bluuebunny/crossref_metadata_2025 huggingface dataset:
Capacity of the Golgi Apparatus for Cargo Transport Prior to Complete Assembly
Authors: Jiang Shu , Rhee Sung W. , Gleeson Paul A. , Storrie Brian
Published: July 2006

In yeast, particular emphasis has been given to endoplasmic reticulum (ER)-derived, cisternal maturation models of Golgi assembly while in mammalian cells more emphasis has been given to golgins as a potentially stable assembly framework. In the case of de novo Golgi formation from the ER after brefeldin A/H89 washout in HeLa cells, we found that scattered, golgin-enriched, structures formed early and contained golgins including giantin, ranging across the entire cis to trans spectrum of the Golgi apparatus. These structures were incompetent in VSV-G cargo transport. Second, we compared Golgi competence in cargo transport to the kinetics of addition of various glycosyltransferases and glycosidases into nascent, golgin-enriched structures after drug washout. Enzyme accumulation was sequential with trans and then medial glycosyltransferases/glycosidases found in the scattered, nascent Golgi. Involvement in cargo transport preceded full accumulation of enzymes or GPP130 into nascent Golgi. Third, during mitosis, we found that the formation of a golgin-positive acceptor compartment in early telophase preceded the accumulation of a Golgi glycosyltransferase in nascent Golgi structures. We conclude that during mammalian Golgi assembly components fit into a dynamic, first-formed, multigolgin-enriched framework that is initially cargo transport incompetent. Resumption of cargo transport precedes full Golgi assembly.
Fab1 Phosphatidylinositol 3-Phosphate 5-Kinase Controls Trafficking but Not Silencing of Endocytosed Receptors
Authors: Rusten Tor Erik , Rodahl Lina M.W. , Pattni Krupa , Englund Camilla , Samakovlis Christos , Dove Stephen , Brech Andreas , Stenmark Harald
Published: July 2006

The trafficking of endocytosed receptors through phosphatidylinositol 3-phosphate [PtdIns(3)P]-containing endosomes is thought to attenuate their signaling. Here, we show that the PtdIns(3)P 5-kinase Fab1/PIKfyve controls trafficking but not silencing of endocytosed receptors. Drosophila fab1 mutants contain undetectable phosphatidylinositol 3,5-bisphosphate levels, show profound increases in cell and organ size, and die at the pupal stage. Mutant larvae contain highly enlarged multivesicular bodies and late endosomes that are inefficiently acidified. Clones of fab1 mutant cells accumulate Wingless and Notch, similarly to cells lacking Hrs, Vps25, and Tsg101, components of the endosomal sorting machinery for ubiquitinated membrane proteins. However, whereas hrs, vps25, and tsg101 mutant cell clones accumulate ubiquitinated cargo, this is not the case with fab1 mutants. Even though endocytic receptor trafficking is impaired in fab1 mutants, Notch, Wingless, and Dpp signaling is unaffected. We conclude that Fab1, despite its importance for endosomal functions, is not required for receptor silencing. This is consistent with the possibility that Fab1 functions at a late stage in endocytic receptor trafficking, at a point when signal termination has occurred.
Remote homology detection based on oligomer distances
Authors: Lingner Thomas , Meinicke Peter
Published: July 2006

Motivation: Remote homology detection is among the most intensively researched problems in bioinformatics. Currently discriminative approaches, especially kernel-based methods, provide the most accurate results. However, kernel methods also show several drawbacks: in many cases prediction of new sequences is computationally expensive, often kernels lack an interpretable model for analysis of characteristic sequence features, and finally most approaches make use of so-called hyperparameters which complicate the application of methods across different datasets.

Results: We introduce a feature vector representation for protein sequences based on distances between short oligomers. The corresponding feature space arises from distance histograms for any possible pair of K-mers. Our distance-based approach shows important advantages in terms of computational speed while on common test data the prediction performance is highly competitive with state-of-the-art methods for protein remote homology detection. Furthermore the learnt model can easily be analyzed in terms of discriminative features and in contrast to other methods our representation does not require any tuning of kernel hyperparameters.

Availability: Normalized kernel matrices for the experimental setup can be downloaded at . Matlab code for computing the kernel matrices is available upon request.

Contact:  thomas@gobics.de, peter@gobics.de
Predicting methylation status of CpG islands in the human brain
Authors: Fang Fang , Fan Shicai , Zhang Xuegong , Zhang Michael Q.
Published: July 2006

Motivation: Over 50% of human genes contain CpG islands in their 5′-regions. Methylation patterns of CpG islands are involved in tissue-specific gene expression and regulation. Mis-epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Large-scale experimental detection of DNA methylation is still both labor-intensive and time-consuming. Therefore, it is necessary to develop in silico approaches for predicting methylation status of CpG islands.

Results: Based on a recent genome-scale dataset of DNA methylation in human brain tissues, we developed a classifier called MethCGI for predicting methylation status of CpG islands using a support vector machine (SVM). Nucleotide sequence contents as well as transcription factor binding sites (TFBSs) are used as features for the classification. The method achieves specificity of 84.65% and sensitivity of 84.32% on the brain data, and can also correctly predict about two-third of the data from other tissues reported in the MethDB database.

Availability: An online predictor based on MethCGI is available at

Contact:  mzhang@cshl.edu

Supplementary Information: Supplementary data available at Bioinformatics online and
ADGO: analysis of differentially expressed gene sets using composite GO annotation
Authors: Nam Dougu , Kim Sang-Bae , Kim Seon-Kyu , Yang Sungjin , Kim Seon-Young , Chu In-Sun
Published: July 2006

Motivation: Genes are typically expressed in modular manners in biological processes. Recent studies reflect such features in analyzing gene expression patterns by directly scoring gene sets. Gene annotations have been used to define the gene sets, which have served to reveal specific biological themes from expression data. However, current annotations have limited analytical power, because they are classified by single categories providing only unary information for the gene sets.

Results: Here we propose a method for discovering composite biological themes from expression data. We intersected two annotated gene sets from different categories of Gene Ontology (GO). We then scored the expression changes of all the single and intersected sets. In this way, we were able to uncover, for example, a gene set with the molecular function F and the cellular component C that showed significant expression change, while the changes in individual gene sets were not significant. We provided an exemplary analysis for HIV-1 immune response. In addition, we tested the method on 20 public datasets where we found many ‘filtered’ composite terms the number of which reached ∼34% (a strong criterion, 5% significance) of the number of significant unary terms on average. By using composite annotation, we can derive new and improved information about disease and biological processes from expression data.

Availability: We provide a web application (ADGO: ) for the analysis of differentially expressed gene sets with composite GO annotations. The user can analyze Affymetrix and dual channel array (spotted cDNA and spotted oligo microarray) data for four species: human, mouse, rat and yeast.

Contact:  chu@kribb.re.kr

Supplementary information:
Typing single polymorphic nucleotides in mitochondrial DNA as a way to access Middle Pleistocene DNA
Authors: Valdiosera Cristina , García Nuria , Dalén Love , Smith Colin , Kahlke Ralf-Dietrich , Lidén Kerstin , Angerbjörn Anders , Arsuaga Juan Luis , Götherström Anders
Published: July 2006

In this study, we have used a technique designed to target short fragments containing informative mitochondrial substitutions to extend the temporal limits of DNA recovery and study the molecular phylogeny of
Ursus deningeri
. We present a cladistic analysis using DNA recovered from 400 kyr old
U. deningeri
remains, which demonstrates
U. deningeri
's relation to
Ursus spelaeus
. This study extends the limits of recovery from skeletal remains by almost 300 kyr. Plant material from permafrost environments has yielded DNA of this age in earlier studies, and our data suggest that DNA in teeth from cave environments may be equally well preserved.
An entropic characterization of protein interaction networks and cellular robustness
Authors: Manke Thomas , Demetrius Lloyd , Vingron Martin
Published: July 2006

The structure of molecular networks is believed to determine important aspects of their cellular function, such as the organismal resilience against random perturbations. Ultimately, however, cellular behaviour is determined by the dynamical processes, which are constrained by network topology. The present work is based on a fundamental relation from dynamical systems theory, which states that the macroscopic resilience of a steady state is correlated with the uncertainty in the underlying microscopic processes, a property that can be measured by entropy. Here, we use recent network data from large-scale protein interaction screens to characterize the diversity of possible pathways in terms of network entropy. This measure has its origin in statistical mechanics and amounts to a global characterization of both structural and dynamical resilience in terms of microscopic elements. We demonstrate how this approach can be used to rank network elements according to their contribution to network entropy and also investigate how this suggested ranking reflects on the functional data provided by gene knockouts and RNAi experiments in yeast and
Caenorhabditis elegans
. Our analysis shows that knockouts of proteins with large contribution to network entropy are preferentially lethal. This observation is robust with respect to several possible errors and biases in the experimental data. It underscores the significance of entropy as a fundamental invariant of the dynamical system, and as a measure of structural and dynamical properties of networks. Our analytical approach goes beyond the phenomenological studies of cellular robustness based on local network observables, such as connectivity. One of its principal achievements is to provide a rationale to study proxies of cellular resilience and rank proteins according to their importance within the global network context.
Packing of twinned circles on a sphere
Authors: Tarnai T , Fowler P.W
Published: July 2006

The twinned-circle problem is to pack 2
N
non-overlapping equal circles forming
N
pairs of twins (rigidly connected neighbours) on a sphere so that the angular radius of the circles will be as large as possible. In the case that the contact graph(s) of the unconstrained circle packing support(s) at least one perfect matching, a complete solution to the twinned circles problem is found, with the same angular radius as the unconstrained problem. Solutions for
N
=2–12 pairs of twins are counted and classified by symmetry. For
N
=2–6 and 12, these are mathematically proven to be the best solutions; for
N
=7–11, they are based on the best known conjectured solutions of the unconstrained problem. Where the contact graph of the unconstrained problem has one or more rattling circles, the twinned problem is most easily solved by finding perfect matchings of an augmented graph in which each rattling circle is supposed to be simultaneously in contact with all its contactable neighbours. The underlying contact graphs for the unconstrained packings for
N
=2–12 are all Hamiltonian, guaranteeing the existence of perfect matchings, but Hamiltonicity is not a necessary condition: the first solution to the twins problem based on an example of a non-Hamiltonian contact graph occurs at
N
=16.
Key strategies for reducing spread of avian influenza among commercial poultry holdings: lessons for transmission to humans
Authors: Le Menach Arnaud , Vergu Elisabeta , Grais Rebecca F , Smith David L , Flahault Antoine
Published: July 2006

Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from around the world have led to fears of a human pandemic. Control of these outbreaks in birds would probably lead to reduced transmission of the avian virus to humans. This study presents a mathematical model based on stochastic farm-to-farm transmission that incorporates flock size and spatial contacts to evaluate the impact of control strategies. Fit to data from the recent epidemic in the Netherlands, we evaluate the efficacy of control strategies and forecast avian influenza dynamics. Our results identify high-risk areas of spread by mapping of the farm level reproductive number. Results suggest that an immediate depopulation of infected flocks following an accurate and quick diagnosis would have a greater impact than simply depopulating surrounding flocks. Understanding the relative importance of different control measures is essential for response planning.
Rates of nausea and vomiting in pregnancy and dietary characteristics across populations
Authors: Pepper Gillian V , Craig Roberts S
Published: July 2006

Nausea and vomiting in pregnancy (NVP) is a pervasive and debilitating phenomenon in humans. Several adaptive explanations for NVP occurrence have been recently proposed, the two most prominent of which predict associations with nutritional intake or specific dietary components. Here we extend previous cross-cultural analyses by analysing associations between NVP prevalence in 56 studies (21 countries) and quantitative estimates ofper capitaintake across major dietary categories, measured for the year of study by the Food and Agriculture Organisation (FAO). Rates of nausea and vomiting in pregnancy were correlated with high intake of macronutrients (kilocalories, protein, fat, carbohydrate), as well as sugars, stimulants, meat, milk and eggs, and with low intake of cereals and pulses. Restricting analyses to studies from North America and Europe caused relationships between macronutrient intake and NVP to disappear, suggesting that they might be influenced by non-dietary confounds associated with geographical region of study. However, factor analysis of dietary components revealed one factor significantly associated with NVP rate, which was characterized by low cereal consumption and high intake of sugars, oilcrops, alcohol and meat. The results provide further evidence for an association between diet and NVP prevalence across populations, and support for the idea that NVP serves an adaptive prophylactic function against potentially harmful foodstuffs.
Darwin at the molecular scale: selection and variance in electron tunnelling proteins including cytochrome
c
oxidase
Authors: Moser Christopher C , Page Christopher C , Dutton P. Leslie
Published: July 2006

Biological electron transfer is designed to connect catalytic clusters by chains of redox cofactors. A review of the characterized natural redox proteins with a critical eye for molecular scale measurement of variation and selection related to physiological function shows no statistically significant differences in the protein medium lying between cofactors engaged in physiologically beneficial or detrimental electron transfer. Instead, control of electron tunnelling over long distances relies overwhelmingly on less than 14 Å spacing between the cofactors in a chain. Near catalytic clusters, shorter distances (commonly less than 7 Å) appear to be selected to generate tunnelling frequencies sufficiently high to scale the barriers of multi-electron, bond-forming/-breaking catalysis at physiological rates. We illustrate this behaviour in a tunnelling network analysis of cytochrome
c
oxidase. In order to surmount the large, thermally activated, adiabatic barriers in the 5–10 kcal mol
−1
range expected for H
+
motion and O
2
reduction at the binuclear centre of oxidase on the 10
3
–10
5
 s
−1
time-scale of respiration, electron access with a tunnelling frequency of 10
9
or 10
10
 s
−1
is required. This is provided by selecting closely placed redox centres, such as haem
a
(6.9 Å) or tyrosine (4.9 Å). A corollary is that more distantly placed redox centres, such as Cu
A
, cannot rapidly scale the catalytic site barrier, but must send their electrons through more closely placed centres, avoiding direct short circuits that might circumvent proton pumping coupled to haems
a
to
a
3
electron transfer. The selection of distances and energetic barriers directs electron transfer from Cu
A
to haem
a
rather than
a
3
, without any need for delicate engineering of the protein medium to ‘hard wire’ electron transfer. Indeed, an examination of a large number of oxidoreductases provides no evidence of such naturally selected wiring of electron tunnelling pathways.
Hydride transfer catalysed by
Escherichia coli
and
Bacillus subtilis
dihydrofolate reductase: coupled motions and distal mutations
Authors: Hammes-Schiffer Sharon , Watney James B
Published: July 2006

This paper reviews the results from hybrid quantum/classical molecular dynamics simulations of the hydride transfer reaction catalysed by wild-type (WT) and mutant
Escherichia coli
and WT
Bacillus subtilis
dihydrofolate reductase (DHFR). Nuclear quantum effects such as zero point energy and hydrogen tunnelling are significant in these reactions and substantially decrease the free energy barrier. The donor–acceptor distance decreases to
ca
2.7 Å at transition-state configurations to enable the hydride transfer. A network of coupled motions representing conformational changes along the collective reaction coordinate facilitates the hydride transfer reaction by decreasing the donor–acceptor distance and providing a favourable geometric and electrostatic environment. Recent single-molecule experiments confirm that at least some of these thermally averaged equilibrium conformational changes occur on the millisecond time-scale of the hydride transfer. Distal mutations can lead to non-local structural changes and significantly impact the probability of sampling configurations conducive to the hydride transfer, thereby altering the free-energy barrier and the rate of hydride transfer.
E. coli
and
B. subtilis
DHFR enzymes, which have similar tertiary structures and hydride transfer rates with 44% sequence identity, exhibit both similarities and differences in the equilibrium motions and conformational changes correlated to hydride transfer, suggesting a balance of conservation and flexibility across species.
The incommensurately and commensurately modulated crystal structures of chromium(II) diphosphate
Authors: Palatinus Lukáš , Dušek Michal , Glaum Robert , El Bali Brahim
Published: July 2006

Chromium(II) diphosphate, Cr2P2O7, has an incommensurately modulated structure at ambient conditions with a = 7.05, b = 8.41, c = 4.63 Å, β = 108.71° and q = (−0.361, 0, 0.471). It undergoes a phase transition towards a commensurate structure with a commensurate q vector, q = (−{1\over 3}, 0, ½), at Tc
= 285 K. The incommensurate structure has been solved by the charge-flipping method, which yielded both the basic positions of the atoms and the shapes of their modulation functions. The structure model for the commensurate structure was derived directly from the incommensurate structure. The structure analysis shows that the modulation leads to a change of the coordination of the Cr2+ ions from distorted octahedra in the average structure towards a sixfold coordination in the form of a more regular octahedron and a fivefold coordination in the form of a square pyramid. The fivefold and sixfold coordination polyhedra alternate along the lattice direction a with the pattern 5-6-5 5-6-5 in the commensurate structure. In the incommensurate structure this pattern is occasionally disturbed by a 5-6-5-5 motif. Both structures can be described in superspace using the same superspace group and a similar modulated structure model. The same superspace model can also be used for the low-temperature phases of other metal diphosphates with the thortveitite stucture type at high temperature. Their low-temperature structures can be obtained from the superspace model by varying the q vector and the origin in the internal dimension t
0.
Structural characterization of selenium and selenium-diiodine analogues of the antithyroid drug 6-n-propyl-2-thiouracil and its alkyl derivatives
Authors: Antoniadis Constantinos D. , Blake Alexander J. , Hadjikakou Sotiris K. , Hadjiliadis Nick , Hubberstey Peter , Schröder Martin , Wilson Claire
Published: July 2006

The structures of four selenium analogues of the antithyroid drug 6-n-propyl-2-thiouracil [systematic name: 2,3-dihydro-6-n-propyl-2-thioxopyrimidin-4(1H)-one], namely 6-methyl-2-selenouracil, C5H6N2OSe (1), 6-ethyl-2-selenouracil, C6H8N2OSe (2), 6-n-propyl-2-selenouracil, C7H10N2OSe (3), and 6-isopropyl-2-selenouracil, C7H10N2OSe (4), are described, along with that of the dichloromethane monosolvate of 6-isopropyl-2-selenouracil, C7H10N2OSe·CH2Cl2 (4·CH2Cl2). The extended structure of (1) is a two-dimensional sheet of topology 63 with a brick-wall architecture. The extended structures of (2) and (4) are analogous, being based on a chain of eight-membered R
8
6(32) hydrogen-bonded rings. In (3) and (4·CH2Cl2), R
2
2(8) hydrogen bonding links molecules into chains. 6-n-Propyl-2-selenouracil·I2, C7H10N2OSe·I2 (7), is a charge-transfer complex with a `spoke' structure, the extended structure of which is based on a linear chain formed principally by intermolecular N—H...O hydrogen bonds. Re-crystallization of 6-ethyl-2-selenouracil or (7) from acetone gave crystals of the diselenides [N-(6′-ethyl-4′-pyrimidone)(6-ethyl-2-selenouracil)2(Se—Se)]·2H2O (9·2H2O) or [N-(6′-n-propyl-4′-pyrimidone)(6-n-propyl-2-selenouracil)2(Se—Se)] (10), respectively: these have similar extended chain structures formed via N—H...O and C—H...O hydrogen bonds, stacked to give two-dimensional sheets. Re-crystallization of (7) from methanol/acetonitrile led via deselenation to the formation of crystals of 6-n-propyl-2-uracil (11), in which six symmetry-related molecules combine to form a six-membered R
6
6(24) hydrogen-bonded ring, with each pair of molecules linked by an R
2
2(8) motif.
Synchrotron and neutron diffraction study of 4-methylpyridine-N-oxide at low temperature
Authors: Damay Françoise , Carretero-Genevrier Adrian , Cousson Alain , Van Beek Wouter , Rodriguez-Carvajal Juan , Fillaux François
Published: July 2006

The structure of 4-methylpyridine-N-oxide has been determined at 250, 100 and 10 K by combined synchrotron (C6H7NO) and neutron (C6D7NO) powder diffraction experiments. At 250 K the space group is I41/amd and the tetragonal unit cell [a = b = 7.941 (2), c = 19.600 (5) Å] contains eight equivalent molecules. At 100 K the structure is orthorhombic, with space group Fddd, a = 12.138 (2), b = 10.237 (2) and c = 19.568 (3) Å. The 16 equivalent molecules are rotated by about 8° around the c axis with respect to positions at high temperature. At 10 K the best structural model corresponds to a tetragonal unit cell with the space group P41, a = b = 15.410 (2) Å and c = 19.680 (3) Å. The 32 molecules (eight molecules in the asymmetric unit) show complex reorientations around the three cell axes. Whereas at 250 and 100 K the deuterated methyl groups are largely disordered, at 10 K they are ordered in-phase along infinite chains parallel to a and b. Face-to-face methyl groups along c are in an eclipsed configuration. The structure at 10 K suggests that the manifold of rotational tunnelling transitions could be due to inequivalent lattice sites for crystallographically independent methyl groups.
Blind crystal structure prediction of a novel second polymorph of 1-hydroxy-7-azabenzotriazole
Authors: Nowell Harriott , Frampton Christopher S. , Waite Julie , Price Sarah L.
Published: July 2006

The commercially available peptide coupling reagent 1-hydroxy-7-azabenzotriazole has been shown to crystallize in two polymorphic forms. The two polymorphs differ in their hydrogen-bonding motif, with form I having an R_2^2(10) dimer motif and form II having a C(5) chain motif. The previously unreported form II was used as an informal blind test of computational crystal structure prediction for flexible molecules. The crystal structure of form II has been successfully predicted blind from lattice-energy minimization calculations following a series of searches using a large number of rigid conformers. The structure for form II was the third lowest in energy with form I found as the global minimum, with the energy calculated as the sum of the ab initio intramolecular energy penalty for conformational distortion and the intermolecular lattice energy which is calculated from a distributed multipole representation of the charge density. The predicted structure was sufficiently close to the experimental structure that it could be used as a starting model for crystal structure refinement. A subsequent limited polymorph screen failed to yield a third polymorphic form, but demonstrated that alcohol solvents are implicated in the formation of the form I dimer structure.
On measuring the size of distortions in coordination polyhedra
Authors: Brown I. David
Published: July 2006

There is no unique index that measures the size of the distortion found in a coordination polyhedron because different indices can result in a different ordering depending on the mode of the distortion (i.e. the third and higher moments of the bond-length distribution). This paper proposes the increase in the average bond length as a suitable index as this is directly related to the increase in volume of the coordination polyhedron and hence of the unit cell. Some examples are discussed.
Hexamer formation in tertiary butyl alcohol (2-methyl-2-propanol, C4H10O)
Authors: McGregor Pamela A. , Allan David R. , Parsons Simon , Clark Stewart J.
Published: July 2006

The crystal structure of phase II of tertiary butyl alcohol (2-methyl-2-propanol, C4H10O) has been solved using a combination of single-crystal X-ray diffraction techniques and ab initio density functional calculations. This trigonal P\overline 3 phase, which is stable at both low temperature and high pressure, and the triclinic P\overline 1 phase (phase IV) have very similar enthalpies, the calculations revealing only a 3.859 kJ mol−1 enthalpy difference at ambient pressure, despite the substantial change of the intermolecular bonding motif from helical catemer to hexamer with an increase in pressure or reduction in temperature. The hexamers in the trigonal phase adopt a chair conformation. There are two unique hexamers: at low temperature these are centred at (0, 0, 1\over2) and (2\over3, 1\over3, 0.961 (13)), and at high pressure the centres are (0, 0, 1\over2) and (2\over3, 1\over3, 0.958 (14)). A slight flattening of the hexamers is observed at high pressure and the calculations confirm that phase II becomes more stable relative to phase IV on pressure increase.
Nine N-aryl-2-chloronicotinamides: supramolecular structures in one, two and three dimensions
Authors: Cuffini Silvia , Glidewell Christopher , Low John N. , de Oliveira Aline G. , de Souza Marcus V. N. , Vasconcelos Thatyana R. A. , Wardell Solange M. S. V. , Wardell James L.
Published: July 2006

Structures are reported here for eight further substituted N-aryl-2-chloronicotinamides, 2-ClC5H3NCONHC6H4
X-4′. When X = H, compound (I) (C12H9ClN2O), the molecules are linked into sheets by N—H...N, C—H...π(pyridyl) and C—H...π(arene) hydrogen bonds. For X = CH3, compound (II) (C13H11ClN2O, triclinic P\bar 1 with Z′ = 2), the molecules are linked into sheets by N—H...O, C—H...O and C—H...π(arene) hydrogen bonds. Compound (III), where X = F, crystallizes as a monohydrate (C12H8ClFN2O·H2O) and sheets are formed by N—H...O, O—H...O and O—H...N hydrogen bonds and aromatic π...π stacking interactions. Crystals of compound (IV), where X = Cl (C12H8Cl2N2O, monoclinic P21 with Z′ = 4) exhibit inversion twinning: the molecules are linked by N—H...O hydrogen bonds into four independent chains, linked in pairs by C—H...π(arene) hydrogen bonds. When X = Br, compound (V) (C12H8BrClN2O), the molecules are linked into sheets by N—H...O and C—H...N hydrogen bonds, while in compound (VI), where X = I (C12H8ClIN2O), the molecules are linked into a three-dimensional framework by N—H...O and C—H...π(arene) hydrogen bonds and an iodo...N(pyridyl) interaction. For X = CH3O, compound (VII) (C13H11ClN2O2), the molecules are linked into chains by a single N—H...O hydrogen bond. Compound (VIII) (C13H8ClN3O, triclinic P\bar 1 with Z′ = 2), where X = CN, forms a complex three-dimensional framework by N—H...N, C—H...N and C—H...O hydrogen bonds and two independent aromatic π...π stacking interactions.
Further errors in polymorph identification: furosemide and finasteride
Authors: Karami Sohrab , Li Yang , Hughes David S. , Hursthouse Michael B. , Russell Andrea E. , Threlfall Terence L. , Claybourn Michael , Roberts Ronald
Published: July 2006

Reassessment of the reported single-crystal X-ray diffraction characterization of polymorphs of furosemide and finasteride shows that, in each case, incomplete data collections have resulted in the mistaken identification of two forms that are, in fact, identical.
Molecular and crystal properties of ethyl 4,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate from experimental and theoretical electron densities
Authors: Tsirelson V. G. , Stash A. I. , Potemkin V. A. , Rykounov A. A. , Shutalev A. D. , Zhurova E. A. , Zhurov V. V. , Pinkerton A. A. , Gurskaya G. V. , Zavodnik V. E.
Published: July 2006

The electron density and electronic energy densities in ethyl 4,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate have been studied from accurate X-ray diffraction measurements at 110 K and theoretical single-molecule and periodic crystal calculations. The Quantum Theory of Atoms in Molecules and Crystals (QTAMC) was applied to analyze the electron-density and electronic energy-density features to estimate their reproducibility in molecules and crystals. It was found that the local electron-density values at the bond critical points derived by different methods are in reasonable agreement, while the Laplacian of the electron density computed from wavefunctions, and electron densities derived from experimental or theoretical structure factors in terms of the Hansen–Coppens multipole model differ significantly. This disagreement results from insufficient flexibility of the multipole model to describe the longitudinal electron-density curvature in the case of shared atomic interactions. This deficiency runs through all the existing QTAMC bonding descriptors which contain the Laplacian term. The integrated atomic characteristics, however, suffer noticeably less from the aforementioned shortcoming. We conclude that the electron-density and electronic energy QTAMC characteristics derived from wavefunctions, especially the integrated quantities, are nowadays the most suitable candidates for analysis of the transferability of atoms and atomic groups in similar compounds.
Structure and phase transitions in Ca2CoSi2O7–Ca2ZnSi2O7 solid-solution crystals
Authors: Jia Z. H. , Schaper A. K. , Massa W. , Treutmann W. , Rager H.
Published: July 2006

While the incommensurability in melilites is well documented, the underlying atomic configurations and the composition-dependent phase behavior are not yet clear. We have studied the transition from the incommensurate phase to the high-temperature normal phase (IC-N), and to the low-temperature commensurate phase (IC-C) of selected members of the Ca2Co1 − x
Zn
x
Si2O7 system using X-ray and single-crystal electron diffraction, as well as calorimetric measurements. The space group of the unmodulated normal phase and of the basic structure of the incommensurate phase is P\bar 4 2_1m; the commensurate lock-in superstructure was refined as a pseudomerohedral twin in the orthorhombic space group P21212. We found that the commensurate modulation is mainly connected with a sawtooth-like periodicity of rotations of the T
1 tetrahedra in the 3 × 3 superstructure. In this structure, the clustering of the low-coordinated Ca2+ ions is not complete so that only imperfect octagons were detected. Generally, the effect of increasing substitution of Co by Zn was a continuous reduction of the IC-N and IC-C transition temperatures.
Expression profiling analysis of the CD5+ diffuse large B‐cell lymphoma subgroup: Development of a CD5 signature
Authors: Suguro Miyuki , Tagawa Hiroyuki , Kagami Yoshitoyo , Okamoto Masataka , Ohshima Koichi , Shiku Hiroshi , Morishima Yasuo , Nakamura Shigeo , Seto Masao
Published: July 2006

Diffuse large B‐cell lymphoma (DLBCL) accounts for 30% of non‐Hodgkin's lymphomas and is known to comprise heterogeneous groups. We previously reported that CD5+ DLBCL is a clinically distinct subgroup of these tumors that is associated with poor prognosis. In our current study, we have used gene expression profiling technology in an attempt to identify new markers and to further characterize the biological features of CD5+ DLBCL. Candidate genes, which showed the greatest difference in expression between 22 CD5+ and 26 CD5− DLBCL cases, were selected from our screening and subjected to clustering analysis. This resulted in identification of a specific mRNA profile (a CD5 signature) for CD5+ DLBCL. The CD5 signature included downregulated extracellular matrix genes such as POSTN, SPARC, COL1A1, COL3A1, CTSK, MMP9 and LAMB3, and comprised upregulated genes including TRPM4. We tested this CD5 signature for its potential use as a relevant marker for CD5+ DLBCL and found that it did indeed recognize this subgroup. The tumors identified by the CD5 signature contained most of the CD5+ DLBCL cases and some CD5− DLBCL cases. Moreover, the subgroup of cases with this CD5 signature showed a poorer prognosis. The subsequent application of the CD5 signature to the analysis of an independent series of DLBCL microarray data resulted in identification of a subgroup of DLBCL cases with a similar clinical outcome, further suggesting that the CD5 signature can be used as a clinically relevant marker of this disease. (Cancer Sci 2006; 97: 868–874)
Expression of Ets‐1 in human clear cell renal cell carcinomas: Implications for angiogenesis
Authors: Mikami Shuji , Oya Mototsugu , Mizuno Ryuichi , Murai Masaru , Mukai Makio , Okada Yasunori
Published: July 2006

Expression of vascular endothelial growth factor (VEGF) has been reported in renal cell carcinoma (RCC), a highly angiogenic carcinoma. However, little or no information is available on the expression of Ets‐1, which is one of the target molecules of VEGF. In the present study, we examined the expression of Ets‐1 and VEGF in RCC by immunohistochemistry and reverse transcription–polymerase chain reaction (RT‐PCR), and correlations between expression and the microvessel density (MVD) were evaluated. Ets‐1 was immunolocalized to carcinoma cells and endothelial cells of the microvessels in clear cell RCC, but not in papillary RCC. Immunohistochemical Ets‐1 expression and MVD were significantly higher in clear cell RCC than in papillary RCC. Predominant mRNA expression of Ets‐1 in clear cell RCC was confirmed by RT‐PCR. The expression of Ets‐1 correlated directly with MVD in clear cell RCC. Hypoxic treatment upregulated the mRNA expression of Ets‐1 and VEGF in cell lines derived from clear cell RCC, suggesting that hypoxia is a key regulator for these molecules. These results demonstrate the expression of Ets‐1 in human clear cell RCC and suggest the possibility that Ets‐1 is involved in angiogenesis in clear cell RCC. (Cancer Sci 2006; 97: 875–882)
Influence of the parathyroid glands on bone metabolism
Authors: Malluche H. H. , Koszewski N. , Monier‐Faugere M. C. , Williams J. P. , Mawad H.
Published: July 2006

Bone is a classic target tissue for parathyroid hormone (PTH), whose calciotropic effect is mediated largely via catabolic actions on this tissue. Paradoxically, PTH also exerts anabolic actions, with intermittent injections of PTH or its amino‐terminal fragments causing an increase in bone formation and bone mass, actions that form the basis for the use of PTH in the treatment of osteoporosis. Besides vitamin D, PTH is the only other known bone anabolic agent. High‐affinity PTH receptors (PTH‐1R) have been detected on osteoblasts and osteoclasts (albeit in lower numbers).

Bone turnover, which includes activation of osteoclasts and osteoblasts, appears to be best reflected not by absolute concentrations of PTH (which can vary based on the assay and antibody used) but by a balance of circulating full‐length PTH‐(1–84) and amino‐terminally truncated C‐PTH fragments. When PTH‐(1–84) is predominant, bone turnover is promoted. Among PTH fragments, PTH‐(7–84) appears to be the most potent antagonist of PTH‐(1–84). The mechanisms involved in these effects are unclear although mediation via unique C‐terminal receptors has been suggested. We propose that, within the range of total PTH (100–1000 pg mL−1), the ratio of PTH‐(1–84)/C‐PTH fragment is a valuable tool for diagnosis of bone turnover. Data indicate that at PTH levels < 100–150 pg mL−1 and > 1000 pg mL−1, the ratio looses its predictive power. Assay type, patient characteristics (race, underlying renal disease) and treatment attributes (vitamin D, corticosteroids, phosphate binders) have an impact on the PTH ratio, and care should be used in interpreting assay results and making subsequent treatment decisions.
Characterization of the integrase of NBU1, a Bacteroides mobilizable transposon
Authors: Rajeev Lara , Salyers Abigail A. , Gardner Jeffrey F.
Published: July 2006

NBU1 is a Bacteroides mobilizable transposon (MTn) that is integrated within the host chromosome and requires CTnDOT functions for its excision and transfer into a new host. The NBU1 integrase IntN1 has been classified as a tyrosine recombinase based on the presence of conserved residues. We created alanine mutants of the residues R291, K314, H393, R396, H419 and the conserved substitution Y429F and tested them for integration efficiency. The results suggest that these residues in IntN1 are important for integration, and Y429 could be the catalytic nucleophile. We employed suicide substrates and partially purified IntN1 to determine the positions of IntN1 cleavage within the 14 bp common core region that is identical in both NBU1 att sites. We show that IntN1 makes 7 bp staggered cuts on the top and bottom strands. From previous mutational analysis of the att sites, we show that two specific mutations near the site of bottom strand cleavage within this 7 bp region increased integration, and mutations of the two bases near top strand cleavage site had no effect on integration. These results indicate that IntN1 lacks the strict requirement for homology between the recombining sites seen with other tyrosine recombinases. We also show that phosphorothioate substitutions at the cleavage site and 1 bp downstream inhibited cleavage by IntN1. This differs from other studied tyrosine recombinases where inhibition occurs by substitutions at the cleavage site only.
Follow up of 12 patients with trachyonychia
Authors: Sakata Shinichiro , Howard Anne , Tosti Antonella , Sinclair Rodney
Published: July 2006

A follow‐up study was performed to determine the outcomes of all patients (five males and seven females, mean age 18.4 years) who were referred to a specialist nail clinic with trachyonychia. The average number of affected nails per patient was 8.8 fingernails and 6.2 toenails. None of our patients tested positive for onychomycosis. Nail biopsies were performed in two patients, revealing non‐specific changes. Eight patients did not present with or develop accompanying skin or mucosal disease. Two patients presented with alopecia areata and two others with psoriasis. Of our patients, 50% showed total resolution or marked improvement in their nail disease within the first 6 years regardless of treatment.
Treatment of palmoplantar warts with a diphencyprone and salicylic acid ointment
Authors: Armour Katherine , Orchard David
Published: July 2006

We report on 50 consecutive suitable patients with one or more palmoplantar warts who were treated with a patient‐applied ointment comprising 0.1% diphencyprone and 15% salicylic acid in white soft paraffin. All patients sensitized to diphencyprone were followed up clinically and assessed by patient questionnaire. The intention to treat success rate in this series was 88%. The time to wart clearance ranged from less than 4 weeks to 4 months. In our patient group, 90% rated their treatment as ‘excellent’ or ‘good’, whereas 10% stated that the reaction induced by diphencyprone was ‘too severe’. Our results are compared with those previously published using diphencyprone in the treatment of palmoplantar warts.
Primary cutaneous mucinous carcinoma: Report of two cases treated with Mohs’ micrographic surgery
Authors: Cecchi Roberto , Rapicano Valentina
Published: July 2006

We present a 72‐year‐old woman who presented with a slowly enlarging, asymptomatic, cystic nodule on the right eyebrow, and a 66‐year‐old woman who had a reddish, nodular lesion on the left lower eyelid. Incisional biopsy from the two neoplasms showed dermal epithelial cell islands embedded in mucin pools. Tumour cells stained positive for cytokeratin 7, oestrogen and progesterone receptors, and negative for vimentin and S‐100 protein. These findings were consistent with a diagnosis of mucinous carcinoma. Extensive work‐ups excluded cutaneous metastases from primary visceral mucinous carcinomas. To ensure complete tumour removal, both patients underwent Mohs’ micrographic surgery (standard fresh‐frozen technique). They remain disease‐free 42 and 26 months after surgical excision, respectively. Mohs’ micrographic surgery appears to be a rational and effective treatment for this uncommon malignancy.
Allergic contact dermatitis to basic red 46 occurring in an HIV‐positive patient
Authors: Curr Nathan , Nixon Rosemary
Published: July 2006

A 41‐year‐old HIV‐positive man presented with a 2‐month history of a generalized pruritic rash, which had started on his feet. Patch testing made a diagnosis of allergic contact dermatitis to the textile dye basic red 46, likely to have been present in his dark‐blue‐coloured socks. Complete resolution of his symptoms occurred with avoidance of these socks. The patient had developed allergic contact dermatitis with a low CD4 T lymphocyte count of 361 cells/µl (normal range 410–1545 cells/µl). This raised the question of the level of CD4 count necessary for an individual to develop allergic contact dermatitis to an allergen, given its role in delayed hypersensitivity. It was concluded that a low CD4 count as a result of HIV infection does not decrease the ability of an individual to develop allergic contact dermatitis. Whereas the effector role in delayed type 4 hypersensitivity reactions is mediated by CD4 T lymphocytes, in allergic contact dermatitis it appears that CD4 T lymphocytes have the suppressor role, with CD8 T lymphocytes having the effector role.
Allergic contact dermatitis to sodium benzoate chloroacetamide in a sorbolene lotion
Authors: Sutton Tina , Nixon Rosemary
Published: July 2006

Sodium benzoate chloroacetamide is sometimes used as a combination preservative in cosmetics to prevent the growth of bacteria, mould, fungi and yeasts. A case of occupational allergic contact dermatitis to this preservative is described in a 32‐year‐old female personal care assistant, who was found to have allergic contact dermatitis involving the hands, caused by the sorbolene lotion supplied in her workplace. Patch testing to chloroacetamide, sodium benzoate chloroacetamide and the sorbolene lotion was positive. Patch testing to sodium benzoate alone was negative. She had been found to react to chloroacetamide 12 months earlier, but the relevance of the reaction had not been ascertained.
A framework for systematically improving occupational therapy expert opinions on work capacity
Authors: Allen Shelley , Carlson Glenys , Ownsworth Tamara , Strong Jenny
Published: July 2006

Aim: To present an evidence‐based framework to improve the quality of occupational therapy expert opinions on work capacity for litigation, compensation and insurance purposes.

Methods: Grounded theory methodology was used to collect and analyse data from a sample of 31 participants, comprising 19 occupational therapists, 6 medical specialists and 6 lawyers. A focused semistructured interview was completed with each participant. In addition, 20 participants verified the key findings.

Results: The framework is contextualised within a medicolegal system requiring increasing expertise. The framework consists of (i) broad professional development strategies and principles, and (ii) specific strategies and principles for improving opinions through reporting and assessment practices.

Conclusions: The synthesis of the participants’ recommendations provides systematic guidelines for improving occupational therapy expert opinion on work capacity.
Pretend play and parents’ view of social competence: The construct validity of the Child‐Initiated Pretend Play Assessment
Authors: Swindells Dianne , Stagnitti Karen
Published: July 2006

Background and Aims:  Play is the primary means through which children develop skills and socially interact with other children. The aim of this study was to investigate the relationship between pretend play and social competence in 4–5‐year‐old typically developing children, thereby adding further knowledge to the construct validity of the Child‐Initiated Pretend Play Assessment (ChIPPA).

Procedure:  The pretend play ability of 35 preschool children aged 4–5 years was assessed using the ChIPPA. Parent/guardians of the children were interviewed regarding their child's social competence using the Vineland Social–Emotional Early Childhood Scales (Vineland SEEC Scales).

Main Findings:  No significant correlations were found between the children's play scores and their Vineland SEEC Scales scores. A significant and negative relationship was found between cooperation and sharing and elaborate play scores, suggesting that children who scored poorly on the play assessment were rated as cooperative by parents.

Principal Conclusions:  Parent report of social competence cannot be inferred from play scores. Reasons for the negative and significant finding are put forward and clinical implications of the findings are discussed. Additional investigations are necessary to further explore the construct validity of inferring social competence using the ChIPPA.