bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simplified approach to disulfide connectivity prediction from protein sequences
Authors: Vincent Marc , Passerini Andrea , Labbé Matthieu , Frasconi Paolo 
Published: January 2008

Abstract

Background
Prediction of disulfide bridges from protein sequences is useful for characterizing structural and functional properties of proteins. Several methods based on different machine learning algorithms have been applied to solve this problem and public domain prediction services exist. These methods are however still potentially subject to significant improvements both in terms of prediction accuracy and overall architectural complexity.

Results
We introduce new methods for predicting disulfide bridges from protein sequences. The methods take advantage of two new decomposition kernels for measuring the similarity between protein sequences according to the amino acid environments around cysteines. Disulfide connectivity is predicted in two passes. First, a binary classifier is trained to predict whether a given protein chain has at least one intra-chain disulfide bridge. Second, a multiclass classifier (plemented by 1-nearest neighbor) is trained to predict connectivity patterns. The two passes can be easily cascaded to obtain connectivity prediction from sequence alone. We report an extensive experimental comparison on several data sets that have been previously employed in the literature to assess the accuracy of cysteine bonding state and disulfide connectivity predictors.

Conclusion
We reach state-of-the-art results on bonding state prediction with a simple method that classifies chains rather than individual residues. The prediction accuracy reached by our connectivity prediction method compares favorably with respect to all but the most complex other approaches. On the other hand, our method does not need any model selection or hyperparameter tuning, a property that makes it less prone to overfitting and prediction accuracy overestimation.
Virulence factor rtx in Legionella pneumophila, evidence suggesting it is a modular multifunctional protein
Authors: D'Auria Giuseppe , Jiménez Núria , Peris-Bondia Francesc , Pelaz Carmen , Latorre Amparo , Moya Andrés 
Published: January 2008

Abstract

Background
The repeats in toxin (Rtx) are an important pathogenicity factor involved in host cells invasion of Legionella pneumophila and other pathogenic bacteria. Its role in escaping the host immune system and cytotoxic activity is well known. Its repeated motives and modularity make Rtx a multifunctional factor in pathogenicity.

Results
The comparative analysis of rtx gene among 6 strains of L. pneumophila showed modularity in their structures. Among compared genomes, the N-terminal region of the protein presents highly dissimilar repeats with functionally similar domains. On the contrary, the C-terminal region is maintained with a fashionable modular configuration, which gives support to its proposed role in adhesion and pore formation. Despite the variability of rtx among the considered strains, the flanking genes are maintained in synteny and similarity.

Conclusion
In contrast to the extracellular bacteria Vibrio cholerae, in which the rtx gene is highly conserved and flanking genes have lost synteny and similarity, the gene region coding for the Rtx toxin in the intracellular pathogen L. pneumophila shows a rapid evolution. Changes in the rtx could play a role in pathogenicity. The interplay of the Rtx toxin with host membranes might lead to the evolution of new variants that are able to escape host cell defences.
Genomic, genetic and structural analysis of pyoverdine-mediated iron acquisition in the plant growth-promoting bacterium Pseudomonas fluorescens SBW25
Authors: Moon Christina D , Zhang Xue-Xian , Matthijs Sandra , Schäfer Mathias , Budzikiewicz Herbert , Rainey Paul B 
Published: January 2008

Abstract

Background
Pyoverdines (PVDs) are high affinity siderophores, for which the molecular mechanisms of biosynthesis, uptake and regulation have been extensively studied in Pseudomonas aeruginosa PAO1. However, the extent to which this regulatory model applies to other pseudomonads is unknown. Here, we describe the results of a genomic, genetic and structural analysis of pyoverdine-mediated iron uptake by the plant growth-promoting bacterium P. fluorescens SBW25.

Results

In silico analysis of the complete, but un-annotated, SBW25 genome sequence identified 31 genes putatively involved in PVD biosynthesis, transport or regulation, which are distributed across seven different regions of the genome. PVD gene iron-responsiveness was tested using 'lacZ fusions to five PVD loci, representative of structural and regulatory genes. Transcription of all fusions increased in response to iron starvation. In silico analyses suggested that regulation of fpvR (which is predicted to encode a cytoplasmic membrane-spanning anti-sigma factor) may be unique. Transcriptional assays using gene expression constructs showed that fpvR is positively regulated by FpvI (an extracytoplasmic family (ECF) sigma factor), and not directly by the ferric uptake regulator (Fur) as for PAO1. Deletion of pvdL, encoding a predicted non-ribosomal peptide synthetase (NRPS) involved in PVD chromophore biosynthesis confirmed the necessity of PvdL for PVD production and for normal growth in iron-limited media. Structural analysis of the SBW25 PVD shows a partly cyclic seven residue peptide backbone, identical to that of P. fluorescens ATCC13525. At least 24 putative siderophore receptor genes are present in the SBW25 genome enabling the bacterium to utilize 19 structurally distinct PVDs from 25 different Pseudomonas isolates.

Conclusion
The genome of P. fluorescens SBW25 contains an extensively dispersed set of PVD genes in comparison to other sequenced Pseudomonas strains. The PAO1 PVD regulatory model, which involves a branched Fpv signaling pathway, is generally conserved in SBW25, however there is a significant difference in fpvR regulation. SBW25 produces PVD with a partly cyclic seven amino acid residue backbone, and is able to utilize a wide variety of exogenous PVDs.
Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex, and location
Authors: Boyd Lauren Becnel , Atmar Robert L , Randall Graham L , Hamill Richard J , Steffen David , Zechiedrich Lynn 
Published: January 2008

Abstract

Background

Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates.

Methods
To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n ≅ 21,000) for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods.

Results
Fluoroquinolone resistance (i) increased with time; (ii) exceeded national averages by 2- to 4-fold; (iii) was higher in males than females, largely because of urinary isolates from male outpatients; (iv) increased with patient age; (v) was 3% in pediatric patients; (vi) was higher in hospitalized patients than outpatients; (vii) was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii) was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested.

Conclusion
Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics.
Chemoradiotherapy with or without consolidation chemotherapy using cisplatin and 5-fluorouracil in anal squamous cell carcinoma: long-term results in 31 patients
Authors: Cho Byoung Chul , Ahn Joong Bae , Seong Jinsil , Roh Jae Kyung , Kim Joo Hang , Chung Hyun Cheol , Sohn Joo Hyuk , Kim Nam Kyu 
Published: January 2008

Abstract

Background
The objectives of this study were to evaluate long-term results of concurrent chemoradiotherapy (CRT) with 5-fluorouracil and cisplatin and the potential benefit of consolidation chemotherapy in patients with anal squamous cell carcinoma (ASCC).

Methods
Between January 1995 and February 2006, 31 patients with ASCC were treated with CRT. Radiotherapy was administered at 45 Gy over 5 weeks, followed by a boost of 9 Gy to complete or partial responders. Chemotherapy consisted of 5-fluorouracil (750 or 1,000 mg/m2) daily on days 1 to 5 and days 29 to 33; and, cisplatin (75 or 100 mg/m2) on day 2 and day 30. Twelve patients had T3–4 disease, whereas 18 patients presented with lymphadenopathy. Twenty-one (67.7%) received consolidation chemotherapy with the same doses of 5-fluorouracil and cisplatin, repeated every 4 weeks for maximum 4 cycles.

Results
Nineteen patients (90.5%) completed all four courses of consolidation chemotherapy. After CRT, 28 patients showed complete responses, while 3 showed partial responses. After a median follow-up period of 72 months, the 5-year overall, disease-free, and colostomy-free survival rates were 84.7%, 82.9% and 96.6%, demonstrating that CRT with 5-fluorouracil and cisplatin yields a good outcome in terms of survival and sphincter preservation. No differences in 5-year OS and DFS rates between patients treated with CRT alone and CRT with consolidation chemotherapy was observed.

Conclusion
our study shows that CRT with 5-FU and cisplatin, with or without consolidation chemotherapy, was well tolerated and proved highly encouraging in terms of long-term survival and the preservation of anal function in ASCC. Further trials with a larger patient population are warranted in order to evaluate the potential role of consolidation chemotherapy.
Enhancement of hybridoma formation, clonability and cell proliferation in a nanoparticle-doped aqueous environment
Authors: Gavrilov-Yusim Natalie , Hahiashvili Ekaterina , Tashker Marina , Yavelsky Victoria , Karnieli Ohad , Lobel Leslie 
Published: January 2008

Abstract

Background
The isolation and production of human monoclonal antibodies is becoming an increasingly important pursuit as biopharmaceutical companies migrate their drug pipelines away from small organic molecules. As such, optimization of monoclonal antibody technologies is important, as this is becoming the new rate-limiting step for discovery and development of new pharmaceuticals. The major limitations of this system are the efficiency of isolating hybridoma clones, the process of stabilizing these clones and optimization of hybridoma cell secretion, especially for large-scale production.
Many previous studies have demonstrated how perturbations in the aqueous environment can impact upon cell biology. In particular, radio frequency (RF) irradiation of solutions can have dramatic effects on behavior of solutions, cells and in particular membrane proteins, although this effect decays following removal of the RF. Recently, it was shown that nanoparticle doping of RF irradiated water (NPD water) produced a stabilized aqueous medium that maintained the characteristic properties of RF irradiated water for extended periods of time. Therefore, the ordering effect in water of the RF irradiation can now be studied in systems that required prolonged periods for analysis, such as eukaryotic cell culture. Since the formation of hybridoma cells involves the formation of a new membrane, a process that is affected by the surrounding aqueous environment, we tested these nanoparticle doped aqueous media formulations on hybridoma cell production.

Results
In this study, we tested the entire process of isolation and production of human monoclonal antibodies in NPD water as a means for further enhancing human monoclonal antibody isolation and production. Our results indicate an overall enhancement of hybridoma yield, viability, clonability and secretion. Furthermore, we have demonstrated that immortal cells proliferate faster whereas primary human fibroblasts proliferate slower in NPD water.

Conclusion
Overall, these studies indicate that NPD water can enhance cell proliferation, clonability and secretion. Furthermore, the results support the hypothesis that NPD water is effectively composed of stable microenvironments.
Polymorphisms of TNF-enhancer and gene for FcγRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population
Authors: Sinha Swapnil , Mishra Shrawan K , Sharma Shweta , Patibandla Phani K , Mallick Prashant K , Sharma Surya K , Mohanty Sanjib , Pati Sudhanshu S , Mishra Saroj K , Ramteke Bheshaj K , Bhatt RM , Joshi Hema , Dash Aditya P , Ahuja Ramesh C , Awasthi Shally ,   Indian Genome Variation Consortium, Venkatesh Vimala , Habib Saman 
Published: January 2008

AbstractBackgroundSusceptibility/resistance toPlasmodium falciparummalaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in theTNFandFCGR2Agenes in determining severity/resistance toP. falciparummalaria in Indian subjects.MethodsAllelic frequency distribution in populations across India was first determined by typing genetic variants of theTNFenhancer and theFCGR2AG/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfo™ version 3.4.ResultsA novel single nucleotide polymorphism (SNP) at position -76 was identified in theTNFenhancer along with other reported variants. FiveTNFenhancer SNPs and theFCGR2AR131H (G/A) SNP were analyzed for association with severity ofP. falciparummalaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions.TNF-1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcγRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context ofP. falciparumseverity/resistance in the Indian population.ConclusionAssociation of specificTNFandFCGR2ASNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.
The role of aldosterone blockade in murine lupus nephritis
Authors: Monrad Seetha U , Killen Paul D , Anderson Marc R , Bradke Amanda , Kaplan Mariana J 
Published: January 2008

Abstract
Background
The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZB × NZW) F1 murine lupus model.

Methods
Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg oral spironolactone or vehicle. Proteinuria, renal function, and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real-time PCR analysis of several differentially expressed genes.

Results
Treatment with spironolactone was well tolerated by the mice throughout the course of their disease progression, with no significant differences in azotemia or serum potassium levels between vehicle-treated and spironolactone-treated animals. By 36 weeks of age, fewer spironolactone-treated mice developed nephrotic range proteinuria as compared with the control mice (control 70.8%, 25 mg/kg spironolactone 51.3%, and 50 mg/kg spironolactone 48.6%). Compared with control mice, mice treated with 25 mg/kg spironolactone had significantly lower serum anti-single-stranded DNA levels (2,042 μg/ml versus 1,036 μg/ml; P = 0.03) and anti-double-stranded DNA levels (3,433 μg/ml versus 614 μg/ml; P = 0.05). Spironolactone-treated mice exhibited decreased histopathologic evidence of inflammation and tissue damage, as compared with control mice. Additionally, spironolactone treatment resulted in decreased expression in the kidney of several inflammatory and proapoptotic genes, including those encoding interferon-γ, B lymphocyte stimulator (BlyS), tumor necrosis factor related apoptosis inducing ligand (TRAIL), tumor necrosis factor related weak inducer of apoptosis (TWEAK), and Fas ligand.

Conclusion
Aldosterone receptor blockade is safe and well tolerated in progressive murine lupus nephritis, and it results in decreased levels of clinical proteinuria, lower serum levels of autoantibodies, and decreased kidney damage. It appears to modulate inflammatory changes during the progression of glomerulonephritis and may also have a previously undescribed role in attenuating apoptosis.
Effects of plasma expansion with albumin and paracentesis on haemodynamics and kidney function in critically ill cirrhotic patients with tense ascites and hepatorenal syndrome: a prospective uncontrolled trial
Authors: Umgelter Andreas , Reindl Wolfgang , Wagner Katrin S , Franzen Michael , Stock Konrad , Schmid Roland M , Huber Wolfgang 
Published: January 2008

Abstract
Introduction
Circulatory dysfunction in cirrhotic patients may cause a specific kind of functional renal failure termed hepato-renal syndrome (HRS). It contributes to the high incidence of renal failure in cirrhotic intensive care unit (ICU) patients. Fluid therapy may aggravate renal failure by increasing ascites and intra-abdominal pressure (IAP). This study investigates the short-term effects of paracentesis on haemodynamics and kidney function in volume resuscitated patients with HRS.

Methods
Nineteen consecutive cirrhotic patients with HRS were studied. Circulatory parameters and renal function were analysed before and after plasma expansion and paracentesis. Haemodynamic monitoring was performed by transpulmonary thermodilution.

Results
After infusion of 200 ml of 20% human albumin solution, mean arterial pressure (MAP) and central venous pressure remained unchanged. Global end-diastolic volume index (GEDVI) increased from 791 ml m-2 (693 to 862) (median and 25th to 75th percentile) to 844 ml m-2 (751 to 933). Cardiac index (CI) increased from 4.1 l min-1 m-2 (3.6 to 5.0) to 4.7 l min-1 m-2 (4.0 to 5.8), whereas systemic vascular resistance index (SVRI) decreased from 1,422 dyn s cm-5 m-2 (1,081 to 1,772) to 1,171 dyn s cm-5 m-2 (893 to 1,705). Creatinine clearance (CC) and fractional excretion of sodium (FeNa) were not affected. During paracentesis, IAP decreased from 22 mmHg (18 to 24) to 9 mmHg (8 to 12). MAP decreased from 81 mmHg (74 to 100) to 80 mmHg (71 to 89), and CI increased from 4.1 l min-1 m-2 (3.2 to 4.3) to 4.2 l min-1 m-2 (3.6 to 4.7), whereas SVRI decreased from 1,639 dyn s cm-5 m-2 (1,168 to 2,037) to 1,301 dyn s cm-5 m-2 (1,124 to 1,751). CC during the 12-hour interval after paracentesis was significantly higher than during the 12 hours before (33 ml min-1 (16 to 50) compared with 23 ml min-1 (12 to 49)). CC remained elevated for the rest of the observation period. FeNa increased after paracentesis but returned to baseline levels after 24 hours.

Conclusion
Paracentesis with parameter-guided fluid substitution and maintenance of central blood volume may improve renal function and is safe in the treatment of ICU patients with hepato-renal failure.
Surface Morphology and Proton Conduction Imaging of Nafion Membrane
Authors: Takimoto Naohiko , Ohira Akihiro , Takeoka Yuko , Rikukawa Masahiro 
Published: January 2008

Abstract
AC-mode atomic force microscopy (AFM) and electrochemical methods were used to identify the proton conducting regions of Nafion membrane. It was found that the surface of Nafion membrane was constructed of small hydrophobic granular domains and that protons passed through the hydrophilic regions formed in the interstices between those domains.
Synthesis of a Hetero-bimetallic Complex with an Inorganic Cyclic Framework Using a Bis(iminophosphorane)iron Complex as a Chelating Ligand
Authors: Kubo Kazuyuki , Akimoto Takashi , Mizuta Tsutomu , Miyoshi Katsuhiko 
Published: January 2008

Abstract
An iron–rhodium bimetallic complex bearing a six-membered metallacycle was synthesized from a lithium bis(iminophosphorane)iron complex, which served as an anionic chelating ligand carrying a bis(iminophosphorano)methanide-like inorganic framework. The metallacycle complex takes a peculiar boat shape, in which the two metal centers are in close proximity and the carbonyl ligand on the iron atom overhangs the rhodium atom, giving a considerably low-frequency IR absorption and assuming a slightly bent structure.
Evaluation of sources of uncertainty in risk assessments conducted for the US Army using a case study approach
Authors: von Stackelberg Katherine , Vorhees Donna , Moore Dwayne , Cura Jerome , Bridges Todd 
Published: January 2008

Abstract
We identify, categorize, and score sources of uncertainty in human health and ecological risk assessments conducted for several US Army sites to identify better analytical practices and opportunities for targeted research to improve risk estimates. The reviewed assessments are from reports completed within the past 8 y and were obtained from the US Army Environmental Technical Information Center (ETIC) at Aberdeen Proving Ground, Maryland, USA. Most of the risk assessments incorporated only qualitative uncertainty analysis to demonstrate the conservatism of selected data and predictive models. Food chain transfer (e.g., concentrations of contaminants across trophic levels) dominated quantifiable sources of uncertainty across the risk assessments evaluated. Factors related to dermal exposures ranked high for human health, and effects assessment for ecological endpoints.