bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations of pre‐mRNA splicing in cancer
Authors: Kalnin̨a Zane , Zayakin Pawel , Silin̨a Kariīna , Linē Aija
Published: January 2005

Recent genomewide analyses of alternative splicing (AS) indicate that up to 70% of human genes may have alternative splice forms, suggesting that AS together with various posttranslational modifications plays a major role in the production of proteome complexity. Splice‐site selection under normal physiological conditions is regulated in the developmental stage in a tissue type‐specific manner by changing the concentrations and the activity of splicing regulatory proteins. Whereas spliceosomal errors resulting in the production of aberrant transcripts rarely occur in normal cells, they seem to be an intrinsic property of cancer cells. Changes in splice‐site selection have been observed in various types of cancer and may affect genes implicated in tumor progression (for example, CD44, MDM2, and FHIT) and in susceptibility to cancer (for example, BRCA1 and APC). Splicing defects can arise from inherited or somatic mutations in cis‐acting regulatory elements (splice donor, acceptor and branch sites, and exonic and intronic splicing enhancers and silencers) or variations in the composition, concentration, localization, and activity of regulatory proteins. This may lead to altered efficiency of splice‐site recognition, resulting in overexpression or down‐regulation of certain splice variants, a switch in splice‐site usage, or failure to recognize splice sites correctly, resulting in cancer‐specific splice forms. At least in some cases, changes in splicing have been shown to play a functionally significant role in tumorigenesis, either by inactivating tumor suppressors or by gain of function of proteins promoting tumor development. Moreover, cancer‐specific splicing events may generate novel epitopes that can be recognized by the host's immune system as cancer specific and may serve as targets for immunotherapy. Thus, the identification of cancer‐specific splice forms provides a novel source for the discovery of diagnostic or prognostic biomarkers and tumor antigens suitable as targets for therapeutic intervention. © 2005 Wiley‐Liss, Inc.
Bile acid deoxycholate induces differential subcellular localisation of the PKC isoenzymes β1, ϵ and δ in colonic epithelial cells in a sodium butyrate insensitive manner
Authors: Looby Eileen , Long Aideen , Kelleher Dermot , Volkov Yuri
Published: January 2005

Elevated levels of bile acids have been implicated in the abnormal morphogenesis of the colonic epithelium thus contributing to colorectal cancer (CRC). Alternatively sodium butyrate (NaB) produced by anaerobic fermentation of dietary fibre is regarded as being protective against colon cancer. Bile acids such as deoxycholic acid (DCA) are thought to mediate some of their actions by differentially activating protein kinase C (PKC). We examined the effects of DCA on the subcellular localisation of PKC‐β1, ‐ϵ and ‐δ and whether these responses could be modulated by NaB. HCT116 cells endogenously express PKC‐ϵ and ‐δ but not PKC‐β. DCA treatment results in endogenous PKC‐ϵ translocation but not PKC‐δ after 1 hr. To study the subcellular localisation of PKC isoforms in response to DCA in real time, PKC‐β1, PKC‐ϵ and PKC‐δ functionally intact green fluorescent protein (GFP) fusion constructs were used. Stimulation with 300 μM DCA induces rapid translocation of PKC‐β1‐GFP and PKC‐ϵ‐GFP but not PKC‐δ‐GFP from the cytosol to the plasma membrane in 15 min. Interestingly, pretreatment with 4mM NaB does not modify the response of the PKC isoenzymes to DCA as PKC‐β1‐GFP and PKC‐ϵ‐GFP translocates to the plasma membrane in 15 min whereas PKC‐δ‐GFP localisation remains unaltered. Immunofluorescence shows that PKC‐β1‐GFP and PKC‐ϵ‐GFP cells treated with DCA colocalise with the cytoskeletal elements actin and tubulin adjacent to the plasma membrane. Our findings demonstrate that the differential activation of the PKC isoenzymes by DCA may be of critical importance for the functional responses of colonic epithelial cells. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html © 2004 Wiley‐Liss, Inc.
Risk factors of incident melanocytic nevi: A longitudinal study in a cohort of 1,232 young German children
Authors: Bauer Jürgen , Büttner Petra , Wiecker Tine Sander , Luther Heike , Garbe Claus
Published: January 2005

The number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic‐moderate and intermittent‐high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3‐year follow‐up was conducted in 1,232 young children 2–7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun‐protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent‐high sun exposure during holidays (p < 0.001) and chronic‐moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic‐moderate or intermittent‐high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts. © 2004 Wiley‐Liss, Inc.
V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential
Authors: Serra Montserrat , Miquel Laia , Domenzain Clelia , Docampo María José , Fabra Angels , Wight Thomas N. , Bassols Anna
Published: January 2005

Versican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma. The expression of increased amounts of versican in the extracellular matrix may play a role in tumor cell growth, adhesion and migration. We have expressed the V3 isoform of versican in human and canine melanoma cell lines. Retroviral overexpression of V3 did not change the morphology of any of the cell lines but markedly reduces cell growth in the V3 versican expressing melanoma cells. The V3‐overexpressing melanoma cells retain their diminished growth potential in vivo because primary tumors arising from these cell lines growth more slowly than their vector only counterparts. This effect was accompanied by increases in cell adhesion on hyaluronan and an enhanced ability to migrate on hyaluronan‐coated transwell chambers. This enhanced migration is blocked when cells are preincubated with soluble hyaluronan, or anti‐CD44 antibodies, suggesting that V3 acts by altering the hyaluronan‐CD44 interaction. Hyaluronan content and CD44 expression are not altered in V3‐overexpressing cells compared to vector‐transduced cells. Our results show that V3 overproduction modulates the in vitro behavior of human and canine melanoma cell lines and reduces their tumorigenicity in vivo. © 2004 Wiley‐Liss, Inc.
Smoking and the risk of endometrial cancer: Results from the Nurses' Health Study
Authors: Viswanathan Akila N. , Feskanich Diane , De Vivo Immaculata , Hunter David J. , Barbieri Robert L. , Rosner Bernard , Colditz Graham A. , Hankinson Susan E.
Published: January 2005

An inverse association between smoking and endometrial cancer has generally been observed, primarily among current smokers. To assess this association, we analyzed data from the prospective Nurses' Health Study. From 1976 to 2000, 702 cases of invasive endometrial cancer were identified during 1.8 million person‐years of follow‐up. Smoking status was assessed in 1976 and updated every 2 years. Cox proportional hazards models were used to calculate multivariate relative risks (RRs), controlling for endometrial cancer risk factors. Compared to never smokers, the multivariate RR of endometrial cancer was significantly lower among both current smokers (RR = 0.63; 95% CI = 0.50–0.79) and past smokers (RR = 0.73; 95% CI = 0.62–0.87). When additionally adjusting for body mass index (BMI), the RR for current smokers was attenuated (RR = 0.72; 95% CI = 0.57–0.90), but the RR for past smokers did not change. Risk was lower among women who smoked 35 or more cigarettes a day (RR = 0.60; 95% CI = 0.39–0.91) and among those who smoked for 40 or more years (RR = 0.63; 95% CI = 0.45–0.87). Tests for trend, which excluded never smokers, were not statistically significant for any of the smoking variables analyzed. These data indicate that both current and past smoking are associated with a lower risk of endometrial cancer. The findings provide insight into disease etiology and suggest that the influence of smoking on endometrial cancer risk occurs even in early adulthood, is long‐lasting, and may not be attributed solely to short‐term hormonal modulation. © 2004 Wiley‐Liss, Inc.
Novel murine B‐cell lymphoma/leukemia model to study BCL2‐driven oncogenesis
Authors: Meijerink Jules P.P. , Van Lieshout Esther M.M. , Beverloo H. Berna , Van Drunen Ellen , Mensink Ewald J.B.M. , Macville Merryn , Pieters Rob
Published: January 2005

The BCL‐2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non‐Hodgkin lymphoma and B‐cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2‐enforced leukemogenesis, we developed a murine B‐cell lymphoma/leukemia model based on the IL‐3‐dependent Balb/C pro‐B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL‐2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL‐2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL‐2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL‐3‐responsive leukemia. Cellular transformation was independent of alterations in c‐Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2‐enforced lymphoma/leukemogenesis. © 2004 Wiley‐Liss, Inc.
CXCR3‐positive B cells found at elevated frequency in the peripheral blood of patients with MALT lymphoma are attracted by MIG and belong to the lymphoma clone
Authors: Suefuji Hiroaki , Ohshima Koichi , Karube Kennosuke , Kawano Riko , Nabeshima Kazuki , Suzumiya Junnji , Hayabuchi Naofumi , Kikuchi Masahiro
Published: January 2005

Chemokine receptors mediate the migration of lymphocytes through binding of their ligands. CXCR3 is expressed in Th1 T cells; however, CXCR3 was recently reported in B‐cell mucosa‐associated lymphoid tissue (MALT)‐type lymphoma and splenic marginal zone lymphoma. To investigate whether CXCR3‐positive B lymphocytes in peripheral blood (PB) migrate to MALT and spleen, and whether the lymphoma clone is present in PB, we studied 16 cases of MALT lymphoma. In MALT cases, CXCR3‐positive B lymphocytes in PB could migrate to MIG, the CXCR3 ligand. Immunohistochemical analysis showed that MALT lymphoma cells expressed CXCR3, whereas epithelial glands and/or stromal cells expressed MIG. In the PCR analysis for VH gene rearrangements, MALT lymphoma showed monoclonal or oligoclonal bands. In addition, in 8 of 16 MALT cases, the VH gene rearrangement of MALT lymphoma had the same bands as the CXCR3‐positive B lymphocytes in PB. In 4 cases, the same clones of DNA sequences were confirmed in MALT lymphoma and CXCR3‐positive B lymphocytes of PB. The findings support the theory that CXCR3‐positive B lymphocytes in PB of MALT patients belong to the lymphoma clone and migrate to MIG‐expressing mucosa‐associated lymphoid tissue. It seemed to be associated with the dissemination of MALT lymphoma. © 2004 Wiley‐Liss, Inc.
Early diagnosis of breast cancer by hair diffraction
Authors: James Veronica , Corino Gary , Robertson Terry , Dutton Nichole , Halas Danka , Boyd Alexandra , Bentel Jacqueline , Papadimitriou John
Published: January 2005

A correlation between the incidence of breast cancer and an observed change in the X‐ray diffraction pattern of hair from the afflicted individuals was first reported in 1999. Since that time, over 500 hair samples have been analyzed in double‐blinded breast cancer studies with no false negatives being detected. To correlate this observed change with the presence of breast cancer, we examined whiskers removed from nude mice prior to and 8 weeks after subcutaneous implantation of a human breast cancer cell line. Here we show that the change observed in human hair was also evident in whiskers and that it appeared soon after cancer cell implantation. © 2004 Wiley‐Liss, Inc.
Anti‐tumor efficacy of the nucleoside analog 1‐(2‐deoxy‐2‐fluoro‐4‐thio‐β‐D‐arabinofuranosyl) cytosine (4′‐thio‐FAC) in human pancreatic and ovarian tumor xenograft models
Authors: Zajchowski Deborah A. , Biroc Sandra L. , Liu Hsaio‐Lai , Chesney Steven K. , Hoffmann Jens , Bauman John , Kirkland Thomas , Subramanyam Babu , Shen Jun , Ho Elena , Tseng Jih‐Lie , Dinter Harald
Published: January 2005

1‐(2‐Deoxy‐2‐fluoro‐4‐thio‐β‐D‐arabinofuranosyl) cytosine (4′‐thio‐FAC) is a deoxycytidine analog that has been shown previously to have impressive anti‐proliferative and cytotoxic effects in vitro and in vivo toward colorectal and gastric tumors. In our present studies, the pharmacokinetic behavior in nude mice and the effectiveness of 4′‐thio‐FAC against human pancreatic and ovarian tumor growth were assessed in comparison with standard chemotherapeutic agents. Potent in vitro anti‐proliferative effects were observed against pancreatic (Capan‐1, MIA‐PaCa‐2, BxPC‐3) and ovarian (SK‐OV‐3, OVCAR‐3, ES‐2) cancer cell lines with IC50 of 0.01–0.2 μM. In vivo anti‐tumor activity was evaluated in nude mice bearing subcutaneously (s.c.) implanted human pancreatic tumor xenografts or intraperitoneally (i.p.) disseminated human ovarian xenografted tumors. Oral daily administration of 4′‐thio‐FAC for 8–10 days significantly inhibited the growth of gemcitabine‐resistant BxPC‐3 pancreatic tumors and induced regression of gemcitabine‐refractory Capan‐1 tumors. 4′‐Thio‐FAC was also a highly effective inhibitor of ovarian peritoneal carcinomatosis. In the SK‐OV‐3 and ES‐2 ovarian cancer models, 4′‐thio‐FAC prolonged survival to a greater extent than that observed with gemcitabine. Furthermore, the superiority of 4′‐thio‐FAC to carboplatin and paclitaxel was demonstrated in the ES‐2 clear cell ovarian carcinoma model. Studies provide evidence that 4′‐thio‐FAC is a promising new alternative to gemcitabine and other chemotherapeutic drugs in the treatment of a variety of tumor indications, including pancreatic and ovarian carcinoma. © 2004 Wiley‐Liss, Inc.
Characterization of dinitroporphyrin zinc complexes by electrospray ionization tandem mass spectrometry. Unusual fragmentations of β‐(1,3‐dinitroalkyl) porphyrins
Authors: Silva E. M. P. , Domingues M. R. M. , Barros C. , Faustino M. A. F. , Tomé J. P. C. , Neves M. G. P. M. S. , Tomé A. C. , Santana‐Marques M. G. , Cavaleiro J. A. S. , Ferrer‐Correia A. J.
Published: January 2005

The zinc complexes of diaryl bis(p‐nitrophenyl)porphyrins and β‐(1,3‐dinitroalkyl)tetraphenylporphyrins were studied by electrospray ionization (ESI) tandem mass spectrometry (MS/MS). All porphyrins showed the protonated molecule under ESI conditions. The protonated molecules were induced to fragment and the corresponding ESI tandem mass spectra were analysed. Porphyrins with two p‐nitrophenyl groups showed, as expected, characteristic fragmentations including either loss of one nitro group, as the major fragment of the tandem mass spectra, and loss of both nitro groups. In contrast, MS/MS of the β‐(1,3‐dinitroalkyl)porphyrins provided interesting and unexpected results such as the absence (or in insignificant abundance) of the ions formed by loss of one nitro group. However, these porphyrins show an abundant fragment due to combined loss of the two nitro groups. Also, the typical β‐cleavage of the alkyl chain is not observed per se, only when combined with loss of HNO2 or •NO2. Instead, α‐cleavage, with loss of the β‐pyrrolic substituent, is the most favourable process. Copyright © 2005 John Wiley & Sons, Ltd.
Resonant scattering of a photon by an electron in the field of a circularly
polarized electromagnetic wave
Authors: Voroshilo A I , Roshchupkin S P
Published: January 2005

This paper presents, for general relativistic case, a
theoretical study of Compton effect in the field of a circularly
polarized wave under resonant condition – resonances related to a
virtual intermediate particle that falls within the mass shell. We
derive the expressions for the resonant amplitude and the
differential cross section when the invariant intensity parameter
of the wave is small (η << 1) and absent interference of the
scattering and annihilation reaction amplitudes. It is
demonstrated that the resonant cross section of scattering may be
several orders of magnitude higher than the cross section of
Compton effect in the absence of the external field.
New mid IR (1.5–2.2 μm) Raman lasers based on barium tungstate
and barium nitrate crystals
Authors: Basiev T T , Doroshenko M E , Osiko V V , Sverchkov S E , Galagan B I
Published: January 2005

Efficient mid IR (1.5–2.2 μm) Raman lasers based
on novel BaWO4 and known Ba(NO3)2 Raman crystals were
developed and investigated. Different Stokes shifted components
were obtained with longest wavelength about 2.2 μm with
efficiency up to 10%.
Optimized high power laser mirror design for low quality degradation and beam analysis
Authors: Ach F , Viöl W
Published: January 2005

The thermally induced deformation of different copper
mirrors for infrared laser beams was simulated using a finite
element method. The deformation is highly dependent on the mirror
design. Several mirror designs with different cooling arrangements
have been simulated.

A mirror design with a set of
straight cooling channels and a stiff body shows the least
deformation. The cooling channel diameter, spacing, surface
distance and overall mirror thickness were varied at this design
and the surface deformation was compared. The mirror design not
only influences the overall expansion of the mirror but also the
shape of the surface deformation.

The optimized mirror
geometry provides small quality degradation at beam guidance and
the possibility of an online beam monitoring method by measurement
of the local surface deformation. The method can serve as a device
for online and beam position detection.
Long‐term botulinum toxin efficacy, safety, and immunogenicity
Authors: Mejia Nicte I. , Vuong Kevin Dat , Jankovic Joseph
Published: January 2005

To determine the long‐term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow‐up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 ± 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0‐to‐4 scale (0 = no effect; 4 = marked improvement) was 3.7 ± 0.6 and the mean total duration of response was 15.4 ± 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab‐negative patients, 16 resumed responsiveness after dose adjustments and2 persisted as nonrespondents. Except for 1 patient, the 4 Ab‐positive and the 2 clinical nonresponders are being treated with BTX‐B. This longest reported follow‐up of BTX injections confirms the long‐term efficacy and safety of this treatment. © 2005 Movement Disorder Society
A new method for identification of protein (sub)families in a set of proteins based on hydropathy distribution in proteins
Authors: Pánek Josef , Eidhammer Ingvar , Aasland Rein
Published: January 2005

Structural similarity among proteins is reflected in the distribution of hydropathicity along the amino acids in the protein sequence. Similarities in the hydropathy distributions are obvious for homologous proteins within a protein family. They also were observed for proteins with related structures, even when sequence similarities were undetectable. Here we present a novel method that employs the hydropathy distribution in proteins for identification of (sub)families in a set of (homologous) proteins. We represent proteins as points in a generalized hydropathy space, represented by vectors of specifically defined features. The features are derived from hydropathy of the individual amino acids. Projection of this space onto principal axes reveals groups of proteins with related hydropathy distributions. The groups identified correspond well to families of structurally and functionally related proteins. We found that this method accurately identifies protein families in a set of proteins, or subfamilies in a set of homologous proteins. Our results show that protein families can be identified by the analysis of hydropathy distribution, without the need for sequence alignment. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Native and modeled disulfide bonds in proteins: Knowledge‐based approaches toward structure prediction of disulfide‐rich polypeptides
Authors: Thangudu Ratna Rajesh , Vinayagam A. , Pugalenthi G. , Manonmani A. , Offmann B. , Sowdhamini R.
Published: January 2005

Structure prediction and three‐dimensional modeling of disulfide‐rich systems are challenging due to the limited number of such folds in the structural databank. We exploit the stereochemical compatibility of substructures in known protein structures to accomodate disulfide bonds in predicting the structures of disulfide‐rich polypeptides directly from disulfide connectivity pattern and amino acid sequence in the absence of structural homologs and any other structural information. This knowledge‐based approach is illustrated using structure prediction of 40 nonredundant bioactive disulfide‐rich polypeptides such as toxins, growth factors, and endothelins available in the structural databank. The polypeptide conformation could be predicted in 35 out of 40 nonredundant entries (87%). Nonhomologous templates could be identified and models could be obtained within 2 Å deviation from the query in 29 peptides (72%). This procedure can be accessed from the World Wide Web (http://www.ncbs.res.in/∼faculty/mini/dsdbase/dsdbase.html). Proteins 2005. © 2005 Wiley‐Liss, Inc.
Prediction of distant residue contacts with the use of evolutionary information
Authors: Vicatos Spyridon , Reddy Boojala V.B. , Kaznessis Yiannis
Published: January 2005

In this work we present a novel correlated mutations analysis (CMA) method that is significantly more accurate than previously reported CMA methods. Calculation of correlation coefficients is based on physicochemical properties of residues (predictors) and not on substitution matrices. This results in reliable prediction of pairs of residues that are distant in protein sequence but proximal in its three dimensional tertiary structure. Multiple sequence alignments (MSA) containing a sequence of known structure for 127 families from PFAM database have been selected so that all major protein architectures described in CATH classification database are represented. Protein sequences in the selected families were filtered so that only those evolutionarily close to the target protein remain in the MSA. The average accuracy obtained for the alpha beta class of proteins was 26.8% of predicted proximal pairs with average improvement over random accuracy (IOR) of 6.41. Average accuracy is 20.6% for the mainly beta class and 14.4% for the mainly alpha class. The optimum correlation coefficient cutoff (cc cutoff) was found to be around 0.65. The first predictor, which correlates to hydrophobicity, provides the most reliable results. The other two predictors give good predictions which can be used in conjunction to those of the first one. When stricter cc cutoff is chosen, the average accuracy increases significantly (38.76% for alpha beta class), but the trade off is a smaller number of predictions. The use of solvent accessible area estimations for filtering false positives out of the predictions is promising. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Protein classification based on text document classification techniques
Authors: Cheng Betty Yee Man , Carbonell Jaime G. , Klein‐Seetharaman Judith
Published: January 2005

The need for accurate, automated protein classification methods continues to increase as advances in biotechnology uncover new proteins. G‐protein coupled receptors (GPCRs) are a particularly difficult superfamily of proteins to classify due to extreme diversity among its members. Previous comparisons of BLAST, k‐nearest neighbor (k‐NN), hidden markov model (HMM) and support vector machine (SVM) using alignment‐based features have suggested that classifiers at the complexity of SVM are needed to attain high accuracy. Here, analogous to document classification, we applied Decision Tree and Naïve Bayes classifiers with chi‐square feature selection on counts of n‐grams (i.e. short peptide sequences of length n) to this classification task. Using the GPCR dataset and evaluation protocol from the previous study, the Naïve Bayes classifier attained an accuracy of 93.0 and 92.4% in level I and level II subfamily classification respectively, while SVM has a reported accuracy of 88.4 and 86.3%. This is a 39.7 and 44.5% reduction in residual error for level I and level II subfamily classification, respectively. The Decision Tree, while inferior to SVM, outperforms HMM in both level I and level II subfamily classification. For those GPCR families whose profiles are stored in the Protein FAMilies database of alignments and HMMs (PFAM), our method performs comparably to a search against those profiles. Finally, our method can be generalized to other protein families by applying it to the superfamily of nuclear receptors with 94.5, 97.8 and 93.6% accuracy in family, level I and level II subfamily classification respectively. Proteins 2005. © 2005 Wiley‐Liss, Inc.
S‐adenosylhomocysteine hydrolase from the archaeon Pyrococcus furiosus: Biochemical characterization and analysis of protein structure by comparative molecular modeling
Authors: Porcelli Marina , Moretti Maria Angela , Concilio Luigi , Forte Sabrina , Merlino Antonello , Graziano Giuseppe , Cacciapuoti Giovanna
Published: January 2005

S‐Adenosylhomocysteine hydrolase (AdoHcyHD) is an ubiquitous enzyme that catalyzes the breakdown of S‐adenosylhomocysteine, a powerful inhibitor of most transmethylation reactions, to adenosine and L‐homocysteine. AdoHcyHD from the hyperthermophilic archaeon Pyrococcus furiosus (PfAdoHcyHD) was cloned, expressed in Escherichia coli, and purified. The enzyme is thermoactive with an optimum temperature of 95°C, and thermostable retaining 100% residual activity after 1 h at 90°C and showing an apparent melting temperature of 98°C. The enzyme is a homotetramer of 190 kDa and contains four cysteine residues per subunit. Thiol groups are not involved in the catalytic process whereas disulfide bond(s) could be present since incubation with 0.8 M dithiothreitol reduces enzyme activity. Multiple sequence alignment of hyperthermophilic AdoHcyHD reveals the presence of two cysteine residues in the N‐terminus of the enzyme conserved only in members of Pyrococcus species, and shows that hyperthermophilic AdoHcyHD lack eight C‐terminal residues, thought to be important for structural and functional properties of the eukaryotic enzyme. The homology‐modeled structure of PfAdoHcyHD shows that Trp220, Tyr181, Tyr184, and Leu185 of each subunit and Ile244 from a different subunit form a network of hydrophobic and aromatic interactions in the central channel formed at the subunits interface. These contacts partially replace the interactions of the C‐terminal tail of the eukaryotic enzyme required for tetramer stability. Moreover, Cys221 and Lys245 substitute for Thr430 and Lys426, respectively, of the human enzyme in NAD‐binding. Interestingly, all these residues are fairly well conserved in hyperthermophilic AdoHcyHDs but not in mesophilic ones, thus suggesting a common adaptation mechanism at high temperatures. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Regional reversion of insecticide resistance in Helicoverpa armigera (Lepidoptera: Noctuidae) is associated with the use of Bt cotton in northern China
Authors: Wu Kongming , Mu Wei , Liang Gemei , Guo Yuyuan
Published: January 2005

A continuous programme for monitoring resistance of Helicoverpa armigera (Hübner) to commonly used insecticides was undertaken for assessing the impact of Bt cotton planting on the evolution of the pest resistance from 1994 to 2002 in China. The bioassay results showed that the resistance levels per year in field populations of H armigera to lambda‐cyhalothrin, phoxim and endosulfan decreased, respectively, to 9–15‐fold, 11–14‐fold and 6–8‐fold in 2001–2002 from 197–262‐fold, 52–74‐fold and 18–38‐fold before the cultivation of Bt cotton in 1997. This significant increase in susceptibility to insecticides is expected to result in a reduction in insecticide application for H armigera control in Bt cotton. It is concluded that Bt cotton is playing an important role in the long‐term management of H armigera by increasing the potential for natural and chemical control of the pest. Copyright © 2005 Society of Chemical Industry
Matrix‐assisted ultraviolet laser desorption/ionization time‐of‐flight mass spectrometry of β‐(1 → 3), β‐(1 → 4)‐xylans from Nothogenia fastigiata using nor‐harmane as matrix
Authors: Fukuyama Yuko , Kolender Adriana A. , Nishioka Masae , Nonami Hiroshi , Matulewicz María C. , Erra‐Balsells Rosa , Cerezo Alberto S.
Published: January 2005

Three xylan fractions isolated from the red seaweed Nothogenia fastigiata (Nemaliales) were analyzed by ultraviolet matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (UV‐MALDI‐TOFMS). UV‐MALDI‐TOFMS was carried out in the linear and reflectron modes, and as routine in the positive and negative ion modes. Of the several matrices tested, nor‐harmane was the only effective one giving good spectra in the positive ion mode. The number‐average molar masses of two of the fractions, calculated from the distribution profiles, were lower than those determined previously by 1H NMR analysis, suggesting a decrease in the ionization efficiency with increasing molecular weight; weight‐average molar mass and polydispersity index were also determined. As the xylans retained small but significant quantities of calcium salts, the influence of added Ca2+ as CaCl2 on UV‐MALDI‐MS was investigated. The simultaneous addition of sodium chloride and calcium chloride was also analyzed. Addition of sodium chloride did not change the distribution profile of the native sample showing that the inhibitory effect is due to Ca2+ and not to Cl−. Addition of calcium chloride with 1:1 analyte/salt molar ratio gave spectra with less efficient desorption/ionization of oligomers; the signals of these oligomers were completely suppressed when the addition of the salt became massive (1:100 analyte/salt molar ratio). Copyright © 2005 John Wiley & Sons, Ltd.
The inactivation of phospholipase A2 by scalaradial: a biomimetic study by electrospray mass spectrometry
Authors: Monti Maria Chiara , Casapullo Agostino , Riccio Raffaele , Gomez‐Paloma Luigi
Published: January 2005

A biomimetic approach was employed to shed light on the nature of chemical reactions occurring in the covalent inactivation of phospholipase A2 (PLA2) by scalaradial (1), a marine dialdehyde terpenoid endowed with potent anti‐inflammatory activity. To this end, a detailed study of the reaction profile between the nitrogenous nucleophile isopropylamine and scalaradial was performed under biologically relevant conditions. Copyright © 2005 John Wiley & Sons, Ltd.
Pro‐oxidant action of phloxine B on fission yeast Schizosaccharomyces pombe
Authors: Mutoh Norihiro , Kawabata Masao , Nakagawa Chiaki W. , Kitajima Satoko
Published: January 2005

A Schizosaccharomyces pombe mutant deficient in Cu,Zn‐superoxide dismutase (sod1 mutant) was hypersensitive to phloxine B, which is used as a food‐colouring agent and also to distinguish diploid strains of Sz. pombe from haploid strains, under illumination with light. The pro‐oxidant nature of phloxine B was confirmed biochemically. The carbonyl content of proteins (which represents protein oxidation) increased, and the reduced form of glutathione was transiently decreased by phloxine B treatment under illumination with light. When cells were treated with phloxine B under light, carbonyl content of proteins in the sod1 mutant was greater than that in the wild‐type and amount of glutathione was much decreased in the sod1 mutant compared with the wild‐type. Genes induced by oxidative stress were induced by phloxine B under illumination with light and some were induced by phloxine B without light. Copyright © 2005 John Wiley & Sons, Ltd.
A new mutation in the yeast aspartate kinase induces threonine accumulation in a temperature‐regulated way
Authors: Velasco I. , Arévalo‐Rodríguez M. , Marina P. , Calderón I. L.
Published: January 2005

In Saccharomyces cerevisiae, aspartate kinase (the HOM3 product) regulates the metabolic flux through the threonine biosynthetic pathway through feedback inhibition by the end product. In order to obtain a strain able to produce threonine in a controlled way, we have isolated a mutant allele (HOM3‐ts31d) that gives rise to a deregulated aspartate kinase. This allele has been isolated as an extragenic suppressor of ilv1, which confers an Ilv+ phenotype at 37 °C but not at 22 °C. We have stated that at high temperature the mutant aspartate kinase is slightly more deregulated and shows a higher specific activity, inducing threonine accumulation. The HOM3‐ts31d allele carries a mutation that leads to a Ser399 → Phe substitution in the postulated regulatory region of the enzyme. We have detected other changes in the nucleotide sequence but they are also present in the parental strain, reflecting the genetic differences between different wild‐type strains. A sequence comparison among all the reported mutant aspartate kinases suggests that not all residues involved in regulation of the activity are clustered in the so‐called regulatory domain, as is the case of that mutated in AK‐R7, another deregulated aspartate kinase obtained with the same strategy of ilv1 suppression. Copyright © 2005 John Wiley & Sons, Ltd.
Influence of low glycolytic activities in gcr1 and gcr2 mutants on the expression of other metabolic pathway genes in Saccharomyces cerevisiae
Authors: Sasaki Hiromi , Uemura Hiroshi
Published: January 2005

A complex of the transcription factors Gcr1p and Gcr2p coordinately regulates the expression of glycolytic genes in Saccharomyces cerevisiae. To understand the effects of gcr mutations on other metabolic pathways, genome‐wide gene expression profiles in gcr1 and gcr2 mutants were examined. The biggest effects of gcr1 and gcr2 mutations were observed on the glycolytic genes and the expressions of most of the glycolytic genes were substantially decreased compared to those in the wild‐type strain in both glucose and glycerol + lactate growth conditions. On the other hand, the expressions of genes encoding the TCA cycle and respiration were increased in gcr mutants when the cells were grown in glucose. RT‐PCR analyses revealed that the expression of SIP4 and HAP5, which are known to affect the expression of some of the gluconeogenic, TCA cycle and respiratory genes, were also increased under this condition. The growth of gcr mutants on glucose was impaired by adding respiration inhibitor antimycin A, whereas the growth of the wild‐type strain was not. The conversion of glucose to biomass was higher and, to the contrary, ethanol yield was lower in the gcr2 mutant compared to those in the wild‐type strain. These results suggest the possibility that the gcr mutants, in which glycolytic activities are low, changed their metabolic patterns under glucose growth condition to enhance the expression of TCA cycle and respiratory genes to produce more energy. Copyright © 2005 John Wiley & Sons, Ltd.
Attitudes toward genetic testing for cystic fibrosis among college students
Authors: Neiger Ran , Abuelo Dianne N. , Passero Mary Ann
Published: January 2005

The knowledge and attitudes of 25 college students toward clinical and genetic aspects of cystic fibrosis (CF) were assessed before and after an 80‐minute presentation about the disease. The students were asked about their plans regarding genetic testing for cystic fibrosis prior to, and during future conceptions. While their knowledge about the disease increased significantly following the lecture, there were no significant changes in their attitudes.
Genetic counselor as a member of an outreach education team
Authors: Schmerler Susan , DeConstanzo Rosemary
Published: January 2005

As part of a program to improve maternal and infant health in New Jersey, the Robert Wood Johnson Foundation has funded seven regional consortia throughout the State. One of the goals of the Northern New Jersey Regional Consortium is to provide a comprehensive educational program for ambulatory care staff. An outreach education team was established that includes a perinatal nurse educator, a neonatal nurse educator, a nutritional counselor and a genetic counselor. Many issues in genetics can be initially addressed by the ambulatory care provider. A good understanding and awareness of the impact of genetic issues in patient care is needed to enhance the ability to recognize patients needing special services. Early assessment of possible risk for developmental disabilities can lead to appropriate comprehensive care and improved pregnancy outcome. Regular in‐service programs, addressing the way heredity contributes to developmental disorders, the latest techniques used in genetics and the available management programs, can be provided. The present study is an evaluation of the effectiveness of the program.
Preconceptional family health evaluation: A regional education program for family planning clients and health professionals
Authors: Lea Dale H. , Gardiner Gale B. , Guttmacher Alan E.
Published: January 2005

The Preconceptional Family Health Evaluation Program was a regional project developed and funded for 2 years by the New England Regional Genetics Group (NERGG) to educate family planning health professionals about genetics, and to offer family planning clients preconceptional identification of genetic and environmental exposure risks. To meet these goals, genetic education was provided on a regional basis to 45 family planning professionals. A self‐administered family health risk questionnaire adaptable to individual family planning settings was developed. Five hundred and twenty‐nine family planning clients voluntarily completed the questionnaire. Cigarette smoking (35%) and alcohol use (57%) were two major categories of risks identified. The Preconceptional Family Health Evaluation Program was well received by all participants and provided an effective means for regional education of family planning health professionals. As a result of the program, state program planners, clinical genetics services, and family planning health professionals developed a strong relationship that will serve future educational and genetic risk screening efforts.
Intraductal Papillary‐mucinous Tumors Arising in Santorini’s Duct: Clinicopathologic Features and the Treatment of Choice
Authors: Hirano Satoshi , Kondo Satoshi , Ambo Yoshiyasu , Tanaka Eiichi , Morikawa Toshiaki , Okushiba Shunichi , Katoh Hiroyuki
Published: January 2005

Almost all reported cases of intraductal papillary‐mucinous tumors of the pancreas (IPMTs) originate from Wirsung’s duct (WD), the main pancreatic duct, or their branches. IPMTs arising from Santorini’s duct (SD) and its branches have rarely been reported. This article presents the clinicopathologic features of IPMTs originating in SD and its branches. Of 36 IPMTs resected in our institution, 5 originated in the region of SD: 3 in SD and 2 from its branches. Both SD and WD were dilated in all cases on radiographic and ultrasonographic studies. The maximum diameter of SD, determined by computed tomography or ultrasonography, was larger than that of WD in all cases. Seven reports of IPMT arising from SD have been published. Four lesions originated from SD and the others from its branches. Overall, 9 of 12 lesions (75%) were considered malignant. In conclusion, the coexistence of an IPMT and a dilated SD suggests an origin in the SD. These tumors have a high malignant potential and should be excised.
Staged Abdominal Repair for Treatment of Moderate to Severe Secondary Peritonitis
Authors: Agalar Fatih , Eroglu Erol , Bulbul Mahmut , Agalar Canan , Tarhan Omar Ridvan , Sari Mustafa
Published: January 2005

The aim of this study was to evaluate the effects of planned relaparotomy and to assess factors that may contribute to mortality in patients with moderate to severe secondary peritonitis. A total of 36 consecutive patients with an Acute Physiologic and Clinical Health Evaluation (APACHE) II score of >10 were enrolled the study for a 2‐year period. The mean age of the patients was 56 years (17‐92 years), and 23% of them were male. One‐third of them had postoperative peritonitis; 152 scheduled operations were done, and the overall mortality rate was 36%. For patients whose septic source was in the upper gastrointestinal system, control of the source was more difficult (p = 0.004). Overall, 28 complications developed in 61% of the patients. Initial and second‐day APACHE II scores were 14.5 (11‐27) and 12.0 (9‐25), respectively. The initial APACHE II score of survivors was lower than that of nonsurvivors [p = 0.0001, 95% confidence interval (CI) ‐9.5, ‐3.6]. Second‐day APACHE II scores were not different (p = 0.19; 95% CI ‐3.79, 0.80). Striking end or lateral duodenal leaks were clearly associated with high mortality. It is found that the initial APACHE II score, the success of controlling the source, the occurrence of complications, and the type of illness are independent factors that may affect mortality. We concluded that staged abdominal repair should be used with caution in the treatment of lateral or end duodenal leaks. It is a good alternative to conventional laparotomy for moderate to severe forms of secondary peritonitis from other sources.
AJCP as a Vehicle for Improving Community Life: An Historic–Analytic Review of the Journal's Contents
Authors: Martin Pamela P. , Lounsbury David W. , Davidson William S.
Published: January 2005

The current article is an analysis of the research represented in American Journal of Community Psychology (AJCP) from 1993 to 1998, including a comparison to two previously published analytic reviews by Lounsbury et al. (J. W. Lounsbury, D. S. Leader, E. P. Meares, & M. P. Cook, 1980) and Speer et al. (P. Speer, A. Dey, P. Griggs, C. Gibson, B. Lubin, & J. Hughey, 1992), respectively. Observed trends are examined with references to major epistemological frameworks and methods used to define community psychology. Four guiding principles were examined to determine the representation of the epistemological frameworks of the articles published in the journal. The frameworks include social action, human diversity and cultural relativity, person–environmental fit, and methodological procedures. The results document the transition of community psychology from its early beginnings to an independent field conducting research consistent with the values articulated at the Swampscott Conference. This paper also comments on how well, after three decades of publication, the journal has served as a vehicle for improving community life.
Crime, Social Capital, and Community Participation
Authors: Saegert Susan , Winkel Gary
Published: January 2005

Social disorganization at the neighborhood and community levels has been consistently linked to various forms of criminal activity. However, a very much smaller body of literature addresses the effects of crime on community organizations. In some studies, crime appears to energize communities while in others, crime leads to withdrawal from community life. Using department of health crime victimization data and interviews with 2,985 low‐income inner city residents living in 487 multi‐family dwellings, a multi‐level model examined the relationships among crime victimization, social organization, and participation in neighborhood organizations. Social organization at the individual and building levels was measured using recent formulations of social capital theory. Findings regarding crime suggested more signs of a chilling effect on participation than of an energizing effect, especially at the building level. Social capital at the building level was more strongly and consistently related to participation in community organizations than was crime.
An Empowerment Evaluation Model for Sexual Assault Programs: Empirical Evidence of Effectiveness
Authors: Campbell Rebecca , Dorey Heather , Naegeli Monika , Grubstein Lori K. , Bennett Kelly K. , Bonter Freya , Smith Patricia K. , Grzywacz Jessica , Baker Patsy K. , Davidson William S.
Published: January 2005

Using an empowerment evaluation approach, the Sexual Assault and Rape Prevention (SARP) Evaluation Project brought together university researchers, public health evaluators, state funders, and program staff to provide evaluation training and consultation to all state‐funded rape prevention and victim services programs in Michigan. In this paper, the specific activities of the SARP project are described, and process and outcome data are presented that address the effectiveness of this empowerment evaluation approach. Based on subjective reports from program staff and objective data obtained from state funders, results suggest that this evaluation model was successful in helping 90% of the prevention programs and 75% of the victim services programs successfully develop and launch program evaluations. One‐year follow‐up data indicate that 90% of the programs had sustained their evaluation efforts after the formal work of the SARP project had ended.