjoint integration. This suggests that simplified physics relative to the forward nonlinear physics may produce significant differences from the desired “true” sensitivity field. The implications of these results for modern applications of adjoint models are discussed.
The “Something More” Than Interpretation Revisited: Sloppiness and Co-Creativity in the Psychoanalytic Encounter
Authors:   The Boston Change Process Study Group
Published: May 2008

Features of dynamical systems thinking can illuminate insufficiently recognized levels of psychoanalytic process. A central aspect of dynamical models is that changes in complex systems are unpredictable and arise out of the interaction of elements. Examination of the moment-by-moment micro-foreground, or local level, of psychoanalytic sessions led to the conclusion that indeterminacy and surprise are inherent properties of intersubjective systems. This indeterminacy, or sloppiness, comprises several interrelated features of the dialogue: “fuzzy” intentionalizing, unpredictability, improvisation, variation, and redundancy. Audiotaped transcripts of two analytic sessions illustrate how these sloppy features generate unpredictable and potentially creative elements that contribute to psychotherapeutic change.
Hidden Shame
Authors: Lansky Melvin R.
Published: May 2008

Shame dynamics, after decades of neglect, reappeared in psychoanalytic thinking with increasing prevalence in the last thirty years. Shame that is hidden is an aspect of complex clinical phenomenology that is particularly likely to be missed and hidden further by partial psychoanalytic explanations that drive shame more and more from view. Shame is often hidden theoretically by formulations limiting conflict to conflict between drives or impulses and something opposing them. By contrast, the incompatible idea model propounded by Freud in Studies on Hysteria emphasizes awareness incompatible with the dictates of conscience, and hence is broader in scope and closer to actual experience. Although shame and guilt arise developmentally earlier than does a true sense of morality, these emotions and their unconscious variants become entwined with the individual's sense of morality as development proceeds. The dynamics of shame and guilt are considerably more complex than their phenomenology as overt emotions. Shame emphasizes weakness, vulnerability, and the likelihood of rejection— so much so that its acknowledgment often generates more shame. Guilt, however, since it is action- and power-oriented, often obscures shame and so defends against it.
Caring and Coercive Aspects of the Psychoanalytic Situation
Authors: Schafer Roy
Published: May 2008

Certain ambivalent reactions to undergoing analysis add content and intensity to the analysand's transference and to some extent to the analyst's countertransference. A significant share of these reactions may be attributed to the structure of the psychoanalytic situation. Among other things, analysands' reactions feature fantasized and sometimes realistic experiences of being coerced by their analyst's counte r-transferences. However, to achieve a clear view of these coercive experiences, they must be considered in relation to another, equally weighty structural feature: ambivalent reactions to the analyst's concerned care. Observation suggests that an intervention can be experienced, simultaneously or sequentially, as both coercive and caring, and that, when analyzed, each of these experiences is usually found to be saturated with mixed feelings.