bluuebunny/crossref_metadata_2025_split huggingface dataset:
11q13 Alterations in two cases of hibernoma: Large heterozygous deletions and rearrangement breakpoints near GARP in 11q13.5
Authors: Maire Georges , Forus Anne , Foa Cyril , Bjerkehagen Bodil , Mainguené Claire , Kresse Stine H. , Myklebost Ola , Pedeutour Florence 
Published: June 2003

AbstractHibernomas are rare, benign tumors with a histological appearance resembling that of brown adipose tissue. The diagnosis of hibernomas may be difficult because some of them contain only a small number of the characteristic multivacuolated fat cells and can be mistakenly classified as well‐differentiated liposarcomas. Cytogenetic information has been reported for 10 cases, showing that these tumors are characterized by structural rearrangements involving 11q13. Previous fluorescence in situ hybridization (FISH) studies revealed consistent and sometimes cryptic losses of the MEN1 region in 11q13.1. Here, we describe the molecular cytogenetic analysis of two new hibernoma cases. Both tumors showed complex rearrangements, simultaneously including translocations, inversions, and deletions affecting the pair of chromosomes 11. The translocation partners were chromosome 5 in one case and chromosomes 16 and 22 in the other case. The 11q13 region was concomitantly rearranged on both chromosomes 11. FISH studies revealed large heterozygous deletions within the 11q13 band, from 11q13.1 to 11q13.5. Genes such as PYGM, MEN1, CCND1, FGF3, ARIX, and GARP were deleted, showing that the size of the 11q13 altered region was larger than previously reported. Furthermore, both tumors had breakpoints in 11q13.5, one of them in the immediate proximity of the GARP gene. Our results suggest that rearrangements of GARP or a neighboring gene may be important for the pathogenesis of hibernomas. © 2003 Wiley‐Liss, Inc.
Xq27–28 deletions in prostate carcinoma
Authors: Kibel Adam S. , Faith Dennis A. , Bova G. Steven , Isaacs William B. 
Published: June 2003

AbstractLinkage studies have implicated a prostate cancer susceptibility locus at Xq27–28 (termed HPCX), estimated to be responsible for approximately 16% of hereditary prostate cancer cases. To date, this region has not been investigated in sporadic disease. In this study, we examined tumor DNA samples prepared from patients with sporadic prostate cancer, prostate cancer cell lines, and prostate cancer xenografts for evidence of genomic alterations within the Xq27–28 region. To facilitate the detection of nullizygosity, we examined a unique series of highly tumor‐enriched DNA samples prepared from men with multi‐sampled metastatic prostate cancer, as well as a series of prostate cancer xenografts and cell lines. PCR amplification of carcinoma and normal DNA templates was performed for 11 loci spanning an Xq27–28 interval of ∼16 cM. Among 19 patients studied, somatic deletions in this region were found in two cases. Within these two cases, each independent metastatic tumor sample available from an individual (n = 4 sites and 8 sites, respectively) showed the same reduction to nullizygosity, suggesting a pre‐metastatic origin for the deletion events in both. Mapping of the deletion boundaries with eight additional sets of markers indicated that both deletions had breakpoints within an ∼500‐ to 800‐kb interval containing FMR1; however, the deletions were non‐overlapping. The lack of a common region of deletion suggests one of three possibilities: (1) that these two deletions are unrelated, (2) that the deletions affect the opposite ends of an as yet unknown gene, or (3) that each deletion has inactivated a single copy of an unknown gene arranged in cis in the region of interest. These data clearly indicate that deletions do occur within the HPCX locus in a subset of sporadic prostate cancers and therefore raises the possibility that the gene at this locus may prove to play a role in sporadic disease. © 2003 Wiley‐Liss, Inc.
Identification of candidate tumor‐suppressor genes in 6q27 by combined deletion mapping and electronic expression profiling in lymphoid neoplasms
Authors: Steinemann Doris , Gesk Stefan , Zhang Yanming , Harder Lana , Pilarsky Christian , Hinzmann Bernd , Martin‐Subero Jose Ignacio , Calasanz Maria Jose , Mungall Andrew , Rosenthal André , Siebert Reiner , Schlegelberger Brigitte 
Published: June 2003

AbstractDeletions in the long arm of chromosome 6 (6q) are among the most frequent chromosome aberrations in lymphoid neoplasms. Recently, the region of minimal deletion (RMD1) in 6q27 was narrowed down to 5–9 Mb. In the present study, we aimed to define the distal border of the commonly lost region in 6q27 more precisely and to identify and investigate tumor‐suppressor genes (TSGs) from this region. Twenty‐nine cases, in which our previous fluorescence in situ hybridization (FISH) screening that used a set of 36 YAC probes revealed loss in 6q25–27, were further investigated by means of FISH. In all cases, deletions of 6q27 extended from yeast artificial chromosome (YAC) 977e10 spanning the proximal border of RMD1 to the most telomeric YAC 933f7 within the recently established YAC‐contig of this region. An interstitial homozygous deletion, flanked by the telomeric probe TelVysion6q and YAC 971g12, was detected, which substantially narrows down the RMD1. To identify candidate TSGs down‐regulated in malignant lymphomas from this region of homozygous loss, we performed electronic profiling of expressed sequences mapped to this region. This analysis suggested the gene PDCD2 originally thought to be involved in programmed cell death to be probably down‐regulated in malignant B‐cell lymphomas compared to normal B lymphocytes. Nevertheless, mutation analyses failed to identify mutations in the coding region of PDCD2 in nine lymphomas with FISH‐proved 6q27 deletions. Furthermore, epigenetic studies in these nine and an additional 48 lymphomas did not show altered methylation of the PDCD2 locus in these tumors. Possibly haploinsufficiency is effectual in accelerating tumor progression. © 2003 Wiley‐Liss, Inc.
Non‐muscle myosin heavy chain (MYH9): A new partner fused to ALK in anaplastic large cell lymphoma
Authors: Lamant Laurence , Gascoyne Randy D. , Duplantier Marie Michèle , Armstrong Florence , Raghab Ashraf , Chhanabhai Mukesh , Rajcan‐Separovic Evica , Raghab Janie , Delsol Georges , Espinos Estelle 
Published: June 2003

AbstractIn anaplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations result in the expression of chimeric ALK transcripts that are translated into fusion proteins with tyrosine kinase activity and oncogenic properties. We report a case showing a restricted cytoplasmic staining pattern of ALK and a novel chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ hybridization analysis. The result of 5′ RACE analysis showed that the ALK gene was fused in‐frame to a portion of the non‐muscle myosin heavy chain gene, MYH9. Nucleotide sequence of the MYH9‐ALK chimeric cDNA revealed that the ALK breakpoint was different from all those previously reported. It is localized in the same exonic sequence as MSN‐ALK, but 6 bp downstream, resulting in an in‐frame fusion of the two partner proteins. In contrast to the previously reported ALK fusion proteins, MYH9‐ALK may lack a functional oligomerization domain. However, biochemical analysis showed that the new fusion protein is tyrosine phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9‐ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins. © 2003 Wiley‐Liss, Inc.
Prenatal chromosomal diversification of leukemia in monozygotic twins
Authors: Kempski Helena , Mensa‐Bonsu Karen A. , Kearney Lyndal , Jalali G. Reza , Hann Ian , Khurshid Mohammed , Greaves Mel 
Published: June 2003

AbstractPrevious studies on concordant acute lymphoblastic leukemia (ALL) in identical twins have identified the leukemia as monoclonal with MLL or ETV6‐RUNX1 gene fusion as early or initiating events in utero. In the latter case, postnatal latency is associated with secondary genetic events such as ETV6 deletion. We describe here a pair of infant twins with concordant acute monoblastic leukemia (AML). They are a unique pair in that their leukemia blasts display extensive intraclonal chromosomal diversity. Comparison of the leukemic cells between the two twins by karyotype and fluorescence in situ hybridization identifies a common or shared stem line and extensive subclonal diversity for which the twins' leukemic populations are divergent. This case of leukemia illustrates in utero initiation with early imposition of chromosomal instability, the progressively divergent evolution of which can be mapped in the twins into pre‐ and postnatal periods. © 2003 Wiley‐Liss, Inc.
Torsional Motion in (tert‐Butyl)ammonium Hemispheraplexes: Rotational Barriers and Energy of Binding
Authors: Maverick Emily F. , Knobler Carolyn B. , Khan Saeed , Canary James W. , Dicker Ira B. , Trueblood Kenneth N. 
Published: June 2003

AbstractThe ADPs (ADPs=atomic anisotropic displacement parameters) from the single‐crystal X‐ray studies of nine related TBA+ (TBA+=(tert‐butyl)ammonium) hemispheraplexes are analyzed, and the results compared to the free energy of binding of this guest by the nine hosts. The lipophilic hosts (Fig. 1) were synthesized over a number of years, with increasing pre‐organization for and specificity of binding. Structural studies for six of the complexes have been published, but the remaining three structures, including those of the strongest binders of TBA+, are disordered and have only now been completed.New area‐detector data has been analyzed for the TBA+ClO$\rm{_{4}^{-}}$ complexes of 5 and of 8 at two temperatures, while the original data for 9⋅TBA+SCN− has been treated with a disorder model. In addition, improved models are presented for the complexes of 6 and 7. Methods for assessing the precision of the ADP analyses are discussed. Although most of the structures are imprecise, the TBA+ groups do demonstrate some of the characteristics of independent motion. The general trend in calculated libration amplitudes for the TBA+ group suggests that the guests with the greatest free energy of binding, and the shortest distances from N+ to the ligand plane, are those with the highest barriers to internal rotation.
Noncovalent Bond Lengths and Their Cooperative Shortening: Dimers of Vancomycin Group Antibiotics in Crystals and in Solution
Authors: Shiozawa Hideyuki , Zerella Rosa , Bardsley Ben , Tuck Kellie L. , Williams Dudley H. 
Published: June 2003

AbstractA wide range of dimerisation constants (Kdim ca. 101–106 M−1) for various glycopeptide antibiotics have been determined. We consider these dimerisation constants in the light of the published X‐ray structures of the antibiotics, in particular, the relationship between Kdim and the length of a specified distance at the dimer interface. In the crystals, we find that this distance is smaller for strongly dimerising antibiotics and larger for weakly dimerising antibiotics. Thus, the dimerisation constant is correlated with tightness at the dimer interface. Despite the crystal‐packing forces exerted between adjacent dimer molecules in the crystals, the noncovalent bond distances at the dimer interface are correlated with the distances in solution (inferred from solution NMR data). These observations can account for the benefits in enthalpy, and costs in entropy, associated with positively cooperative binding.
Syntheses and CD‐Spectroscopic Investigations of Longer‐Chain β‐Peptides: Preparation by Solid‐Phase Couplings of Single Amino Acids, Dipeptides, and Tripeptides
Authors: Arvidsson Per I. , Frackenpohl Jens , Seebach Dieter 
Published: June 2003

AbstractThe synthesis and CD‐spectroscopic analysis of eleven water‐soluble β‐peptides composed of all‐β3 or alternating β2‐ and β3‐amino acids is described. Different approaches for the efficient syntheses of longer‐chain β‐peptides (>9 residues) were investigated. They were synthesized on solid phase with Fmoc‐protected amino acids or Fmoc‐protected di‐ or tripeptide fragments (assembled using solution‐phase synthesis). The use of preformed fragments significantly increased the purity of the crude peptides and facilitated purification. Especially, the use of Fmoc‐protected β2/β3‐dipeptides for the synthesis of a ‘mixed' β2/β3‐nonapeptide proved to be remarkably effective, yielding the crude peptide in 95% purity and without detectable epimerization of the β2‐amino acid residues. This is a significant improvement over previously reported procedures for the solid‐phase synthesis of β‐peptides, and foreshadows that the field of β‐peptide research will now switch from synthesis to the design and study of complex functional ‘β‐proteins'.
From Crystal Structures and Their Analysis to the in silico Prediction of Toxic Phenomena
Authors: Dobler Max , Lill Markus A. , Vedani Angelo 
Published: June 2003

AbstractWhile the development of potential drug molecules based on the known three‐dimensional structure of the macromolecular target is doubtless one of the more‐potent approaches to rational drug design, the estimation of associated changes in the free energy of ligand binding is all but trivial. Major obstacles include the treatment of long‐range electrostatic effects and charge transfer, the calculation of solvation energies, the treatment of entropic effects, and the quantification of induced fit. In the last decade, a number of computational concepts have nonetheless matured into powerful tools for the development of drug‐candidate molecules. These concepts have mainly focussed on the binding of the small molecule to a bioregulator. More recently, need has arisen to develop tools for a safe prediction of more‐complex phenomena such as metabolism, toxicity, and bioavailability. We describe the ongoing development of a virtual laboratory on the Internet to allow for a reliable in silico estimation of harmful effects triggered by drugs, chemicals, and their metabolites. For this, we used our recently developed underlying technology (5D‐QSAR, based on five‐dimensional quantitative structure‐activity relationships) and compiled a pilot project, including the models of five receptor systems known to mediate adverse effects (the aryl hydrocarbon (Ah), 5 HT2A, cannabinoid, GABAA, and estrogen receptor, resp.) which were already validated against 280 compounds (drugs, chemicals, toxins). Within this setup, we could demonstrate that our virtual laboratory is able both to recognize toxic compounds substantially different from those used in the training set as well as to classify harmless compounds as being nontoxic. The results suggest that our approach can be used for the prediction of adverse effects of drug molecules and chemicals and, thus, bears a significant potential to recognize hazardous compounds early in the development process hence improving resource and waste management and reducing animal testing. It is the aim to provide free access to this technology – particularly to universities, hospitals, and regulatory bodies.
Theory of Stereomutation Dynamics and Parity Violation in Hydrogen Thioperoxide Isotopomers 1,2,3HSO1,2,3H
Authors: Quack Martin , Willeke Martin 
Published: June 2003

AbstractWe present quantitative calculations of the mode‐selective stereomutation tunneling and parity violation in chiral hydrogen thioperoxide (‘oxadisulfane') isotopomers XSOY with X, Y=H, D, and T. The torsional tunneling stereomutation dynamics are investigated with a quasi‐adiabatic channel quasi‐harmonic reaction path Hamiltonian approach, which treats the torsional motion anharmonically in detail and all remaining coordinates as harmonic (but anharmonically coupled to the reaction coordinate). We predict how stereomutation is catalyzed or inhibited by excitation of various vibrational modes compared to the corresponding stereomutation dynamics of the vibrational ground state. Parity‐violating potentials were calculated with our recent multiconfiguration linear response (MC‐LR) approach in the random phase approximation (RPA). We find that, in agreement with general scaling expectations, the parity‐violating energy difference for the equilibrium structures of the two HSOH enantiomers (ca. 5×10−12J mol−1) is situated intermediate between HOOH and HSSH. Our results on the stereomutation dynamics and the influence of parity violation on these are discussed in relation to investigations for the analogous molecules H2O2, H2S2, and Cl2S2. As expected in XSOY (X, Y=H, D, and T), this influence is much larger than in the corresponding H2O2 isotopomers, but smaller than in H2S2 or Cl2S2.
Structure and Function of the Ribosomal Frameshifting Pseudoknot RNA from Beet Western Yellow Virus
Authors: Egli Martin , Sarkhel Sanjay , Minasov George , Rich Alexander 
Published: June 2003

AbstractMany viruses reprogram ribosomes to produce two different proteins from two different reading frames. So‐called −1 frameshifting often involves pairwise alignment of two adjacent tRNAs at a ‘slippery' sequence in the ribosomal A and P sites such that an overlapping codon is shifted upstream by one base relative to the zero frame. In the majority of cases, an RNA pseudoknot located downstream stimulates this type of frameshift. Crystal structures of the frameshifting RNA pseudoknot from Beet Western Yellow Virus (BWYV) have provided a detailed picture of the tertiary interactions stabilizing this folding motif, including a minor‐groove triplex and quadruple‐base interactions. The structure determined at atomic resolution revealed the locations of several magnesium ions and provided insights into the role of structured water stabilizing the RNA. Systematic in vitro and in vivo mutational analyses based on the structural results revealed specific tertiary interactions and regions in the pseudoknot that drastically change frameshifting efficiency. Here, we summarize recent advances in our understanding of pseudoknot‐mediated ribosomal frameshifting on the basis of the insights gained from structural and functional studies of the RNA pseudoknot from BWYV.
Gas‐Phase Electron‐Diffraction Investigation and Quantum‐Chemical Calculations of the Structure of 1,5‐Dimethylsemibullvalene‐2,4,6,8‐tetracarboxylic Dianhydride
Authors: Samdal Svein , Richardson Alan D. , Hedberg Kenneth , Gadgil Vijay R. , Meyer Matthew M. , Williams Richard Vaughan 
Published: June 2003

AbstractThe bridged homotropilidines have been of interest for decades because their molecules offer the potential for homoaromaticity. Although many of these have been shown not to be homoaromatic, the energy differences of the delocalized (homoaromatic) forms and the localized (nonhomoaromatic) ones, and the barriers to the interconversion of the localized forms via a Cope rearrangement, have been found to vary greatly. The title compound is a strong candidate for homoaromaticity, and, since the structures of the possible localized and delocalized forms could differ significantly, we have carried out an electron‐diffraction investigation of it augmented by quantum‐mechanical calculations with different basis sets at several levels of theory. Three models were explored: one representing a localized form of Cs symmetry, one a delocalized form of C2v symmetry, and one a 2 : 1 mixture of the localized/delocalized forms. Although none of the models could be ruled out, the experimental evidence slightly favors the Cs form. These results are consistent with those from the DFT B3PW91 calculations with basis sets ranging from 6‐31G(d) to cc‐pVTZ, which, surprisingly, predict essentially equal thermally corrected free energies for each. The results are discussed.
Potent New Heterogeneous Asymmetric Catalysts
Authors: Rouzaud Jacques , Jones Matthew D. , Raja Robert , Johnson Brian F. G. , Meurig Thomas John , Duer Melinda J. 
Published: June 2003

AbstractA set of new, air‐stable, RhI‐based heterogeneous asymmetric hydrogenation catalysts have been synthesised, characterised, and tested. Individual members of this new family all exhibit good enantioselectivity.
Cadherin switching in ovarian cancer progression
Authors: Patel Ila S. , Madan Pavneesh , Getsios Spiro , Bertrand Monique A. , MacCalman Colin D. 
Published: June 2003

AbstractThe roles of the cadherins in the progression of ovarian cancer to the late stages of the disease state when malignant cells have disseminated within the peritoneal cavity remain poorly understood. In view of these observations, we have undertaken a comprehensive survey of the cadherin subtypes present in normal ovarian surface epithelium and peritoneum and in the tumors and peritoneal effusions of women diagnosed with Stage I or Stage II primary ovarian cancer using a degenerate cloning strategy for sequences highly conserved among this family of cell adhesion molecules. On the basis of the nucleotide sequences of the resultant PCR products, multiple cadherin subtypes (E‐, N‐, P‐cadherin, and cadherin‐4, ‐6, and ‐11) were found to be present in these normal and malignant tissues and cells. P‐cadherin was determined to be the predominant cadherin subtype in normal peritoneum, peritoneal effusions and Stage II tumor masses. An increase in P‐cadherin mRNA and protein expression levels in ovarian tumor masses with progression to later stages of the disease state was confirmed by Northern and Western blot analysis, respectively. In addition, we have determined that the cadherin‐associated protein, known as β‐catenin, is expressed in normal peritoneum, ovarian tumors and malignant cell effusions obtained from women with Stage I or Stage II cancer. Immunoprecipitation studies demonstrated that P‐cadherin was capable of interacting with β‐catenin in these normal and malignant tissues and cells. Collectively, these findings suggest that the regulated expression of P‐cadherin/β‐catenin complexes in ovarian tumor cells may represent a key step in disease progression. © 2003 Wiley‐Liss, Inc.