bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dock around the Clock – Current Status of Small Molecule Docking and Scoring
Authors: Rester Ulrich 
Published: February 2006

AbstractThe early phases of commercial drug discovery programs are increasingly guided by information extracted from three‐dimensional structures of the target proteins and in silico design techniques. This review addresses key issues of docking and scoring, a popular technique in structure‐based drug design. The pros and cons of computational tools currently used will be outlined as well as the integration of these methods in the lead finding and lead optimization process.
An engineered nonsense URA3 allele provides a versatile system to detect the presence, absence and appearance of the [PSI+] prion in Saccharomyces cerevisiae
Authors: Manogaran Anita L. , Kirkland Kathryn T. , Liebman Susan W. 
Published: February 2006

AbstractCommon methods to identify yeast cells containing the prion form of the Sup35 translation termination factor, [PSI+], involve a nonsense suppressor phenotype. Decreased function of Sup35p in [PSI+] cells leads to read‐through of certain nonsense mutations in a few auxotrophic markers, e.g. ade1‐14. This read‐through results in growth on adenine‐deficient media. While this powerful tool has dramatically facilitated the study of [PSI+], it is limited to a narrow range of laboratory strains and cannot easily be used to screen for cells that have lost the [PSI+] prion. Therefore we have engineered a nonsense mutation in the widely used URA3 gene, termed the ura3‐14 allele. Introduction of the ura3‐14 allele into an array of genetic backgrounds, carrying a loss‐of‐function URA3 mutation and [PSI+], allows for growth on media lacking uracil, indicative of decreased translational termination efficiency. This ura3‐14 allele is able to distinguish various forms of the [PSI+] prion, called variants, and is able to detect the de novo appearance of [PSI+] in strains carrying the prion form of Rnq1p, [PIN+]. Furthermore, 5‐fluoroorotic acid, which kills cells making functional Ura3p, provides a means to select for [psi−] derivatives in a population of [PSI+] cells marked with the ura3‐14 allele, making this system much more versatile than previous methods. Copyright © 2006 John Wiley & Sons, Ltd.
Nocturnal behavior in a group of female African elephants
Authors: Wilson Megan L. , Bashaw Meredith J. , Fountain Kimberly , Kieschnick Sarah , Maple Terry L. 
Published: February 2006

AbstractThe nocturnal behavior of a stable group of female, African elephants (Loxodonta africana africana) was studied to: (1) examine their behavior as a function of hour of night; (2) qualitatively compare the elephants' activity budgets to those reported in a previous study; and (3) document the presence of aggressive and stereotypic behaviors that might necessitate a change in their management. The elephants were systematically observed at least five times per week for 10 weeks between 17:00 and 08:00. Instantaneous focal samples of behavior, location, and proximity were taken every minute on a rotating basis, and all observed occurrences of social behavior were recorded. The hour of night affected elephant activity: significant relationships were found between hour of night and percent of time they spent feeding, lying, and standing. The overall activity budgets of the elephants were similar to the activity budgets reported in a previous study, although differences were evident in lying, stereotypic, and social behaviors. These differences might be a function of age. Affiliative behaviors accounted for 57% of the elephants' social behaviors, and agonistic behaviors among the elephants occurred infrequently and caused no injuries. Additionally, the elephants used all areas to which they had access. These findings provide compelling evidence that unrestricted social access during the night is the appropriate management strategy for these elephants. The results from the present study also highlight the importance of replicating existing studies and using multiple behavioral measures to make decisions regarding the welfare and management of stable groups of captive elephants. Zoo Biol 25:173–186, 2006. © 2006 Wiley‐Liss, Inc.
Synaptic targeting by Aβ oligomers (ADDLS) as a basis for memory loss in early Alzheimer's disease
Authors: Klein William L. 
Published: February 2006

AbstractEarly diagnosis and treatment of Alzheimer's Disease (AD) ultimately will require identification of its pathogenic mechanism. Such a mechanism must explain the hallmark of early AD—a profound inability to form new memories. For many years, the most promising hypothesis maintained that memory failure derived from neuron death induced by insoluble deposits of amyloid fibrils. Newer findings, however, suggest that memory loss, especially in early AD, may be a failure in synaptic plasticity caused by small soluble Aβ oligomers (“ADDLs”). ADDLs are neurologically potent toxins that rapidly inhibit long‐term potentiation and reversal of long‐term depression, classic paradigms for learning and memory. In human samples, ADDLs show striking increases in AD brain and CSF. The ADDL hypothesis is considerably reinforced by nerve cell biology studies showing that ADDLs specifically attack synapses, essentially acting as gain‐of‐function pathogenic ligands. Selective damage by ADDLs to memory‐linked synaptic mechanisms provides an appealing explanation for early AD memory loss and suggests that ADDLs provide a valid target for therapeutics and diagnostics.
Nosocomial Transmission of Hepatitis B Virus Infection Among Residents with Diabetes in a Skilled Nursing Facility
Authors: Khan Amy J. , Cotter Suzanne M. , Schulz Beth , Hu Xiaolei , Rosenberg Jon , Robertson Betty H. , Fiore Anthony E. , Bell Beth P. 
Published: February 2006

Objective:To identify exposures associated with acute hepatitis B virus (HBV) infection among residents with diabetes in a skilled nursing facility.Design:Residents from Unit 3 and other skilled nursing facility residents with diabetes were tested for serologic evidence of HBV infection. Two retrospective cohort studies were conducted. Potential routes of HBV transmission were evaluated by statistical comparison of attack rates.Setting:A 269-bed skilled nursing facility.Participants:All skilled nursing facility residents with diabetes and skilled nursing facility residents who lived on the same unit as the index case (Unit 3) for some time during the case's incubation period.Results:All 5 residents with acute HBV infection had diabetes and resided in Unit 3. The attack rate among the 12 patients with diabetes in Unit 3 was 42%, compared with 0% among 43 patients without diabetes (relative risk, 37.2; 95% confidence interval, 4.7 to ∞). Acutely infected patients with diabetes received more morning insulin doses (P = .05), and more insulin doses (P = .03) and finger sticks (P = .02) on Wednesdays than did noninfected patients with diabetes. Two chronically infected patients with diabetes in Unit 3 were positive for hepatitis B e antigen and regularly received daily insulin and finger sticks. Of the 4 acute and 3 chronically infected residents from whom HBV DNA was amplified, all were genotype F and had an identical 678-bp S region sequence. Although no component of the lancets or injection devices was shared among residents, opportunities for HBV contamination of diabetes care supplies were identified.Conclusions:Contamination of diabetes care supplies resulted in resident-to-resident transmission of HBV. In any setting in which diabetes care is performed, staff need to be educated regarding appropriate infection control practices.
A Nosocomial and Occupational Cluster of Hepatitis A Virus Infection in a Pediatric Ward
Authors: Petrosillo Nicola , Raffaele Barbara , Martini Lorena , Nicastri Emanuele , Nurra Giuseppina , Anzidei Gianfranco , Ippolito Giuseppe 
Published: February 2006

AbstractWe describe a cluster of acute hepatitis A virus (HAV) infection that involved two patients and one physician in the pediatric unit where two children with acute HAV infection had been housed. An interview with the unit personnel revealed several breaches in infection control measures and the lack of vaccination of healthcare workers against HAV.
Incidence of Surgical-Site Infections and the Validity of the National Nosocomial Infections Surveillance System Risk Index in a General Surgical Ward in Santa Cruz, Bolivia
Authors: Soleto Lorena , Pirard Marianne , Boelaert Marleen , Peredo Remberto , Vargas Reinerio , Gianella Alberto , Stuyft Patrick Van der 
Published: February 2006

AbstractObjectives:To estimate the frequency of and risk factors for surgical-site infections (SSIs) in Bolivia, and to study the performance of the National Nosocomial Infections Surveillance (NNIS) System risk index in a developing country.Design:A prospective study with patient follow-up until the 30th postoperative day.Setting:A general surgical ward of a public hospital in Santa Cruz, Bolivia.Patients:Patients admitted to the ward between July 1998 and June 1999 on whom surgical procedures were performed.Results:Follow-up was complete for 91.5% of 376 surgical procedures. The overall SSI rate was 12%. Thirty-four (75.6%) of the 45 SSIs were culture positive. A logistic regression model retained an American Society of Anesthesiologists score of more than 1 (odds ratio [OR], 1.87), a not-clean wound class (OR, 2.28), a procedure duration of more than 1 hour (OR, 1.81), and drain (OR, 1.98) as independent risk factors for SSI. There was no significant association between the NNIS System risk index and SSI rates. However, a “local” risk index constructed with the above cut-off points showed a linear trend with SSI (P < .001) and a relative risk of 3.18 for risk class 3 versus a class of less than 3.Conclusions:SSIs cause considerable morbidity in Santa Cruz. Appropriate nosocomial infection surveillance and control should be introduced. The NNIS System risk index did not discriminate between patients at low and high risk for SSI in this hospital setting, but a risk score based on local cutoff points performed substantially better.
A Prospective Study of Tobacco Smoking as a Predictor of Complications in General Surgery
Authors: Delgado-Rodríguez Miguel , Medina-Cuadros Marcelino , Martínez-Gallego Gabriel , Gómez-Ortega Antonio , Mariscal-Ortiz Marcial , Palma-Pérez Silvia , Sillero-Arenas María 
Published: February 2006

AbstractObjective:To analyze whether tobacco smoking is related to nosocomial infection, admission to the intensive care unit, in-hospital death, and length of stay.Design:A prospective cohort study.Setting:The Service of General Surgery of a tertiary-care hospital.Patients:A consecutive series of patients admitted for more than 1 day (N = 2,989).Results:Sixty-two (2.1%) patients died and 503 (16.8%) acquired a nosocomial infection, of which 378 (12.6%) were surgical site and 44 (1.5%) were lower respiratory tract. Smoking (mainly past smoking) was associated with a worse health status (eg, longer preoperative stay and higher American Society of Anesthesiologists score). A long history of smoking (≥ 51 pack-years) increased post-operative admission to the intensive care unit (adjusted odds ratio [OR] = 2.86; 95% confidence interval [CI95], 1.21 to 6.77) and in-hospital mortality (adjusted OR = 2.56; CI95, 1.10 to 5.97). There was no relationship between current smoking and surgical-site infection (adjusted OR = 0.99; CI95, 0.72 to 1.35), whereas a relationship was observed between past smoking and surgical-site infection (adjusted OR = 1.46; CI95, 1.02 to 2.09). Current smoking and, to a lesser degree, past smoking augmented the risk of lower respiratory tract infection (adjusted OR = 3.21; CI95, 1.21 to 8.51). Smokers did not undergo additional surgical procedures more frequently during hospitalization. In the multivariate analysis, length of stay was similar for smokers and nonsmokers.Conclusion:Smoking increases in-hospital mortality, admission to the intensive care unit, and lower respiratory tract infection, but not surgical-site infection. Deleterious effects of smoking are also observed in past smokers and they cannot be counteracted by hospital cessation programs.
The Prevalence and Estimates of the Cumulative Incidence of Hospital-Acquired Infections Among Patients Admitted to Auckland District Health Board Hospitals in New Zealand
Authors: Graves Nicholas , Nicholls Tanya M. , Wong Christopher G. S. , Morris Arthur J. 
Published: February 2006

AbstractObjectives:To report the pooled results of seven prevalence surveys of hospital-acquired infections conducted between November 1996 and November 1999, and to use the data to predict the cumulative incidence of hospital-acquired infections in the same patient group.Design:The summary and modeling of data gathered from the routine surveillance of the point prevalence of hospital-acquired infections.Setting:Auckland District Health Board Hospitals (Auckland DHBH), the largest publicly funded hospital group in New Zealand supplying secondary and tertiary services.Patients:All inpatients.Method:Point-prevalence surveys were conducted including all patients in Auckland DHBH. Standard definitions of hospital-acquired infection were used. The data from the seven surveys were pooled and used in a modeling exercise to predict the cumulative incidence of hospital-acquired infection. An existing method for the conversion of prevalence to cumulative incidence was applied. Results are presented for all patients and stratified by clinical service and site of hospital-acquired infection.Results:The underlying patterns of hospital-acquired infection by site and service were stable during the seven time periods. The prevalence rate for all patients was 9.5%, with 553 patients identified with one or more hospital-acquired infections from a population of 5,819. The predicted cumulative incidence for all patients was 6.33% (95% confidence interval, 6.20% to 6.46%).Conclusions:The prevalence and the predicted cumulative incidence are similar to rates reported in the international literature. The validity of the predicted cumulative incidence derived here is not known. If it were accurate, then the application of this method would represent a cost-effective alternative to incidence studies.
Recco: recombination analysis using cost optimization
Authors: Maydt Jochen , Lengauer Thomas 
Published: February 2006

AbstractMotivation: Recombination plays an important role in the evolution of many pathogens, such as HIV or malaria. Despite substantial prior work, there is still a pressing need for efficient and effective methods of detecting recombination and analyzing recombinant sequences.Results: We introduce Recco, a novel fast method that, given a multiple sequence alignment, scores the cost of obtaining one of the sequences from the others by mutation and recombination. The algorithm comes with an illustrative visualization tool for locating recombination breakpoints. We analyze the sequence alignment with respect to all choices of the parameter α weighting recombination cost against mutation cost. The analysis of the resulting cost curve yields additional information as to which sequence might be recombinant. On random genealogies Recco is comparable in its power of detecting recombination with the algorithm Geneconv (Sawyer, 1989). For specific relevant recombination scenarios Recco significantly outperforms Geneconv.Availability: Recco is available atContact: jmaydt@mpi-inf.mpg.de
Pedigree-drawing with R and graphviz
Authors: Zhao Jing Hua 
Published: February 2006

Abstract
Summary: Two functions for pedigree-drawing available in R (): plot.pedigree in kinship and pedtodot in gap are described. The latter requires graphviz (). They can produce many pedigree diagrams quickly into a single file, serving as alternatives to programs that only offer interactive use.
Availability: Packages kinship and gap are available from .
Contact: jinghua.zhao@mrc-epid.cam.ac.uk
Structural bioinformatics of DNA: a web-based tool for the analysis of molecular dynamics results and structure prediction
Authors: Dixit Surjit B. , Beveridge David L. 
Published: February 2006

AbstractSummary: We report here the release of a web-based tool (MDDNA) to study and model the fine structural details of DNA on the basis of data extracted from a set of molecular dynamics (MD) trajectories of DNA sequences involving all the unique tetranucleotides. The dynamic web interface can be employed to analyze the first neighbor sequence context effects on the 10 unique dinucleotide steps of DNA. Functionality is included to build all atom models of any user-defined sequence based on the MD results. The backend of this interface is a relational database storing the conformational details of DNA obtained in 39 different MD simulation trajectories comprising all the 136 unique tetranucleotide steps. Examples of the use of this data to predict DNA structures are included.Availability: Contact: sdixit@wesleyan.eduSupplementary information: Supplementary data including color figures are available at Bioinformatics online.
Chemical Imaging of Poplar Wood Cell Walls by Confocal Raman Microscopy
Authors: Gierlinger Notburga , Schwanninger Manfred 
Published: February 2006

Abstract
Confocal Raman microscopy was used to illustrate changes of molecular composition in secondary plant cell wall tissues of poplar (Populus nigra × Populus deltoids) wood. Two-dimensional spectral maps were acquired and chemical images calculated by integrating the intensity of characteristic spectral bands. This enabled direct visualization of the spatial variation of the lignin content without any chemical treatment or staining of the cell wall. A small (0.5 μm) lignified border toward the lumen was observed in the gelatinous layer of poplar tension wood. The variable orientation of the cellulose was also characterized, leading to visualization of the S1 layer with dimensions smaller than 0.5 μm. Scanning Raman microscopy was thus shown to be a powerful, nondestructive tool for imaging changes in molecular cell wall organization with high spatial resolution.
The Role of Hydrogen Peroxide-Producing and Hydrogen Peroxide-Consuming Peroxidases in the Leaf Apoplast of Cowpea in Manganese Tolerance
Authors: Fecht-Christoffers Marion Maria , Führs Hendrik , Braun Hans-Peter , Horst Walter Johannes 
Published: February 2006

Abstract
The apoplast is considered the leaf compartment decisive for manganese (Mn) toxicity and tolerance in cowpea (Vigna unguiculata). Particularly apoplastic peroxidases (PODs) were proposed to be key enzymes in Mn toxicity-induced processes. The presented work focuses on the characterization of the role of hydrogen peroxide (H2O2)-producing (NADH peroxidase) and H2O2-consuming peroxidase (guaiacol POD) in the apoplastic washing fluid (AWF) of leaves for early stages of Mn toxicity and genotypic differences in Mn tolerance of cowpea. Leaf AWF of the Mn-sensitive cultivar (cv) TVu 91 but not of the Mn-tolerant cv 1987 showed an increase of guaiacol-POD and NADH-peroxidase activities at elevated AWF Mn concentrations. two-dimensional resolutions of AWF proteins revealed that cv TVu 91 expressed more and additional proteins at high Mn treatment, whereas Mn-tolerant cv TVu 1987 remained nearly unaffected. In both cultivars, NADH-peroxidase activity and accompanied H2O2 formation rate in vitro were significantly affected by Mn2+, p-coumaric acid, and metabolites occurring in the AWF. The total phenol concentration in the AWF was indicative of advanced stages of Mn toxicity but was rather unrelated to early stages of Mn toxicity and genotypic differences in Mn tolerance. The NADH oxidation by AWF PODs was significantly delayed or enhanced in the presence of the protein-free AWF from cv TVu 1987 or cv TVu 91, respectively. High-performance liquid chromatography analysis of AWF indicates the presence of phenols in cv TVu 1987 not observed in cv TVu 91. We conclude from our studies that the H2O2-producing NADH peroxidase and its modulation by stimulating or inhibiting phenolic compounds in the leaf apoplast play a major role for Mn toxicity and Mn tolerance in cowpea.
Mutations in the NB-ARC Domain of I-2 That Impair ATP Hydrolysis Cause Autoactivation
Authors: Tameling Wladimir I.L. , Vossen Jack H. , Albrecht Mario , Lengauer Thomas , Berden Jan A. , Haring Michel A. , Cornelissen Ben J.C. , Takken Frank L.W. 
Published: February 2006

Abstract
Resistance (R) proteins in plants confer specificity to the innate immune system. Most R proteins have a centrally located NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4) domain. For two tomato (Lycopersicon esculentum) R proteins, I-2 and Mi-1, we have previously shown that this domain acts as an ATPase module that can hydrolyze ATP in vitro. To investigate the role of nucleotide binding and hydrolysis for the function of I-2 in planta, specific mutations were introduced in conserved motifs of the NB-ARC domain. Two mutations resulted in autoactivating proteins that induce a pathogen-independent hypersensitive response upon expression in planta. These mutant forms of I-2 were found to be impaired in ATP hydrolysis, but not in ATP binding, suggesting that the ATP- rather than the ADP-bound state of I-2 is the active form that triggers defense signaling. In addition, upon ADP binding, the protein displayed an increased affinity for ADP suggestive of a change of conformation. Based on these data, we propose that the NB-ARC domain of I-2, and likely of related R proteins, functions as a molecular switch whose state (on/off) depends on the nucleotide bound (ATP/ADP).
A Reassessment of Substrate Specificity and Activation of Phytochelatin Synthases from Model Plants by Physiologically Relevant Metals
Authors: Loscos Jorge , Naya Loreto , Ramos Javier , Clemente Maria R. , Matamoros Manuel A. , Becana Manuel 
Published: February 2006

Abstract
Phytochelatin synthases (PCS) catalyze phytochelatin (PC) synthesis from glutathione (GSH) in the presence of certain metals. The resulting PC-metal complexes are transported into the vacuole, avoiding toxic effects on metabolism. Legumes have the unique capacity to partially or completely replace GSH by homoglutathione (hGSH) and PCs by homophytochelatins (hPCs). However, the synthesis of hPCs has received little attention. A search for PCS genes in the model legume Lotus (Lotus japonicus) resulted in the isolation of a cDNA clone encoding a protein (LjPCS1) highly homologous to a previously reported homophytochelatin synthase (hPCS) of Glycine max (GmhPCS1). Recombinant LjPCS1 and Arabidopsis (Arabidopsis thaliana) PCS1 (AtPCS1) were affinity purified and their polyhistidine-tags removed. AtPCS1 catalyzed hPC synthesis from hGSH alone at even higher rates than did LjPCS1, indicating that GmhPCS1 is not a genuine hPCS and that a low ratio of hPC to PC synthesis is an inherent feature of PCS1 enzymes. For both enzymes, hGSH is a good acceptor, but a poor donor, of γ-glutamylcysteine units. Purified AtPCS1 and LjPCS1 were activated (in decreasing order) by Cd2+, Zn2+, Cu2+, and Fe3+, but not by Co2+ or Ni2+, in the presence of 5 mm GSH and 50 μm metal ions. Activation of both enzymes by Fe3+ was proven by the complete inhibition of PC synthesis by the iron-specific chelator desferrioxamine. Plants of Arabidopsis and Lotus accumulated (h)PCs only in response to a large excess of Cu2+ and Zn2+, but to a much lower extent than did with Cd2+, indicating that (h)PC synthesis does not significantly contribute in vivo to copper, zinc, and iron detoxification.