bluuebunny/crossref_metadata_2025 huggingface dataset:
Genealogy of the computer screen
Authors: Gere Charlie
Published: June 2006

This article proposes that the modern computer screen is derived more from the radar screen rather than, as might be expected, the television screen, which has important ramifications for how the computer has developed and been understood. These ramifications are being obscured by the current drive towards the ‘convergence’ of television and computing. This article traces the modern computer screen back to the development of nuclear early warning systems in the 1960s (based on the British radar networks of the Second World War) and to the work of ex-radar operator Douglas Engelbart and his Augmentation Research Center at Stanford Research Institute, both of which were instrumental in how we now understand and use computers as ‘real-time’ machines.
The poetics of augmented space
Authors: Manovich Lev
Published: June 2006

This article discusses how people experience spatial forms when they are filled in with dynamic and rich multimedia information; spaces such as shopping or entertainment areas or other spaces where various information can be accessed wirelessly. The author calls such spaces ‘augmented space’: the physical space overlaid with dynamically changing information, multimedia in form and localized for each user. The article asks whether this form becomes irrelevant and ‘invisible’ or if people end up with a new experience in which the spatial and information layers are equally important. The author also discusses the general dynamic between spatial form and information and how this might function differently in today’s computer culture. Throughout the article, augmentation is reconceptualized as an idea and cultural and aesthetic practice rather than as technology. Various practices in professional and vernacular architecture and built environments, cinema, 20th-century art and media art are discussed in terms of augmentation.
DIgR2, dendritic cell-derived immunoglobulin receptor 2, is one representative of a family of IgSF inhibitory receptors and mediates negative regulation of dendritic cell-initiated antigen-specific T-cell responses
Authors: Shi Liyun , Luo Kun , Xia Dajing , Chen Taoyong , Chen Guoyou , Jiang Yingming , Li Nan , Cao Xuetao
Published: June 2006

Dendritic cells (DCs) are specialized antigen-presenting cells that play crucial roles in the initiation and regulation of immune responses. Maturation and activation of DCs are controlled by a balance of the inhibitory and activating signals transduced through distinct surface receptors. Many inhibitory receptors expressed by DCs have been identified, whereas the new members and their functions need further investigation. In this study, we functionally characterized DC-derived immunoglobulin receptor 2 (DIgR2) as a novel representative of a family of inhibitory receptors belonging to the immunoglobulin superfamily. We show that DIgR2 contains 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic region and that DIgR2 associates with Src homology-2 domain-containing protein tyrosine phosphatases-1 (SHP-1). Blockade of DIgR2 on DCs by pretreatment with DIgR2-Ig fusion protein or by silencing with specific small interfering RNA enhances DC-initiated T-cell proliferation and antigen-specific T-cell responses both in vitro and in vivo. Furthermore, immunization of mice with antigen-pulsed, DIgR2-silenced DCs elicits more potent antigen-specific CD4+ and CD8+ T-cell responses, thus protecting the vaccinated mice from tumor challenge more effectively. Our data suggest that DIgR2 is a functionally inhibitory receptor and can mediate negative signaling to regulate DC-initiated antigen-specific T-cell responses.
CAVER: a new tool to explore routes from protein clefts, pockets and cavities
Authors: Petřek Martin , Otyepka Michal , Banáš Pavel , Košinová Pavlína , Koča Jaroslav , Damborský Jiří
Published: June 2006

Background

The main aim of this study was to develop and implement an algorithm for the rapid, accurate and automated identification of paths leading from buried protein clefts, pockets and cavities in dynamic and static protein structures to the outside solvent.

Results

The algorithm to perform a skeleton search was based on a reciprocal distance function grid that was developed and implemented for the CAVER program. The program identifies and visualizes routes from the interior of the protein to the bulk solvent. CAVER was primarily developed for proteins, but the algorithm is sufficiently robust to allow the analysis of any molecular system, including nucleic acids or inorganic material. Calculations can be performed using discrete structures from crystallographic analysis and NMR experiments as well as with trajectories from molecular dynamics simulations. The fully functional program is available as a stand-alone version and as plug-in for the molecular modeling program PyMol. Additionally, selected functions are accessible in an online version.

Conclusion

The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web sitehttp://loschmidt.chemi.muni.cz/caver/.
PSMIX: an R package for population structure inference via maximum likelihood method
Authors: Wu Baolin , Liu Nianjun , Zhao Hongyu
Published: June 2006

Background

Inference of population stratification and individual admixture from genetic markers is an integrative part of a study in diverse situations, such as association mapping and evolutionary studies. Bayesian methods have been proposed for population stratification and admixture inference using multilocus genotypes and widely used in practice. However, these Bayesian methods demand intensive computation resources and may run into convergence problem in Markov Chain Monte Carlo based posterior samplings.

Results

We have developed PSMIX, an R package based on maximum likelihood method using expectation-maximization algorithm, for inference of population stratification and individual admixture.

Conclusion

Compared with software based on Bayesian methods (e.g., STRUCTURE), PSMIX has similar accuracy, but more efficient computations.

PSMIX and its supplemental documents are freely available athttp://bioinformatics.med.yale.edu/PSMIX.
Differentiated evolutionary rates in alternative exons and the implications for splicing regulation
Authors: Plass Mireya , Eyras Eduardo
Published: June 2006

Background

Alternatively spliced exons play an important role in the diversification of gene function in most metazoans and are highly regulated by conserved motifs in exons and introns. Two contradicting properties have been associated to evolutionary conserved alternative exons: higher sequence conservation and higher rate of non-synonymous substitutions, relative to constitutive exons. In order to clarify this issue, we have performed an analysis of the evolution of alternative and constitutive exons, using a large set of protein coding exons conserved between human and mouse and taking into account the conservation of the transcript exonic structure. Further, we have also defined a measure of the variation of the arrangement of exonic splicing enhancers (ESE-conservation score) to study the evolution of splicing regulatory sequences. We have used this measure to correlate the changes in the arrangement of ESEs with the divergence of exon and intron sequences.

Results

We find evidence for a relation between the lack of conservation of the exonic structure and the weakening of the sequence evolutionary constraints in alternative and constitutive exons. Exons in transcripts with non-conserved exonic structures have higher synonymous (dS) and non-synonymous (dN) substitution rates than exons in conserved structures. Moreover, alternative exons in transcripts with non-conserved exonic structure are the least constrained in sequence evolution, and at high EST-inclusion levels they are found to be very similar to constitutive exons, whereas alternative exons in transcripts with conserved exonic structure have a dS significantly lower than average at all EST-inclusion levels. We also find higher conservation in the arrangement of ESEs in constitutive exons compared to alternative ones. Additionally, the sequence conservation at flanking introns remains constant for constitutive exons at all ESE-conservation values, but increases for alternative exons at high ESE-conservation values.

Conclusion

We conclude that most of the differences in dN observed between alternative and constitutive exons can be explained by the conservation of the transcript exonic structure. Low dS values are more characteristic of alternative exons with conserved exonic structure, but not of those with non-conserved exonic structure. Additionally, constitutive exons are characterized by a higher conservation in the arrangement of ESEs, and alternative exons with an ESE-conservation similar to that of constitutive exons are characterized by a conservation of the flanking intron sequences higher than average, indicating the presence of more intronic regulatory signals.
PHOG: a database of supergenomes built from proteome complements
Authors: Merkeev Igor V , Novichkov Pavel S , Mironov Andrey A
Published: June 2006

Background

Orthologs and paralogs are widely used terms in modern comparative genomics. Existing procedures for resolving orthologous/paralogous relationships are often based on manual revision of clusters of orthologous groups and/or lack any rigorous evolutionary base.

Description

We developed a completely automated procedure that creates clusters of orthologous groups at each node of the taxonomy tree (PHOGs – Phylogenetic Orthologous Groups). As a result of this procedure, a tree of orthologous groups was obtained. Each cluster is a "supergene" and it is represented by an "ancestral" sequence obtained from the multiple alignment of orthologous and paralogous genes.

The procedure has been applied to the taxonomy tree of organisms from all three domains of life. Protein complements from 50 bacterial, archaeal and eukaryotic species were used to create PHOGs at all tree nodes. 51367 PHOGs were obtained at the root node.

Conclusion

The PHOG database demonstrates that it is possible to automatically process any number of sequenced genomes and to reconstruct orthologous and paralogous relationships between genomes using a rigorous evolutionary approach. This database can become a very useful tool in various areas of comparative genomics.
Does a preceding hand wash and drying time after surgical hand disinfection influence the efficacy of a propanol-based hand rub?
Authors: Hübner Nils-Olaf , Kampf Günter , Kamp Philipp , Kohlmann Thomas , Kramer Axel
Published: June 2006

Background

Recently, a propanol-based hand rub has been described to exceed the efficacy requirements of the European standard EN 12791 in only 1.5 min significantly. But the effect of a 1 min preceding hand wash and the effect of one additional minute for evaporation of the alcohol after its application on the efficacy after a 1.5 min application time has never been studied.

Methods

We have investigated a propanol-based hand rub (Sterillium®, based on 45% propan-2-ol, 30% propan-1-ol and 0.2% mecetronium etilsulfate) in three variations: with (A) and without (B) a 1 min hand wash before the disinfection of 1.5 min with immediate sampling after the disinfection; and (C) without a hand wash before the disinfection but with sampling 1 min after the disinfection. The efficacy of the three variations was compared to the reference treatment of EN 12791. All experiments were performed in a Latin-square design with 20 volunteers. Pre- and post-values (immediate and after 3 hr) were obtained according to EN 12791.

Results

The 3 min reference disinfection reduced resident hand bacteria on average by 1.8 log10 steps (immediate effect) and 1.4 log10-steps (sustained effect) respectively. Method A was equally effective as the reference (immediate efficacy: 1.5 log10-steps; sustained efficacy: 1.6 log10-steps). Method B seemed to be more effective (immediate efficacy: 2.3 log10-steps; sustained efficacy: 1.7 log10-steps). Method C revealed the best efficacy (immediate efficacy: 2.3 log10-steps; sustained efficacy: 2.0 log10-steps). A comparison of all three treatment variations and the reference treatment revealed a significant difference for the immediate efficacy (p = 0.026; Friedman test), but not for the sustained efficacy (p = 0.430). A post-hoc-test for the immediate efficacy indicated a significant difference between methods A and C (p < 0.05; Wilcoxon-Wilcox test). Hence, none of the treatment variations was significantly less effective than the reference treatment.

Conclusion

An application of the propanol-based hand rub for 1.5 min after 1 min hand wash fulfills the efficacy requirements of EN 12791. The efficacy can be improved to some extent by omitting the preceding hand wash and by awaiting the evaporation of the alcohol which is clinical practice anyway. The preceding hand wash has the most negative effect on the immediate effect. Based on our data hands should not be routinely washed before the disinfection period unless there is a good reason for it such as visible soiling.
Insulin-like growth factor-1 (IGF-1) induces the activation/phosphorylation of Akt kinase and cAMP response element-binding protein (CREB) by activating different signaling pathways in PC12 cells
Authors: Zheng Wen-Hua , Quirion Rémi
Published: June 2006

Background

Insulin-like growth factor-1 (IGF-1) is a polypeptide growth factor with a variety of functions in both neuronal and non-neuronal cells. IGF-1 plays anti-apoptotic and other functions by activating multiple signaling pathways including Akt kinase, a serine/threonine kinase essential for cell survival. The nuclear transcription factor cAMP response element-binding protein (CREB) may also be involved although relationships between these two proteins in IGF-1 receptor signaling and protection is not clear, especially in neuronal cells.

Results

IGF-1, in a concentration- and time-dependent manner, induces the activation/phosphorylation of Akt and CREB in PC12 cells by activating different signaling pathways. IGF-1 induced a sustained phosphorylation of Akt while only a transient one was seen for CREB. The phosphorylation of Akt is mediated by the PI3 kinase pathway while that of CREB is dependent on the activation of both MAPK kinase and p38 MAPK. Moreover, the stimulation of PKC attenuated the phosphorylation of Akt induced by IGF-1 while enhancing that of CREB. Survival assays with various kinase inhibitors suggested that the activation/phosphorylation of both Akt and CREB contributes to IGF-1 mediated cell survival in PC12 cells.

Conclusion

These data suggest that IGF-1 induced the activation of Akt and CREB using distinct pathways in PC12 cells.
Endothelial progenitor cells display clonal restriction in multiple myeloma
Authors: Braunstein Marc , Özçelik Tayfun , Bağişlar Sevgi , Vakil Varsha , Smith Eric LP , Dai Kezhi , Akyerli Cemaliye B , Batuman Olcay A
Published: June 2006

Background

In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization.

Methods

A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH).

Results

In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI.

Conclusion

Our results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM.
Histological response of peritoneal carcinomatosis after hyperthermic intraperitoneal chemoperfusion (HIPEC) in experimental investigations
Authors: Pelz Joerg OW , Doerfer J , Dimmler A , Hohenberger W , Meyer T
Published: June 2006

Background

In selected patients with peritoneal carcinomatosis from colorectal cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. The aim of this study was to evaluate the tumor response of peritoneal carcinomatosis in tumor-bearing rats treated with HIPEC.

Methods

CC531 colon carcinoma (2,5 × 106 cells), implanted intraperitoneally in Wag/Rija rats, was treated by hyperthermic intraperitoneal chemotherapy. After 10 days of tumor growth the animals were randomized into five groups of six animals each: group I: control (n = 6), group II: sham operated animals (n = 6), group III: hyperthermic intraperitoneal perfusion (HIP) without cytostatic drugs, group IV: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group V: mitomycin C i.p. alone in a concentration of 10 mg/m2 (n = 6). After 10 days the extent of tumor spread and histological outcome were analysed by autopsy.

Results

All control animals developed extensive intraperitoneal tumor growth. Histological tumor load was significantly reduced in group III and group V and was lowest in group IV. In group II tumor load was significantly higher than in group I. Implanted metastases were significantly decreased in group IV compared with group I and group II.

Conclusion

These findings indicate that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread.
The prevalence of pseudoexfoliation syndrome in Pakistan. Hospital based study
Authors: Rao Rashad Qamar , Arain Tariq Mehmood , Ahad Muhammad Ali
Published: June 2006

Background

Pseudoexfoliation syndrome (PXS) is the most common identifiable cause of secondary glaucoma, the prevalence of which varies considerably among different ethnicities. The aim of this study was to assess the prevalence of pseudoexfoliation syndrome in Pakistan.

Methods

A prospective study conducted in the period from January 2003 to June 2004 in a teaching hospital serving a population of about 7.6 million. 1860 patients aged 45 or above attending the general ophthalmic clinics were recruited for this study. A detailed evaluation including ophthalmic and general history, slit lamp biomicroscopy, intraocular pressure measurement, gonioscopy and dilated eye examination was performed on all patients.

Results

120(6.45%) subjects were found to have PXS with a male to female ratio of 1.5:1. All 120 (100%) cases were bilateral and 48(40%) patients had high intraocular pressure.

Conclusion

To the best of our knowledge, this is the first study conducted in a Pakistani population to determine the prevalence of PXS. The prevalence rate of 6.45% is similar to other studies conducted in south Asia, however all cases were bilateral and quite a high percentage of patients had high intra-ocular pressure.
In planta production of two peptides of the Classical Swine Fever Virus (CSFV) E2 glycoprotein fused to the coat protein of potato virus X
Authors: Marconi Gianpiero , Albertini Emidio , Barone Pierluigi , De Marchis Francesca , Lico Chiara , Marusic Carla , Rutili Domenico , Veronesi Fabio , Porceddu Andrea
Published: June 2006

Background

Classical Swine Fever (CSFV) is one of the most important viral infectious diseases affecting wild boars and domestic pigs. The etiological agent of the disease is the CSF virus, a single stranded RNA virus belonging to the family Flaviviridae.

All preventive measures in domestic pigs have been focused in interrupting the chain of infection and in avoiding the spread of CSFV within wild boars as well as interrupting transmission from wild boars to domestic pigs. The use of plant based vaccine against CSFV would be advantageous as plant organs can be distributed without the need of particular treatments such as refrigeration and therefore large areas, populated by wild animals, could be easily covered.

Results

We report the in planta production of peptides of the classical swine fever (CSF) E2 glycoprotein fused to the coat protein of potato virus X. RT-PCR studies demonstrated that the peptide encoding sequences are correctly retained in the PVX construct after three sequential passage in Nicotiana benthamiana plants. Sequence analysis of RT-PCR products confirmed that the epitope coding sequences are replicated with high fidelity during PVX infection. Partially purified virions were able to induce an immune response in rabbits.

Conclusion

Previous reports have demonstrated that E2 synthetic peptides can efficiently induce an immunoprotective response in immunogenized animals. In this work we have showed that E2 peptides can be expressed in planta by using a modified PVX vector. These results are particularly promising for designing strategies for disease containment in areas inhabited by wild boars.
Effectiveness of a Chinese herbal medicine preparation in the treatment of cough in uncomplicated upper respiratory tract infection: a randomised double-blinded placebo-control trial
Authors: WCW Wong , A Lee , AT Lam , KT Li , CYM Leung , PC Leung , ELY Wong , JL Tang
Published: June 2006

Background

Rigorous scientific and well-designed clinical trials to evaluate the effect of traditional Chinese medicine (TCM) is lacking. We, therefore, designed this study to evaluate the effectiveness of a commonly used TCM preparation in treating acute cough of uncomplicated URTI in adults and to search for a safe, effective and affordable alternative treatment for this common condition.

Methods

A randomised, double-blinded, placebo-control study comparing this TCM preparation with a placebo was conducted in 82 patients who attended the Family Medicine Training Centre, Prince of Wales Hospital, Hong Kong between November and December, 2003. The TCM herbal preparation includes nine commonly used TCM herbs for cough such as chuanbei, fangfeng, jiegeng, gancao and baibu (see Table 1) The treatment lasted for 5 days and patients were followed-up for another 6 days. Patients were asked to fill in a cough score and validated Leicester cough questionnaire (LCQ).

Results

62 patients (75.6%) had completed the trial and no adverse effects were reported. Both intervened and control groups had improved in cough score and LCQ in the follow-up period, despite no overall statistical significance was observed in the differences of scores between the two groups. Women taking TCM had significantly fewer problems with sputum production (p = 0.03) and older subjects (>35 years of age) reported a significant improvement in hoarseness (p = 0.05) when compared to those using placebo.

Conclusion

TCM was well-tolerated and received among the Hong Kong Chinese population. This TCM preparation appeared to have some benefits in the treatment of cough. Future research on TCM should concentrate more on commonly encountered conditions such as UTRI and cough. Our experience on the sensitivity of assessment tools used in detecting subtle differences in an otherwise self-limiting illness and clinical trial methodology when applying the underlying theory of how TCM works in disease management was invaluable.
Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes
Authors: Kim Hyun Ah , Won Kim Dae , Park Jinseu , Choi Soo Young
Published: June 2006

This study was performed to investigate the transduction of a full-length superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat) into human chondrocytes, and to determine the regulatory function of transduced Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD expression vector was constructed to express the basic domain of HIV-1 Tat as a fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were cultured in both a monolayer and an explant. For the transduction of fusion proteins, cells/explants were treated with a variety of concentrations of fusion proteins. The transduced protein was detected by fluorescein labeling, western blotting and SOD activity assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression was assessed by the Griess reaction and reverse transcriptase PCR, respectively. Tat-SOD was successfully delivered into both the monolayer and explant cultured chondrocytes, whereas the control SOD was not. The intracellular transduction of Tat-SOD into cultured chondrocytes was detected after 1 hours, and the amount of transduced protein did not change significantly after further incubation. SOD enzyme activity increased in a dose-dependent manner. NO production and iNOS mRNA expression, in response to IL-1 stimulation, was significantly down-regulated by pretreatment with Tat-SOD fusion proteins. This study shows that protein delivery employing the Tat-protein transduction domain is feasible as a therapeutic modality to regulate catabolic processes in cartilage. Construction of additional Tat-fusion proteins that can regulate cartilage metabolism favorably and application of this technology in in vivo models of arthritis are the subjects of future studies.
Study protocol: Home-based physical rehabilitation for survivors of a critical illness [ACTRN12605000166673]
Authors: Elliott Doug , McKinley Sharon , Alison Jennifer A , Aitken Leanne M , King Madeleine T
Published: June 2006

Introduction

Numerous primary studies and several review papers have highlighted delayed physical and psychological recovery for survivors of critical illness, often beyond 6 months after discharge. This randomized controlled trial with blinded assessment aims to test the effects of an 8-week, home-based, individually tailored physical rehabilitation programme on physical and psychological recovery for survivors of a critical illness after discharge from hospital.

Method

Participants are survivors of a critical illness discharged from nine intensive care units (ICUs) in Australia, who are aged 18 years or older, in an ICU longer than 48 hours, discharged home to self-care or carer (non-institutional care), able to participate in physical rehabilitation, and within the hospitals' local geographical areas for home visits. The study is based in participants' home environments. Blinded assessments at weeks 1, 8 and 26 after hospital discharge examine physical functioning, exercise capacity, health-related quality of life and psychological well being. The intervention is graded, individualized endurance and strength training prescribed by a pulmonary rehabilitation physiotherapist over an 8-week period, with three home visits, five follow-up phone calls, and a printed exercise manual supporting the training. Initial focus is on lower limb exercises and walking, with warm-up stretches, and progresses to the addition of core stabilization and upper limb exercises.

Results

The burden of a critical illness is well documented. This novel study will determine whether a home-based physical rehabilitation programme improves the recovery trajectory for survivors of critical illness. The projected sample size of 200 patients aims to detect a clinically important 10% improvement in physical functioning. The study will also examine whether other important physical and psychological measures are improved.

Conclusion

This multicentre, randomized controlled trial will examine outcomes that are meaningful to patients, their family and society, namely functional ability and well being. The study will also target a health problem that is likely to increase as the population ages. If the programme is effective, it will provide a model that can be easily adapted and adopted by existing primary care or community services to improve the recovery of individuals following critical illness.
Measurement of alveolar derecruitment in patients with acute lung injury: computerized tomography versus pressure–volume curve
Authors: Lu Qin , Constantin Jean-Michel , Nieszkowska Ania , Elman Marilia , Vieira Silvia , Rouby Jean-Jacques
Published: June 2006

Introduction

Positive end-expiratory pressure (PEEP)-induced lung derecruitment can be assessed by a pressure–volume (P–V) curve method or by lung computed tomography (CT). However, only the first method can be used at the bedside. The aim of the study was to compare both methods for assessing alveolar derecruitment after the removal of PEEP in patients with acute lung injury or acute respiratory distress syndrome.

Methods

P–V curves (constant-flow method) and spiral CT scans of the whole lung were performed at PEEPs of 15 and 0 cmH2O in 19 patients with acute lung injury or acute respiratory distress syndrome. Alveolar derecruitment was defined as the difference in lung volume measured at an airway pressure of 15 cmH2O on P–V curves performed at PEEPs of 15 and 0 cmH2O, and as the difference in the CT volume of gas present in poorly aerated and nonaerated lung regions at PEEPs of 15 and 0 cmH2O.

Results

Alveolar derecruitments measured by the CT and P–V curve methods were 373 ± 250 and 345 ± 208 ml (p = 0.14), respectively. Measurements by both methods were tightly correlated (R = 0.82, p < 0.0001). The derecruited volume measured by the P–V curve method had a bias of -14 ml and limits of agreement of between -158 and +130 ml in comparison with the average derecruited volume of the CT and P–V curve methods.

Conclusion

Alveolar derecruitment measured by the CT and P–V curve methods are tightly correlated. However, the large limits of agreement indicate that the P–V curve and the CT method are not interchangeable.
The Six Spot Step Test: a new measurement for walking ability in multiple sclerosis
Authors: Nieuwenhuis M M , Van Tongeren H , Sørensen P S , Ravnborg M
Published: June 2006

Objective The primary objective of this study was to develop a quantitative test to assess ambulation in multiple sclerosis (MS) patients that is more accurate and sensitive than the Timed 25-foot walk (T25FW). For this purpose, we developed the Six Spot Step Test (SSST), which besides speed includes co-ordination and balance, to be a lower limb counterpart to the 9-Hole Peg Test (9HPT).

Background The T25FW, which is the ambulation test of the MS Functional Composite (MSFC), reflects only the speed component of walking. The lack of sensitivity to other components of gait adds to the floor effect.

Methods and patients In the SSST, the patient is instructed to walk as quickly as possible from one end to the other of a rectangular field measuring 1× 5 m, while kicking five cylinder blocks out of five circles marked on the floor. Some 151 MS patients with the Expanded Disability Status Scale (EDSS) score 0-6.5 and 64 normal controls performed the SSST and the T25FW. In addition, 41 patients performed the tests twice.

Results The range of the SSST (4.7-35.1 seconds) was wider than that of the T25FW (3.5-22.6 seconds). Using control mean+ 2 SD as cut off, 107 patients had abnormal SSST, while 100 patients had abnormal T25FW. The T25FW (mean) increased 2.1 seconds over the EDSS range of 0-4.0, while the SSST increased 4.9 seconds. The intra-class correlation between repeated tests (r) was 0.95 for the SSST and 0.96 for the T25FW. The correlation between the SSST and the T25FW was high ( r=0.92).

Conclusion The SSST seems to be superior to the T25FW in terms of dynamic range, floor effect and discriminatory power. The SSST is a relevant alternative for the T25FW as the ambulation component of the MSFC.
Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional study
Authors: Chang K H , Lyu R K , Chen C M , Hsu W C , Wu Y R , Chen S T , Ro L S
Published: June 2006

This study reviewed the clinical characteristics of multiple sclerosis (MS) in Taiwanese patients from 1993 to 2001. Of the 75 MS patients with a mean age of onset of 35.6±12.6 years, the female-to-male ratio was 4.4 (61/14). In 42 (56%) optico-spinal MS (OS-MS) patients, the age of onset (37.6±11.1 years) tended to be older than conventional MS (C-MS) patients (33.1±14.1 years, P = 0.08). In 60 cerebrospinal fluid (CSF) specimens, raised IgG index (>0.7) and oligoclonal bands were noted in 26 (43.3%) and two (3.3%) cases, respectively. The frequency of raised IgG index was lower in OSMS (31.3%) than in C-MS (57.1%, P = 0.07). The CSF total protein concentrations were significantly higher in OS-MS (64.5 mg/dL) than in C-MS (46.6 mg/dL, P = 0.047). The mean annual relapse rate was 54.1%, and was significantly higher within the first year (59.7%, P<0.001). The mean annual relapse rate in OS-MS (62.7%) was significantly higher than in C-MS (41.2%, P = 0.01). The differences in the annual relapse rate and total protein concentration in CSF between OS-MS and C-MS suggest probably two distinct immunopathogenesis. The higher first year relapse rate of MS patients in Taiwan may address the importance of early intervention with immunomodulatory therapy.
Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone
Authors: Téllez Nieves , Comabella Manuel , Julià E va , Río Jordi , Tintoré M ar , Brieva Luís , Nos Carlos , Montalban Xavier
Published: June 2006

Background and objective Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers.

Methods We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were ≤5.0 at all time points, and as non-fatigued when FSS scores were ≤5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point.

Results Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored ≤5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue ( P=0.01 and P=0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [ F(1,31)=6.14, P=0.019 for DHEAS; F(1,32)= 6.63, P=0.015 for DHEA].

Conclusions Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.
Sleep and fatigue in multiple sclerosis
Authors: Stanton B R , Barnes F , Silber E
Published: June 2006

Fatigue is common in multiple sclerosis (MS) and is an important cause of disability. However, the cause of fatigue is poorly understood. This study aimed to describe the frequency and pattern of sleep disturbance in a group of outpatients with MS, and to investigate the relationship between sleep disturbance and fatigue. Sixty outpatients with MS completed the Fatigue Severity Scale (FSS) and the Epworth Sleepiness Scale and kept a sleep diary for seven days. Fatigue and excessive daytime sleepiness were common in this group of patients (64 and 32%). Sleep problems on at least two nights per week occurred frequently, including initial insomnia in 42%, middle insomnia in 53% and terminal insomnia in 58%. The reasons cited for different types of insomnia varied, with anxiety and pain/discomfort being the commonest causes of initial insomnia and nocturia the commonest cause of middle insomnia. Middle insomnia was significantly correlated with daytime fatigue, a relationship that remained after controlling for disability. Sleep disturbance is common in MS and is associated with treatable symptoms, including pain and nocturia. Sleep disturbance may be an important factor contributing to fatigue in patients with MS.
JAK/STAT signalling inDrosophila: insights into conserved regulatory and cellular functions
Authors: Arbouzova Natalia I. , Zeidler Martin P.
Published: June 2006

High levels of interspecies conservation characterise all signal transduction cascades and demonstrate the significance of these pathways over evolutionary time. Here, we review advances in the field of JAK/STAT signalling, focusing on recent developments in Drosophila. In particular, recent results from genetic and genome-wide RNAi screens, as well as studies into the developmental roles played by this pathway, highlight striking levels of physical and functional conservation in processes such as cellular proliferation, immune responses and stem cell maintenance. These insights underscore the value of model organisms for improving our understanding of this human disease-relevant pathway.
Coordinated cell-shape changes control epithelial movement in zebrafish andDrosophila
Authors: Köppen Mathias , Fernández Beatriz García , Carvalho Lara , Jacinto Antonio , Heisenberg Carl-Philipp
Published: June 2006

Epithelial morphogenesis depends on coordinated changes in cell shape, a process that is still poorly understood. During zebrafish epiboly and Drosophila dorsal closure, cell-shape changes at the epithelial margin are of critical importance. Here evidence is provided for a conserved mechanism of local actin and myosin 2 recruitment during theses events. It was found that during epiboly of the zebrafish embryo, the movement of the outer epithelium (enveloping layer) over the yolk cell surface involves the constriction of marginal cells. This process depends on the recruitment of actin and myosin 2 within the yolk cytoplasm along the margin of the enveloping layer. Actin and myosin 2 recruitment within the yolk cytoplasm requires the Ste20-like kinase Msn1, an orthologue of DrosophilaMisshapen. Similarly, in Drosophila, actin and myosin 2 localization and cell constriction at the margin of the epidermis mediate dorsal closure and are controlled by Misshapen. Thus, this study has characterized a conserved mechanism underlying coordinated cell-shape changes during epithelial morphogenesis.
Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo
Authors: Furuta Chie , Ema Hideo , Takayanagi Shin-ichiro , Ogaeri Takunori , Okamura Daiji , Matsui Yasuhisa , Nakauchi Hiromitsu
Published: June 2006

Vasculogenesis and hematopoiesis are thought to arise in hemangioblasts,the common progenitors of cells in vessels and in blood. This scheme was challenged by kinetic analysis of vascular endothelial and hematopoietic progenitors in early gastrulating mouse embryos. The OP-9 co-culture system with a combination of cytokines permitted the detection of endothelial progenitors, as well as stroma-dependent hematopoietic progenitors. Endothelial progenitors were detected as early as embryonic day (E) 5.50,after which time their numbers increased. Stroma-dependent hematopoietic progenitors were detected at E6.75, the time point when hemangioblasts reportedly emerge. Colony-forming units in culture (CFU-c), most likely generated from stroma-dependent hematopoietic progenitors via contact with the microenvironment, were detected at E7.50, concomitant with the onset of primitive hematopoiesis in the yolk sac. The presence of nucleated erythrocytes and the expression of an embryonic-type globin in erythroid colonies derived from stroma-dependent hematopoietic progenitors and from CFU-c support the notion that these progenitors coordinately establish primitive hematopoiesis. Using Oct3/4 promoter-driven GFP transgenic mice,early endothelial progenitors, stroma-dependent hematopoietic progenitors, and CFU-c were all shown to express the Oct3/4 transcription factor. Among Oct3/4-positive cells, both endothelial and hematopoietic progenitors were present in the CD31-positive fraction, leaving a subset of endothelial progenitors in the CD31-negative fraction. These data imply that Oct3/4-positive mesoderm gives rise to CD31-negative angioblasts,CD31-positive angiboblasts and CD31-positive hemangioblasts. We propose a distinct developmental pathway in which the angioblast lineage directly diverges from mesoderm prior to and independent of hemangioblast development.
The roof plate regulates cerebellar cell-type specification and proliferation
Authors: Chizhikov Victor V. , Lindgren Anne G. , Currle D. Spencer , Rose Matthew F. , Monuki Edwin S. , Millen Kathleen J.
Published: June 2006

During embryogenesis, the isthmic organizer, a well-described signaling center at the junction of the mid-hindbrain, establishes the cerebellar territory along the anterior/posterior axis of the neural tube. Mechanisms specifying distinct populations within the early cerebellar anlage are less defined. Using a newly developed gene expression map of the early cerebellar anlage, we demonstrate that secreted signals from the rhombomere 1 roof plate are both necessary and sufficient for specification of the adjacent cerebellar rhombic lip and its derivative fates. Surprisingly, we show that the roof plate is not absolutely required for initial specification of more distal cerebellar cell fates, but rather regulates progenitor proliferation and cell position within the cerebellar anlage. Thus, in addition to the isthmus, the roof plate represents an important signaling center controlling multiple aspects of cerebellar patterning.
A morphogenetic wave ofp27Kip1transcription directs cell cycle exit during organ of Corti development
Authors: Lee Yun-Shain , Liu Feng , Segil Neil
Published: June 2006

The molecular mechanisms coordinating cell cycle exit with cell differentiation and organogenesis are a crucial, yet poorly understood, aspect of normal development. The mammalian cyclin-dependent kinase inhibitor p27Kip1 is required for the correct timing of cell cycle exit in developing tissues, and thus plays a crucial role in this process. Although studies of p27Kip1 regulation have revealed important posttranscriptional mechanisms regulating p27Kip1 abundance, little is known about how developmental patterns of p27Kip1 expression,and thus cell cycle exit, are achieved. Here, we show that during inner ear development transcriptional regulation of p27Kip1 is the primary determinant of a wave of cell cycle exit that dictates the number of postmitotic progenitors destined to give rise to the hair cells and supporting cells of the organ of Corti. Interestingly, transcriptional induction from the p27Kip1 gene occurs normally in p27Kip1-null mice, indicating that developmental regulation of p27Kip1 transcription is independent of the timing of cell cycle exit. In addition, cell-type-specific patterns of p27Kip1 transcriptional regulation are observed in the mature organ of Corti and retina, suggesting that this mechanism is important in differential regulation of the postmitotic state. This report establishes a link between the spatial and temporal pattern of p27Kip1transcription and the control of cell number during sensory organ morphogenesis.
Prdm1 acts downstream of a sequential RA, Wnt and Fgf signaling cascade during zebrafish forelimb induction
Authors: Mercader Nadia , Fischer Sabine , Neumann Carl J.
Published: June 2006

Vertebrate limb induction is triggered in the lateral plate mesoderm (LPM)by a cascade of signaling events originating in the axial mesoderm. While it is known that Fgf, Wnt and retinoic acid (RA) signals are involved in this cascade, their precise regulatory hierarchy has not been determined in any species. tbx5 is the earliest gene expressed in the limb bud mesenchyme. Recently, another transcription factor, Prdm1, has been shown to be crucial for zebrafish forelimb development. Here, we show that Prdm1 is downstream of RA, Wnt2b and Tbx5 activity. We find that RA activity, but not Fgf signaling, is necessary for wnt2b expression. Fgf signaling is required for prdm1 expression in the fin bud, but is not necessary for the initiation of tbx5 expression. We propose a model in which RA signaling from the somitic mesoderm leads to activation of wnt2bexpression in the intermediate mesoderm, which then signals to the LPM to trigger tbx5 expression. tbx5 is required for Fgf signaling in the limb bud leading to activation of prdm1 expression, which in turn is required for downstream activation of fgf10 expression.
An antagonistic role for theC. elegansSchnurri homolog SMA-9 in modulating TGFβ signaling during mesodermal patterning
Authors: Foehr Marisa L. , Lindy Amanda S. , Fairbank Rachel C. , Amin Nirav M. , Xu Ming , Yanowitz Judith , Fire Andrew Z. , Liu Jun
Published: June 2006

In C. elegans, the Sma/Mab TGFβ signaling pathway regulates body size and male tail patterning. SMA-9, the C. elegans homolog of Schnurri, has been shown to function as a downstream component to mediate the Sma/Mab TGFβ signaling pathway in these processes. We have discovered a new role for SMA-9 in dorsoventral patterning of the C. eleganspost-embryonic mesoderm, the M lineage. In addition to a small body size, sma-9 mutant animals exhibit a dorsal-to-ventral fate transformation within the M lineage. This M lineage defect of sma-9 mutants is unique in that animals carrying mutations in all other known components of the TGFβ pathway exhibit no M lineage defects. Surprisingly, mutations in the core components of the Sma/Mab TGFβ signaling pathway suppressed the M lineage defects of sma-9 mutants without suppressing their body size defects. We show that this suppression specifically happens within the M lineage. Our studies have uncovered an unexpected role of SMA-9 in antagonizing the TGFβ signaling pathway during mesodermal patterning,suggesting a novel mode of function for the SMA-9/Schnurri family of proteins.