bluuebunny/crossref_metadata_2025 huggingface dataset:
Review: Brain—immune communication psychoneuroimmunology of multiple sclerosis
Authors: Kern S. , Ziemssen T.
Published: September 2007

The central nervous system (CNS) and the immune system are two extremely complex and highly adaptive systems. In the face of a real or anticipated threat, be it physical (eg, infection) or psychological (eg, psychosocial stress) in nature, the two systems act in concert to provide optimal adaptation to the demanding internal or environmental conditions. During instances of well being, the communication between these two systems is well tuned and balanced. However, a disturbed crosstalk between the CNS and the immune system is thought to play a major role in a wide series of disorders characterized by a hyporesponsive or hyperresponsive immune system. In multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease, an excess of inflammatory processes seems to be a hallmark and there is growing evidence for a disturbed communication between the CNS and the immune system as a crucial pathogenic factor. While the exact mechanisms for these phenomena are still poorly understood, the young discipline of psychoneuroimmunology (PNI), which focuses on the mechanism underlying the brain to immune crosstalk, might offer some insights into the existing pathogenic mechanisms. Findings from the field of PNI might also help to gain a better understanding regarding the origin and course of MS clinical symptoms such as fatigue and depression.
Ten years of adverse drug reaction reports for the multiple sclerosis immunomodulatory therapies: a Canadian perspective
Authors: Tremlett H.L. , Oger J.
Published: September 2007

Adverse drug reaction (ADR) reporting is essential in the post-marketing surveillance of drugs, detection of serious adverse reactions, and has been the basis for drug withdrawals. The study aimed to examine ADR reporting patterns to the multiple sclerosis (MS) immunomodulatory drugs (IMD) in Canada. All ADRs reported to the Canadian ADR Monitoring Program (CADRMP) from 1965 to March 2006 ( n = 193 208) were accessed and ADRs in which an IMD for MS (beta-interferon or glatiramer acetate) was the suspected drug extracted ( n = 888 reports were dated March/96—March/06). Almost half of all IMD ADRs reports (438/888) were sourced through the patient compared to 14.9% (10 649/71 373) of all ADRs reported to CADRMP over the same period. Of IMD ADR reports, 88.7% (788/888) were directed through the manufacturer compared to 57.7% (41197/71373) of all ADRs. Encouragement to others involved in patient care, such as pharmacists, nurses and physicians might enhance reporting of MS ADRs. Despite the limitations of ADR reporting data, previously unpublished case reports in several understudied MS populations were detailed: paediatrics (≤16 years old, n = 4), the elderly (≥65 years, n = 23) and during pregnancy ( n = 12). In addition, 46 deaths suspected by the reporter as being related to IMD treatment were detailed as well as three possible drug interactions. Multiple Sclerosis 2008; 14: 94—105. http://msj.sagepub.com
Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?
Authors: Gonsette R.E.
Published: September 2007

There is increasing evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. In neurodegenerative diseases, neuronal and axonal loss is mediated by oxidative stress and excitotoxicity which constitute a final common toxic pathway. Importantly, peroxynitrite is the key mediator of those two intertwined pathomechanisms. In MS, peroxynitrite is consistently associated with active lesions and produces highly toxic nitrating and oxidizing radical species that alter lipid, protein, DNA and mitochondrial structures and functions. During the remitting phase, peroxynitrite participates to neuron and oligodendrocyte damage in association with inflammatory processes. During the chronic phase, peroxynitrite contributes to self-perpetuating mechanisms responsible for disease progression. Neutralization of oxidative stress and excitotoxicity, and in particular of peroxynitrite derived free radicals, might represent a therapeutic approach to provide neuroprotection in MS. Multiple Sclerosis 2008; 14: 22—34. http://msj.sagepub.com
Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma
Authors: Young Ken H. , Weisenburger Dennis D. , Dave Bhavana J. , Smith Lynette , Sanger Warren , Iqbal Javeed , Campo Elias , Delabie Jan , Gascoyne Randy D. , Ott German , Rimsza Lisa , Müller-Hermelink H. Konrad , Jaffe Elaine S. , Rosenwald Andreas , Staudt Louis M. , Chan Wing C. , Greiner Timothy C.
Published: September 2007

Mutations of the TP53 tumor suppressor gene have been associated with poor survival in some series of diffuse large B-cell lymphoma (DLBCL) but not in other studies. The purpose of this study was to identify the frequency of TP53 alterations (mutations or deletions), characterize the gene expression of mutant/deleted cases, and determine the effects of mutations on survival. In a series of DLBCL that had previous gene expression profiling, we identified 24 mutations in 113 cases (21%). There was no difference in the frequency of mutations in the molecular subgroups of DLBCL. Twelve (50%) of the 24 cases had mutations localized to the DNA-binding codons in the core domain of TP53. The presence of any TP53 mutation correlated with poor overall survival (OS; P = .044), but DNA-binding mutations were the most significant predictor of poor OS (P < .001). Multivariate analysis confirmed that the International Prognostic Index, tumor size, and TP53 DNA-binding mutations were independent predictors of OS. Gene expression analysis showed that TRAILreceptor-2 (DR5) was the most differentially underexpressed gene in the TP53 mutated cases. Investigation is warranted into targeted therapy toward TRAIL receptor-2, to potentially bypass the adverse effect of mutated TP53 in DLBCL.
Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia
Authors: Olavarria Eduardo , Siddique Shamyla , Griffiths Michael J. , Avery Sharon , Byrne Jenny L. , Piper Karen P. , Lennard Anne L. , Pallan Lalit , Arrazi Julie M. , Perz Jolanta B. , O'Shea Derville , Goldman John M. , Apperley Jane F. , Craddock Charles F.
Published: September 2007

Disease relapse is a major cause of treatment failure after reduced-intensity allografts and while donor lymphocyte infusions (DLIs) can be effective salvage therapy they are associated with severe graft-versus-host disease (GVHD) when administered early after transplantation. We have therefore examined whether imatinib mesylate can delay relapse and postpone the requirement for DLI in 22 patients with chronic myeloid leukemia (CML) allografted using a reduced-intensity regimen. Imatinib was commenced on day + 35 and continued until 1 year after transplantation. Posttransplantation imatinib was well tolerated and abolished the risk of relapse during this period. Twenty-one patients completed 11 months of imatinib therapy, 15 of whom subsequently relapsed and received DLI. Ten patients to date have achieved molecular remission after DLI. Adjunctive targeted therapy allows the kinetics of disease relapse after a reduced-intensity allograft to be manipulated and represents a novel strategy by which outcome may be improved in patients who undergo transplantation for CML and other leukemias.
CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency
Authors: Saleh Suha , Solomon Ajantha , Wightman Fiona , Xhilaga Miranda , Cameron Paul U. , Lewin Sharon R.
Published: September 2007

Latent HIV-1 infection of resting memory CD4+ T cells represents the major barrier to HIV-1 eradication. To determine whether the CCR7 ligands involved in lymphocyte migration can alter HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells after incubation with the chemokines CCL19 and CCL21. Incubation with CCL19 or CCL21 did not alter markers of T-cell activation or proliferation. However, after HIV-1 infection of CCL19- or CCL21-treated CD4+ T-cells, we observed low-level HIV-1 production but high concentrations of integrated HIV-1 DNA, approaching that seen in mitogen-stimulated T-cell blasts. Restimulation of CCL19-treated infected CD4+ T cells resulted in virus production consistent with establishment of postintegration latency. CCR7 ligands facilitate efficient entry of HIV-1 into resting CD4+ T cells. These studies demonstrate a unique action of the chemokines CCL19 and CCL21 and provide a novel model with which to study HIV-1 latency in vitro.
Structural and functional implications of positive selection at the primate angiogenin gene
Authors: Osorio Daniel S , Antunes Agostinho , Ramos Maria J
Published: September 2007

Background

Angiogenesis, the formation of new blood vessels, is a primordial process in development and its dysregulation has a central role in the pathogenesis of many diseases. Angiogenin (ANG), a peculiar member of the RNase A superfamily, is a potent inducer of angiogenesis involved in many different types of cancer, amyotrophic lateral sclerosis and also with a possible role in the innate immune defense. The evolutionary path of this family has been a highly dynamic one, where positive selection has played a strong role. In this work we used a combined gene and protein level approach to determine the main sites under diversifying selection on the primate ANG gene and analyze its structural and functional implications.

Results

We obtained evidence for positive selection in the primate ANG gene. Site specific analysis pointed out 15 sites under positive selection, most of which also exhibited drastic changes in amino acid properties. The mapping of these sites in the ANG 3D-structure described five clusters, four of which were located in functional regions: two in the active site region, one in the nucleolar location signal and one in the cell-binding site. Eight of the 15 sites under selection in the primate ANG gene were highly or moderately conserved in the RNase A family, suggesting a directed event and not a simple consequence of local structural or functional permissiveness. Moreover, 11 sites were exposed to the surface of the protein indicating that they may influence the interactions performed by ANG.

Conclusion

Using a maximum likelihood gene level analysis we identified 15 sites under positive selection in the primate ANG genes, that were further corroborated through a protein level analysis of radical changes in amino acid properties. These sites mapped onto the main functional regions of the ANG protein. The fact that evidence for positive selection is present in all ANG regions required for angiogenesis may be a good indication that angiogenesis is the process under selection. However, other possibilities to be considered arise from the possible involvement of ANG in innate immunity and the potential influence or co-evolution with its interacting proteins and ligands.
Quantitative measurement of pathogen specific human memory T cell repertoire diversity using a CDR3β-specific microarray
Authors: Wang Xujing , Jia Shuang , Meyer Lisa , Yassai Maryam B , Naumov Yuri N , Gorski Jack , Hessner Martin J
Published: September 2007

Background

Providing quantitative microarray data that is sensitive to very small differences in target sequence would be a useful tool in any number of venues where a sample can consist of a multiple related sequences present in various abundances. Examples of such applications would include measurement of pseudo species in viral infections and the measurement of species of antibodies or T cell receptors that constitute immune repertoires. Difficulties that must be overcome in such a method would be to account for cross-hybridization and for differences in hybridization efficiencies between the arrayed probes and their corresponding targets. We have used the memory T cell repertoire to an influenza-derived peptide as a test case for developing such a method.

Results

The arrayed probes were corresponded to a 17 nucleotide TCR-specific region that distinguished sequences differing by as little as a single nucleotide. Hybridization efficiency between highly related Cy5-labeled subject sequences was normalized by including an equimolar mixture of Cy3-labeled synthetic targets representing all 108 arrayed probes. The same synthetic targets were used to measure the degree of cross hybridization between probes. Reconstitution studies found the system sensitive to input ratios as low as 0.5% and accurate in measuring known input percentages (R2= 0.81, R = 0.90, p < 0.0001). A data handling protocol was developed to incorporate the differences in hybridization efficiency. To validate the array in T cell repertoire analysis, it was used to analyze human recall responses to influenza in three human subjects and compared to traditional cloning and sequencing. When evaluating the rank order of clonotype abundance determined by each method, the approaches were not found significantly different (Wilcoxon rank-sum test, p > 0.05).

Conclusion

This novel strategy appears to be robust and can be adapted to any situation where complex mixtures of highly similar sequences need to be quantitatively resolved.
Gene duplication and paleopolyploidy in soybean and the implications for whole genome sequencing
Authors: Schlueter Jessica A , Lin Jer-Young , Schlueter Shannon D , Vasylenko-Sanders Iryna F , Deshpande Shweta , Yi Jing , O'Bleness Majesta , Roe Bruce A , Nelson Rex T , Scheffler Brian E , Jackson Scott A , Shoemaker Randy C
Published: September 2007

Background

Soybean, Glycine max (L.) Merr., is a well documented paleopolyploid. What remains relatively under characterized is the level of sequence identity in retained homeologous regions of the genome. Recently, the Department of Energy Joint Genome Institute and United States Department of Agriculture jointly announced the sequencing of the soybean genome. One of the initial concerns is to what extent sequence identity in homeologous regions would have on whole genome shotgun sequence assembly.

Results

Seventeen BACs representing ~2.03 Mb were sequenced as representative potential homeologous regions from the soybean genome. Genetic mapping of each BAC shows that 11 of the 20 chromosomes are represented. Sequence comparisons between homeologous BACs shows that the soybean genome is a mosaic of retained paleopolyploid regions. Some regions appear to be highly conserved while other regions have diverged significantly. Large-scale "batch" reassembly of all 17 BACs combined showed that even the most homeologous BACs with upwards of 95% sequence identity resolve into their respective homeologous sequences. Potential assembly errors were generated by tandemly duplicated pentatricopeptide repeat containing genes and long simple sequence repeats. Analysis of a whole-genome shotgun assembly of 80,000 randomly chosen JGI-DOE sequence traces reveals some new soybean-specific repeat sequences.

Conclusion

This analysis investigated both the structure of the paleopolyploid soybean genome and the potential effects retained homeology will have on assembling the whole genome shotgun sequence. Based upon these results, homeologous regions similar to those characterized here will not cause major assembly issues.
Multidisciplinary outpatient care program for patients with chronic low back pain: design of a randomized controlled trial and cost-effectiveness study [ISRCTN28478651]
Authors: Lambeek Ludeke C , Anema Johannes R , van Royen Barend J , Buijs Peter C , Wuisman Paul I , van Tulder Maurits W , van Mechelen Willem
Published: September 2007

Background

Chronic low back pain (LBP) is a major public and occupational health problem, which is associated with very high costs. Although medical costs for chronic LBP are high, most costs are related to productivity losses due to sick leave. In general, the prognosis for return to work (RTW) is good but a minority of patients will be absent long-term from work. Research shows that work related problems are associated with an increase in seeking medical care and sick leave. Usual medical care of patients is however, not specifically aimed at RTW.

The objective is to present the design of a randomized controlled trial, i.e. the BRIDGE-study, evaluating the effectiveness in improving RTW and cost-effectiveness of a multidisciplinary outpatient care program situated in both primary and outpatient care setting compared with usual clinical medical care for patients with chronic LBP.

Methods/Design

The design is a randomized controlled trial with an economic evaluation alongside. The study population consists of patients with chronic LBP who are completely or partially sick listed and visit an outpatient clinic of one of the participating hospitals in Amsterdam (the Netherlands). Two interventions will be compared. 1. a multidisciplinary outpatient care program consisting of a workplace intervention based on participatory ergonomics, and a graded activity program using cognitive behavioural principles. 2. usual care provided by the medical specialist, the occupational physician, the patient's general practitioner and allied health professionals. The primary outcome measure is sick leave duration until full RTW. Sick leave duration is measured monthly by self-report during one year. Data on sick leave during one-year follow-up are also requested form the employers. Secondary outcome measures are pain intensity, functional status, pain coping, patient satisfaction and quality of life. Outcome measures are assessed before randomization and 3, 6, and 12 months later. All statistical analysis will be performed according to the intension-to-treat principle.

Discussion

Usual care of primary and outpatient health services isn't directly aimed at RTW, therefor it is desirable to look for care which is aimed at RTW. Research shows that several occupational interventions in primary care are aimed at RTW. They have shown a significant reduction of sick leave for employee with LBP. If a comparable reduction of sick leave duration of patients with chronic LBP of who attend an outpatient clinic can be achieved, such reductions will be obviously substantial for the Netherlands and will have a considerable impact.

Trial registration

ISRCTN28478651
Collecting data for sexually transmitted infections (STI) surveillance: what do patients prefer in Flanders?
Authors: Verhoeven Veronique , Colliers Annelies , Verster Ann , Avonts Dirk , Peremans Lieve , Van Royen Paul
Published: September 2007

Background

STI surveillance systems are subject to qualitative and quantitative underreporting. General practitioners (GPs), who are key subjects in case reporting, explain their underreporting partly by their observation that taking a sexual history is embarrassing for patients, and that patients are reluctant to disclose information on their sexual practices. In this study we examine patients' willingness to provide data for STI surveillance.

Methods

A questionnaire-based survey in a stratified population sample of 300 patients aged 18–60 years.

Results

The large majority of respondents stated to be willing to give information on their sexual practices for the purpose of STI surveillance. They preferred to answer sexual history questions to their GP; filling in a form on the internet was the second best option.

Conclusion

Based on these results, it is unlikely that the cooperation of patients would be a weak link in STI surveillance strategies. This observation, together with the fact that the majority of patients at risk for STIs have regular access to general practice services, justify renewed efforts to enliven primary care-based STI surveillance strategies.
Trends in hyperlipidemia and hypertension management in type 2 diabetes patients from 1998–2004: a longitudinal observational study
Authors: Greving Jacoba P , Denig Petra , de Zeeuw Dick , Bilo Henk JG , Haaijer-Ruskamp Flora M
Published: September 2007

Background

Lack of treatment initiation or intensification might explain why some patients with type 2 diabetes do not reach target goals. The objective is to assess trends in risk factor treatment, and identify determinants for medication adjustments in patients with uncontrolled hypertension and/or hyperlipidemia.

Methods

We conducted a cohort study using data from the Zwolle Outpatient Diabetes project Integrated Available Care (ZODIAC)-study in The Netherlands. Management of hypertension and hyperlipidemia was assessed yearly from 1998–2004 by measuring the percentage of patients receiving a treatment initiation or intensification among all patients with elevated risk factor levels. Generalized estimating equation analyses were performed.

Results

During the study period, the percentage of patients with an elevated total cholesterol/high-density lipoproteins ratio (>6) decreased considerably (from 29% to 4%) whereas the percentage of hypertensive patients decreased only slightly (≥ 150/85 mmHg; from 58% to 51%). Initiation of lipid-lowering therapy and intensification of antihypertensive therapy was higher in more recent years. However, still two-third of patients with insufficiently controlled blood pressure in 2003 did not receive an initiation or intensification of antihypertensive treatment in the following year. Treatment changes were mainly determined by elevated levels of the corresponding risk factor. We did not observe increased initiation rates for lipid-lowering therapy in patients with both hypertension and hyperlipidemia.

Conclusion

Hypertension and hyperlipidemia management in type 2 diabetes patients has improved in the past decade but further improvement is possible. Greater effort is needed to stimulate medication adjustments in patients with insufficiently controlled hypertension and combined risk factors.
Tissue distribution of DNA-Hsp65/TDM-loaded PLGA microspheres and uptake by phagocytic cells
Authors: Trombone Ana Paula F , Silva Celio L , Almeida Luciana P , Rosada Rogerio S , Lima Karla M , Oliver Constance , Jamur Maria C , Coelho-Castelo Arlete AM
Published: September 2007

This study aimed to demonstrate that microspheres, used as delivery vehicle of DNA-Hsp65/TDM [plasmid DNA encoding heat shock protein 65 (Hsp65) coencapsulated with trehalose dimycolate (TDM) into PLGA microspheres], are widely spread among several organs after intramuscular administration in BALB/c mice. In general, we showed that these particles were phagocytosed by antigen presenting cells, such as macrophages and dendritic cells. Besides, it was demonstrated herein that draining lymph node cells presented a significant increase in the number of cells expressing costimulatory molecules (CD80 and CD86) and MHC class II, and also that the administration of the DNA-Hsp65/TDM and vector/TDM formulations resulted in the up-regulation of CD80, CD86 and MHC class II expression when compared to control formulations (vector/TDM and empty). Regarding the intracellular trafficking we observed that following phagocytosis, the microspheres were not found in the late endosomes and/or lysosomes, until 15 days after internalization, and we suggest that these constructions were hydrolysed in early compartments. Overall, these data expand our knowledge on PLGA [poly (lactic-co- glycolic acid)] microspheres as gene carriers in vaccination strategies, as well as open perspectives for their potential use in clinical practice.
Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p
Authors: Suter Bernhard , Pogoutse Oxana , Guo Xinghua , Krogan Nevan , Lewis Peter , Greenblatt Jack F , Rine Jasper , Emili Andrew
Published: September 2007

Background

Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4.

Results

Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC). While mutational inactivation of the histone acetyltransferase (HAT) gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2) exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork.

Conclusion

We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p). The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.
Ankyrin repeat domain-encoding genes in the wPip strain of Wolbachia from the Culex pipiens group
Authors: Walker Thomas , Klasson Lisa , Sebaihia Mohammed , Sanders Mandy J , Thomson Nicholas R , Parkhill Julian , Sinkins Steven P
Published: September 2007

Background

Wolbachia are obligate endosymbiotic bacteria maternally transmitted through the egg cytoplasm that are responsible for several reproductive disorders in their insect hosts, such as cytoplasmic incompatibility (CI) in infected mosquitoes. Species in the Culex pipiens complex display an unusually high number of Wolbachia-induced crossing types, and based on present data, only the wPip strain is present.

Results

The sequencing of the wPip strain of Wolbachia revealed the presence of 60 ankyrin repeat domain (ANK) encoding genes and expression studies of these genes were carried out in adult mosquitoes. One of these ANK genes, pk2, is shown to be part of an operon of three prophage-associated genes with sex-specific expression, and is present in two identical copies in the genome. Another homolog of pk2 is also present that is differentially expressed in different Cx. pipiens group strains. A further two ANK genes showed sex-specific regulation in wPip-infected Cx. pipiens group adults.

Conclusion

The high number, variability and differential expression of ANK genes in wPip suggest an important role in Wolbachia biology, and the gene family provides both markers and promising candidates for the study of reproductive manipulation.
Pathologist performed fine needle aspirations & implementation of JCAHO Universal Protocol and “Time out”
Authors: Siddiqui Momin T
Published: September 2007

The adherence to the principles of the Universal Protocol for preventing wrong site, wrong procedure and wrong person surgical or invasive procedures is a requirement for all Joint Commission accredited organizations. Fine needle aspirations are considered invasive procedures, and cytopathologists performing this procedure need to be cognizant and compliant with the requirements of this Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Protocol. This article gives background perspective on the development of the Universal Protocol. It also elaborates the JCAHO National Patients Safety Goals regarding the performance of fine needle aspirations. The compliance with the Universal Protocol for performance of fine needle aspirations is now mandated for all cytopathologists who perform fine needle aspirations and this present paper provides a guideline for fulfilling the requirements of the Universal Protocol for practicing cytopathologists.
Ion channel diversity, channel expression and function in the choroid plexuses
Authors: Millar Ian D , Bruce Jason IE , Brown Peter D
Published: September 2007

Knowledge of the diversity of ion channel form and function has increased enormously over the last 25 years. The initial impetus in channel discovery came with the introduction of the patch clamp method in 1981. Functional data from patch clamp experiments have subsequently been augmented by molecular studies which have determined channel structures. Thus the introduction of patch clamp methods to study ion channel expression in the choroid plexus represents an important step forward in our knowledge understanding of the process of CSF secretion.

Two K+ conductances have been identified in the choroid plexus: Kv1 channel subunits mediate outward currents at depolarising potentials; Kir 7.1 carries an inward-rectifying conductance at hyperpolarising potentials. Both K+ channels are localised at the apical membrane where they may contribute to maintenance of the membrane potential while allowing the recycling of K+ pumped in by Na+-K+ ATPase. Two anion conductances have been identified in choroid plexus. Both have significant HCO3
- permeability, and may play a role in CSF secretion. One conductance exhibits inward-rectification and is regulated by cyclic AMP. The other is carried by an outward-rectifying channel, which is activated by increases in cell volume. The molecular identity of the anion channels is not known, nor is it clear whether they are expressed in the apical or basolateral membrane. Recent molecular evidence indicates that choroid plexus also expresses the non-selective cation channels such as transient receptor potential channels (TRPV4 and TRPM3) and purinoceptor type 2 (P2X) receptor operated channels. In conclusion, good progress has been made in identifying the channels expressed in the choroid plexus, but determining the precise roles of these channels in CSF secretion remains a challenge for the future.
Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting
Authors: Maeda Takuya T , Ajioka Itsuki , Nakajima Kazunori
Published: September 2007

Background

Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population.

Results

We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement.

Conclusion

We constructed an in silico cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model could predict directional cell movement and its mobility are important in the "inside and outside" pattern of cell sorting. Those behaviors are altered by signal molecules and consequently affect the global pattern of the cell sorting. Our model is also applicable to other developmental processes beyond cell sorting.
IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcεRI signals
Authors: Ho Lien H , Ohno Tatsukuni , Oboki Keisuke , Kajiwara Naoki , Suto Hajime , Iikura Motoyasu , Okayama Yoshimichi , Akira Shizuo , Saito Hirohisa , Galli Stephen J , Nakae Susumu
Published: September 2007

The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-FcεRI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly understood. We found that IL-33, but not IL-1β or IL-18, induced IL-13 and IL-6 production by mouse bone marrow-derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE-7 IgE without specific antigen, IL-33, IL-1β, and IL-18 each promoted IL-13 and IL-6 production, but the effects of IL-33 were more potent than those of IL-1β or IL-18. IL-33 promoted cytokine production via a MyD88-dependent but Toll/IL-1R domain-containing adaptor-inducing IFN-β-independent pathway. By contrast, IL-33 neither induced nor enhanced mast cell degranulation. At 200 ng/ml, IL-33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE-7 IgE, whereas at 100 ng/ml, IL-33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL-33 in mast cell- and Th2 cytokine-associated immune responses and disorders.
HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production
Authors: Waggoner Stephen N , Hall Caroline H T , Hahn Young S
Published: September 2007

Dendritic cells (DCs) isolated from patients with chronic hepatitis C virus (HCV) infection display an impaired capacity to generate type 1 CD4+ T cell immunity. Several reports have described an immunomodulatory function for the HCV core protein, and circulating core has been shown to associate with the putative gC1q receptor, gC1qR, expressed on host immune cells. However, the molecular mechanism(s) of HCV core-mediated DC dysfunction has not been defined. Herein, ligation of gC1qR on human monocyte-derived DCs (MDDCs) with HCV core or anti-gC1qR agonist antibody was shown to inhibit TLR-induced IL-12 production but not the production of other TLR-stimulated cytokines. Furthermore, engagement of gC1qR on MDDCs resulted in reduced IFN-γ secretion by allogeneic CD4+ T lymphocytes during mixed lymphocyte culture. Differentiation of CD4+ T cells cocultured with HCV core- or anti-gC1qR antibody-treated MDDCs was also skewed toward production of Th2 cytokines, including IL-4. Importantly, that addition of IL-12 rescued IFN-γ production and Th1 differentiation by CD4+ T cells. Therefore, engagement of gC1qR on DCs by HCV core limits the induction of Th1 responses and may contribute to viral persistence.
Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4
Authors: Astorga Jeanette , Carlsson Peter
Published: September 2007

The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo-/-) has no effect on Foxf1expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1-/- phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo-/- yolk sacs can be rescued by exogenous Bmp4,consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
Tramtrack regulates different morphogenetic events duringDrosophilatracheal development
Authors: Araújo Sofia J. , Cela Carolina , Llimargas Marta
Published: September 2007

Tramtrack (Ttk) is a widely expressed transcription factor, the function of which has been analysed in different adult and embryonic tissues in Drosophila. So far, the described roles of Ttk have been mainly related to cell fate specification, cell proliferation and cell cycle regulation. Using the tracheal system of Drosophila as a morphogenetic model, we have undertaken a detailed analysis of Ttk function. Ttk is autonomously and non-autonomously required during embryonic tracheal formation. Remarkably, besides a role in the specification of different tracheal cell identities, we have found that Ttk is directly involved and required for different cellular responses and morphogenetic events. In particular, Ttk appears to be a new positive regulator of tracheal cell intercalation. Analysis of this process in ttk mutants has unveiled cell shape changes as a key requirement for intercalation and has identified Ttk as a novel regulator of its progression. Moreover, we define Ttk as the first identified regulator of intracellular lumen formation and show that it is autonomously involved in the control of tracheal tube size by regulating septate junction activity and cuticle formation. In summary, the involvement of Ttk in different steps of tube morphogenesis identifies it as a key player in tracheal development.
The development of the bladder trigone, the center of the anti-reflux mechanism
Authors: Viana Renata , Batourina Ekatherina , Huang Hongying , Dressler Gregory R. , Kobayashi Akio , Behringer Richard R. , Shapiro Ellen , Hensle Terry , Lambert Sarah , Mendelsohn Cathy
Published: September 2007

The urinary tract is an outflow system that conducts urine from the kidneys to the bladder via the ureters that propel urine to the bladder via peristalsis. Once in the bladder, the ureteral valve, a mechanism that is not well understood, prevents backflow of urine to the kidney that can cause severe damage and induce end-stage renal disease. The upper and lower urinary tract compartments form independently, connecting at mid-gestation when the ureters move from their primary insertion site in the Wolffian ducts to the trigone, a muscular structure comprising the bladder floor just above the urethra. Precise connections between the ureters and the trigone are crucial for proper function of the ureteral valve mechanism; however, the developmental events underlying these connections and trigone formation are not well understood. According to established models, the trigone develops independently of the bladder, from the ureters, Wolffian ducts or a combination of both; however, these models have not been tested experimentally. Using the Cre-lox recombination system in lineage studies in mice, we find, unexpectedly, that the trigone is formed mostly from bladder smooth muscle with a more minor contribution from the ureter, and that trigone formation depends at least in part on intercalation of ureteral and bladder muscle. These studies suggest that urinary tract development occurs differently than previously thought, providing new insights into the mechanisms underlying normal and abnormal development.
Laboratory Medicine: Challenges and Opportunities
Authors: Bossuyt Xavier , Verweire Kurt , Blanckaert Norbert
Published: September 2007

Technologic innovations have substantially improved the productivity of clinical laboratories, but the services provided by clinical laboratories are increasingly becoming commoditized. We reflect on how current developments may affect the future of laboratory medicine and how to deal with these changes. We argue that to be prepared for the future, clinical laboratories should enhance efficiency and reduce costs by forming alliances and networks; consolidating, integrating, or outsourcing; and more importantly, create additional value by providing knowledge services related to in vitro diagnostics.
Generalized Fourier expansion in kernels of convolution operators on Fourier hyperfunctions
Authors: Langenbruch Michael
Published: September 2007

We prove that the kernels of surjective convolution operators on Fourier hyperfunctions (and on Fourier ultra-hyperfunctions) admit a basis of exponential solutions. The corresponding coefficient spaces are explicitly determined.
Stein's extension operator for sets with Lipγ-boundary
Authors: Frerick Leonhard
Published: September 2007

We modify Stein's extension operator to obtain a generalization of Bierstone's extension result for sets with Lip
On some representation formulas involving moduli of Blaschke products
Authors: Gluchoff Alan , Gorkin Pamela , Mortini Raymond
Published: September 2007

Starting from an integral formula in harmonic analysis, we derive some representation formulas for (1–|
Univalence of a complex linear combination of two extremal parallel slit mappings
Authors: Shiba Masakazu
Published: September 2007

Any convex combination of the so-called extremal horizontal and vertical slit mappings of a plane domain is known to be univalent. In his study on the conformal welding of annuli F. Maitani needed to know when a complex linear combination is univalent and he gave a partial answer to this problem. In the present article we give a complete answer to his and to generalized problems.
Lacunary (R, p, M)-summability
Authors: Gharibyan Tatevik L. , Luh Wolfgang , Müller Jürgen
Published: September 2007

In this article summability methods of weighted mean type are considered which are generated by a lacunary sequence of positive minimal density. The interdependencies between the topological structure of the summability domain for the geometric sequence (and as its consequences for general power series) are discussed. In addition some results on universal approximation are proved.
MacLane functions with prescribed zeros and interpolation properties
Authors: Nieß Markus
Published: September 2007

An entire function ϕ is called universal in the sense of MacLane (for short MacLane function) if for any preassigned entire function

It is shown that for every appropriate choice of designated zeros in ℂ, there exists a MacLane function having zeros exactly in these points, of preassigned order. Moreover, there exist MacLane functions satisfying an interpolation problem in addition.
Tehat the Weaver
Authors: Franzmann Majella
Published: September 2007

There is noise in the distance, someone shouting, a child runs by, calling as she passes the house. The woman at the weaving loom stops abruptly and comes to the door, shading her eyes to look against the glare of the sun towards the distance where the slow line of camels signals the return of the camel freight train to the town of Kellis. She is a business woman, owning a part of the thriving weaving business and perhaps also a part of the camel freight business. She is the Manichaean woman, Tehat.
The Limits of Inventing Tradition
Authors: Weiss Rick
Published: September 2007

Eric Hobsbawm and Terence Rangers’ influential volume, The Invention of Tradition, remains a milestone in scholarly approaches to the study of tradition. However, in emphasizing conscious manipulations of tradition, and in employing a notion of invention that lacks nuance, the authors of that volume do not sufficiently acknowledge the degree to which invented traditions draw from prior traditions. I explore here the limits of conscious constructions of tradition, arguing that traditions that serve as powerful touchstones for identity cannot be invented ex nihilo. I look at an instance of elite formulation of tradition, the Dravidian Movement in Tamil Nadu, South India, in the first half of the twentieth century, which articulated a new formulation of Tamil tradition based largely on European models and ideals. The leaders of this movement envisioned an ancient Tamil community that was egalitarian, scientific, and non-Hindu, and they employed this vision in their development of policies for education, religious institutions, and industrialization. Their failure to mobilize popular support for their cause was repeatedly demonstrated in their electoral defeats at the hands of the Congress Party, which promoted a reformist tradition based on Hindu symbols and ritual practices. I argue that the Dravidian Movement failed to win political support because they discarded nearly all the components of prior Tamil tradition, and the novel tradition they authored in turn was unrecognizable to ordinary Tamils.
Civil Religion and the Invention of Traditions
Authors: Kong Lily
Published: September 2007

In this article, I adopt the concept of civil religion, and particularly those aspects that emphasize the importance of rituals and traditions in the construction of a ‘nation’, to examine the ways in which a particular nation—Singapore—is politically and socially constructed. Using two specific examples of invented rituals and traditions, I illustrate the ways in which the state attempts to build a sense of community and identity. The two examples I use are an annual choreography of spectacle and display to celebrate Singapore’s National Day, and the production of a tapestry currently on exhibition as a very public symbol of community and belonging.
Heritability of Cold Tolerance in Red Drum
Authors: Ma Liang , Saillant Eric , Gatlin Delbert M. , Neill William H , Vega Robert R , Gold John R
Published: September 2007

Heritability (h  2) of cold tolerance was estimated for red drum Sciaenops ocellatus, an economically important sciaenid fish in the southern USA. Nineteen families were generated via environmentally induced spawning of multiple sets of five broodfish (three dams × two sires) and were mixed in three common-garden replicate tanks for cold tolerance challenge. All offspring were assigned postmortem to parents based on genotypes at nuclear-encoded microsatellites. The cold tolerance trial was initiated when offspring were 230–251 d old (total length mean ± SD = 182 ± 26 mm). Temperature was decreased progressively from 25°C to 3°C over a 30-d period and was maintained at an average of 3.1°C until all fish expired. Mortality began when temperature reached 5°C. Cold tolerance of individual fish was quantified based on survival time and a cooling-degree-hours (CDH) index. The h  2of cold tolerance was estimated using an animal mixed model and a restricted maximum likelihood algorithm. The h  2 (mean ± SE) estimate was 0.32 ± 0.12 and indicated a significant genetic component to cold tolerance in red drum. Phenotypic correlations between cold tolerance and body weight or length were positive but low (0.18 and 0.23, respectively), suggesting that selective breeding for increased growth rate in red drum would not have a negative impact on cold tolerance in the selected strain.