bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional results and complications following locking palmar plating on the distal radius: a retrospective study
Authors: Hakimi M. , Jungbluth P. , Windolf J. , Wild M.
Published: August 2009

This retrospective study investigates the radiological and the functional results as well as complications following locking palmar plating on the distal radius. Eighty-nine adult patients with a dorsally displaced distal radius fracture were treated using a locking palmar plate at our clinic over a period of 25 months. The radiological and functional results as well as the DASH score were recorded for 77 out of 89 patients in the routine final examinations conducted on average 12 months later. The radiological examinations showed a relevant shortening of the radius among five patients. A dorsal angulation of more than 20° as well as a radial inclination of less than 10° was observed in 11 patients. Most of the patients showed good to excellent functional and radiological results as well as good results on the DASH score. A3 fractures in elderly patients and the majority of C1 and C2 fractures can be safely treated with locking palmar plating.
Radiolunate fusion in the rheumatoid wrist with Shapiro staples: clinical and radiological results of 22 cases
Authors: Gaulke R. , Suppelna G. , Hildebrand F. , Citak M. , Hüfner T. , Krettek C.
Published: August 2009

We performed a retrospective clinical and radiological case control study on 22 rheumatoid wrists following radiolunate fusion via Shapiro staples with a mean follow-up of 5 years. Radiographs showed one early loosening through dorsal staple migration and four nonunions. Six wrists fused in mild ulnopalmar dislocation of the lunate. Primary intra-articular positioning of a staple was found in nine wrists, secondary intra-articular staple dislocation was found in two wrists. Dorsal staple dislocation was found in four fused arthrodeses. Osteolysis around the staples was found in all but two wrists. In contrast to unsatisfactory radiological results the clinical results were good or excellent in 18 patients. Good and excellent clinical results in the majority of the patients following radiolunate fusion does not depend on the fixation device. Nevertheless staple fixation of the radiolunate joint in the rheumatoid wrist is associated with a high rate of radiological complications.
Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor
Authors: Riddell Anne F. , Gomez Keith , Millar Carolyn M. , Mellars Gillian , Gill Saher , Brown Simon A. , Sutherland Megan , Laffan Mike A. , McKinnon Thomas A. J.
Published: August 2009

Investigation of 3 families with bleeding symptoms demonstrated a defect in the collagen-binding activity of von Willebrand factor (VWF) in association with a normal VWF multimeric pattern. Genetic analysis showed affected persons to be heterozygous for mutations in the A3 domain of VWF: S1731T, W1745C, and S1783A. One person showed compound heterozygosity for W1745C and R760H. W1745C and S1783A have not been reported previously. The mutations were reproduced by site-directed mutagenesis and mutant VWF expressed in HEK293T cells. Collagen-binding activity measured by immunosorbent assay varied according to collagen type: W1745C and S1783A were associated with a pronounced binding defect to both type I and type III collagen, whereas the principal abnormality in S1731T patients was a reduction in binding to type I collagen only. The multimer pattern and distribution of mutant proteins were indistinguishable from wild-type recombinant VWF, confirming that the defect in collagen binding resulted from the loss of affinity at the binding site and not impairment of high-molecular-weight multimer formation. Our findings demonstrate that mutations causing an abnormality in the binding of VWF to collagen may contribute to clinically significant bleeding symptoms. We propose that isolated collagen-binding defects are classified as a distinct subtype of von Willebrand disease.
A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion
Authors: Kleinman Steven H. , Glynn Simone A. , Lee Tzong-Hae , Tobler Leslie H. , Schlumpf Karen S. , Todd Deborah S. , Qiao Hannah , Yu Mei-ying W. , Busch Michael P.
Published: August 2009

Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA–positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients. We assessed 112 B19V DNA–positive components from 105 donors (of 12 529 tested donations) transfused into a population of surgical patients with a pretransfusion B19V IgG seroprevalence of 78%. We found no transmission to 24 susceptible recipients from transfusion of components with B19V DNA at concentrations less than 106 IU/mL (upper 95% confidence interval, 11.7%). We found an anamnestic IgG response in one pretransfusion seropositive recipient transfused with a component containing greater than 1010 IU/mL B19V DNA. These findings show either that transmission from components with less than 106 IU/mL does not occur, or, if it does, it is an uncommon event. These data do not support the need to routinely screen blood donations with a sensitive B19V DNA nucleic acid assay.
A fast and efficient gene-network reconstruction method from multiple over-expression experiments
Authors: Stokić Dejan , Hanel Rudolf , Thurner Stefan
Published: August 2009

Background

Reverse engineering of gene regulatory networks presents one of the big challenges in systems biology. Gene regulatory networks are usually inferred from a set of single-gene over-expressions and/or knockout experiments. Functional relationships between genes are retrieved either from the steady state gene expressions or from respective time series.

Results

We present a novel algorithm for gene network reconstruction on the basis of steady-state gene-chip data from over-expression experiments. The algorithm is based on a straight forward solution of a linear gene-dynamics equation, where experimental data is fed in as a first predictor for the solution. We compare the algorithm's performance with the NIR algorithm, both on the well known E. coli experimental data and on in-silico experiments.

Conclusion

We show superiority of the proposed algorithm in the number of correctly reconstructed links and discuss computational time and robustness. The proposed algorithm is not limited by combinatorial explosion problems and can be used in principle for large networks.
Moorean tree snail survival revisited: a multi-island genealogical perspective
Authors: Lee Taehwan , Burch John B , Coote Trevor , Pearce-Kelly Paul , Hickman Carole , Meyer Jean-Yves , Ó Foighil Diarmaid
Published: August 2009

Background

The mass extirpation of the island of Moorea's endemic partulid tree snail fauna, following the deliberate introduction of the alien predator Euglandina rosea, represents one of the highest profile conservation crises of the past thirty years. All of the island's partulids were thought to be extirpated by 1987, with five species persisting in zoos, but intensive field surveys have recently detected a number of surviving wild populations. We report here a mitochondrial (mt) phylogenetic estimate of Moorean partulid wild and captive lineage survival calibrated with a reference museum collection that pre-dates the predator's introduction and that also includes a parallel dataset from the neighboring island of Tahiti.

Results

Although severe winnowing of Moorea's mt lineage diversity has occurred, seven of eight (six Partula; two Samoana) partulid tip clades remain extant. The extinct mt clade occurred predominantly in the P. suturalis species complex and it represented a major component of Moorea's endemic partulid treespace. Extant Moorean mt clades exhibited a complex spectrum of persistence on Moorea, in captivity, and (in the form of five phylogenetically distinct sister lineages) on Tahiti. Most notably, three Partula taxa, bearing two multi-island mt lineages, have survived decades of E. rosea predation on Moorea (P. taeniata) and in the valleys of Tahiti (P. hyalina and P. clara). Their differential persistence was correlated with intrinsic attributes, such as taxonomy and mt lineages, rather than with their respective within-island distribution patterns.

Conclusion

Conservation efforts directed toward Moorean and Tahitian partulids have typically operated within a single island frame of reference, but our discovery of robust genealogical ties among survivors on both islands implies that a multi-island perspective is required. Understanding what genetic and/or ecological factors have enabled Partula taeniata, P. hyalina and P. clara to differentially survive long-term direct exposure to the predator may provide important clues toward developing a viable long term conservation plan for Society Island partulid tree snails.
High throughput sequencing in mice: a platform comparison identifies a preponderance of cryptic SNPs
Authors: Walter Nicole AR , Bottomly Daniel , Laderas Ted , Mooney Michael A , Darakjian Priscila , Searles Robert P , Harrington Christina A , McWeeney Shannon K , Hitzemann Robert , Buck Kari J
Published: August 2009

Background

Allelic variation is the cornerstone of genetically determined differences in gene expression, gene product structure, physiology, and behavior. However, allelic variation, particularly cryptic (unknown or not annotated) variation, is problematic for follow up analyses. Polymorphisms result in a high incidence of false positive and false negative results in hybridization based analyses and hinder the identification of the true variation underlying genetically determined differences in physiology and behavior. Given the proliferation of mouse genetic models (e.g., knockout models, selectively bred lines, heterogeneous stocks derived from standard inbred strains and wild mice) and the wealth of gene expression microarray and phenotypic studies using genetic models, the impact of naturally-occurring polymorphisms on these data is critical. With the advent of next-generation, high-throughput sequencing, we are now in a position to determine to what extent polymorphisms are currently cryptic in such models and their impact on downstream analyses.

Results

We sequenced the two most commonly used inbred mouse strains, DBA/2J and C57BL/6J, across a region of chromosome 1 (171.6 – 174.6 megabases) using two next generation high-throughput sequencing platforms: Applied Biosystems (SOLiD) and Illumina (Genome Analyzer). Using the same templates on both platforms, we compared realignments and single nucleotide polymorphism (SNP) detection with an 80 fold average read depth across platforms and samples. While public datasets currently annotate 4,527 SNPs between the two strains in this interval, thorough high-throughput sequencing identified a total of 11,824 SNPs in the interval, including 7,663 new SNPs. Furthermore, we confirmed 40 missense SNPs and discovered 36 new missense SNPs.

Conclusion

Comparisons utilizing even two of the best characterized mouse genetic models, DBA/2J and C57BL/6J, indicate that more than half of naturally-occurring SNPs remain cryptic. The magnitude of this problem is compounded when using more divergent or poorly annotated genetic models. This warrants full genomic sequencing of the mouse strains used as genetic models.
The degree of microbiome complexity influences the epithelial response to infection
Authors: Mans Jeffrey J , von Lackum Kate , Dorsey Cassandra , Willis Shaun , Wallet Shannon M , Baker Henry V , Lamont Richard J , Handfield Martin
Published: August 2009

Background

The human microflora is known to be extremely complex, yet most pathogenesis research is conducted in mono-species models of infection. Consequently, it remains unclear whether the level of complexity of a host's indigenous flora can affect the virulence potential of pathogenic species. Furthermore, it remains unclear whether the colonization by commensal species affects a host cell's response to pathogenic species beyond the direct physical saturation of surface receptors, the sequestration of nutrients, the modulation of the physico-chemical environment in the oral cavity, or the production of bacteriocins. Using oral epithelial cells as a model, we hypothesized that the virulence of pathogenic species may vary depending on the complexity of the flora that interacts with host cells.

Results

This is the first report that determines the global epithelial transcriptional response to co-culture with defined complex microbiota. In our model, human immortalized gingival keratinocytes (HIGK) were infected with mono- and mixed cultures of commensal and pathogenic species. The global transcriptional response of infected cells was validated and confirmed phenotypically. In our model, commensal species were able to modulate the expression of host genes with a broad diversity of physiological functions and antagonize the effect of pathogenic species at the cellular level. Unexpectedly, the inhibitory effect of commensal species was not correlated with its ability to inhibit adhesion or invasion by pathogenic species.

Conclusion

Studying the global transcriptome of epithelial cells to single and complex microbial challenges offers clues towards a better understanding of how bacteria-bacteria interactions and bacteria-host interactions impact the overall host response. This work provides evidence that the degree of complexity of a mixed microbiota does influence the transcriptional response to infection of host epithelial cells, and challenges the current dogma regarding the potential versus the actual pathogenicity of bacterial species. These findings support the concept that members of the commensal oral flora have evolved cellular mechanisms that directly modulate the host cell's response to pathogenic species and dampen their relative pathogenicity.
msbB deletion confers acute sensitivity to CO2 in Salmonella enterica serovar Typhimurium that can be suppressed by a loss-of-function mutation in zwf
Authors: Karsten Verena , Murray Sean R , Pike Jeremy , Troy Kimberly , Ittensohn Martina , Kondradzhyan Manvel , Low K Brooks , Bermudes David
Published: August 2009

Background

Pathogens tolerate stress conditions that include low pH, oxidative stress, high salt and high temperature in order to survive inside and outside their hosts. Lipopolysaccharide (LPS), which forms the outer-leaflet of the outer membrane in Gram-negative bacteria, acts as a permeability barrier. The lipid A moiety of LPS anchors it to the outer membrane bilayer. The MsbB enzyme myristoylates the lipid A precursor and loss of this enzyme, in Salmonella, is correlated with reduced virulence and severe growth defects that can both be compensated with extragenic suppressor mutations.

Results

We report here that msbB (or msbB somA) Salmonella are highly sensitive to physiological CO2 (5%), resulting in a 3-log reduction in plating efficiency. Under these conditions, msbB Salmonella form long filaments, bulge and lyse. These bacteria are also sensitive to acidic pH and high osmolarity. Although CO2 acidifies LB broth media, buffering LB to pH 7.5 did not restore growth of msbB mutants in CO2, indicating that the CO2-induced growth defects are not due to the effect of CO2 on the pH of the media. A transposon insertion in the glucose metabolism gene zwf compensates for the CO2 sensitivity of msbB Salmonella. The msbB zwf mutants grow on agar, or in broth, in the presence of 5% CO2. In addition, msbB zwf strains show improved growth in low pH or high osmolarity media compared to the single msbB mutant.

Conclusion

These results demonstrate that msbB confers acute sensitivity to CO2, acidic pH, and high osmolarity. Disruption of zwf in msbB mutants restores growth in 5% CO2 and results in improved growth in acidic media or in media with high osmolarity. These results add to a growing list of phenotypes caused by msbB and mutations that suppress specific growth defects.
Functional mapping of the fission yeast DNA polymerase δ B-subunit Cdc1 by site-directed and random pentapeptide insertion mutagenesis
Authors: Sanchez Garcia Javier , Baranovskiy Andrey G , Knatko Elena V , Gray Fiona C , Tahirov Tahir H , MacNeill Stuart A
Published: August 2009

Background

DNA polymerase δ plays an essential role in chromosomal DNA replication in eukaryotic cells, being responsible for synthesising the bulk of the lagging strand. In fission yeast, Pol δ is a heterotetrameric enzyme comprising four evolutionarily well-conserved proteins: the catalytic subunit Pol3 and three smaller subunits Cdc1, Cdc27 and Cdm1. Pol3 binds directly to the B-subunit, Cdc1, which in turn binds the C-subunit, Cdc27. Human Pol δ comprises the same four subunits, and the crystal structure was recently reported of a complex of human p50 and the N-terminal domain of p66, the human orthologues of Cdc1 and Cdc27, respectively.

Results

To gain insights into the structure and function of Cdc1, random and directed mutagenesis techniques were used to create a collection of thirty alleles encoding mutant Cdc1 proteins. Each allele was tested for function in fission yeast and for binding of the altered protein to Pol3 and Cdc27 using the two-hybrid system. Additionally, the locations of the amino acid changes in each protein were mapped onto the three-dimensional structure of human p50. The results obtained from these studies identify amino acid residues and regions within the Cdc1 protein that are essential for interaction with Pol3 and Cdc27 and for in vivo function. Mutations specifically defective in Pol3-Cdc1 interactions allow the identification of a possible Pol3 binding surface on Cdc1.

Conclusion

In the absence of a three-dimensional structure of the entire Pol δ complex, the results of this study highlight regions in Cdc1 that are vital for protein function in vivo and provide valuable clues to possible protein-protein interaction surfaces on the Cdc1 protein that will be important targets for further study.
Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells
Authors: Woo Sun-Mi , Kim Janghwan , Han Hyo-Won , Chae Jung-Il , Son Mi-Young , Cho Sunwha , Chung Hyung-Min , Han Yong-Mahn , Kang Yong-Kook
Published: August 2009

Background

Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.

Results

From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.

Conclusion

Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.
Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo
Authors: Kern Johann , Steurer Michael , Gastl Günther , Gunsilius Eberhard , Untergasser Gerold
Published: August 2009

Background

The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on in vitro and in vivo angiogenesis.

Methods

Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. In vivo effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model.

Results

Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts in vitro, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers α-smooth muscle cell actin (ASMA) and proteoglycan (NG2).

Conclusion

Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels.
Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ
Authors: Chen Yunn-Yi , DeVries Sandy , Anderson Joseph , Lessing Juan , Swain Rebecca , Chin Koei , Shim Veronica , Esserman Laura J , Waldman Frederic M , Hwang E Shelley
Published: August 2009

Background

Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations.

Methods

Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months.

Biomarker changes were compared to a cohort of patients who had not received preoperative treatment.

Results

Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery.

Conclusion

Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention.

Trial Registration

ClinicalTrials.gov NCT00290745
A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review
Authors: Paganin Fabrice , Prevot Martine , Noel Jean Baptiste , Frejeville Marie , Arvin-Berod Claude , Bourdin Arnaud
Published: August 2009

Background

Solitary endobronchial papillomas (SEP) are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease.

Case Presentation

We report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery) was effective with no relapse.

Conclusion

This lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists.
Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy
Authors: Aydar Ebru , Yeo Syn , Djamgoz Mustafa , Palmer Christopher
Published: August 2009

Background

Ca2+ is known to be involved in a number of metastatic processes including motility and proliferation which can result in store-depletion of Ca2+. Up regulation of genes which contribute to store operated channel (SOC) activity may plausibly be necessary for these processes to take place efficiently. TRPC proteins constitute a family of conserved Ca2+-permeable channels that have been shown to contribute to SOC activity.

Results

In breast cancer biopsy tissues, TRPC3 and TRPC6 were the predominant TRPC genes expressed with TRPC3 and TRPC6 being significantly up regulated compared to normal breast tissue. In the lowly metastatic breast cancer cell line MCF-7, TRPC6 was the chief TRPC gene expressed while in the highly metastatic breast cancer cell line MDA-MB-231 both TRPC3 and TRPC6 were the predominant TRPC genes expressed. Western blotting, immunoconfocal analysis and immunoprecipitation experiments confirmed that the MDA-MB-231 cell line expressed both TRPC3 and TRPC6 protein with the majority of protein being intracellular. TRPC3 and TRPC6 were found to be in an immunoprecipitatble complex and co-localize within the cell. To demonstrate the potential of targeting TRP channels in breast cancer, hyperforin reportably a specific activator of TRPC6 significantly reduced the growth and viability of the breast cancer cell lines but had no effect on the non-cancerous breast cell line. Silencing of TRPC6 in MDA-MB-231 cells resulted in a significant reduction in cell growth but not viability.

Conclusion

TRPC channels may be potential future targets for breast cancer diagnosis and therapy and deserve further investigation to evaluate their role in cancer cell physiology.
Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors
Authors: Hsieh Yi-Wen , Yang Xian-Jie
Published: August 2009

Background

The paired homeobox protein Pax6 is essential for proliferation and pluripotency of retinal progenitors. However, temporal changes in Pax6 protein expression associated with the generation of various retinal neurons have not been characterized with regard to the cell cycle. Here, we examine the dynamic changes of Pax6 expression among chicken retinal progenitors as they progress through the neurogenic cell cycle, and determine the effects of altered Pax6 levels on retinogenesis.

Results

We provide evidence that during the preneurogenic to neurogenic transition, Pax6 protein levels in proliferating progenitor cells are down-regulated. Neurogenic retinal progenitors retain a relatively low level of Pax6 protein, whereas postmitotic neurons either elevate or extinguish Pax6 expression in a cell type-specific manner. Cell imaging and cell cycle analyses show that neurogenic progenitors in the S phase of the cell cycle contain low levels of Pax6 protein, whereas a subset of progenitors exhibits divergent levels of Pax6 protein upon entering the G2 phase of the cell cycle. We also show that M phase cells contain varied levels of Pax6, and some correlate with the onset of early neuronal marker expression, forecasting cell cycle exit and cell fate commitment. Furthermore, either elevating or knocking down Pax6 attenuates cell proliferation and results in increased cell death. Reducing Pax6 decreases retinal ganglion cell genesis and enhances cone photoreceptor and amacrine interneuron production, whereas elevating Pax6 suppresses cone photoreceptor and amacrine cell fates.

Conclusion

These studies demonstrate for the first time quantitative changes in Pax6 protein expression during the preneurogenic to neurogenic transition and during the neurogenic cell cycle. The results indicate that Pax6 protein levels are stringently controlled in proliferating progenitors. Maintaining a relatively low Pax6 protein level is necessary for S phase re-entry, whereas rapid accumulation or reduction of Pax6 protein during the G2/M phase of the cell cycle may be required for specific neuronal fates. These findings thus provide novel insights on the dynamic regulation of Pax6 protein among neurogenic progenitors and the temporal frame of neuronal fate determination.
Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes
Authors: Thorell Kaisa , Bergman Annika , Carén Helena , Nilsson Staffan , Kogner Per , Martinsson Tommy , Abel Frida
Published: August 2009

Background

One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified.

Methods

In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples.

Results

By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours,ATBF1,CACNA2D3,CNTNAP2,FUSIP1,GNB1,SLC35E2, andTFAP2B. The gene that showed the highest fold change in the TLDA analysis,POU4F2, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site geneCNTNAP2that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses ofPOU4F2andCNTNAP2showed no genetic alterations that could explain a lower expression in unfavourable NB tumours.

Conclusion

Through two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts,CACNA2D3,GNB1,SLC35E2, andTFAP2B, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic.
Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis
Authors: Rehnberg Maria , Amu Sylvie , Tarkowski Andrej , Bokarewa Maria I , Brisslert Mikael
Published: August 2009

Introduction

In the present study we evaluated changes in the B cell phenotype in peripheral blood and bone marrow (BM) of patients with rheumatoid arthritis (RA) following anti-CD20 treatment using rituximab.

Methods

Blood and BM samples were obtained from 37 patients with RA prior to rituximab treatment. Ten of these patients were resampled 1 month following rituximab, 14 patients after 3 months and the remaining 13 patients were included in the long-term follow up. B cell populations were characterized by CD27/IgD/CD38/CD24 expression.

Results

One and three months following rituximab BM retained up to 30% of B cells while circulation was totally depleted of B cells. Analysis of the remaining BM B cells showed prevalence of immature and/or transitional B cells (CD38++CD24++) and CD27+IgD- memory cells, while IgD+ cells were completely depleted. A significant reduction of CD27+ cells in BM and in circulation was observed long after rituximab treatment (mean 22 months), while levels of naive B cells in BM and in circulation were increased. The levels of rheumatoid factor decline after rituximab treatment but returned to baseline levels at the time of retreatment.

Conclusions

Anti-CD20 treatment achieves a depletion of IgD+ B cells shortly after the treatment. At the long term follow up, a reduction of CD27+ B cells was observed in blood and BM. The prolonged inability to up-regulate CD27 may inhibit the renewal of memory B cells. This reduction of CD27+ B cells does not prevent autoantibody production suggesting that mechanisms regulating the formation of auto reactive clones are not disrupted by rituximab.
Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis
Authors: van der Heijde Désirée M , Revicki Dennis A , Gooch Katherine L , Wong Robert L , Kupper Hartmut , Harnam Neesha , Thompson Chris , Sieper Joachim ,   the ATLAS Study Group
Published: August 2009

Introduction

We evaluated the three-year impact of adalimumab on patient-reported physical function and health-related quality-of-life (HRQOL) outcomes in patients with active ankylosing spondylitis (AS).

Methods

The Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) is an ongoing five-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period, followed by open-label extension treatment with adalimumab. Clinical and HRQOL data collected for up to three years from ATLAS were used for these analyses. Patients were randomized to receive adalimumab 40 mg or placebo by subcutaneous injection every other week. Physical function was assessed by the Bath AS Functional Index (BASFI), as well as by the Short Form 36 (SF-36) Health Survey Physical Component Summary (PCS) and Physical Function subscale scores. HRQOL was assessed using the AS Quality of Life (ASQOL) questionnaire. Disease activity was assessed by the Bath AS Disease Activity Index (BASDAI).

Results

Of 315 patients enrolled in ATLAS, 288 (91%) participated in an open-label adalimumab treatment extension and 82% provided three-year outcome data. During the 24-week double-blind phase, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the BASDAI (P < 0.001), BASFI (P < 0.001), ASQOL (P < 0.001), and both the SF-36 PCS (P < 0.001) and Physical Function subscale (P < 0.001) scores, but not the SF-36 Mental Component Summary score (P = 0.181) and Mental Health subscale scores (P = 0.551). Mean changes from baseline through three years of adalimumab treatment were statistically significant for the BASDAI (change score: -3.9, P < 0.001), BASFI (change score: -29.6, P < 0.001), SF-36 PCS (change score: 11.6, P < 0.001), and Physical Function (change score: 23.3, P < 0.001). Comparable results were observed for the other SF-36 scores and for the ASQOL (all P < 0.001).

Conclusions

Adalimumab significantly improved disease activity, patient-reported physical function, and HRQOL. These benefits were maintained over three years of treatment in patients with AS.

Trial registration

ClinicalTrials.gov NCT00085644.
Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1
Authors: Hogg A E , Bowick G C , Herzog N K , Cloyd M W , Endsley J J
Published: August 2009

PBMC infected with HIV-1 inhibit cytokine signaling and antimicrobial protein expression in human CD8+ T cells.

Immunosuppression following infection with HIV-1 predisposes patients to a myriad of opportunistic pathogens, one of the most important of which is Mtb. Granulysin, expressed by NK cells and CTL, exhibits potent antimicrobial activity against Mtb and several other opportunistic pathogens associated with HIV-1 infection. The immune signals that promote granulysin expression in human CTL are not fully understood. Using primary human CD8+ T cells, in this study, we identify IL-21 as a strong inducer of granulysin, demonstrate that IL-21 and IL-15 activate granulysin expression within CD8+ CD45RO+ T cells, and establish a role for Jak/STAT signaling in the regulation of granulysin within CD8+ T cells. We show that infection of PBMC from healthy donors in vitro with HIV-1 suppresses granulysin expression by CD8+ T cells, concomitant with reduced p-STAT3 and p-STAT5, following activation with IL-15 and IL-21. Of note, simultaneous signaling through IL-15 and IL-21 could partially overcome the immunosuppressive effects of HIV-1 on granulysin expression by CD8+ T cells. These results suggest that HIV-1 infection of PBMC may reduce the antimicrobial profile of activated CD8+ T cells by disrupting signaling events that are critical for the induction of granulysin. Understanding the effects of HIV-1 on CD8+ T cell activation is essential to understanding the physiological basis for inadequate cytotoxic lymphocyte activity in HIV+ patients and for informed guidance of cytokine-based therapy to restore T cell function.
Effect of bearing number on non-linear dynamic behaviour of aerodynamic non-circular journal bearing systems
Authors: Rashidi R , Mohammadi Karami A , Bakhtiari-Nejad F
Published: August 2009

The present article presents the effect of bearing number on non-linear dynamic behaviour of a rigid rotor supported by aerodynamic non-circular journal bearings. A finite-element method has been employed to solve the Reynolds equation in static and dynamical states and the dynamical equations are solved using the Runge-Kutta method. To analyse the behaviour of the rotor centre in the horizontal and vertical directions under different operating conditions, dynamic trajectory, power spectra, Poincare maps, and bifurcation diagrams are used. The results of this study reveal how the complex dynamic behaviour of these three types of non-circular bearing systems comprising periodic and KT-periodic responses of the rotor centre varies with changes in bearing number values.
Wet adhesive wear characteristics of untreated oil palm fibre-reinforced polyester and treated oil palm fibre-reinforced polyester composites using the pin-on-disc and block-on-ring techniques
Authors: Yousif B F , El-Tayeb N S M
Published: August 2009

This article presents an investigation on the wear and friction characteristics of oil palm fibre-reinforced polyester (OPRP) composites sliding against a polished stainless steel counterface under wet contact conditions. Two different types of OPRP composites were fabricated, which were based on treated and untreated oil palm fibres (treated oil palm fibre-reinforced polyester (T-OPRP) and untreated oil palm fibre-reinforced polyester (UT-OPRP), respectively). The experiments were conducted using two different techniques, pin-on-disc (POD) and block-on-ring (BOR), integrated into the same tribo-machine. The tests were conducted at different rotational speeds (500 and 700 r/min) and 50 N applied load for different durations (10-60 min). The specific wear rate ( Ws) and the friction coefficient were presented as a function of sliding distance. The morphology of the worn surfaces was observed using scanning electron microscopy (SEM) and the damage features were characterized. The results revealed that treating oil palm fibres has a significant effect on the wear and frictional performance of OPRP composites. Treating the oil palm fibres enhanced the wear properties of polyester by about 35-52 and 65-75 per cent in the case of the POD and BOR techniques, respectively. The observations on the worn surfaces showed various features of the damages such as debonding and breakage of fibres in the UT-OPRP composite.
Anharmonic variations in elastohydrodynamic film thickness resulting from harmonically varying entrainment velocity
Authors: Kumar P , Khonsari M M , Bair S
Published: August 2009

A comprehensive thermal line contact solution has been obtained by using measured rheological properties, both shear and bulk properties, of the two liquids employed in the Glovnea and Spikes experimental observations of anharmonic variation of film thickness. The appearance of the anharmonic response to harmonic variation of velocity was material and frequency dependent. One of the experimental liquids crosses the liquid to glass boundary within the contact and the volume anomaly arising from differences in glass pressure because of temperature variation has been modelled. This is the first thermal elastohydrodynamic analysis to include the history-dependent equation of state (the glass transition). It can be established that anharmonic variation of film thickness from harmonic variation of entrainment velocity cannot be realistically explained from solutions of the Reynolds equation.
New method for dynamics modelling and analysis on a flexible plate undergoing large overall motion
Authors: Rong B , Rui X-T , Wang G-P
Published: August 2009

Flexible plates are general components in many engineering fields such as aircrafts and vehicles, and their efficient dynamics analysis has an important significance. In this article, by combining discrete time transfer matrix method of multi-body system (MS-DT-TMM) with finite-element method (FEM), the dynamics equations of a flexible plate moving in space are deduced, and its transfer equation and transfer matrix are presented. Finally, a high-efficient modelling method is developed for dynamics analysis on a flexible plate undergoing large overall motion. Compared with ordinary dynamics methods, this method combines the modelling flexibility of MS-DT-TMM with applicability for the two-dimension structure of FEM. By using this method, the global dynamics equations of the system are not needed, the orders of involved matrices are always very small, and the computational speed is high irrespective of the size of the system. The method has advantages for dynamics design of complex flexible multi-body systems (FMS) with flexible plates. Formulations of the method as well as a numerical example of a FMS with a rectangular flexible plate are given to validate the method.
The effects of impact management materials in ice hockey helmets on head injury criteria
Authors: Rousseau P , Post A , Hoshizaki T B
Published: August 2009

The objective of this study was to compare the capacity of vinyl nitrile and expanded polypropylene, two materials commonly used in ice hockey helmets, to reduce the peak linear acceleration, peak angular acceleration, and head injury criterion values during a direct impact to a hybrid III headform. Six different ice hockey helmets were tested using a pneumatic linear impactor at velocities similar to those in hockey. The results showed that helmets using expanded polypropylene foam liners are significantly better at reducing linear acceleration; however, helmets using vinyl nitrile foam liners are significantly better at reducing angular acceleration. Furthermore, the impact location influenced the performance of the liner.
Interview with Edmund S. Phelps
Authors: Vane Howard R , Mulhearn Chris
Published: August 2009

Edmund S. Phelps has been McVickar Professor of Political Economy at Columbia University in New York City, New York, since 1982 and director of the Center on Capitalism and Society at Columbia University's Earth Institute since 2001. In 2006, he was awarded the Nobel Memorial Prize in Economic Science “for his analysis of intertemporal tradeoffs in macroeconomic policy.” We interviewed Professor Phelps at his hotel in San Francisco, on January 3, 2009, while attending the annual meeting of the Allied Social Science Associations.
World Oil: Market or Mayhem?
Authors: Smith James L
Published: August 2009

Many observers regard the world oil market as a puzzle. Why are oil prices so volatile? Why did prices spike in the summer of 2008, and what role did speculators play? How important is OPEC? Where are oil prices headed in the long run? Is “peak oil” a genuine concern? Any attempt to answer these questions must be informed and disciplined by economics. We examine the evidence on each of these issues and provide an interpretation of developments in the world oil market from the perspective of economic theory.
The Three Arab Worlds
Authors: Rauch James E , Kostyshak Scott
Published: August 2009

Given the attention currently focused on the Arab world in part as a result of adjustments in U.S. foreign policy, a fresh look at Arab socioeconomic performance is in order. The Arab world is defined by language rather than ethnicity. The League of Arab States, formed in 1945, consists of all countries in which (a dialect of) Arabic is the spoken language of the majority. It is useful to compare the human development diversity of the Arab world to that of Latin America, another vast geographic area defined by language and culture. Our strategy in this article is therefore to disaggregate the Arab world into Arab sub-Saharan Africa, Arab fuel-endowed economies, and a remainder we call the Arab Mediterranean, and to compare these three Arab worlds to non-Arab sub-Saharan Africa, non-Arab fuel endowed economies, and the rest of the non-Arab world. We will evaluate Arab socioeconomic progress from 1970 to as close to the present as the data allow.