bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOVIS: an implementation for high-throughput virtual screening using AutoDock
Authors: Zhang Shuxing , Kumar Kamal , Jiang Xiaohui , Wallqvist Anders , Reifman Jaques 
Published: February 2008

Abstract

Background
Molecular-docking-based virtual screening is an important tool in drug discovery that is used to significantly reduce the number of possible chemical compounds to be investigated. In addition to the selection of a sound docking strategy with appropriate scoring functions, another technical challenge is to in silico screen millions of compounds in a reasonable time. To meet this challenge, it is necessary to use high performance computing (HPC) platforms and techniques. However, the development of an integrated HPC system that makes efficient use of its elements is not trivial.

Results
We have developed an application termed DOVIS that uses AutoDock (version 3) as the docking engine and runs in parallel on a Linux cluster. DOVIS can efficiently dock large numbers (millions) of small molecules (ligands) to a receptor, screening 500 to 1,000 compounds per processor per day. Furthermore, in DOVIS, the docking session is fully integrated and automated in that the inputs are specified via a graphical user interface, the calculations are fully integrated with a Linux cluster queuing system for parallel processing, and the results can be visualized and queried.

Conclusion
DOVIS removes most of the complexities and organizational problems associated with large-scale high-throughput virtual screening, and provides a convenient and efficient solution for AutoDock users to use this software in a Linux cluster platform.
Molecular evolution of rDNA in early diverging Metazoa: First comparative analysis and phylogenetic application of complete SSU rRNA secondary structures in Porifera
Authors: Voigt Oliver , Erpenbeck Dirk , Wörheide Gert 
Published: February 2008

Abstract

Background
The cytoplasmic ribosomal small subunit (SSU, 18S) ribosomal RNA (rRNA) is the most frequently-used gene for molecular phylogenetic studies. However, information regarding its secondary structure is neglected in most phylogenetic analyses. Incorporation of this information is essential in order to apply specific rRNA evolutionary models to overcome the problem of co-evolution of paired sites, which violates the basic assumption of the independent evolution of sites made by most phylogenetic methods. Information about secondary structure also supports the process of aligning rRNA sequences across taxa. Both aspects have been shown to increase the accuracy of phylogenetic reconstructions within various taxa.
Here, we explore SSU rRNA secondary structures from the three extant classes of Phylum Porifera (Grant, 1836), a pivotal, but largely unresolved taxon of early branching Metazoa. This is the first phylogenetic study of poriferan SSU rRNA data to date that includes detailed comparative secondary structure information for all three sponge classes.

Results
We found base compositional and structural differences in SSU rRNA among Demospongiae, Hexactinellida (glass sponges) and Calcarea (calcareous sponges). We showed that analyses of primary rRNA sequences, including secondary structure-specific evolutionary models, in combination with reconstruction of the evolution of unusual structural features, reveal a substantial amount of additional information. Of special note was the finding that the gene tree topologies of marine haplosclerid demosponges, which are inconsistent with the current morphology-based classification, are supported by our reconstructed evolution of secondary structure features. Therefore, these features can provide alternative support for sequence-based topologies and give insights into the evolution of the molecule itself. To encourage and facilitate the application of rRNA models in phylogenetics of early metazoans, we present 52 SSU rRNA secondary structures over the taxonomic range of Porifera in a database, along with some basic tools for relevant format-conversion.

Conclusion
We demonstrated that sophisticated secondary structure analyses can increase the potential phylogenetic information of already available rDNA sequences currently accessible in databases and conclude that the importance of SSU rRNA secondary structure information for phylogenetic reconstruction is still generally underestimated, at least among certain early branching metazoans.
Vesicle-independent extracellular release of a proinflammatory outer membrane lipoprotein in free-soluble form
Authors: Karched Maribasappa , Ihalin Riikka , Eneslätt Kjell , Zhong Deyu , Oscarsson Jan , Wai Sun N , Chen Casey , Asikainen Sirkka E 
Published: February 2008

AbstractBackgroundAggregatibacter actinomycetemcomitansis an oral bacterium associated with aggressively progressing periodontitis. Extracellular release of bacterial outer membrane proteins has been suggested to mainly occur via outer membrane vesicles. This study investigated the presence and conservation of peptidoglycan-associated lipoprotein (AaPAL) amongA. actinomycetemcomitansstrains, the immunostimulatory effect of AaPAL, and whether live cells release this structural outer membrane lipoprotein in free-soluble form independent of vesicles.ResultsThepallocus and its gene product were confirmed in clinicalA. actinomycetemcomitansstrains by PCR-restriction fragment length polymorphism and immunoblotting. Culturing under different growth conditions revealed no apparent requirement for the AaPAL expression. Inactivation ofpalin a wild-type strain (D7S) and in its spontaneous laboratory variant (D7SS) resulted in pleiotropic cellular effects. In a cell culture insert model (filter pore size 0.02 μm), AaPAL was detected from filtrates when strains D7S and D7SS were incubated in serum or broth in the inserts. Electron microscopy showed thatA. actinomycetemcomitansvesicles (0.05–0.2 μm) were larger than the filter pores and that there were no vesicles in the filtrates. The filtrates were immunoblot negative for a cytoplasmic marker, cyclic AMP (cAMP) receptor protein. An ex vivo model indicated cytokine production from human whole blood stimulated by AaPAL.ConclusionFree-soluble AaPAL can be extracellularly released in a process independent of vesicles.
Gastrointestinal symptoms and motility disorders in patients with systemic scleroderma
Authors: Di Ciaula Agostino , Covelli Michele , Berardino Massimo , Wang David QH , Lapadula Giovanni , Palasciano Giuseppe , Portincasa Piero 
Published: February 2008

Abstract

Background
Studies on gastrointestinal symptoms, dysfunctions, and neurological disorders in systemic scleroderma are lacking so far.

Methods
Thirty-eight scleroderma patients (34 limited, 4 diffuse), 60 healthy controls and 68 dyspeptic controls were scored for upper and lower gastrointestinal symptoms (dyspepsia, bowel habits), gastric and gallbladder emptying to liquid meal (functional ultrasonography) and small bowel transit (H2-breath test). Autonomic nerve function was assessed by cardiovascular tests.

Results
The score for dyspepsia (mainly gastric fullness) was greater in scleroderma patients than healthy controls, but lower than dyspeptic controls who had multiple symptoms, instead. Scleroderma patients with dyspepsia had a longer disease duration. Fasting antral area and postprandial antral dilatation were smaller in scleroderma patients than dyspeptic and healthy controls. Gastric emptying was delayed in both scleroderma patients (particularly in those with abnormal dyspeptic score) and dyspeptic controls, who also showed a larger residual area. Despite gallbladder fasting and postprandial volumes were comparable across the three groups, gallbladder refilling appeared delayed in dyspeptic controls and mainly dependent on delayed gastric emptying in scleroderma. Small intestinal transit was also delayed in 74% of scleroderma and 66% of dyspeptic controls. Bowel habits were similar among the three groups. Autonomic neuropathy was not associated with dyspepsia, gastric and gallbladder motility and small intestinal transit.

Conclusion
In scleroderma patients dyspepsia (mainly gastric fullness), restricted distension of the gastric antrum and diffuse gastrointestinal dysmotility are frequent features. These defects are independent from the occurrence of autonomic neuropathy.
Individual nutrition therapy and exercise regime: A controlled trial of injured, vulnerable elderly (INTERACTIVE trial)
Authors: Thomas Susie K , Humphreys Karen J , Miller Michelle D , Cameron Ian D , Whitehead Craig , Kurrle Susan , Mackintosh Shylie , Crotty Maria 
Published: February 2008

Abstract

Background
Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers.

Methods and Design
This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders.

Discussion
The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers.

Trial registration
Australian Clinical Trials Registry: ACTRN12607000017426.
Effect of ionic strength and presence of serum on lipoplexes structure monitorized by FRET
Authors: Madeira Catarina , Loura Luís MS , Prieto Manuel , Fedorov Aleksander , Aires-Barros M Raquel 
Published: February 2008

Abstract

Background
Serum and high ionic strength solutions constitute important barriers to cationic lipid-mediated intravenous gene transfer. Preparation or incubation of lipoplexes in these media results in alteration of their biophysical properties, generally leading to a decrease in transfection efficiency. Accurate quantification of these changes is of paramount importance for the success of lipoplex-mediated gene transfer in vivo.

Results
In this work, a novel time-resolved fluorescence resonance energy transfer (FRET) methodology was used to monitor lipoplex structural changes in the presence of phosphate-buffered saline solution (PBS) and fetal bovine serum. 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/pDNA lipoplexes, prepared in high and low ionic strength solutions, are compared in terms of complexation efficiency. Lipoplexes prepared in PBS show lower complexation efficiencies when compared to lipoplexes prepared in low ionic strength buffer followed by addition of PBS. Moreover, when serum is added to the referred formulation no significant effect on the complexation efficiency was observed. In physiological saline solutions and serum, a multilamellar arrangement of the lipoplexes is maintained, with reduced spacing distances between the FRET probes, relative to those in low ionic strength medium.

Conclusion
The time-resolved FRET methodology described in this work allowed us to monitor stability and characterize quantitatively the structural changes (variations in interchromophore spacing distances and complexation efficiencies) undergone by DOTAP/DNA complexes in high ionic strength solutions and in presence of serum, as well as to determine the minimum amount of potentially cytotoxic cationic lipid necessary for complete coverage of DNA. This constitutes essential information regarding thoughtful design of future in vivo applications.
Switching the mode of sucrose utilization by Saccharomyces cerevisiae
Authors: Badotti Fernanda , Dário Marcelo G , Alves Sergio L , Cordioli Maria Luiza A , Miletti Luiz C , de Araujo Pedro S , Stambuk Boris U 
Published: February 2008

Abstract

Background
Overflow metabolism is an undesirable characteristic of aerobic cultures of Saccharomyces cerevisiae during biomass-directed processes. It results from elevated sugar consumption rates that cause a high substrate conversion to ethanol and other bi-products, severely affecting cell physiology, bioprocess performance, and biomass yields. Fed-batch culture, where sucrose consumption rates are controlled by the external addition of sugar aiming at its low concentrations in the fermentor, is the classical bioprocessing alternative to prevent sugar fermentation by yeasts. However, fed-batch fermentations present drawbacks that could be overcome by simpler batch cultures at relatively high (e.g. 20 g/L) initial sugar concentrations. In this study, a S. cerevisiae strain lacking invertase activity was engineered to transport sucrose into the cells through a low-affinity and low-capacity sucrose-H+ symport activity, and the growth kinetics and biomass yields on sucrose analyzed using simple batch cultures.

Results
We have deleted from the genome of a S. cerevisiae strain lacking invertase the high-affinity sucrose-H+ symporter encoded by the AGT1 gene. This strain could still grow efficiently on sucrose due to a low-affinity and low-capacity sucrose-H+ symport activity mediated by the MALx1 maltose permeases, and its further intracellular hydrolysis by cytoplasmic maltases. Although sucrose consumption by this engineered yeast strain was slower than with the parental yeast strain, the cells grew efficiently on sucrose due to an increased respiration of the carbon source. Consequently, this engineered yeast strain produced less ethanol and 1.5 to 2 times more biomass when cultivated in simple batch mode using 20 g/L sucrose as the carbon source.

Conclusion
Higher cell densities during batch cultures on 20 g/L sucrose were achieved by using a S. cerevisiae strain engineered in the sucrose uptake system. Such result was accomplished by effectively reducing sucrose uptake by the yeast cells, avoiding overflow metabolism, with the concomitant reduction in ethanol production. The use of this modified yeast strain in simpler batch culture mode can be a viable option to more complicated traditional sucrose-limited fed-batch cultures for biomass-directed processes of S. cerevisiae.
Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED
Authors: Rakotobe Dina , Violot Sébastien , Hong Saw See , Gouet Patrice , Boulanger Pierre 
Published: February 2008

Abstract

Background
The human EED protein, a member of the superfamily of Polycomb group proteins, is involved in multiple cellular protein complexes. Its C-terminal domain, which is common to the four EED isoforms, contains seven repeats of a canonical WD-40 motif. EED is an interactor of three HIV-1 proteins, matrix (MA), integrase (IN) and Nef. An antiviral activity has been found to be associated with isoforms EED3 and EED4 at the late stage of HIV-1 replication, due to a negative effect on virus assembly and genomic RNA packaging. The aim of the present study was to determine the regions of the EED C-terminal core domain which were accessible and available to protein interactions, using three-dimensional (3D) protein homology modelling with a WD-40 protein of known structure, and epitope mapping of anti-EED antibodies.

Results
Our data suggested that the C-terminal domain of EED was folded as a seven-bladed β-propeller protein. During the completion of our work, crystallographic data of EED became available from co-crystals of the EED C-terminal core with the N-terminal domain of its cellular partner EZH2. Our 3D-model was in good congruence with the refined structural model determined from crystallographic data, except for a unique α-helix in the fourth β-blade. More importantly, the position of flexible loops and accessible β-strands on the β-propeller was consistent with our mapping of immunogenic epitopes and sites of interaction with HIV-1 MA and IN. Certain immunoreactive regions were found to overlap with the EZH2, MA and IN binding sites, confirming their accessibility and reactivity at the surface of EED. Crystal structure of EED showed that the two discrete regions of interaction with MA and IN did not overlap with each other, nor with the EZH2 binding pocket, but were contiguous, and formed a continuous binding groove running along the lateral face of the β-propeller.

Conclusion
Identification of antibody-, MA-, IN- and EZH2-binding sites at the surface of the EED isoform 3 provided a global picture of the immunogenic and protein-protein interacting regions in the EED C-terminal domain, organized as a seven-bladed β-propeller protein. Mapping of the HIV-1 MA and IN binding sites on the 3D-model of EED core predicted that EED-bound MA and IN ligands would be in close vicinity at the surface of the β-propeller, and that the occurrence of a ternary complex MA-EED-IN would be possible.
Perforated diverticulitis presenting as necrotising fasciitis of the leg
Authors: Underwood Timothy J , Southgate Jeremy , Talbot Robert , Nash Guy F 
Published: February 2008

Abstract
Diverticulosis of the colon is a common condition of increasing age. Complications of diverticulitis including stricture, perforation and fistula formation often require surgery. Perforated diverticulitis may rarely present with spreading superficial sepsis. We describe for the first time, to our knowledge, a case of retroperitoneal diverticula perforation presenting as necrotising fasciitis of the leg necessitating hind-quarter amputation.
Cellular automata simulation of topological effects on the dynamics of feed-forward motifs
Authors: Apte Advait A , Cain John W , Bonchev Danail G , Fong Stephen S 
Published: February 2008

Abstract

Background
Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems.

Results
Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production.

Conclusion
It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models.
What do we know about communicating risk? A brief review and suggestion for contextualising serious, but rare, risk, and the example of cox-2 selective and non-selective NSAIDs
Authors: Moore R Andrew , Derry Sheena , McQuay Henry J , Paling John 
Published: February 2008

Abstract
Background
Communicating risk is difficult. Although different methods have been proposed – using numbers, words, pictures or combinations – none has been extensively tested. We used electronic and bibliographic searches to review evidence concerning risk perception and presentation. People tend to underestimate common risk and overestimate rare risk; they respond to risks primarily on the basis of emotion rather than facts, seem to be risk averse when faced with medical interventions, and want information on even the rarest of adverse events.

Methods
We identified observational studies (primarily in the form of meta-analyses) with information on individual non-steroidal anti-inflammatory drug (NSAID) or selective cyclooxygenase-2 inhibitor (coxib) use and relative risk of gastrointestinal bleed or cardiovascular event, the background rate of events in the absence of NSAID or coxib, and the likelihood of death from an event. Using this information we present the outcome of additional risk of death from gastrointestinal bleed and cardiovascular event for individual NSAIDs and coxibs alongside information about death from other causes in a series of perspective scales.

Results
The literature on communicating risk to patients is limited. There are problems with literacy, numeracy and the human tendency to overestimate rare risk and underestimate common risk. There is inconsistency in how people translate between numbers and words. We present a method of communicating information about serious risks using the common outcome of death, using pictures, numbers and words, and contextualising the information. The use of this method for gastrointestinal and cardiovascular harm with NSAIDs and coxibs shows differences between individual NSAIDs and coxibs.

Conclusion
Although contextualised risk information can be provided on two possible adverse events, many other possible adverse events with potential serious consequences were omitted. Patients and professionals want much information about risks of medical interventions but we do not know how best to meet expectations. The impact of contextualised information remains to be tested.