bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe personality disorder emerging in childhood: a proposal for a new developmental disorder
Authors: Vizard Eileen , French Lesley , Hickey Nicole , Bladon Emily
Published: March 2006

Background

The concept of ‘severe personality disorder’ is currently applied to adults with a history of serious antisocial and offending behaviour. There is, however, no similar classification that can be applied to the sub‐group of children and adolescents who display persistent and serious offending from an early age. This omission from diagnostic nomenclature prevents the appropriate early identification, assessment and management of these young people.

Method

This paper therefore proposes a new developmental disorder: ‘severe personality disorder emerging in childhood’. The existing evidence base strongly supports the presence of a developmental trajectory from childhood to adult life for the small number of children who show early signs of severe personality disorder (SPD). Based on a review of the literature and the experience of working in a specialist, forensic Child and Adolescent Mental Health Service (CAMHS), a multi‐factorial model is proposed that outlines the developmental trajectory of SPD. This model includes neurobiological, psychosocial, environmental and systemic factors, within a developmental framework, and contributes to a more developmentally appropriate understanding of the genesis of severe personality disorder. Copyright © 2004 Whurr Publishers Ltd.
The antisocial attitudes and associates of sex offenders
Authors: Mills Jeremy F. , Anderson Dana , Kroner Daryl G.
Published: March 2006

Introduction

Meta‐analyses have demonstrated that attitudes and associates (peer group behaviour) are among the best predictors of antisocial behaviour in offender populations. Research on sex offender attitudes has typically focused on sex‐related content and not antisocial attitudes in general. This study investigates the antisocial attitudes of sex offenders by comparing them with non‐sex offenders on responses to the Measures of Criminal Attitudes and Associates (MCAA).

Method

The MCAA comprises two parts. Part A is a quantified self‐report measure of criminal friends. Part B contains four attitude scales: Violence, Entitlement, Antisocial Intent and Associates. Ninety sex offenders were compared with 119 nonsex offenders on their endorsement of the MCAA and criminal history.

Results

Sex offenders endorsed fewer antisocial attitudes, reported fewer criminal friends and had fewer incarcerations than did non‐sex offenders. Rapists endorsed antisocial attitudes more than did child molesters and incest offenders. However, these differences disappeared on controlling for age. A finding of fewer previous incarcerations among sex offenders was robust even controlling for age.

Conclusion

The MCAA appears to be a reliable and valid instrument with sex offender samples. General antisocial attitudes appear to have a similar relationship with criminal history for both sex offenders and non‐sex offenders, and should not be ignored in future studies or clinical practice. While a general sense of entitlement was not associated with sex offending per se, its stronger association with incarceration among sex offenders than non‐sex offenders might suggest that this has the potential for identifying an important, perhaps more serious sub‐group of sex offenders. Copyright © 2004 Whurr Publishers Ltd.
Enhancing fraud prevention and detection by profiling fraud offenders
Authors: Kapardis Andreas , Krambia‐Kapardis Maria
Published: March 2006

Aims

The paper first focuses on the crime of fraud and then on approaches to profiling offenders before examining closely studies of fraud offenders and their motivation.

Method

Drawing on the existing empirical literature, a profile of the serious fraud offender is presented and critiqued together with a taxonomy of such offenders comprising 12 types.

Conclusions

The implications of the findings for fraud detection and prevention are discussed. Copyright © 2004 Whurr Publishers Ltd.
The language of the psychopath: Characteristics of prisoners' performance in a sentence completion test
Authors: Endres Johann
Published: March 2006

Aim and background

Verbal productions of prisoners were studied as possible correlates of psychopathic personality.

Method

A sample of 76 inmates of a German high‐security prison were administered a new sentence completion test (SCT). The subjects' verbal responses to 63 sentence cues were coded using 23 content and linguistic categories which had been derived from Loevinger's stage model of ego development. Moreover, the Psychopathy Checklist–Revised (PCL–R) was scored for each subject after a clinical interview and a perusal of the prisoner's file.

Results

Moderate positive correlations were found between PCL–R scores and cognitive and linguistic characteristics in the SCT (concerns with exerting power and being dominated, use of coarse language and the expression of dysphoric emotions). These characteristics were highly sensitive but not specific to psychopaths.

Conclusions

In the context of recent research, verbal patterns are seen, together with interpersonal behaviour patterns and linguistic properties, as valid indicators of psychopathy and might be particularly useful when biographical information is lacking. Copyright © 2004 Whurr Publishers Ltd.
The structural coherence of clinically derived dynamic indicators of reoffending risk
Authors: Philipse Martien W. G. , Koeter Maarten W. J. , van den Brink Wim , van der Staak Cees P. F.
Published: March 2006

Background

Forensic psychiatrists aim to reduce the risk of reoffending through treatment. With few exceptions, research evidence tends to favour risk assessment aids reliant on fixed historical rather than clinical data, but transparency in the making of clinical judgements is lacking.

Aims

To evaluate further a clinically derived 47‐item dynamic risk assessment checklist; specifically to test first whether it has a meaningful dimensional structure and, second, the extent to which items and underlying dimensions are associated with a separate, direct clinical judgement of risk of reoffending.

Methods

Data sets from four previous studies on the reliability and validity of the Clinical Inventory of Dynamic Reoffending Risk Indicators (CIDRRI) were merged, yielding 370 cases. The resulting data set was analysed using principal axis (common) factor analysis, with orthogonal (varimax) rotation. In addition, receiver operating characteristic (ROC) curves were calculated.

Results

The model of best fit depended on treatment stage; for those in residential treatment it was a six‐factor model (responsibility, self‐reliance, antisocial/narcissistic traits, treatment compliance, goal attainment and avoidance); for those back in the community a five‐actor model in which, effectively, the compliance and goal attainment factors became one, provided a better fit. These dimensions and some individual scale items were associated with clinical judgement of risk of reoffending.

Conclusions and clinical implications

This study provides evidence that the CIDRRI is an adequate operationalization of underpinnings of clinical risk assessment, and that these underpinnings are part of meaningful higher‐order dimensions. The CIDRRI is a viable instrument for clinical use, taking only 15 minutes to complete and identifying dynamic risk factors, the validity of which needs to be further established. Copyright © 2004 Whurr Publishers Ltd.
Management algorithm in pulmonary atresia with intact ventricular septum
Authors: Alwi Mazeni
Published: March 2006

Pulmonary atresia with intact ventricular septum (PAIVS) is a disease with remarkable morphologic variability, affecting not only the pulmonary valve but also the tricuspid valve, the RV cavity and coronary arteries. With advances in interventional techniques and congenital heart surgery, the management of PAIVS continues to evolve. This review is an attempt at providing a practical approach to the management of this disease. The basis of our approach is morphologic classification as derived from echocardiography and angiography. Group A, patients with good sized RV and membranous atresia, the primary procedure at presentation is radiofrequency (RF) valvotomy. Often it is the only procedure required in this group with the most favourable outcome. Patients with severely hypoplastic RV (Group C) are managed along the lines of hearts with single ventricle physiology. The treatment at presentation is patent ductus arteriosus (PDA) stenting with balloon atrial septostomy or conventional modified Blalock Taussig (BT) shunt. Bidirectional Glenn shunt may be done 6–12 months later followed by Fontan completion after a suitable interval. Patients in Group B, the intermediate group, are those with borderline RV size, usually with attenuated trabecular component but well developed infundibulum. The treatment at presentation is RF valvotomy and PDA stenting ± balloon atrial septostomy. Surgical re‐interventions are not uncommonly required viz. bidirectional Glenn shunt when the RV fails to grow adequately (1½ – ventricle repair) and right ventricular outflow tract (RVOT) reconstruction for subvalvar obstruction or small pulmonary annulus. Catheter based interventions viz. repeat balloon dilatation or device closure of patent foramen ovale (PFO) may also be required in some patients. © 2006 Wiley‐Liss, Inc.
Neuropeptide FF distribution in the human and rat forebrain: A comparative immunohistochemical study
Authors: Goncharuk Valeri D. , Buijs Ruud M. , Mactavish David , Jhamandas Jack H.
Published: March 2006

Neuropeptide FF (NPFF) is an octapeptide implicated in a variety of physiological functions, including nociception, cardiovascular responses, and neuroendocrine regulation. The NPFF gene and its mRNA are highly conserved across species. A comparative study of NPFF distribution in the human and rat forebrain was carried out by using single NPFF and double NPFF + vasopressin (VP) immunohistochemistry. NPFF is extensively localized within neurochemical circuits of human and rat forebrain. Semiquantitative analysis revealed that the densities of NPFF cells and fibers in many forebrain nuclei in the human correlate well with those observed for the same structures in the rat. High numbers of NPFF positive neurons in the dorsomedial hypothalamic nucleus and a dense plexus of NPFF fibers surrounding the fornix within the bed nucleus of the stria terminalis were identified in the human and rat forebrain. Within the hypothalamus of both species, dense NPFF innervation was observed in the perinuclear zone of the supraoptic nucleus (SO) just dorsolateral to the VP‐positive neurons. Extensive NPFF innervation of ventricular ependyma and brain microvasculature were common for both species. At the same time, obvious differences in NPFF localization between the two species were also apparent. For example, in contrast to the rat SO, no NPFF‐ or NPFF‐ + VP‐immunostained cells were observed in the human SO. Knowledge of NPFF neuroanatomical localization in the human brain and the relationship of these observations to those in the rat brain may provide insight into the role of this peptide in central cardiovascular and neuroendocrine regulation. J. Comp. Neurol. 496:572–593, 2006. © 2006 Wiley‐Liss, Inc.
Characterization of glucagon‐expressing neurons in the chicken retina
Authors: Fischer Andy J. , Skorupa Dana , Schonberg David L. , Walton Nathaniel A.
Published: March 2006

We recently identified large glucagon‐expressing neurons that densely ramify neurites in the peripheral edge of the retina and regulate the proliferation of progenitors in the circumferential marginal zone (CMZ) of the postnatal chicken eye (Fischer et al. [2005] J Neurosci 25:10157–10166). However, nothing is known about the transmitters and proteins that are expressed by the glucagon‐expressing neurons in the avian retina. We used antibodies to cell‐distinguishing markers to better characterize the different types of glucagon‐expressing neurons. We found that the large glucagon‐expressing neurons were immunoreactive for substance P, neurofilament, Pax6, AP2α, HuD, calretinin, trkB, and trkC. Colocalization of glucagon and substance P in the large glucagon‐expressing neurons indicates that these cells are the “bullwhip cells” that have been briefly described by Ehrlich et al. ([1987] J Comp Neurol 266:220–233). Similar to the bullwhip cells, the conventional glucagon‐expressing amacrine cells were immunoreactive for calretinin, HuD, Pax6, and AP2α. Unlike bullwhip cells, the conventional glucagon‐expressing amacrine cells were immunoreactive for GABA. While glucagon‐immunoreactive amacrine cells were negative for substance P in central regions of the retina, a subset of this type of amacrine cell was immunoreactive for substance P in far peripheral regions of the retina. An additional type of glucagon/substance P‐expressing neuron, resembling the bullwhip cells, was found in far peripheral and dorsal regions of the retina. Based on morphology, distribution within the retina, and histological markers, we conclude that there may be four different types of glucagon‐expressing neurons in the avian retina. J. Comp. Neurol. 496:479–494, 2006. © 2006 Wiley‐Liss, Inc.
Time frame of mitral cell development in the mice olfactory bulb
Authors: Blanchart Albert , De Carlos Juan A. , López‐Mascaraque Laura
Published: March 2006

Along with tufted cells, mitral cells are the principal projection neurons in the olfactory bulb (OB). During the development of the OB, mitral cells migrate from the ventricular zone to the intermediate zone, where they begin to send axons along the lateral olfactory tract (LOT) to the cortical olfactory zones. Subsequently, they lose their tangential orientation, enabling them to make contact with the axons of the olfactory sensory neurons (OSN) that innervate the whole OB. Here, we investigated the distinct morphological features displayed by developing mitral cells and analyzed the relationship between the changes undertaken by these neurons and the arrival of the OSN axons. Immunostaining for specific markers of developing axons and dendrites, coupled with the use of fluorescent tracers, revealed the morphological changes, the continuous reorientation, and the final refinement that these cells undergo. We found that some of these changes are dependent on the arrival of the OSN axons. Indeed, we identified three main chronological events: 1) newly generated neurons become established in the intermediate zone and project to the LOT; 2) the cells reorient and spread their dendrites at the same time as OSN axons penetrate the OB (this is a sensitive period between embryonic day (E)15–16, in which the arrival of afferents establishes a spatial and temporal gradient that facilitates protoglomerulus and glomerulus formation); and 3) final refinement of the radially orientated cells to adopt a mature morphology. These results suggest that both afferent inputs and intrinsic factors participate to produce the well‐defined sensory system. J. Comp. Neurol. 495:529–543, 2006. © 2006 Wiley‐Liss, Inc.
Single nucleotide polymorphisms in the proximal promoter region of apolipoprotein M gene (apoM) confer the susceptibility to development of type 2 diabetes in Han Chinese
Authors: Niu Nifang , Zhu Xilin , Liu Yang , Du Te , Wang Xin , Chen Dongmei , Sun Bei , Gu Harvest F. , Liu Ying
Published: March 2006

Objective

Dyslipidemia correlating to insulin resistance is one of the key features in type 2 diabetes (T2D). Recent studies have demonstrated that apolipoprotein M (apoM) is important for the formation of preβ‐high‐density lipoprotein (HDL) and cholesterol (CHO) efflux in macrophages to HDL. In the present study, we investigated the potential association of apoM genetic variation with the development of T2D.

Methods

Single nucleotide polymorphisms (SNPs) C‐1065A, T‐855C and T‐778C in the proximal promoter region of apoM gene were validated to represent in Han Chinese. Further genotyping experiments in 170 T2D patients and 156 non‐diabetic control subjects were performed with polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP).

Results

Single marker analysis for SNP T‐778C indicated that T2D patients had increased frequency of C allele in comparison with non‐diabetic controls (10.6% versus 5.8%, P = 0.026, OR = 1.934). In non‐diabetic controls, the carriers with CT and CC genotypes had higher plasma CHO (221.7 versus 204.2 mg/dL, P = 0.033) and fasting plasma glucose (FPG) (92.6 versus 89.7 mg/dL, P = 0.041) levels than the subjects with TT genotype. Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287). Haplotype analysis for those three SNPs, however, indicated that the common haplotypes were less informative than studying the role of the T‐778C variant independently of the haplotype context.

Conclusion

The present study provided the first evidence that SNP T‐778C in the proximal promoter region of apoM gene was associated with the levels of plasma CHO and FPG and also conferred the risk in the development of T2D among Han Chinese. Copyright © 2006 John Wiley & Sons, Ltd.
pH‐Specific Synthesis and Structural and Spectroscopic Characterization of a Complex between CoII and N,N‐Bis(phosphonomethyl)glycine: Cobalt–Phosphonate Interactions in the Solid State and in Solution
Authors: Mateescu Anca , Raptopoulou Catherine P. , Terzis Aris , Tangoulis Vassilis , Salifoglou Athanasios
Published: March 2006

The presence of cobalt in biological systems has been associated with a variety of regulatory roles as an inorganic cofactor. Its involvement in (bio)chemical processes, where it contributes to the integrity of the physiology of humans, underscores its ability to promote (bio)chemistry with molecular targets of variable mass and biological properties. Given the fact that organic phosphonates are widespread substrates/ligands in biological fluids, we sought to investigate the relevant chemistry with CoII. With the organophosphonate ligand N,N‐bis(phosphonomethyl)glycine (H5NTA2P) as the main metal ion binder, aqueous reactions with CoII were examined, ultimately leading to the isolation of the complex [Co(C4H9O8NP2)(H2O)2]·2H2O (1) at pH 1.5. This complex was characterized analytically, spectroscopically (FT‐IR, UV/Vis, EPR), magnetically, and by cyclic voltammetry. X‐ray crystallography shows that 1 is a compound with a molecular type of lattice. The complex consists of a mononuclear, octahedral CoII center coordinated by oxygen atoms belonging to the terminal phosphonate and carboxylate groups of H3NTA2P2–, the ligand nitrogen, and two bound water molecules. It should be emphasized that similar structural features have been observed in other metal organophosphonate lattices of materials with potential catalytic and chemical reactivity. The magnetic and EPR data for 1 suggest the presence of a high‐spin octahedral CoII, with a ground state of an effective spin S = 1/2. The solution UV/Vis and EPR spectra suggest retention of the integrity of 1, which is consistent with the magnetization measurements in the solid state. Collectively, the data suggest a soluble CoII–organodiphosphonate species, not unlike those expected in bio‐fluids containing the specific ligand or ligands structurally akin to H3NTA2P2–.The biological relevance of 1 to species in bio‐fluids and the structural association with CoII–organophosphonate materials is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Facile and Selected‐Control Synthesis of β‐MnO2 Nanorods and Their Magnetic Properties
Authors: Wang Guangli , Tang Bo , Zhuo Linhai , Ge Jiechao , Xue Mei
Published: March 2006

Single crystal β‐MnO2 nanorods were successfully synthesized employing a facile in‐situ redox precipitation hydrothermal process. The effects of various experimental conditions on the morphology of the products were investigated. The mechanism of formation of the nanorods was investigated and discussed based on the experimental results. The magnetic measurement of the nanorods with a diameter of 25–40 nm and a length of 240–440 nm indicates that the Néel magnetic transition temperature is about 6 K higher than that of the bulk β‐MnO2 crystal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Syntheses, Spectroscopic Studies, and Crystal Structures of Chiral [Rh(aminocarboxylato)(η4‐cod)] and Chiral [Rh(amino alcohol)(η4‐cod)](acetate) Complexes with an Example of a Spontaneous Resolution of a Racemic Mixture into Homochiral Helix‐Enantiomers
Authors: Enamullah Mohammed , Sharmin Aisha , Hasegawa Miki , Hoshi Toshihiko , Chamayou Anne‐Christine , Janiak Christoph
Published: March 2006

The dimeric complex acetato(η4‐cycloocta‐1,5‐diene)rhodium(I), [Rh(O2CMe)(η4‐cod)]2 (cod = cycloocta‐1,5‐diene), reacts with amino acids [HAA = L‐alanine, (S)‐2‐amino‐2‐phenylacetic acid (L‐phenylglycine), N‐methylglycine, and N‐phenylglycine] and with the amino alcohol (S)‐2‐amino‐2‐phenylethanol to afford the aminocarboxylato(η4‐cycloocta‐1,5‐diene)rhodium(I) complexes [Rh(AA)(η4‐cod)] (AA = deprotonated amino acid = aminocarboxylato ligand) and [(S)‐2‐amino‐2‐phenylethanol](η4‐cycloocta‐1,5‐diene)rhodium(I) acetate, [Rh{(S)‐HOCH2–CH(Ph)‐NH2}(η4‐cod)](O2CMe) (V). The complexes are characterized by IR, UV/Vis, 1H/13C NMR and mass spectroscopy. The achiral N‐phenylglycine ligand gives a chiral N‐phenylglycinato complex [Rh(O2C–CH2–NHPh)(η4‐cod)] (IV) with the amine nitrogen atom becoming the stereogenic center upon metal coordination. Complex IV crystallizes in the tetragonal, chiral space group P43 and the crystal structure reveals twofold spontaneous resolution of a racemic mixture into homochiral helix‐enantiomers. The investigated crystal contained only one type of helix, namely (left‐handed or M‐) 43‐helical chains. This is traced first to an intermolecular N–H···O hydrogen bonding from the stereogenic amino group to a neighboring unligated carboxyl oxygen atom that connects only molecules of the same (R)‐configuration into (left‐handed or M‐) 43‐helical chains. This intrachain homochirality is supplemented, secondly, by the interlocking of adjacent chains with their corrugated van der Waals surface to allow for an interchain transmission of the sense of helicity, building the single crystal from the same homochiral helix‐enantiomer. The enantiomeric amino alcohol complex V crystallizes in the monoclinic, noncentrosymmetric (Sohncke) space group P21. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Syntheses and Fluxional Processes of Diphenyl(2‐thienyl)phosphane Derivatives of Triosmium Clusters
Authors: Kiriakidou Kazemifar Nitsa K. , Stchedroff Marc J. , Mottalib M. Abdul , Selva Simona , Monari Magda , Nordlander Ebbe
Published: March 2006

Thermal treatment of [Os3(CO)12] with diphenyl(2‐thienyl)phosphane, Ph2P(C4H3S), results in the formation of [Os3(CO)12–x{Ph2P(C4H3S)}x] (x = 1–3, 1–3), but no C–H bond activation was observed. Reaction of [H2Os3(CO)10] with diphenyl(2‐thienyl)phosphane at ambient temperature affords [HOs3(μ‐H)(CO)10{Ph2P(C4H3S)}] (4), but when the samereaction is repeated at elevated temperatures, the cyclometallated species [(μ‐H)Os3(CO)9{μ3‐Ph2P(C4H2S)}] (5) and[(μ‐H)Os3(CO)8{μ3‐Ph2P(C4H2S)}{Ph2P(C4H3S)}] (6) are formed. In addition, two more products, tentatively assigned as [(μ‐H)Os3(CO)6{μ3‐Ph2P(C4H2S)}{μ‐Ph2P(C4H3S)}{Ph2P(C4H3S)}] (7) and [(μ‐H)Os3(CO)7{μ‐Ph2P(C4H2S)}{μ‐Ph2P(C4H3S)}{Ph2P(C4H3S)}] (8) are obtained. The dynamic behaviours of 2, 5 and 6 have been studied by variable‐temperature (VT) 1H and 31P{1H} NMR spectroscopy. The VT 31P{1H} NMR spectra of [Os3(CO)10{Ph2P(C4H3S)}2] (2) demonstrate that a mixture of two isomers, which are in rapid exchange at room temperature, is present and that the less common cis‐trans isomer, whose structure has been determined by X‐ray crystallography, is favoured for this cluster. The VT 1H NMR spectra of 5 indicate the presence of two isomers which are proposed to arise from an oscillation of the σ,η2‐vinyl group of the thienyl moiety between two metal atoms. A similar fluxional process is proposed to occur in 6 and the assignment of the room‐temperature structure(s) of this cluster was confirmed by 1H‐187Os 2D HMQC spectroscopy. In addition to 2, the solid‐state structures of 3, 5 and 6 have been determined by X‐ray crystallography. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Flood control of urban stormwater conduit systems using the finite element method
Authors: Kurahashi T. , Kawahara M.
Published: March 2006

This paper presents a method of controlling the water levels in a conduit system by employing optimal control theory and the finite element method. A shallow‐water equation is employed for the analysis of flow behaviour. Optimal control theory is utilized to obtain a control value for the target state value. The Sakawa–Shindo method is employed as a minimization technique. For the computational storage requirements, the time domain decomposition method is applied. The Crank–Nicolson method is used for temporal discretization. In addition to a method for optimally controlling water level, a method is presented for determining transversality conditions, the terminal condition of the Lagrange multiplier. Copyright © 2006 John Wiley & Sons, Ltd.
A genome wide linkage search for breast cancer susceptibility genes
Authors: Smith Paula , McGuffog Lesley , Easton Douglas F. , Mann Graham J. , Pupo Gulietta M. , Newman Beth , Chenevix‐Trench Georgia , Szabo Csilla , Southey Melissa , Renard Hélène , Odefrey Fabrice , Lynch Henry , Stoppa‐Lyonnet Dominique , Couch Fergus , Hopper John L. , Giles Graham G. , McCredie Margaret R. E. , Buys Saundra , Andrulis Irene , Senie Ruby , Goldgar David E. , Oldenburg Rogier , Kroeze‐Jansema Karin , Kraan Jaennelle , Meijers‐Heijboer Hanne , Klijn Jan G. M. , van Asperen Christi , van Leeuwen Inge , Vasen Hans F. A. , Cornelisse Cees J. , Devilee Peter , Baskcomb Linda , Seal Sheila , Barfoot Rita , Mangion Jon , Hall Anita , Edkins Sarah , Rapley Elizabeth , Wooster Richard , Chang‐Claude Jenny , Eccles Diana , Evans D. Gareth , Futreal P. Andrew , Nathanson Katherine L. , Weber Barbara L. , Rahman Nazneen , Stratton Michael R.
Published: March 2006

Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome‐wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2. © 2006 Wiley‐Liss, Inc.
Microarray‐based survey of CpG islands identifies concurrent hyper‐ and hypomethylation patterns in tissues derived from patients with breast cancer
Authors: Piotrowski Arkadiusz , Benetkiewicz Magdalena , Menzel Uwe , de Ståhl Teresita Díaz , Mantripragada Kiran , Grigelionis Gintautas , Buckley Patrick G. , Jankowski Michał , Hoffman Jacek , Bała Dariusz , Śrutek Ewa , Laskowski Ryszard , Zegarski Wojciech , Dumanski Jan P.
Published: March 2006

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper‐ or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2006 Wiley‐Liss, Inc.
Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen‐inducible DNA recombinase variant CreERT2
Authors: Hirrlinger Petra G. , Scheller Anja , Braun Christian , Hirrlinger Johannes , Kirchhoff Frank
Published: March 2006

Inducible gene modification using the Cre/loxP system provides a valuable tool for the analysis of gene function in the active animal. GFAP‐Cre transgenic mice have been developed to achieve gene recombination in astrocytes, the most abundant cells of the central nervous system, with pivotal roles during brain function and pathology. Unfortunately, these mice displayed neuronal recombination as well, since the GFAP promoter is also active in embryonic radial glia, which possess a substantial neurogenic potential. To enable the temporal control of gene deletions in astrocytes only, we generated a transgenic mouse with expression of CreERT2, a fusion protein of the DNA recombinase Cre and a mutated ligand‐binding domain of the estrogen receptor, under the control of the human GFAP promoter. In offspring originating from crossbreedings of GFAP‐CreERT2‐transgenic mice with various Cre‐sensitive reporter mice, consecutive intraperitoneal injections of tamoxifen induced genomic recombination selectively in astrocytes of almost all brain regions. In Bergmann glia, which represent the main astroglial cell population of the cerebellum, virtually all cells showed successful gene recombination. When adult mice received cortical stab wound lesions, simultaneously given tamoxifen induced substantial recombination in reactive glia adjacent to the site of injury. These transgenic GFAP‐CreERT2 mice will allow the functional analysis of loxP‐modified genes in astroglia of the postnatal and adult brain. © 2006 Wiley‐Liss, Inc.
Functional source separation from magnetoencephalographic signals
Authors: Barbati Giulia , Sigismondi Roberto , Zappasodi Filippo , Porcaro Camillo , Graziadio Sara , Valente Giancarlo , Balsi Marco , Rossini Paolo Maria , Tecchio Franca
Published: March 2006

We propose a novel cerebral source extraction method (functional source separation, FSS) starting from extra‐cephalic magnetoencephalographic (MEG) signals in humans. It is obtained by adding a functional constraint to the cost function of a basic independent component analysis (ICA) model, defined according to the specific experiment under study, and removing the orthogonality constraint, (i.e., in a single‐unit approach, skipping decorrelation of each new component from the subspace generated by the components already found). Source activity was obtained all along processing of a simple separate sensory stimulation of thumb, little finger, and median nerve. Being the sources obtained one by one in each stage applying different criteria, the a posteriori “interesting sources selection” step is avoided. The obtained solutions were in agreement with the homuncular organization in all subjects, neurophysiologically reacting properly and with negligible residual activity. On this basis, the separated sources were interpreted as satisfactorily describing highly superimposed and interconnected neural networks devoted to cortical finger representation. The proposed procedure significantly improves the quality of the extraction with respect to a standard BSS algorithm. Moreover, it is very flexible in including different functional constraints, providing a promising tool to identify neuronal networks in very general cerebral processing. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Differentiation‐related changes in mitochondrial properties as indicators of stem cell competence
Authors: Lonergan Thomas , Brenner Carol , Bavister Barry
Published: March 2006

Several methods may be used to assess stem cell competence, including the expression of cell surface markers and telomerase activity. We hypothesized that mitochondrial characteristics might be an additional and reliable way to verify stem cell competence. In a multipotent, adult monkey stromal stem cell line, previously shown to differentiate into adipocytes, chondrocytes, and osteocytes, we found that several mitochondrial properties change with increasing passage number in culture. Cells from the earliest passage (P11) versus those from a later passage (P17) are characterized by: (a) a much higher percentage of cells (85% vs. 18%) with a perinuclear arrangement of mitochondria; (b) a much lower percentage of cells (1% vs. 57%) with an aggregated mitochondrial arrangement, in which mitochondria appear to coalesce into large clumps; (c) a much lower percentage of cells with lipid droplets (1% vs. 36%), suggesting less differentiation into adipocytes; (d) a 5.6‐fold lower ATP content per cell (0.45 vs. 2.51 pmoles ATP/cell; and (e) a 10‐fold higher rate of oxygen consumption (37.8 vs. 3.8 nmoles O2/min/103 cells), indicating a higher metabolic activity. Collectively, these data indicate that the perinuclear arrangement of mitochondria, accompanied by a low ATP/cell content and a high rate of oxygen consumption, may be valid indicators of stem cell differentiation competence, while departures from this profile indicate that cells are differentiating or perhaps becoming senescent. These results represent the first characterization of mitochondrial properties reported for a primate stem cell line. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Highlights from the 5th annual meeting of the Italian society of virology
Authors: Salata Cristiano , Calistri Arianna , Palù Giorgio
Published: March 2006

The 5th National Congress of the Italian Society of Virology (SIV) was attended by junior‐ and senior‐level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus‐host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti‐viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was “HIV: determinants of pathogenicity and clinical implications.” The final program and the abstract book can be found at the web site http://www.siv‐virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Nitric oxide and p38 MAP kinase mediate shear stress‐dependent inhibition of MMP‐2 production in microvascular endothelial cells
Authors: Milkiewicz Malgorzata , Kelland Cassandra , Colgan Stephen , Haas Tara L.
Published: March 2006

Chronic exposure of the skeletal muscle microcirculation to elevated shear stress‐induces angiogenesis. Previous studies observed that shear stress‐induced capillary growth involves luminal sprouting, or internal division, of the capillaries, which is characterized by a minimal proliferative response and the retention of an intact basement membrane. Matrix metalloproteinases (MMPs) are associated with the process of abluminal sprouting angiogenesis, but may not be required for the process of luminal division during capillary growth. We analyzed the production of MMP‐2, using both the in vivo model of prazosin‐induced angiogenesis in rat skeletal muscle, and cultured microvascular endothelial cells exposed to laminar shear stress. We found that MMP‐2 was not elevated in capillaries of shear stress‐stimulated skeletal muscle, despite a significant increase in capillary number in response to a shear stress stimulus. In cultured microvascular endothelial cells, MMP‐2 mRNA and protein levels were attenuated significantly in response to shear stress exposure. This effect on MMP‐2 was reversed by nitric oxide (NO) synthase inhibition using LNNA. In contrast, exposure of static cultures of endothelial cells to NO donors significantly reduced MMP‐2 production. Shear stress exposure and NO donors both modified phosphorylation levels of several members of the MAPK family. Treatment of shear stress‐exposed cells with the p38 MAPK inhibitor, SB203580, abolished the shear stress‐mediated reduction in MMP‐2 mRNA. Thus, our data provide strong evidence that elevated shear stress inhibits MMP‐2 production in microvascular endothelial cells, an effect that is mediated by signal pathways involving both production of NO and activation of p38 MAPK. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
SLURP‐2: A novel cholinergic signaling peptide in human mucocutaneous epithelium
Authors: Arredondo Juan , Chernyavsky Alexander I. , Jolkovsky David L. , Webber Robert J. , Grando Sergei A.
Published: March 2006

The biologic role of novel cholinergic toxin‐like signaling peptides termed SLURP (secreted mammalian Ly‐6/uPAR‐related protein) in the mucocutaneous epithelium is a subject of intense research. Previous studies demonstrated that SLURP‐1 activates the α7 subtype of keratinocyte nicotinic acetylcholine receptors (nAChRs) and facilitates keratinization and programmed cell death, and that the level of SLURP‐2 was found to be upregulated several fold in the hyperproliferative skin of patients with psoriasis. In this study, we demonstrated for the first time that human epidermal and oral keratinocytes secrete SLURP‐2. We cloned human SLURP‐2 and produced the mouse monoclonal antibody 341F10‐1F12 that visualized SLURP‐2 in the cytoplasm of normal human epidermal and oral keratinocytes grown in culture. In epidermis, SLURP‐2 was found predominantly in the suprabasal compartment, whereas in the attached gingiva—in the lowermost epithelial layers. Recombinant SLURP‐2 (rSLURP‐2) competed with nicotinic radioligands for binding to keratinocytes, showing a higher affinity to the [3H]epibatidine‐ than [3H]nicotine‐labeled sites. Treatment withrSLURP‐2 significantly (P < 0.05) increased the number of keratinocytes in culture and their resistance to apoptosis, which could be abolished by mecamylamine more efficiently than α‐bungarotoxin. By real‐time PCR and in‐cell western,rSLURP‐2 significantly (P < 0.05) downregulated gene expression of the differentiation markers loricrin, filaggrin, and cytokeratins 1 and 10, and pro‐apoptotic Bax, Bad, and caspase 3 which were elevated by high extracellular calcium, andrSLURP‐2 also abolished activation of caspases 3 and 8 caused by camptothecin. These results indicated that SLURP‐2 competes with acetylcholine predominantly at the α3 nAChR, and that receptor ligation with SLURP‐2 delays keratinocyte differentiation and prevents apoptosis. Thus, the different effects observed for SLURP‐1 and ‐2 can be explained by their differential binding to the nAChR subtypes expressed in keratinocytes. These findings present a novel paradigm of the physiologic regulation of mucocutaneous epithelial cells by locally produced small hormone‐like peptide molecules, and open novel directions toward better understanding and treating of skin and mucosal diseases. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.
Regenerated Silk Fibroin Nanofibers: Water Vapor‐Induced Structural Changes and Their Effects on the Behavior of Normal Human Cells
Authors: Min Byung‐Moo , Jeong Lim , Lee Kuen Yong , Park Won Ho
Published: March 2006

Summary: Nanofibrous non‐woven matrices were prepared by electrospinning a regenerated silk fibroin (SF) solution, and the structural changes of SF nanofibers treated with water vapor were investigated using time‐resolved IR and 13C CP/MAS NMR spectroscopy. Conformational transitions of SF from random coil to β‐sheet structures were induced by water vapor treatment and were strongly dependent on the treatment time and temperature. Water vapor treatment provided a useful means of stabilizing the SF nanofiber matrices, resulting in the formation of matrices with a decreased solubility in water and increased mechanical strength. The adhesion and spreading of both normal human keratinocytes and fibroblasts onto the SF nanofiber matrices were also investigated, and the water vapor‐treated SF nanofiber matrices showed good cellular compatibility, in comparison with traditional methanol‐treated ones. This approach to controlling the conformational changes of SF nanofibers by water vapor treatment may be useful in the design and tailoring of novel materials for biomedical applications, including wound dressings and scaffolds for tissue engineering.

Scanning electron microscopic pictures of water vapor‐treated SF nanofibers.

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Scanning electron microscopic pictures of water vapor‐treated SF nanofibers.
pH Dependent Equilibria of Poly(anilineboronic acid)‐Saccharide Complexation in Thin Films
Authors: Deore Bhavana A. , Braun Monica D. , Freund Michael S.
Published: March 2006

Summary: The complexation of saccharides with poly(anilineboronic acid) as a function of pH has been studied with simultaneous measurements of open‐circuit potential and mass change. This study provides an insight into this reaction as well as the relationship between complexation and open‐circuit potential and the optimum pH for complexation of D‐fructose and D‐glucose. The optimum pH values for poly(anilineboronic acid)‐D‐fructose and ‐D‐glucose complexation are near the pKa values of the complex reported in homogeneous solution. At physiological pH (7.4), the apparent binding constant of D‐fructose and D‐glucose with poly(anilineboronic acid) is 19.2 and 0.2 M−1, respectively. In contrast, at pH 9.0, the apparent binding constant of D‐glucose with poly(anilineboronic acid) is 12 M−1, double than that of D‐fructose. The decrease in complexation in the polymer films at pH values above the pKa of the complexes is in contrast to the behavior in homogeneous solutions. This trend is observed for both D‐fructose and D‐glucose using open‐circuit potential, mass change and polarization modulated infrared reflection absorption spectroscopic measurements. Also, the complexation is limited in the polymer film, i.e., ≤23% boron is involved. These results suggest that steric and/or electrostatic interactions may play an important role in complexation within polymer films.

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Process Intensification in the Production of Specialty Waterborne Polymers
Authors: Alarcia Felipe , de la Cal José C. , Asua José M.
Published: March 2006

Summary: The feasibility of obtaining specialty waterborne adhesives in a CSTR was investigated facing the possibility of replacing the traditional semi‐batch reactors, which are commonly used in their production by a more efficient system. The key aspects focused on this work were the safety of the process, the kinetic feasibility, and the quality of the products, having as a reference the adhesive performance of the polymers produced in the semi‐batch reactors. Simulations showed that the production of 280 tons per week could be safely carried out even using mean residence times as short as 10 min. From a kinetic point of view, it was found that under these conditions, reasonable high conversions could be achieved in the reactor, resulting on a high production per unit volume of reactor. Furthermore, the adhesive properties of the latex were analyzed, and a much higher shear resistance was found for the latexes produced in the continuous reactor, while peel resistance and tack were found to be very similar disregarding the type of reactor used.

Safe process conditions in a CSTR.

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Safe process conditions in a CSTR.
Cover Picture: Macromol. Rapid Commun. 7/2006
Authors: Wang Zhen‐Gang , Xu Zhi‐Kang , Wan Ling‐Shu , Wu Jian , Innocent Christophe , Seta Patrick
Published: March 2006

Cover: Nanofibrous membranes possessing reactive groups and combining the advantages of carbon nanotubes with electrospinning techniques provide great potentials for the covalent immobilization of redox enzymes such as catalase. One promising application is in biosensors with high performance. Further details can be found in the article by Z.‐G. Wang, Z.‐K. Xu,* L.‐S. Wan, J. Wu, C. Innocent, and P. Seta on page 516.
Synaptotagmin I is involved in the regulation of cortical granule exocytosis in the sea urchin
Authors: Leguia Mariana , Conner Sean , Berg Linnea , Wessel Gary M.
Published: March 2006

Cortical granules are stimulus‐dependent secretory vesicles found in the egg cortex of most vertebrates and many invertebrates. Upon fertilization, an increase in intracellular calcium levels triggers cortical granules to exocytose enzymes and structural proteins that permanently modify the extracellular surface of the egg to prevent polyspermy. Synaptotagmin is postulated to be a calcium sensor important for stimulus‐dependent secretion and to test this hypothesis for cortical granule exocytosis, we identified the ortholog in two sea urchin species that is present selectively on cortical granules. Characterization by RT‐PCR, in‐situ RNA hybridization, Western blot and immunolocalization shows that synaptotagmin I is expressed in a manner consistent with it having a role during cortical granule secretion. We specifically tested synaptotagmin function during cortical granule exocytosis using a microinjected antibody raised against the entire cytoplasmic domain of sea urchin synaptotagmin I. The results show that synaptotagmin I is essential for normal cortical granule dynamics at fertilization in the sea urchin egg. Identification of this same protein in other developmental stages also shown here will be important for interpreting stimulus‐dependent secretory events for signaling throughout embryogenesis. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Error estimation of stress intensity factors for mixed‐mode cracks
Authors: Gallimard L. , Panetier J.
Published: March 2006

This paper presents an a posteriori error estimator for mixed‐mode stress intensity factors in plane linear elasticity. A surface integral over an arbitrary crown is used for the separate calculation of the combined mode's stress intensity factors. The error in the quantity of interest is based on goal‐oriented error measures and estimated through an error in the constitutive relation. Copyright © 2006 John Wiley & Sons, Ltd.