bluuebunny/crossref_metadata_2025_split huggingface dataset:
British Society of Haematology, Slide Session presented at the Annual Scientific Meeting, Brighton 2009
Authors: McLORNAN D. P. , BURTHEM J. , DUNCOMBE A. , HATTON C. , HUTCHINSON C. V. , MARSDEN K. , MACARTNEY C. M. , SMITH‐STRANEY T. , UPRICHARD J. , WALLIS J. , WEBB S. , WILKINS B. S. , McMULLIN M. F. 
Published: May 2010

SummarySeven cases were discussed by an expert panel at the 2009 Annual Scientific Meeting of the British Society of Haematology. These cases are presented in a similar format to that adopted for the meeting. There was an initial discussion of the presenting morphology, generation of differential diagnoses and then, following display of further presenting and diagnostic information, each case was concluded with provision of a final diagnosis.
Robust and General Method for Determining Surface Fluid Flow Boundary
Conditions in Articular Cartilage Contact Mechanics Modeling
Authors: Pawaskar Sainath Shrikant , Fisher John , Jin Zhongmin 
Published: May 2010

Abstract
Contact detection in cartilage contact mechanics is an important feature of any analytical or computational modeling investigation when the biphasic nature of cartilage and the corresponding tribology are taken into account. The fluid flow boundary conditions will change based on whether the surface is in contact or not, which will affect the interstitial fluid pressurization. This in turn will increase or decrease the load sustained by the fluid phase, with a direct effect on friction, wear, and lubrication. In laboratory experiments or clinical hemiarthroplasty, when a rigid indenter or metallic prosthesis is used to apply load to the cartilage, there will not be any fluid flow normal to the surface in the contact region due to the impermeable nature of the indenter/prosthesis. In the natural joint, on the other hand, where two cartilage surfaces interact, flow will depend on the pressure difference across the interface. Furthermore, in both these cases, the fluid would flow freely in non-contacting regions. However, it should be pointed out that the contact area is generally unknown in advance in both cases and can only be determined as part of the solution. In the present finite element study, a general and robust algorithm was proposed to decide nodes in contact on the cartilage surface and, accordingly, impose the fluid flow boundary conditions. The algorithm was first tested for a rigid indenter against cartilage model. The algorithm worked well for two-dimensional four-noded and eight-noded axisymmetric element models as well as three-dimensional models. It was then extended to include two cartilages in contact. The results were in excellent agreement with the previous studies reported in the literature.
Advantages and Drawbacks of Proximal Interphalangeal Joint Fusion Versus Flexor Tendon Transfer in the Correction of Hammer and Claw Toe Deformity. A Finite-Element Study
Authors: Bayod Javier , Losa-Iglesias Marta , Becerro de Bengoa-Vallejo Ricardo , Prados-Frutos Juan Carlos , Jules Kevin T. , Doblaré Manuel 
Published: May 2010

AbstractCorrection of claw or hammer toe deformity can be achieved using various techniques, including proximal interphalangeal joint arthrodesis (PIPJA), flexor digitorum longus tendon transfer (FDLT), and flexor digitorum brevis transfer. PIPJA is the oldest technique, but is associated with significant complications (infection, fracture, delayed union, and nonunion). FDLT eliminates the deformity, but leads to loss of stability during gait. Flexor digitorum brevis tendon transfer (FDBT) seems to be the best surgical alternative, but it is a recent technique with still limited results. In this work, these three techniques have been analyzed by means of the finite-element method and a comparative analysis was done with the aim of extracting advantages and drawbacks. The results show that the best technique for reducing dorsal displacement of the proximal phalanx is PIPJA (2.28 mm versus 2.73 mm for FDLT, and 3.31 mm for FDBT). However, the best technique for reducing stresses on phalanges is FDLT or FDBT (a reduction of approximately 35% regarding the pathologic case versus the increase of 7% for the PIPJA in tensile stresses, and a reduction of approximately 40% versus 25% for the PIPJA in compression stresses). Moreover, the distribution of stresses in the entire phalanx is different for the PIPJA case. These facts could cause problems for patients, in particular, those with pain in the surgical toe.
Inhibition of Dengue Virus RNA Synthesis by an Adenosine Nucleoside
Authors: Chen Yen-Liang , Yin Zheng , Duraiswamy Jeyaraj , Schul Wouter , Lim Chin Chin , Liu Boping , Xu Hao Ying , Qing Min , Yip Andy , Wang Gang , Chan Wai Ling , Tan Hui Pen , Lo Melissa , Liung Sarah , Kondreddi Ravinder Reddy , Rao Ranga , Gu Helen , He Handan , Keller Thomas H. , Shi Pei-Yong 
Published: May 2010

ABSTRACT

We recently reported that (2
R
,3
R
,4
R
,5
R
)-2-(4-amino-pyrrolo[2,3-
d
]pyrimidin-7-yl)-3-ethynyl-5-hydroxy-methyl-tetrahydro-furan-3,4-diol is a potent inhibitor of dengue virus (DENV), with 50% effective concentration (EC
50
) and cytotoxic concentration (CC
50
) values of 0.7 μM and >100 μM, respectively. Here we describe the synthesis, structure-activity relationship, and antiviral characterization of the inhibitor. In an AG129 mouse model, a single-dose treatment of DENV-infected mice with the compound suppressed peak viremia and completely prevented death. Mode-of-action analysis using a DENV replicon indicated that the compound blocks viral RNA synthesis. Recombinant adenosine kinase could convert the compound to a monophosphate form. Suppression of host adenosine kinase, using a specific inhibitor (iodotubercidin) or small interfering RNA (siRNA), abolished or reduced the compound's antiviral activity in cell culture. Studies of rats showed that
14
C-labeled compound was converted to mono-, di-, and triphosphate metabolites
in vivo
. Collectively, the results suggest that this adenosine inhibitor is phosphorylated to an active (triphosphate) form which functions as a chain terminator for viral RNA synthesis.
Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas' Disease Treatment
Authors: Batista Denise da Gama Jaén , Batista Marcos Meuser , Oliveira Gabriel Melo de , Amaral Patrícia Borges do , Lannes-Vieira Joseli , Britto Constança Carvalho , Junqueira Angela , Lima Marli Maria , Romanha Alvaro José , Sales Junior Policarpo Ademar , Stephens Chad E. , Boykin David W. , Soeiro Maria de Nazaré Correia 
Published: May 2010

ABSTRACT

Chagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite
Trypanosoma cruzi
. The goal of this work is to investigate the
in vitro
and
in vivo
effects of the arylimidamide (AIA) DB766 against
T. cruzi
. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC
50
s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively. DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activity
in vitro
than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiac tissue and presents efficacy similar to that of benznidazole in mouse models of
T. cruzi
infection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment.
Spatial and Temporal Patterns of Biocide Action against
Staphylococcus epidermidis
Biofilms
Authors: Davison William M. , Pitts Betsey , Stewart Philip S. 
Published: May 2010

ABSTRACT

The dynamic antimicrobial action of chlorine, a quaternary ammonium compound, glutaraldehyde, and nisin within biofilm cell clusters of
Staphylococcus epidermidis
was investigated using time-lapse confocal scanning laser microscopy. The technique allowed for the simultaneous imaging of changes in biofilm structure and disruption of cellular membrane integrity through the loss of an unbound fluorophore loaded into bacterial cells prior to antimicrobial challenge. Each of the four antimicrobial agents produced distinct spatial and temporal patterns of fluorescence loss. The antimicrobial action of chlorine was localized around the periphery of biofilm cell clusters. Chlorine was the only antimicrobial agent that caused any biofilm removal. Treatment with the quaternary ammonium compound caused membrane permeabilization that started at the periphery of cell clusters, then migrated steadily inward. A secondary pattern superimposed on the penetration dynamic suggested a subpopulation of less-susceptible cells. These bacteria lost fluorescence much more slowly than the majority of the population. Nisin caused a rapid and uniform loss of green fluorescence from all parts of the biofilm without any removal of biofilm. Glutaraldehyde caused no biofilm removal and also no loss of membrane integrity. Measurements of biocide penetration and action time at the center of cell clusters yielded 46 min for 10 mg liter
−1
chlorine, 21 min for 50 mg liter
−1
chlorine, 25 min for the quaternary ammonium compound, and 4 min for nisin. These results underscore the distinction between biofilm removal and killing and reinforce the critical role of biocide reactivity in determining the rate of biofilm penetration.
Susceptibility of Gram-Negative Pathogens Isolated from Patients with Complicated Intra-Abdominal Infections in the United States, 2007-2008: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART)
Authors: Hoban Daryl J. , Bouchillon Samuel K. , Hawser Stephen P. , Badal Robert E. , LaBombardi Vincent J. , DiPersio Joseph 
Published: May 2010

ABSTRACT

During 2007-2008, 1,036 Gram-negative bacilli were isolated from patients with complicated intra-abdominal infections in the United States. Against members of the family
Enterobacteriaceae
, the most active agents
in vitro
were ertapenem, imipenem, and amikacin, while the least active agent was ampicillin-sulbactam. Ertapenem and imipenem were active against all extended-spectrum-beta-lactamase (ESBL)-positive
Escherichia coli
. Antimicrobial resistance in Gram-negative bacilli isolated from patients with complicated intra-abdominal infections in the United States continues to increase.
Enterotoxigenic
Escherichia coli
Elicits Immune Responses to Multiple Surface Proteins
Authors: Roy Koushik , Bartels Scott , Qadri Firdausi , Fleckenstein James M. 
Published: May 2010

ABSTRACT

Enterotoxigenic
Escherichia
coli
(ETEC) causes considerable morbidity and mortality due to diarrheal illness in developing countries, particularly in young children. Despite the global importance of these heterogeneous pathogens, a broadly protective vaccine is not yet available. While much is known regarding the immunology of well-characterized virulence proteins, in particular the heat-labile toxin (LT) and colonization factors (CFs), to date, evaluation of the immune response to other antigens has been limited. However, the availability of genomic DNA sequences for ETEC strains coupled with proteomics technology affords opportunities to examine novel uncharacterized antigens that might also serve as targets for vaccine development. Analysis of whole or fractionated bacterial proteomes with convalescent-phase sera can potentially accelerate identification of secreted or surface-expressed targets that are recognized during the course of infection. Here we report results of an immunoproteomics approach to antigen discovery with ETEC strain H10407. Immunoblotting of proteins separated by two-dimensional electrophoresis (2DE) with sera from mice infected with strain H10407 or with convalescent human sera obtained following natural ETEC infections demonstrated multiple immunoreactive molecules in culture supernatant, outer membrane, and outer membrane vesicle preparations, suggesting that many antigens are recognized during the course of infection. Proteins identified by this approach included established virulence determinants, more recently identified putative virulence factors, as well as novel secreted and outer membrane proteins. Together, these studies suggest that existing and emerging proteomics technologies can provide a useful complement to ongoing approaches to ETEC vaccine development.
Overexpression of therecAGene Decreases Oral but Not Intraperitoneal Fitness ofSalmonella enterica
Authors: Medina-Ruiz Laura , Campoy Susana , Latasa Cristina , Cardenas Paula , Alonso Juan Carlos , Barbé Jordi 
Published: May 2010

ABSTRACTTranscription of theSalmonella enterica recAgene is negatively controlled by the LexA protein, the repressor of the SOS response. The introduction of a mutation (recAo6869) in the LexA binding site, in the promoter region of theS. entericaATCC 14028recAgene, allowed the analysis of the effect that RecA protein overproduction has on the fitness of this virulent strain. The fitness of orally but not intraperitoneally inoculatedrecAo6869cells decreased dramatically. However, the SOS response of this mutant was induced normally, and there was no increase in the sensitivity of the strain toward DNA-damaging agents, bile salts, or alterations in pH. Nevertheless,S. enterica recAo6869cells were unable to swarm and their capacity to cross the intestinal epithelium was significantly reduced. The swarming deficiency inrecAo6869cells is independent of the flagellar phase. Moreover, swimming activity of therecAo6869strain was not diminished with respect to the wild type, indicating that the flagellar synthesis is not affected by RecA protein overproduction. In contrast, swarming was recovered in arecAo6869derivative that overproduced CheW, a protein known to be essential for this function. These data demonstrate that an equilibrium between the intracellular concentrations of RecA and CheW is necessary for swarming inS. enterica. Our results are the first to point out that the SOS response plays a critical role in the prevention of DNA damage by abolishing bacterial swarming in the presence of a genotoxic compound.
In VitroCalcification of Immature Bovine Articular Cartilage
Authors: Hwang Jennifer , Kyubwa Espoir M. , Bae Won C. , Bugbee William D. , Masuda Koichi , Sah Robert L. 
Published: May 2010

Introduction:The zone of calcified cartilage (ZCC) anchors articular cartilage (AC) to subchondral bone through a layer of intermediate stiffness. The regulation and functional consequences of cartilage calcification may vary with depth from the articular surface. The hypothesis of this study was that the in vitro calcification of immature AC occurs selectively in the deep region and is associated with a local increase in stiffness.Methods:AC and growth plate cartilage (GPC) from calves were incubated in DMEM, 1% fetal bovine serum, 100 µg/mL ascorbate, and ±10 mM β-glycerophosphate (βGP) for up to 3 weeks. To assess the time course and effects of cell viability and βGP, full-depth strips of AC and GPC were analyzed by histology, indentation, and45Ca++uptake. To assess the effect of tissue zone, disks harvested from surface and deep zone AC and from reserve and hypertrophic zone of GPC were incubated independently and analyzed by compression and for45Ca++uptake and biochemical components.Results:The deep ~20% of immature AC calcified within 3 weeks, with calcification dependent on cell viability and βGP. Mineral was deposited continuously around cells in AC but only between cell columns in GPC. The deep zone of AC exhibited a compressive modulus of 0.53 MPa after βGP-induced calcification, ~4-fold stiffer than AC incubated without βGP.Conclusions:Cartilage explants exhibit inherent zone-specific calcification processes, resulting in an increase in stiffness associated with cartilage calcification. Such properties may be useful for engineering a biomimetic ZCC tissue to integrate cartilaginous tissue to bone, thereby forming a mechanically functional osteochondral unit.
Myeloid-specific inactivation of p15Ink4b results in monocytosis and predisposition to myeloid leukemia
Authors: Bies Juraj , Sramko Marek , Fares Joanna , Rosu-Myles Michael , Zhang Steven , Koller Richard , Wolff Linda 
Published: May 2010

AbstractInactivation of p15INK4b, an inhibitor of cyclin-dependent kinases, through DNA methylation is one of the most common epigenetic abnormalities in myeloid leukemia. Although this suggests a key role for this protein in myeloid disease suppression, experimental evidence to support this has not been reported. To address whether this event is critical for premalignant myeloid disorders and leukemia development, mice were generated that have loss of p15Ink4b specifically in myeloid cells. The p15Ink4bfl/fl-LysMcre mice develop nonreactive monocytosis in the peripheral blood accompanied by increased numbers of myeloid and monocytic cells in the bone marrow resembling the myeloproliferative form of chronic myelomonocytic leukemia. Spontaneous progression from chronic disease to acute leukemia was not observed. Nevertheless, MOL4070LTR retrovirus integrations provided cooperative genetic mutations resulting in a high frequency of myeloid leukemia in knockout mice. Two common retrovirus insertion sites near c-myb and Sox4 genes were identified, and their transcript up-regulated in leukemia, suggesting a collaborative role of their protein products with p15Ink4b-deficiency in promoting malignant disease. This new animal model demonstrates experimentally that p15Ink4b is a tumor suppressor for myeloid leukemia, and its loss may play an active role in the establishment of preleukemic conditions.
A central role of GPIb-IX in the procoagulant function of platelets that is independent of the 45-kDa GPIbα N-terminal extracellular domain
Authors: Ravanat Catherine , Strassel Catherine , Hechler Béatrice , Schuhler Simone , Chicanne Gaëtan , Payrastre Bernard , Gachet Christian , Lanza François 
Published: May 2010

Abstract
Activated platelets become procoagulant and efficiently promote the conversion of prothrombin to thrombin. A role of the GPIb-V-IX complex has long been postulated in view of the decreased prothrombin consumption in Bernard-Soulier patients. We evaluated the impact of GPIb-V-IX deficiency and the requirement for the GPIbα extracellular domain. In GPIbβ−/− mice, thrombin generation was profoundly decreased in tissue factor– or collagen-related peptide (CRP)–activated platelet-rich plasma and in washed platelets supplemented with normal plasma or with FVa, FXa, and prothrombin. Phosphatidylserine (PS) exposure was similarly decreased in response to thrombin, CRP, or CRP + PAR4 peptide despite a normal platelet phospholipid composition. The hypothesis that these defects originate from lack of the GPIbα N-terminal domain was evaluated after its removal from normal mouse and human platelets with Nk protease or O-sialoglycoprotein endopeptidase. Unexpectedly, the treated platelets exhibited normal thrombin generation and PS exposure, indicating that GPIb-V-IX regulates procoagulant activity independently of its GPIbα-binding region. These results suggested a more general structuring role through intracellular cytoskeleton-anchoring portions regulating responses leading to PS exposure. This hypothesis was supported by the decreased calcium mobilization observed in GPIbβ−/− platelets in response to several agonists, some acting independently of GPIb, in contrast to the normal calcium responses in Nk protease–treated platelets.
Computational prediction of the osmoregulation network in Synechococcus sp. WH8102
Authors: Mao Xizeng , Olman Victor , Stuart Rhona , Paulsen Ian T , Palenik Brian , Xu Ying 
Published: May 2010

Abstract

Background
Osmotic stress is caused by sudden changes in the impermeable solute concentration around a cell, which induces instantaneous water flow in or out of the cell to balance the concentration. Very little is known about the detailed response mechanism to osmotic stress in marine Synechococcus, one of the major oxygenic phototrophic cyanobacterial genera that contribute greatly to the global CO2 fixation.

Results
We present here a computational study of the osmoregulation network in response to hyperosmotic stress of Synechococcus sp strain WH8102 using comparative genome analyses and computational prediction. In this study, we identified the key transporters, synthetases, signal sensor proteins and transcriptional regulator proteins, and found experimentally that of these proteins, 15 genes showed significantly changed expression levels under a mild hyperosmotic stress.

Conclusions
From the predicted network model, we have made a number of interesting observations about WH8102. Specifically, we found that (i) the organism likely uses glycine betaine as the major osmolyte, and others such as glucosylglycerol, glucosylglycerate, trehalose, sucrose and arginine as the minor osmolytes, making it efficient and adaptable to its changing environment; and (ii) σ38, one of the seven types of σ factors, probably serves as a global regulator coordinating the osmoregulation network and the other relevant networks.
Functional analysis of an intergenic non-coding sequence within mce1 operon of M.tuberculosis
Authors: Joon Monika , Bhatia Shipra , Pasricha Rashmi , Bose Mridula , Brahmachari Vani 
Published: May 2010

Abstract

Background
The mce operons play an important role in the entry of M. tuberculosis into macrophages and non-phagocytic cells. Their non-redundant function as well as complex regulation is implied by the phenotype of mce mutants. Recently, mce1 operon was found to extend over 13 genes, fadD5 (Rv0166) being the first gene of the operon. The presence of a non-coding sequence of 200 base pairs between Rv0166 and Rv0167 is peculiar to mce1 among the four mce operons of M.tuberculosis. We have examined the function of this region.

Results
We predicted putative promoter activity of the 200 base pairs of non-coding, intergenic region between Rv0166 and Rv0167 in silico using MEME software and designate it as intergenic promoter, IGPr. We demonstrate both promoter activity and a putative negative regulatory function of this fragment by reporter assays carried out in the surrogate host M.smegmatis. We find that the repressive elements not only control the native promoter but also repress a heterologous promoter of M.smegmatis. The higher activity of the intergenic promoter in a clinical isolate in comparison with the wild type sequence from M.tuberculosis H37Rv could be correlated with a point mutation within the negative element. We have mapped two transcription start sites for mce1 operon both of which are utilized in M.tuberculosis H37Rv as well as the clinical isolate VPCI591. Our studies show that the promoter activity in the non-coding region is relevant not only in reporter gene expression but also in the expression of mce1 operon in M. tuberculosis cells grown in synthetic medium.

Conclusion
The mce operon of M.tuberculosis H37Rv potentially can be transcribed from two promoters P1 and P2, former mapping upstream of Rv0166 and the latter in the non-coding intergenic region between Rv0166 and Rv0167. The transcription initiation from P1 results in a transcript with Rv0166 while that from P2 will be without it. The sequences between the translation start site of Rv0167 and the promoter P2 have a negative regulatory role, as point mutation within the sequence leads to enhanced activity of P2 as well as a heterologous promoter from M.smegmatis. The mutation detected in the clinical isolate VPCI591 therefore behaves like a gain-of-function mutation.