bluuebunny/crossref_metadata_2025 huggingface dataset:
Histidine-rich glycoprotein binds factor XIIa with high affinity and inhibits contact-initiated coagulation
Authors: MacQuarrie Jessica L. , Stafford Alan R. , Yau Jonathan W. , Leslie Beverly A. , Vu Trang T. , Fredenburgh James C. , Weitz Jeffrey I.
Published: February 2011

Histidine-rich glycoprotein (HRG) circulates in plasma at a concentration of 2μM and binds plasminogen, fibrinogen, and thrombospondin. Despite these interactions, the physiologic role of HRG is unknown. Previous studies have shown that mice and humans deficient in HRG have shortened plasma clotting times. To better understand this phenomenon, we examined the effect of HRG on clotting tests. HRG prolongs the activated partial thromboplastin time in a concentration-dependent fashion but has no effect on tissue factor–induced clotting, localizing its effect to the contact pathway. Plasma immunodepleted of HRG exhibits a shortened activated partial thromboplastin time that is restored to baseline with HRG replenishment. To explore how HRG affects the contact pathway, we examined its binding to factors XII, XIIa, XI, and XIa. HRG binds factor XIIa with high affinity, an interaction that is enhanced in the presence of Zn2+, but does not bind factors XII, XI, or XIa. In addition, HRG inhibits autoactivation of factor XII and factor XIIa–mediated activation of factor XI. These results suggest that, by binding to factor XIIa, HRG modulates the intrinsic pathway of coagulation, particularly in the vicinity of a thrombus where platelet release of HRG and Zn2+ will promote this interaction.
Dendritic cells with lymphocyte-stimulating activity differentiate from human CD133 positive precursors
Authors: Bonetti Maria Ida , Pieri Laura , Domenici Lola , Urbani Serena , Romano Giovanni , Aldinucci Alessandra , Ballerini Clara , Monici Monica , Saccardi Riccardo , Basile Venere , Bosi Alberto , Romagnoli Paolo
Published: February 2011

CD133 is a hallmark of primitive myeloid progenitors. We have addressed whether human cord blood cells selected for CD133 can generate dendritic cells, and Langerhans cells in particular, in conditions that promote that generation from CD34+ progenitors. Transforming growth factor-β1 (TGF-β1) and anti–TGF-β1 antibody, respectively, were added in some experiments. With TGF-β, monocytoid cells were recognized after 7 days. Immunophenotypically immature dendritic cells were present at day 14. After 4 more days, the cells expressed CD54, CD80, CD83, and CD86 and were potent stimulators in mixed lymphocyte reaction; part of the cells expressed CD1a and langerin, but not Birbeck granules. Without TGF-β, only a small fraction of cells acquired a dendritic shape and expressed the maturation-related antigens, and lymphocytes were poorly stimulated. With anti–TGF-β, the cell growth was greatly hampered, CD54 and langerin were never expressed, and lymphocytes were stimulated weakly. In conclusion, CD133+ progenitors can give rise in vitro, through definite steps, to mature, immunostimulatory dendritic cells with molecular features of Langerhans cells, although without Birbeck granules. Addition of TGF-β1 helps to stimulate cell growth and promotes the acquisition of mature immunophenotypical and functional features. Neither langerin nor Birbeck granules proved indispensable for lymphocyte stimulation.
Mechanisms of enhanced thrombus formation in cerebral microvessels of mice expressing hemoglobin-S
Authors: Gavins Felicity N. E. , Russell Janice , Senchenkova Elena L. , De Almeida Paula Lidiana , Damazo Amílcar S. , Esmon Charles T. , Kirchhofer Daniel , Hebbel Robert P. , Granger D. Neil
Published: February 2011

The microvasculature assumes an inflammatory and procoagulant state in a variety of different diseases, including sickle cell disease (SCD), which may contribute to the high incidence of ischemic stroke in these patients. This study provides evidence for accelerated thrombus formation in arterioles and venules in the cerebral vasculature of mice that express hemoglobin-S (βs mice). Enhanced microvascular thrombosis in βs mice was blunted by immunologic or genetic interventions that target tissue factor, endothelial protein C receptor, activated protein C, or thrombin. Platelets from βs mice also exhibited enhanced aggregation velocity after stimulation with thrombin but not ADP. Neutropenia also protected against the enhanced thrombosis response in βs mice. These results indicate that the cerebral microvasculature is rendered vulnerable to thrombus formation in βs mice via a neutrophil-dependent mechanism that is associated with an increased formation of and enhanced platelet sensitivity to thrombin.
β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up
Authors: De Santis Maria , Inzitari Rosanna , Bosello Silvia L , Peluso Giusy , Fanali Chiara , Iavarone Federica , Zizzo Gaetano , Bocci Mario , Cabras Tiziana , Messana Irene , Fuso Leo , Varone Francesco , Pagliari Gabriella , Castagnola Massimo , Ferraccioli Gianfranco
Published: February 2011

Background

β-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters.

Methods

β-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls.

Results

Thymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis.

Conclusions

We describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.
Tree pruner: An efficient tool for selecting data from a biased genetic database
Authors: Krishnamoorthy Mohan , Patel Pragneshkumar , Dimitrijevic Mira , Dietrich Jonathan , Green Margaret , Macken Catherine
Published: February 2011

Background

Large databases of genetic data are often biased in their representation. Thus, selection of genetic data with desired properties, such as evolutionary representation or shared genotypes, is problematic. Selection on the basis of epidemiological variables may not achieve the desired properties. Available automated approaches to the selection of influenza genetic data make a tradeoff between speed and simplicity on the one hand and control over quality and contents of the dataset on the other hand. A poorly chosen dataset may be detrimental to subsequent analyses.

Results

We developed a tool, Tree Pruner, for obtaining a dataset with desired evolutionary properties from a large, biased genetic database. Tree Pruner provides the user with an interactive phylogenetic tree as a means of editing the initial dataset from which the tree was inferred. The tree visualization changes dynamically, using colors and shading, reflecting Tree Pruner actions. At the end of a Tree Pruner session, the editing actions are implemented in the dataset.

Currently, Tree Pruner is implemented on the Influenza Research Database (IRD). The data management capabilities of the IRD allow the user to store a pruned dataset for additional pruning or for subsequent analysis. Tree Pruner can be easily adapted for use with other organisms.

Conclusions

Tree Pruner is an efficient, manual tool for selecting a high-quality dataset with desired evolutionary properties from a biased database of genetic sequences. It offers an important alternative to automated approaches to the same goal, by providing the user with a dynamic, visual guide to the ongoing selection process and ultimate control over the contents (and therefore quality) of the dataset.
Evolutionary patterns of two major reproduction candidate genes (Zp2 and Zp3) reveal no contribution to reproductive isolation between bovine species
Authors: Chen Shanyuan , Costa Vânia , Beja-Pereira Albano
Published: February 2011

Background

It has been established that mammalian egg zona pellucida (ZP) glycoproteins are responsible for species-restricted binding of sperm to unfertilized eggs, inducing the sperm acrosome reaction, and preventing polyspermy. In mammals, ZP apparently represents a barrier to heterospecific fertilization and thus probably contributes to reproductive isolation between species. The evolutionary relationships between some members of the tribe Bovini are complex and highly debatable, particularly, those involving Bos and Bison species for which interspecific hybridization is extensively documented. Because reproductive isolation is known to be a major precursor of species divergence, testing evolutionary patterns of ZP glycoproteins may shed some light into the speciation process of these species. To this end, we have examined intraspecific and interspecific genetic variation of two ZP genes (Zp2 and Zp3) for seven representative species (111 individuals) from the Bovini tribe, including five species from Bos and Bison, and two species each from genera Bubalus and Syncerus.

Results

A pattern of low levels of intraspecific polymorphism and interspecific divergence was detected for the two sequenced fragments each for Zp2 and Zp3. At intraspecific level, none of neutrality tests detected deviations from neutral equilibrium expectations for the two genes. Several haplotypes in both genes were shared by multiple species from Bos and Bison.

Conclusions

Here we argue that neither ancestral polymorphism nor introgressive hybridization alone can fully account for haplotype sharing among species from Bos and Bison, and that both scenarios have contributed to such a pattern of haplotype sharing observed here. Additionally, codon-based tests revealed strong evidence for purifying selection in the Zp3 coding haplotype sequences and weak evidence for purifying selection in the Zp2 coding haplotype sequences. Contrary to a general genetic pattern that genes or genomic regions contributing to reproductive isolation between species often evolve rapidly and show little or no gene flow between species, these results demonstrate that, particularly, those sequenced exons of the Zp2 and the Zp3 did not show any contribution to reproductive isolation between the bovine species studied here.
Comparative phylogenies and host specialization in the alder ectomycorrhizal fungi Alnicola, Alpova and Lactarius (Basidiomycota) in Europe
Authors: Rochet Juliette , Moreau Pierre-Arthur , Manzi Sophie , Gardes Monique
Published: February 2011

Background

Mycorrhizal fungi form intimate associations with their host plants that constitute their carbon resource and habitat. Alnus spp. (Betulaceae) are known to host an exceptional species-poor and specialized ectomycorrhizal (ECM) fungal community compared to other tree species, but the host-specificity pattern and its significance in terms of fungal diversification and speciation remain poorly documented. The degree of parallel speciation, host switching, and patterns of biogeography were explored in the historical associations between alders and three ECM taxa of Basidiomycetes: Alnicola (Agaricales), Alpova (Boletales), and Lactarius (Russulales). The aim was to develop an evolutionary framework on host specificity and diversification of Basidiomycetes in this highly specialized plant-fungus symbiosis.

Results

Sporocarps of Alnicola (220), Lactarius (61) and Alpova (29) were collected from stands of the four European alder species (A. alnobetula including the endemic subsp. suaveolens in Corsica, A. cordata, A. glutinosa, A. incana) in Western Europe (mainly in France and Austria), from 1995 to 2009. Specimens were morphologically identified to the species level. From these, 402 sequences of four DNA regions (ITS, rpb2, gpd, and the V9 domain of the mit-SSU rDNA) were successfully obtained and analyzed in addition with 89 sequences available in GenBank and UNITE databases. Phylogenetic analyses were conducted on all sequence data sets (individual and combined) using maximum likelihood reconstruction and Bayesian inference. Fungal phylogenies are compared and discussed in relation to the host, with a focus on species boundaries by associating taxonomic, systematic and molecular information.

Conclusions

Patterns of host specificity and phylogenies of Alnicola and Lactarius suggest coevolution as a basal factor of speciation in relation with the subgeneric diversification of Alnus, possibly due to the very selective pressure of the host. A second element of the historical associations between Alnus and its fungal symbionts is a host-dependent speciation (radiation without host change), here observed in Alnicola and Alpova in relation with Alnus subgen. Alnus. Finally host shifts from Alnus subgen. Alnus to A. alnobetula are found in most lineages of Alnicola (at least four times), Alpova (twice) and Lactarius (once), but they do not represent such a common event as could be expected by geographic proximity of trees from the two subgenera. However, active or very recent host extensions clearly occurred in Corsica, where some fungi usually associated with Alnus glutinosa on mainland Europe locally extend there to A. alnobetula subsp. suaveolens without significant genetic or morphological deviation.
Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
Authors: Haiko Johanna , Laakkonen Liisa , Westerlund-Wikström Benita , Korhonen Timo K
Published: February 2011

Background

Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic Erwinia pyrifoliae exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of Yersinia pestis. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.

Results

Pla and Epo expressed in Escherichia coli are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.

Conclusions

We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.
The transcription factor PHR1 plays a key role in the regulation of sulfate shoot-to-root flux upon phosphate starvation in Arabidopsis
Authors: Rouached Hatem , Secco David , Arpat Bulak , Poirier Yves
Published: February 2011

Background

Sulfate and phosphate are both vital macronutrients required for plant growth and development. Despite evidence for interaction between sulfate and phosphate homeostasis, no transcriptional factor has yet been identified in higher plants that affects, at the gene expression and physiological levels, the response to both elements. This work was aimed at examining whether PHR1, a transcription factor previously shown to participate in the regulation of genes involved in phosphate homeostasis, also contributed to the regulation and activity of genes involved in sulfate inter-organ transport.

Results

Among the genes implicated in sulfate transport in Arabidopsis thaliana, SULTR1;3 and SULTR3;4 showed up-regulation of transcripts in plants grown under phosphate-deficient conditions. The promoter of SULTR1;3 contains a motif that is potentially recognizable by PHR1. Using the phr1 mutant, we showed that SULTR1;3 up-regulation following phosphate deficiency was dependent on PHR1. Furthermore, transcript up-regulation was found in phosphate-deficient shoots of the phr1 mutant for SULTR2;1 and SULTR3;4, indicating that PHR1 played both a positive and negative role on the expression of genes encoding sulfate transporters. Importantly, both phr1 and sultr1;3 mutants displayed a reduction in their sulfate shoot-to-root transfer capacity compared to wild-type plants under phosphate-deficient conditions.

Conclusions

This study reveals that PHR1 plays an important role in sulfate inter-organ transport, in particular on the regulation of the SULTR1;3 gene and its impact on shoot-to-root sulfate transport in phosphate-deficient plants. PHR1 thus contributes to the homeostasis of both sulfate and phosphate in plants under phosphate deficiency. Such a function is also conserved in Chlamydomonas reinhardtii via the PHR1 ortholog PSR1.
Dengue-2 Structural Proteins Associate with Human Proteins to Produce a Coagulation and Innate Immune Response Biased Interactome
Authors: Folly Brenda B , Weffort-Santos Almeriane M , Fathman CG , Soares Luis RB
Published: February 2011

Background

Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem.

Methods

A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology.

Results

Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis.

Conclusions

Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti-viral response processes, and predicts that the interaction of dengue proteins with a proposed human protein interaction network produces a modified biological outcome that may be behind the hallmark pathologies of dengue infection.
Multimodal microscopy for automated histologic analysis of prostate cancer
Authors: Kwak Jin Tae , Hewitt Stephen M , Sinha Saurabh , Bhargava Rohit
Published: February 2011

Background

Prostate cancer is the single most prevalent cancer in US men whose gold standard of diagnosis is histologic assessment of biopsies. Manual assessment of stained tissue of all biopsies limits speed and accuracy in clinical practice and research of prostate cancer diagnosis. We sought to develop a fully-automated multimodal microscopy method to distinguish cancerous from non-cancerous tissue samples.

Methods

We recorded chemical data from an unstained tissue microarray (TMA) using Fourier transform infrared (FT-IR) spectroscopic imaging. Using pattern recognition, we identified epithelial cells without user input. We fused the cell type information with the corresponding stained images commonly used in clinical practice. Extracted morphological features, optimized by two-stage feature selection method using a minimum-redundancy-maximal-relevance (mRMR) criterion and sequential floating forward selection (SFFS), were applied to classify tissue samples as cancer or non-cancer.

Results

We achieved high accuracy (area under ROC curve (AUC) >0.97) in cross-validations on each of two data sets that were stained under different conditions. When the classifier was trained on one data set and tested on the other data set, an AUC value of ~0.95 was observed. In the absence of IR data, the performance of the same classification system dropped for both data sets and between data sets.

Conclusions

We were able to achieve very effective fusion of the information from two different images that provide very different types of data with different characteristics. The method is entirely transparent to a user and does not involve any adjustment or decision-making based on spectral data. By combining the IR and optical data, we achieved high accurate classification.
Need for continual education about disaster medicine for health professionals in China-a pilot study
Authors: Huang Bo , Li Jing , Li Yunkai , Zhang Weidong , Pan Futang , Miao Shujun
Published: February 2011

Background

Disaster Medicine training is not included in medical education curriculum in China, even though the country has suffered various disasters annually. We intended to assess the need for continual education regarding disaster management for health professionals in China.

Methods

A survey was conducted among 324 health professionals who participated in the response to the Wenchuan earthquake medical relief and public health assessment in October, 2008.

Results

The most of participants (67.3%) received informal disaster medicine training, and only a few (12.7%) participated in disaster drills. Most of the participants wanted to get continual education about disaster medicine training (89.8%), but prefer on-line training course for the flexibility of time scheduling and travel through China.

Conclusion

The need for continual disaster medicine training is high; health professionals should be equipped with knowledge and skills for disaster management.
A telemedicine instrument for remote evaluation of tremor: design and initial applications in fatigue and patients with Parkinson's Disease
Authors: Barroso Mário C , Esteves Guilherme P , Nunes Thiago P , Silva Lucia MG , Faria Alvaro CD , Melo Pedro L
Published: February 2011

Introduction

A novel system that combines a compact mobile instrument and Internet communications is presented in this paper for remote evaluation of tremors. The system presents a high potential application in Parkinson's disease and connects to the Internet through a TCP/IP protocol. Tremor transduction is carried out by accelerometers, and the data processing, presentation and storage were obtained by a virtual instrument. The system supplies the peak frequency (fp), the amplitude (Afp) and power in this frequency (Pfp), the total power (Ptot), and the power in low (1-4 Hz) and high (4-7 Hz) frequencies (Plf and Phf, respectively).

Methods

The ability of the proposed system to detect abnormal tremors was initially demonstrated by a fatigue study in normal subjects. In close agreement with physiological fundamentals, the presence of fatigue increased fp, Afp, Pfp and Pt (p < 0.05), while the removal of fatigue reduced all the mentioned parameters (p < 0.05). The system was also evaluated in a preliminary in vivo test in parkinsonian patients. Afp, Pfp, Ptot, Plf and Phf were the most accurate parameters in the detection of the adverse effects of this disease (Se = 100%, Sp = 100%), followed by fp (Se = 100%, Sp = 80%). Tests for Internet transmission that realistically simulated clinical conditions revealed adequate acquisition and analysis of tremor signals and also revealed that the user could adequately receive medical recommendations.

Conclusions

The proposed system can be used in a wide spectrum of telemedicine scenarios, enabling the home evaluation of tremor occurrence under specific medical treatments and contributing to reduce the costs of the assistance offered to these patients.
Discussion on the thermal conductivity enhancement of nanofluids
Authors: Xie Huaqing , Yu Wei , Li Yang , Chen Lifei
Published: February 2011

Increasing interests have been paid to nanofluids because of the intriguing heat transfer enhancement performances presented by this kind of promising heat transfer media. We produced a series of nanofluids and measured their thermal conductivities. In this article, we discussed the measurements and the enhancements of the thermal conductivity of a variety of nanofluids. The base fluids used included those that are most employed heat transfer fluids, such as deionized water (DW), ethylene glycol (EG), glycerol, silicone oil, and the binary mixture of DW and EG. Various nanoparticles (NPs) involving Al2O3 NPs with different sizes, SiC NPs with different shapes, MgO NPs, ZnO NPs, SiO2 NPs, Fe3O4 NPs, TiO2 NPs, diamond NPs, and carbon nanotubes with different pretreatments were used as additives. Our findings demonstrated that the thermal conductivity enhancements of nanofluids could be influenced by multi-faceted factors including the volume fraction of the dispersed NPs, the tested temperature, the thermal conductivity of the base fluid, the size of the dispersed NPs, the pretreatment process, and the additives of the fluids. The thermal transport mechanisms in nanofluids were further discussed, and the promising approaches for optimizing the thermal conductivity of nanofluids have been proposed.
Strain-induced high ferromagnetic transition temperature of MnAs epilayer grown on GaAs (110)
Authors: Xu Pengfa , Lu Jun , Chen Lin , Yan Shuai , Meng Haijuan , Pan Guoqiang , Zhao Jianhua
Published: February 2011

MnAs films are grown on GaAs surfaces by molecular beam epitaxy. Specular and grazing incidence X-ray diffractions are used to study the influence of different strain states of MnAs/GaAs (110) and MnAs/GaAs (001) on the first-order magnetostructural phase transition. It comes out that the first-order magnetostructural phase transition temperature Tt, at which the remnant magnetization becomes zero, is strongly affected by the strain constraint from different oriented GaAs substrates. Our results show an elevated Tt of 350 K for MnAs films grown on GaAs (110) surface, which is attributed to the effect of strain constraint from different directions.

PACS: 68.35.Rh, 61.50.Ks, 81.15.Hi, 07.85.Qe
Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea maysstrongly determine their eventual anti-HIV activity
Authors: Hoorelbeke Bart , Van Damme Els JM , Rougé Pierre , Schols Dominique , Van Laethem Kristel , Fouquaert Elke , Balzarini Jan
Published: February 2011

Background

In a recent report, the carbohydrate-binding specificities of the plant lectins Galanthus nivalis (GNA) and the closely related lectin from Zea mays (GNAmaize) were determined by glycan array analysis and indicated that GNAmaize recognizes complex-type N-glycans whereas GNA has specificity towards high-mannose-type glycans. Both lectins are tetrameric proteins sharing 64% sequence similarity.

Results

GNAmaize appeared to be ~20- to 100-fold less inhibitory than GNA against HIV infection, syncytia formation between persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T-lymphocyte SupT1 cells, HIV-1 capture by DC-SIGN and subsequent transmission of DC-SIGN-captured virions to uninfected CD4+ T-lymphocyte cells. In contrast to GNA, which preferentially selects for virus strains with deleted high-mannose-type glycans on gp120, prolonged exposure of HIV-1 to dose-escalating concentrations of GNAmaize selected for mutant virus strains in which one complex-type glycan of gp120 was deleted. Surface Plasmon Resonance (SPR) analysis revealed that GNA and GNAmaize interact with HIV IIIB gp120 with affinity constants (KD) of 0.33 nM and 34 nM, respectively. Whereas immobilized GNA specifically binds mannose oligomers, GNAmaize selectively binds complex-type GlcNAcβ1,2Man oligomers. Also, epitope mapping experiments revealed that GNA and the mannose-specific mAb 2G12 can independently bind from GNAmaize to gp120, whereas GNAmaize cannot efficiently bind to gp120 that contained prebound PHA-E (GlcNAcβ1,2man specific) or SNA (NeuAcα2,6X specific).

Conclusion

The markedly reduced anti-HIV activity of GNAmaize compared to GNA can be explained by the profound shift in glycan recognition and the disappearance of carbohydrate-binding sites in GNAmaize that have high affinity for mannose oligomers. These findings underscore the need for mannose oligomer recognition of therapeutics to be endowed with anti-HIV activity and that mannose, but not complex-type glycan binding of chemotherapeutics to gp120, may result in a pronounced neutralizing activity against the virus.
Neuropathic Nav1.3-Mediated Sensitization to P2X Activation is Regulated by Protein Kinase C
Authors: Mo Gary , Grant Rebecca , O'Donnell Dajan , Ragsdale David S , Cao Chang-Qing , Séguéla Philippe
Published: February 2011

Background:

Increased neuronal excitability and spontaneous firing are hallmark characteristics of injured sensory neurons. Changes in expression of various voltage-gated Na+ channels (VGSCs) have been observed under neuropathic conditions and there is evidence for the involvement of protein kinase C (PKC) in sensory hyperexcitability. Here we demonstrate the contribution of PKC to P2X-evoked VGSC activation in dorsal root ganglion (DRG) neurons in neuropathic conditions.

Results:

Using the spinal nerve ligation (SNL) model of neuropathic pain and whole-cell patch clamp recordings of dissociated DRG neurons, we examined changes in excitability of sensory neurons after nerve injury and observed that P2X3 purinoceptor-mediated currents induced by α,β-meATP triggered activation of TTX-sensitive VGSCs in neuropathic nociceptors only. Treatment of neuropathic DRGs with the PKC blocker staurosporine or calphostin C decreased the α,β-meATP-induced Na+ channels activity and reversed neuronal hypersensitivity. In current clamp mode, α,β-meATP was able to evoke action-potentials more frequently in neuropathic neurons than in controls. Pretreatment with calphostin C significantly decreased the proportion of sensitized neurons that generated action potentials in response to α,β-meATP. Recordings measuring VGSC activity in neuropathic neurons show significant change in amplitude and voltage dependence of sodium currents. In situ hybridization data indicate a dramatic increase in expression of embryonic Nav1.3 channels in neuropathic DRG neurons. In a CHO cell line stably expressing the Nav1.3 subunit, PKC inhibition caused both a significant shift in voltage-dependence of the channel in the depolarizing direction and a decrease in current amplitude.

Conclusion:

Neuropathic injury causes primary sensory neurons to become hyperexcitable to ATP-evoked P2X receptor-mediated depolarization, a phenotypic switch sensitive to PKC modulation and mediated by increased activity of TTX-sensitive VGSCs. Upregulation in VGSC activity after injury is likely mediated by increased expression of the Nav1.3 subunit, and the function of the Nav1.3 channel is regulated by PKC.
Evolutionary patterns of phosphorylated serines
Authors: Kurmangaliyev Yerbol Z , Goland Alexander , Gelfand Mikhail S
Published: February 2011

Posttranslationally modified amino acids are chemically distinct types of amino acids and in terms of evolution they might behave differently from their non-modified counterparts. In order to check this possibility, we reconstructed the evolutionary history of phosphorylated serines in several groups of organisms. Comparisons of substitution vectors have revealed some significant differences in the evolution of modified and corresponding non-modified amino acids. In particular, phosphoserines are more frequently substituted to aspartate and glutamate, compared to non-phosphorylated serines.

Reviewers

This article was reviewed by Arcady Mushegian and Sandor Pongor.
The efficacy and safety study of dietary supplement PURIAM110 on non-insulin taking Korean adults in the stage of pre-diabetes and diabetes mellitus: protocol for a randomized, double-blind, placebo-controlled, and multicenter trial-pilot study
Authors: Park Sunju , Park Jeong-Su , Go Hoyeon , Jang Bo-Hyoung , Shin Yongcheol , Ko Seong-Gyu
Published: February 2011

Background

Diabetes has already become a threat to the nation and the individual due to its high prevalence rates and high medical expenses. Therefore, preventing diabetes at an earlier stage is very important. Despite advances in antidiabetic agents, we have not yet achieved any satisfying results in treating diabetes. Among various treatments, medicinal herbs and supplements for diabetes are reported to show generally good efficacy and safety data. In particular, PURIAM110, a compound from orange fruits and mulberry leaves, is supposed to prevent the progress of type II diabetes mellitus and improve diabetic symptoms. This is the first reported pilot study about the protective effect of the orange fruits and mulberry leaves mixture against pre-diabetes on Korean adults. Based on these positive results of herb-derived components, extended studies of dietary supplements have to be done to suggest confirmative evidences.

Methods/Design

The efficacy and safety study of PURIAM110 is a double-blinded, placebo-controlled, randomized, and multi-center clinical trial. A total of 45 subjects will participate in this study for 6 weeks.

Discussion

The present protocol will confirm the efficacy and safety of PURIAM110 for pre-diabetes, suggesting more basic knowledge to conduct further randomized controlled trials (RCT). In addition, PURIAM110 can be an alternative dietary supplemental remedy for diabetes patients.

Trial Registration

ISRCTN: ISRCTN44779824
Rapid analysis of seed size in Arabidopsis for mutant and QTL discovery
Authors: Herridge Rowan P , Day Robert C , Baldwin Samantha , Macknight Richard C
Published: February 2011

Background

Arabidopsis thaliana is a useful model organism for deciphering the genetic determinants of seed size; however the small size of its seeds makes measurements difficult. Bulk seed weights are often used as an indicator of average seed size, but details of individual seed is obscured. Analysis of seed images is possible but issues arise from variations in seed pigmentation and shadowing making analysis laborious. We therefore investigated the use of a consumer level scanner to facilitate seed size measurements in conjunction with open source image-processing software.

Results

By using the transmitted light from the slide scanning function of a flatbed scanner and particle analysis of the resulting images, we have developed a method for the rapid and high throughput analysis of seed size and seed size distribution. The technical variation due to the approach was negligible enabling us to identify aspects of maternal plant growth that contribute to biological variation in seed size. By controlling for these factors, differences in seed size caused by altered parental genome dosage and mutation were easily detected. The method has high reproducibility and sensitivity, such that a mutant with a 10% reduction in seed size was identified in a screen of endosperm-expressed genes. Our study also generated average seed size data for 91 Arabidopsis accessions and identified a number of quantitative trait loci from two recombinant inbred line populations, generated from Cape Verde Islands and Burren accessions crossed with Columbia.

Conclusions

This study describes a sensitive, high-throughput approach for measuring seed size and seed size distribution. The method provides a low cost and robust solution that can be easily implemented into the workflow of studies relating to various aspects of seed development.
Pseudomonas aeruginosa acquisition on an intensive care unit: relationship between antibiotic selective pressure and patients' environment
Authors: Boyer Alexandre , Doussau Adélaïde , Thiébault Rodolphe , Venier Anne Gaëlle , Tran Van , Boulestreau Hélène , Bébéar Cécile , Vargas Frédéric , Hilbert Gilles , Gruson Didier , Rogues Anne Marie
Published: February 2011

Introduction

The purpose of this study was to investigate the relationship among Pseudomonas aeruginosa acquisition on the intensive care unit (ICU), environmental contamination and antibiotic selective pressure against P. aeruginosa.

Methods

An open, prospective cohort study was carried out in a 16-bed medical ICU where P. aeruginosa was endemic. Over a six-month period, all patients without P. aeruginosa on admission and with a length of stay >72 h were included. Throat, nasal, rectal, sputum and urine samples were taken on admission and at weekly intervals and screened for P. aeruginosa. All antibiotic treatments were recorded daily. Environmental analysis included weekly tap water specimen culture and the presence of other patients colonized with P. aeruginosa.

Results

A total of 126 patients were included, comprising 1,345 patient-days. Antibiotics were given to 106 patients (antibiotic selective pressure for P. aeruginosa in 39). P. aeruginosa was acquired by 20 patients (16%) and was isolated from 164/536 environmental samples (31%). Two conditions were independently associated with P. aeruginosa acquisition by multivariate analysis: (i) patients receiving ≥3 days of antibiotic selective pressure together with at least one colonized patient on the same ward on the previous day (odds ratio (OR) = 10.3 ((% confidence interval (CI): 1.8 to 57.4); P = 0.01); and (ii) presence of an invasive device (OR = 7.7 (95% CI: 2.3 to 25.7); P = 0.001).

Conclusions

Specific interaction between both patient colonization pressure and selective antibiotic pressure is the most relevant factor for P. aeruginosa acquisition on an ICU. This suggests that combined efforts are needed against both factors to decrease colonization with P. aeruginosa.
Analyses of vibrator and geophone behavior on hard and soft ground
Authors: Wei Zhouhong , Hall Michael A.
Published: February 2011

The vibroseis method has, for half a century, achieved great success in land seismic exploration. However, some practical issues still arise that have remained theoretically unexplained. For example, on soft ground, the vibrator produces subharmonics and ultra-subharmonics in addition to main harmonics; whereas on hard ground, the vibrator generates harmonics only. Geophones on soft ground also behave abnormally while geophones on hard ground behave normally. This paper analyzes these phenomena and demonstrates that the softness of the ground's top layer is responsible for subharmonics and ultra-subharmonics. This soft ground layer causes the geophone abnormality as well. Unfortunately, quantification for this behavior has not been achieved.
Introduction to this special section: Near-surface geophysics
Authors: Miller Rick , Baker Greg
Published: February 2011

Near-surface geophysical data have become an increasingly key component in the development of accurate hydrologic models, the engineering of robust structures, and the responsible exploration/exploitation of Earth's resources—ultimately improving the quality of life and stewardship of our environment and resources. Whether the objective of a geophysical survey of the near surface is estimating soil stiffness, mapping layer geometries, interpreting lithologies, or measuring material properties, the overarching goal is improving our understanding of those many shallow subsurface complexities that rarely interpolate accurately. That relatively miniscule volume of the Earth considered the near surface is commonly cursed as the bane of explorationists, hydrologists, and engineers alike because significant vertical and horizontal heterogeneities often occurring over small distances.
Evaluating the quality of cement-soil mixing piles by inversion of surface waves
Authors: Liu Jiangping , Xi Yongzai , Qu Niannian , Wang Xiaoliu
Published: February 2011

Deep cement-soil mixing piles to reinforce soft soil have many advantages—simple construction, no vibration and pollution in the construction process, and no adverse impact on the surrounding environment. Therefore, since the 1980s, this technology has been increasingly used in China and has a large number of applications in soft-soil reinforcement for highways, railways, airports, deep excavation engineering, and foundation treatment of construction sites for multistory buildings. However, due to complex geological conditions of the bottom layer, groundwater presence and flow, poor workmanship, and substandard economic specifications, problems (e.g., erratic consistency in the length of the piles) may occur that would seriously affect the stability of piles and cause them to be incapable of standard bearing capacity.
Near-surface, downhole shear-wave surveys: A primer
Authors: Crice Doug
Published: February 2011

Downhole shear-wave surveys may be used for a wide variety of applications that include determining the shear-wave velocity function with depth for static corrections or time-to-depth conversions for petroleum surveys involving shear-wave reflections. However, the principal nonpetroleum application is for investigations of engineering sites.
Geophysical mapping of the Hockley growth fault in northwest Houston, USA, and recent surface observations
Authors: Saribudak Mustafa
Published: February 2011

Active growth faults cutting the land surface around the coast of the Gulf of Mexico represent a serious geohazard. Considering the average movement of these faults is a few inches per decade, the potential is high for structural damage to highways, industrial buildings, residential houses, and railroads that cross these features.
High-resolution shallow geophysics and geology in the Hudson-Raritan Estuary Ecosystem Restoration, New Jersey
Authors: Murphy William , Ward W. Bruce , Boyd Beckett , Fleming Gary , Murphy William , Nolen-Hoeksema Richard , Art Matthew , Rosales Daniel A.
Published: February 2011

The Hudson-Raritan Estuary of New York and New Jersey is one of the largest estuaries on the East Coast of the United States. It includes part of the New York City metropolitan area and includes the Port of New York and New Jersey. The estuary is an important economic, environmental, and recreational resource and asset for the region. Fresh water enters the estuary from the Hudson, Hackensack, Passaic, and Raritan rivers. Since the 17th century, the estuary has experienced industrialization and residential growth that have profoundly altered the estuary and surrounding land from its precolonial state.
17β-Estradiol, Aging, Inflammation, and the Stress Response in the Female Heart
Authors: Stice James P. , Chen Le , Kim Se-Chan , Jung J. S. , Tran A. L. , Liu T. T. , Knowlton Anne A.
Published: February 2011

Heat shock proteins (HSPs) are a cardioprotective class of proteins induced by stress and regulated by the transcription factor, heat shock factor (HSF)-1. 17β-estradiol (E2) indirectly regulates HSP expression through rapid activation of nuclear factor-κB (NF-κB) and HSF-1 and protects against hypoxia. As males experience a loss of protective cellular responses in aging, we hypothesized that aged menopausal (old ovariectomized) rats would have an impaired HSP response, which could be prevented by immediate in vivo E2 replacement. After measuring cardiac function in vivo, cardiac myocytes were isolated from ovariectomized adult and old rats with and without 9 weeks of E2 replacement. Myocytes were treated with E2in vitro and analyzed for activation of NF-κB, HSF-1, and HSP expression. In addition, we measured inflammatory cytokine expression and susceptibility to hypoxia/reoxygenation injury. Cardiac contractility was reduced in old ovariectomized rats and could prevented by immediate E2 replacement in vivo. Subsequent investigations in isolated cardiac myocytes found that in vitro E2 activated NF-κB, HSF-1, and increased HSP 72 expression in adult but not old rats. In response to hypoxia/reoxygenation, myocytes from adult, but not old, rats had increased HSP 72 expression. In addition, expression of the inflammatory cytokines TNF-α and IL-1β, as well as oxidative stress, were increased in myocytes from old ovariectomized rats; only the change in cytokine expression could be attenuated by in vivo E2 replacement. This study demonstrates that while aging in female rats led to a loss of the cardioprotective HSP response, E2 retains its protective cellular properties.
Insulin-Like Growth Factor-I:Vitronectin Complex-Induced Changes in Gene Expression Effect Breast Cell Survival and Migration
Authors: Kashyap Abhishek S. , Hollier Brett G. , Manton Kerry J. , Satyamoorthy K. , Leavesley David I. , Upton Zee
Published: February 2011

Recent studies have demonstrated that IGF-I associates with vitronectin (VN) through IGF-binding proteins (IGFBP), which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment, and migration. Because IGFs play important roles in transformation and progression of breast tumors, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of phosphoinositide 3-kinase/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and phosphoinositide 3-kinase pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion, and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue ([L24][A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of extracellular matrix and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.