bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics and development of neural tube defects
Authors: Copp Andrew J , Greene Nicholas DE 
Published: November 2009

AbstractCongenital defects of neural tube closure (neural tube defects; NTDs) are among the commonest and most severe disorders of the fetus and newborn. Disturbance of any of the sequential events of embryonic neurulation produce NTDs, with the phenotype (eg anencephaly, spina bifida) varying depending on the region of neural tube that remains open. While mutation of > 200 genes is known to cause NTDs in mice, the pattern of occurrence in humans suggests a multifactorial polygenic or oligogenic aetiology. This emphasizes the importance of gene–gene and gene–environment interactions in the origins of these defects. A number of cell biological functions are essential for neural tube closure, with defects of the cytoskeleton, cell cycle and molecular regulation of cell viability prominent among the mouse NTD mutants. Many transcriptional regulators and proteins that affect chromatin structure are also required for neural tube closure, although the downstream molecular pathways regulated by these proteins is unknown. Some key signalling pathways for NTDs have been identified: over‐activation of sonic hedgehog signalling and loss of function in the planar cell polarity (non‐canonical Wnt) pathway are potent causes of NTD, with requirements also for retinoid and inositol signalling. Folic acid supplementation is an effective method for primary prevention of a proportion of NTDs in both humans and mice, although the embryonic mechanism of folate action remains unclear. Folic acid‐resistant cases can be prevented by inositol supplementation in mice, raising the possibility that this could lead to an additional preventive strategy for human NTDs in future. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The pathobiology of splicing
Authors: Ward Amanda J , Cooper Thomas A 
Published: November 2009

AbstractNinety‐four percent of human genes are discontinuous, such that segments expressed as mRNA are contained within exons and separated by intervening segments, called introns. Following transcription, genes are expressed as precursor mRNAs (pre‐mRNAs), which are spliced co‐transcriptionally, and the flanking exons are joined together to form a continuous mRNA. One advantage of this architecture is that it allows alternative splicing by differential use of exons to generate multiple mRNAs from individual genes. Regulatory elements located within introns and exons guide the splicing complex, the spliceosome, and auxiliary RNA binding proteins to the correct sites for intron removal and exon joining. Misregulation of splicing and alternative splicing can result from mutations in cis‐regulatory elements within the affected gene or from mutations that affect the activities of trans‐acting factors that are components of the splicing machinery. Mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. An understanding of the role of splicing in disease expands potential opportunities for therapeutic intervention by either directly addressing the cause or by providing novel approaches to circumvent disease processes. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Conformational analysis and inversion process in some perhydrodipyrido[1,2‐b;1′2′‐e]‐1,4,2,5‐ dioxadiazines
Authors: Ali Shaikh A. , AlSbaiee Alaaeddin , Wazeer Mohamed I. M. 
Published: November 2009

AbstractThe stereoselectivity in the cyclodimerization of several six‐membered cyclic nitrones has been investigated. The configurational/conformational analysis of the dimers (i.e. perhydrodipyrido[1,2‐b;1′2′‐e]‐1,4,2,5‐dioxadiazines) has been carried out by NMR spectroscopy. The NMR spectra of the dimers at lower temperatures indicated the presence of either a single or two invertomer(s). The nitrogen inversion barriers are determined using complete line–shape analysis. The invertomer ratios have been used to estimate the relative energies associated with the cis and trans ring fusion in these tricycles. A mechanistic rationale for the observed stereochemistry of the dimerization process has been presented. Copyright © 2009 John Wiley & Sons, Ltd.
Influence of solvent on theorthosubstituent effect in the alkaline hydrolysis of phenyl esters of substituted benzoic acids
Authors: Nummert Vilve , Piirsalu Mare , Koppel Ilmar A. 
Published: November 2009

AbstractThe second‐order rate constantsk(dm3 mol−1 s−1) for the alkaline hydrolysis of phenyl esters ofmeta‐,para‐ andortho‐substituted benzoic acids in aqueous 5.3 M NaClO4and 1.0 M Bu4NBr were measured by UV/Vis spectrophotometry at 25 °C. The variations in theorthoinductive,orthoresonance, as well asmetaandparapolar effects with solvent parameters were studied using data for the alkaline hydrolysis of phenyl esters of substituted benzoic acids in various media. The dependence of theorthosubstituent effect on solvent can be precisely described with the following equation: Δlogkortho = logkortho − logkH = 0.059 + 2.19σI + 0.304σ°R + 2.79E − 0.016ΔEσI − 0.085ΔEσ°R, where ΔEis the solvent electrophilicity, ΔE = ES − EH2O, characterizing the hydrogen‐bond donating power of the solvent. The increase in themetaandparapolar substituent effects with decrease in the solvent hydrogen‐bond donor capacity (electrophilicity) was approximately to the same extent (−0.068ΔEσ°m,p) as the resonance term for theorthosubstituents. The steric term oforthosubstituents was independent of the solvent parameters. The variations in theorthoinductive,orthoresonance, as well asmetaandparapolar substituent effects with the solvent electrophilicity were to the same extent as in phenyl benzoates containing the substituents in the phenyl part. The substituent effects in the alkaline hydrolysis of ethyl benzoates appeared to vary with the solvent electrophilicity nearly to the same extent as in the alkaline hydrolysis of substituted phenyl esters of benzoic acids. Copyright © 2009 John Wiley & Sons, Ltd.
Spirituality and well‐being in cancer patients: a review
Authors: Visser Anja , Garssen Bert , Vingerhoets Ad 
Published: November 2009

AbstractObjective: Cancer places many demands on the patient and threatens the person's sense of meaning to life. It has been shown that cancer patients use their spirituality to cope with these experiences. The present literature review summarizes the research findings on the relationship between spirituality and emotional well‐being. Special attention is given to the strength of the research findings.Methods: A literature search was performed in Pubmed and Web of Science. Spirituality does not necessarily coincide with religiosity. Therefore, studies were excluded that focused on religiosity. Forty publications met the inclusion criteria: Twenty‐seven studies that investigated the relationship between spirituality and well‐being, and 13 publications that explored the relationship between meaning in life and well‐being.Results: The majority of the cross‐sectional studies (31 of 36) found a positive association between spirituality and well‐being. The four studies with a longitudinal design showed mixed results. The significance of the findings is challenged, because most spirituality questionnaires contain several items that directly refer to emotional well‐being.Conclusions: Despite that the majority of the studies concluded that spirituality was associated with higher well‐being, no definitive conclusions on this relationship can be drawn due to major methodological shortcomings of these studies. Longitudinal research utilizing spirituality and well‐being measures that do not overlap in content is recommended. Copyright © 2009 John Wiley & Sons, Ltd.
Videotaped simulated interviews to improve medical students' skills in disclosing a diagnosis of cancer
Authors: Bonnaud‐Antignac Angélique , Campion Loïc , Pottier Pierre , Supiot Stéphane 
Published: November 2009

AbstractObjective: To assess the performance of the training course on the disclosure of a diagnosis of cancer intended for fifth year medical students of the University of Nantes.Methods: The course comprised three sessions: (1) a group discussion that taught a six‐point protocol (SPIKES) for delivering a diagnosis, (2) a videotaped simulated interview to assess protocol implementation and communication skills, and (3) feedback from a senior physician. The learning objectives were memorisation and implementation of the protocol, use of appropriate communication techniques to deal with the patient's response, and identifying one's own reactions in a stressful situation. Two types of assessments were performed before and after each session: self‐assessments by the students and a quantitative and qualitative external assessment by a psychologist and senior physician. In addition, recall of the six‐point protocol was assessed during the end‐of‐the‐year examination.Results: Overall, 108 students took part in the course during the 2004–2005 academic year. They felt that their competence improved after each session in terms of the three learning objectives. However, recall of the six‐point protocol was inadequate. It was best among students who considered they had progressed most.Conclusions: Our training course on communication techniques helps students acquire confidence in their skills in breaking bad news by backing theory with practice and feedback. The students make progress despite the psychological stress generated by simulated real‐life conditions. Copyright © 2009 John Wiley & Sons, Ltd.
Coordination sphere of the third metal site is essential to the activity and metal selectivity of alkaline phosphatases
Authors: Koutsioulis Dimitris , Lyskowski Andrzej , Mäki Seija , Guthrie Ellen , Feller Georges , Bouriotis Vassilis , Heikinheimo Pirkko 
Published: November 2009

AbstractAlkaline phosphatases (APs) are commercially applied enzymes that catalyze the hydrolysis of phosphate monoesters by a reaction involving three active site metal ions. We have previously identified H135 as the key residue for controlling activity of the psychrophilic TAB5 AP (TAP). In this article, we describe three X‐ray crystallographic structures on TAP variants H135E and H135D in complex with a variety of metal ions. The structural analysis is supported by thermodynamic and kinetic data. The AP catalysis essentially requires octahedral coordination in the M3 site, but stability is adjusted with the conformational freedom of the metal ion. Comparison with the mesophilic Escherichia coli, AP shows differences in the charge transfer network in providing the chemically optimal metal combination for catalysis. Our results provide explanation why the TAB5 and E. coli APs respond in an opposite way to mutagenesis in their active sites. They provide a lesson on chemical fine tuning and the importance of the second coordination sphere in defining metal specificity in enzymes. Understanding the framework of AP catalysis is essential in the efforts to design even more powerful tools for modern biotechnology.
The importance of valine 114 in ligand binding in β2‐adrenergic receptor
Authors: Arakawa Makoto , Yanamala Naveena , Upadhyaya Jasbir , Halayko Andrew , Klein‐Seetharaman Judith , Chelikani Prashen 
Published: November 2009

AbstractG‐protein coupled receptors (GPCRs) are transmembrane signaling molecules, with a majority of them performing important physiological roles. β2‐Adrenergic receptor (β2‐AR) is a well‐studied GPCRs that mediates natural responses to the hormones adrenaline and noradrenaline. Analysis of the ligand‐binding region of β2‐AR using the recently solved high‐resolution crystal structures revealed a number of highly conserved amino acids that might be involved in ligand binding. However, detailed structure‐function studies on some of these residues have not been performed, and their role in ligand binding remains to be elucidated. In this study, we have investigated the structural and functional role of a highly conserved residue valine 114, in hamster β2‐AR by site‐directed mutagenesis. We replaced V114 in hamster β2‐AR with a number of amino acid residues carrying different functional groups. In addition to the complementary substitutions V114I and V114L, the V114C and V114E mutants also showed significant ligand binding and agonist dependent G‐protein activation. However, the V114G, V114T, V114S, and V114W mutants failed to bind ligand in a specific manner. Molecular modeling studies were conducted to interpret these results in structural terms. We propose that the replacement of V114 influences not only the interaction of the ethanolamine side‐chains but also the aryl‐ring of the ligands tested. Results from this study show that the size and orientation of the hydrophobic residue at position V114 in β2‐AR affect binding of both agonists and antagonists, but it does not influence the receptor expression or folding.
Novel localization of low affinity NGF receptor (p75) in the stroma of prostate cancer and possible implication in neoplastic invasion: An immunohistochemical and ultracytochemical study
Authors: Rende Mario , Rambotti Maria G. , Stabile Anna M. , Pistilli Alessandra , Montagnoli Claudia , Chiarelli Maria T. , Mearini Ettore 
Published: November 2009

AbstractBACKGROUNDThe localization of low affinity nerve growth factor receptor (p75) in prostate carcinogenesis is still unclear. Our aim was to reinvestigate the localization of p75 in normal and pathological prostate and to check a possible correlation to neoplastic grading.METHODSSpecimens from 33 prostate cancers and from normal prostatic tissue were analyzed for p75 expression at light and ultrastructural levels.RESULTSIn normal tissue p75‐immunoreactivity was restricted to basal cells in the epithelial compartment and to nerves and blood vessel in stroma. During carcinogenesis, p75‐immunoreactivity progressively decreased at the periphery of the foci according to the increase in malignancy. No p75‐immunoreactivity was detected inside of the foci. On the contrary, in stroma we found a dramatic increase in p75‐immunoreactivity correlated to an increase in malignancy. In this compartment, for the first time ultrastructural analysis identified p75‐immunoreactivity in smooth muscle cells (SMC) that are p75‐negative in normal conditions.CONCLUSIONThe present study confirms at ultrastructural level a malignant‐dependent p75 decrease in basal cells of neoplastic foci. Furthermore, we show a novel, malignant‐dependent localization of p75 in SMC in the stroma around the neoplastic foci. Since p75 expression is present in muscle cells only during the earliest stages of differentiation and mature muscle cells lose this expression, we hypothesize that p75 re‐expression in stromal SMC is a further mechanism related to the general de‐differentiation of the stroma connected to the neoplastic invasion. According to this hypothesis, our results suggest that p75 analysis could be a novel prognostic marker for prostate cancer. Prostate 70: 555–561, 2010. © 2009 Wiley‐Liss, Inc.
Capturing Dynamic Processes of Change in GROW Mutual Help Groups for Mental Health
Authors: Finn Lizzie D. , Bishop Brian J. , Sparrow Neville 
Published: November 2009

AbstractThe need for a model that can portray dynamic processes of change in mutual help groups for mental health (MHGMHs) is emphasized. A dynamic process model has the potential to capture a more comprehensive understanding of how MHGMHs may assist their members. An investigation into GROW, a mutual help organization for mental health, employed ethnographic, phenomenological and collaborative research methods. The study examined how GROW impacts on psychological well being. Study outcomes aligned with the social ecological paradigm (Maton in Understanding the self‐help organization: frameworks and findings. Sage, Thousand Oaks 1994) indicating multifactorial processes of change at and across three levels of analysis: group level, GROW program/community level and individual level. Outcome themes related to life skills acquisition and a change in self‐perception in terms of belonging within community and an increased sense of personal value. The GROW findings are used to assist development of a dynamic multi‐dimensional process model to explain how MHGMHs may promote positive change.
Is ultrasound screening for DDH in babies born breech sufficient?
Authors: Imrie Meghan , Scott Vanessa , Stearns Philip , Bastrom Tracey , Mubarak Scott J. 
Published: November 2009

Purpose To review our incidence of developmental dysplasia of the hip (DDH) in breech infants referred for ultrasound screening and to determine if subsequent follow-up radiographs are necessary in these patients with normal clinical and ultrasound examinations. Methods A review of the clinical data and imaging studies of all children with the risk factor of breech presentation that were referred for orthopedic evaluation over a 5-year period was conducted. All patients were examined by a fellowship-trained pediatric orthopedic surgeon and all ultrasounds were done at approximately 6 weeks of age by an experienced ultrasonographer. Ultrasounds were evaluated using the dynamic method as described by Harcke. As per our protocol, all patients with normal screening ultrasounds were brought back for a final clinical examination and radiographic check at 4–6 months. Acetabular dysplasia was indicated by radiographic parameters—if there was severe blunting of the sourcil, abnormal acetabular index for age, or if there was significant asymmetry of acetabular indices side-to-side—in the setting of clinical parameters—if there was greater than 10° difference in side-to-side abduction or symmetric abduction of less than 60°. Results Three hundred patients with the risk factor of breech presentation were included. Thirty-four patients had clinically unstable hips; 266 had clinically stable hips and were screened by ultrasound. Sixty-four percent were female and 36% were male. Twenty-seven percent of these breech patients had abnormal screening ultrasounds and were subsequently treated. Of the remaining 73% with normal ultrasounds, who were returned per protocol at a mean of 5 months, 29% had evidence of dysplasia and underwent treatment. The diagnosis of dysplasia following a normal ultrasound was based on both radiographic and clinical parameters. Of the hips treated with a Pavlik harness, 62% had acetabular indices at least two standard deviations from the age-corrected average versus 26% of patients not treated. The average length of follow-up was 10 months. Conclusions Retrospectively, we found that, at approximately 6 weeks of age, ultrasound screening of breech patients with clinically stable hips produces an incidence of DDH of 27%. In those patients with a normal ultrasound, 29%, at 4–6 months radiographic follow-up, were found to have dysplasia requiring treatment. This data supports breech as the most important risk factor for hip dysplasia and we, therefore, recommend careful and longitudinal evaluation of these patients with: a careful newborn physical examination, an ultrasound at age 6 weeks, and an anteroposterior (AP) pelvis and frog lateral radiograph at 6 months, as the risk of subsequent dysplasia is too high to discharge patients after a normal ultrasound.
Brief report: The association between non‐suicidal self‐injury, self‐concept and acquaintance with self‐injurious peers in a sample of adolescents
Authors: Claes Laurence , Houben Adinda , Vandereycken Walter , Bijttebier Patricia , Muehlenkamp Jennifer 
Published: November 2009

ABSTRACTThe current study investigated the association between non‐suicidal self‐injury (NSSI), self‐concept and acquaintance with NSSI peers in a sample of 150 high school students (60% female) with a mean age of 15.56 (SD = 2.00) years. Analyses showed that students with NSSI rated themselves lower on academic intelligence, physical attractiveness, social skills and emotional stability than their non‐NSSI peers. The self‐injurers also had more friends who engaged in NSSI, and having more NSSI acquaintances was negatively related to self‐esteem. It could be that adolescents with lower self‐esteem are more attracted to self‐injuring peers, or that adolescents with low self‐esteem are more vulnerable to copy NSSI to deal with their problems or to gain a certain identity in their peer group. Future studies must test these possible NSSI pathways.
A chain morphism for Adams operations on rational algebraic K-theory
Authors: Feliu Elisenda 
Published: November 2009

AbstractFor any regular noetherian scheme X and every k ≥ 1, we define a chain morphism ψk between two chain complexes whose homology with rational coefficients is isomorphic to the algebraic K-groups of X tensored by ℚ. It is shown that the morphisms ψk induce in homology the Adams operations defined by Gillet and Soulé or the ones defined by Grayson.
Interpretation of Late Ordovician glaciogenic reservoirs from 3-D seismic data: an example from the Murzuq Basin, Libya
Authors: LE HERON DANIEL PAUL 
Published: November 2009

AbstractUnderstanding the recessional behaviour of ancient pre-Cenozoic ice sheets based on seismic reflection studies is generally difficult through scarcity of data. In North Africa, however, hydrocarbon exploration has produced high quality seismic reflection datasets that permit an analysis of the morphology and internal sedimentary architecture of incisions of Late Ordovician age related to the Hirnantian glaciation. Analysis of a high-resolution 3-D seismic dataset covering a small area in western Libya (the N Murzuq Basin) reveals a sharply defined, WNW–ESE-oriented palaeo-escarpment, with a higher (cliff-forming) western margin and a lower (basin-forming) eastern margin. The palaeo-escarpment defines the western flank of a sub-basin extending up to 60 km in width, known as the Awbari Trough. The escarpment and the trough are interpreted as the morphological expression of a major unconformity dividing pre-glacial sediments below from Late Ordovician (?Hirnantian) glacially related sediments above. Two hypotheses are considered for the origins of both the escarpment and the Awbari Trough: (1) as a tectonic feature such as a half graben that was active during sedimentation and (2) a glacially related palaeotopography, with the latter interpretation preferred, owing to the lack of evidence for syn-sedimentary fault activity. The width of the Awbari Trough compares to the large-scale cross-shelf troughs in modern high latitude settings, such as the Barents Shelf, produced by ice streams. The Awbari Trough was progressively filled in by gravity flow deposits throughout the course of the glaciation, until the initial incision became filled in with sediments during an overall glacial retreat phase and ceased to influence sedimentation patterns. Glacial re-advance across the basin produced a second unconformity observed in seismic data. Above this unconformity, meltwater processes incised a shallow (~ 20 m) and wide (~ 5 km) subglacial tunnel valley. Stabilization of the ice front prior to its ultimate retreat resulted in the deposition of a delta complex prior to the Early Silurian transgression.
Regulatory compliance in Lake Victoria fisheries
Authors: EGGERT HÅKAN , LOKINA RAZACK B. 
Published: November 2009

ABSTRACTThis paper analyzes the causes for regulatory compliance, using traditional deterrence variables and potential moral and social variables. We use self-reported data from 459 Tanzanian artisanal fishers in Lake Victoria. The results indicate that the decision to be either a non-violator or a violator, as well as the violation rate – if the latter – are influenced by changes in deterrence variables like the probability of detection and punishment and also by legitimacy and social variables. We also identify a small group of fishers who react neither to normative aspects nor to traditional deterrence variables but persistently violate the regulation.