Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H

Although the importance of CD4(+) T cell responses to human cytonnegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4(+) CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HICMV isolates revealed that the gB and gH epitope sequences recognized by human CD4(+) T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4(+) CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse pepticle-sensitized Patr-DR7(+) cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class 11 lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.

Patients with chronic neck pain demonstrate altered patterns of muscle activation during performance of a functional upper limb task

Study Design. Cross-sectional study. Objective. This study compared neck muscle activation patterns during and after a repetitive upper limb task between patients with idiopathic neck pain, whiplash-associated disorders, and controls. Summary of Background Data. Previous studies have identified altered motor control of the upper trapezius during functional tasks in patients with neck pain. Whether the cervical flexor muscles demonstrate altered motor control during functional activities is unknown. Methods. Electromyographic activity was recorded from the sternocleidomastoid, anterior scalenes, and upper trapezius muscles. Root mean square electromyographic amplitude was calculated during and on completion of a functional task. Results. A general trend was evident to suggest greatest electromyograph amplitude in the sternocleidomastoid, anterior scalenes, and left upper trapezius muscles for the whiplash-associated disorders group, followed by the idiopathic group, with lowest electromyographic amplitude recorded for the control group. A reverse effect was apparent for the right upper trapezius muscle. The level of perceived disability ( Neck Disability Index score) had a significant effect on the electromyographic amplitude recorded between neck pain patients. Conclusions. Patients with neck pain demonstrated greater activation of accessory neck muscles during a repetitive upper limb task compared to asymptomatic controls. Greater activation of the cervical muscles in patients with neck pain may represent an altered pattern of motor control to compensate for reduced activation of painful muscles. Greater perceived disability among patients with neck pain accounted for the greater electromyographic amplitude of the superficial cervical muscles during performance of the functional task.

Integration of autonomic and local mechanisms in regulating cardiovascular responses to heating and cooling in a reptile (Crocodylus porosus)

Reptiles change heart rate and blood flow patterns in response to heating and cooling, thereby decreasing the behavioural cost of thermoregulation. We tested the hypothesis that locally produced vasoactive substances, nitric oxide and prostaglandins, mediate the cardiovascular response of reptiles to heat. Heart rate and blood pressure were measured in eight crocodiles (Crocodylus porosus) during heating and cooling and while sequentially inhibiting nitric-oxide synthase and cyclooxygenase enzymes. Heart rate and blood pressure were significantly higher during heating than during cooling in all treatments. Power spectral density of heart rate and blood pressure increased significantly during heating and cooling compared to the preceding period of thermal equilibrium. Spectral density of heart rate in the high frequency band (0.19-0.70 Hz) was significantly greater during cooling in the saline treatment compared to when nitric-oxide synthase and cyclooxygenase enzymes were inhibited. Cross spectral analysis showed that changes in blood pressure preceded heart rate changes at low frequencies (

Facilitating cross-organisational workflows with a workflow view approach

Interconnecting business processes across systems and organisations is considered to provide significant benefits, such as greater process transparency, higher degrees of integration, facilitation of communication, and consequently higher throughput in a given time interval. However, to achieve these benefits requires tackling constraints. In the context of this paper these are privacy-requirements of the involved workflows and their mutual dependencies. Workflow views are a promising conceptional approach to address the issue of privacy; however this approach requires addressing the issue of interdependencies between workflow view and adjacent private workflow. In this paper we focus on three aspects concerning the support for execution of cross-organisational workflows that have been modelled with a workflow view approach: (i) communication between the entities of a view-based workflow model, (ii) their impact on an extended workflow engine, and (iii) the design of a cross-organisational workflow architecture (CWA). We consider communication aspects in terms of state dependencies and control flow dependencies. We propose to tightly couple private workflow and workflow view with state dependencies, whilst to loosely couple workflow views with control flow dependencies. We introduce a Petri-Net-based state transition approach that binds states of private workflow tasks to their adjacent workflow view-task. On the basis of these communication aspects we develop a CWA for view-based cross-organisational workflow execution. Its concepts are valid for mediated and unmediated interactions and express no choice of a particular technology. The concepts are demonstrated by a scenario, run by two extended workflow management systems. (C) 2004 Elsevier B.V. All rights reserved.

Identification of two evolutionarily conserved and functional regulatory elements in intron 2 of the human BRCA1 gene

Cross-species comparative genomics is a powerful strategy for identifying functional regulatory elements within noncoding DNA. In this paper, comparative analysis of human and mouse intronic sequences in the breast cancer susceptibility gene (BRCA1) revealed two evolutionarily conserved noncoding sequences (CNS) in intron 2, 5 kb downstream of the core BRCA1 promoter. The functionality of these elements was examined using homologous-recombination-based mutagenesis of reporter gene-tagged cosmids incorporating these regions and flanking sequences from the BRCA1 locus. This showed that CNS-1 and CNS-2 have differential transcriptional regulatory activity in epithelial cell lines. Mutation of CNS-1 significantly reduced reporter gene expression to 30% of control levels. Conversely mutation of CNS-2 increased expression to 200% of control levels. Regulation is at the level of transcription and shows promoter specificity. Both elements also specifically bind nuclear proteins in vitro. These studies demonstrate that the combination of comparative genomics and functional analysis is a successful strategy to identify novel regulatory elements and provide the first direct evidence that conserved noncoding sequences in BRCA1 regulate gene expression. (c) 2005 Elsevier Inc. All rights reserved.

Information integration in molecular bioscience

Integrating information in the molecular biosciences involves more than the cross-referencing of sequences or structures. Experimental protocols, results of computational analyses, annotations and links to relevant literature form integral parts of this information, and impart meaning to sequence or structure. In this review, we examine some existing approaches to integrating information in the molecular biosciences. We consider not only technical issues concerning the integration of heterogeneous data sources and the corresponding semantic implications, but also the integration of analytical results. Within the broad range of strategies for integration of data and information, we distinguish between platforms and developments. We discuss two current platforms and six current developments, and identify what we believe to be their strengths and limitations. We identify key unsolved problems in integrating information in the molecular biosciences, and discuss possible strategies for addressing them including semantic integration using ontologies, XML as a data model, and graphical user interfaces as integrative environments.

Predicting functional capacity outcome 12 months after hospitalized injury

Background: There is a recognized need to move from mortality to morbidity outcome predictions following traumatic injury. However, there are few morbidity outcome prediction scoring methods and these fail to incorporate important comorbidities or cofactors. This study aims to develop and evaluate a method that includes such variables. Methods: This was a consecutive case series registered in the Queensland Trauma Registry that consented to a prospective 12-month telephone conducted follow-up study. A multivariable statistical model was developed relating Trauma Registry data to trichotomized 12-month post-injury outcome (categories: no limitations, minor limitations and major limitations). Cross-validation techniques using successive single hold-out samples were then conducted to evaluate the model's predictive capabilities. Results: In total, 619 participated, with 337 (54%) experiencing no limitations, 101 (16%) experiencing minor limitations and 181 (29%) experiencing major limitations 12 months after injury. The final parsimonious multivariable statistical model included whether the injury was in the lower extremity body region, injury severity, age, length of hospital stay, pulse at admission and whether the participant was admitted to an intensive care unit. This model explained 21% of the variability in post-injury outcome. Predictively, 64% of those with no limitations, 18% of those with minor limitations and 37% of those with major limitations were correctly identified. Conclusion: Although carefully developed, this statistical model lacks the predictive power necessary for its use as a basis of a useful prognostic tool. Further research is required to identify variables other than those routinely used in the Trauma Registry to develop a model with the necessary predictive utility.

Formal considerations of rule-based messaging for Business Process Integration

In the last decade, with the expansion of organizational scope and the tendency for outsourcing, there has been an increasing need for Business Process Integration (BPI), understood as the sharing of data and applications among business processes. The research efforts and development paths in BPI pursued by many academic groups and system vendors, targeting heterogeneous system integration, continue to face several conceptual and technological challenges. This article begins with a brief review of major approaches and emerging standards to address BPI. Further, we introduce a rule-driven messaging approach to BPI, which is based on the harmonization of messages in order to compose a new, often cross-organizational process. We will then introduce the design of a temporal first order language (Harmonized Messaging Calculus) that provides the formal foundation for general rules governing the business process execution. Definitions of the language terms, formulae, safety, and expressiveness are introduced and considered in detail.

Kidney side population reveals multilineage potential and renal functional capacity but also cellular heterogeneity

Side population (SP) cells in the adult kidney are proposed to represent a progenitor population. However, the size, origin, phenotype, and potential of the kidney SP has been controversial. In this study, the SP fraction of embryonic and adult kidneys represented 0.1 to 0.2% of the total viable cell population. The immunophenotype and the expression profile of kidney SP cells was distinct from that of bone marrow SP cells, suggesting that they are a resident nonhematopoietic cell population. Affymetrix expression profiling implicated a role for Notch signaling in kidney SP cells and was used to identify markers of kidney SP. Localization by in situ hybridization confirmed a primarily proximal tubule location, supporting the existence of a tubular niche, but also revealed considerable heterogeneity, including the presence of renal macrophages. Adult kidney SP cells demonstrated multilineage differentiation in vitro, whereas microinjection into mouse metanephroi showed that SP cells had a 3.5- to 13-fold greater potential to contribute to developing kidney than non-SP main population cells. However, although reintroduction of SP cells into an Adriamycin-nephropathy model reduced albuminuria:creatinine ratios, this was without significant tubular integration, suggesting a humoral role for SP cells in renal repair. The heterogeneity of the renal SP highlights the need for further fractionation to distinguish the cellular subpopulations that are responsible for the observed multilineage capacity and transdifferentiative and humoral activities.

Signal integration between IFN gamma and TLR signalling pathways in macrophages

Macrophages are major effector cells of the innate immune system, and appropriate regulation of macrophage function requires the integration of multiple signalling inputs derived from the recognition of host factors (e.g. interferon-gamma/IFN gamma) and pathogen products (e.g. toll-like receptor/TLR agonists). The profound effects of IFN gamma pre-treatment (priming) on TLR-induced macrophage activation have long been recognised, but many of the mechanisms underlying the priming phenotype have only recently been identified. This review summarises the known mechanisms of integration between the IFN gamma and TLR signalling pathways. Synergy occurs at multiple levels, ranging from signal recognition to convergence of signals at the promoters of target genes. In particular, the cross-talk between the IFN gamma and LPS and CpG DNA signalling pathways is discussed. (c) 2006 Elsevier GmbH. All rights reserved.

In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation

Load-induced extravascular fluid flow has been postulated to play a role in mechanotransduction of physiological loads at the cellular level. Furthermore, the displaced fluid serves as a carrier for metabolites, nutrients, mineral precursors and osteotropic agents important for cellular activity. We hypothesise that load-induced fluid flow enhances the transport of these key substances, thus helping to regulate cellular activity associated with processes of functional adaptation and remodelling. To test this hypothesis, molecular tracer methods developed previously by our group were applied in vivo to observe and quantify the effects of load-induced fluid flow under four-point-bending loads. Preterminal tracer transport studies were carried out on 24 skeletally mature Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis. Mechanical loading showed a highly significant effect on the number of periosteocytic spaces exhibiting tracer within the cross section of each bone. For all loading rates studied, the concentration of Procion Red tracer was consistently higher in the tibia subjected to pure bending loads than in the unloaded, contralateral tibia, Furthermore, the enhancement of transport was highly site-specific. In bones subjected to pure bending loads, a greater number of periosteocytic spaces exhibited the presence of tracer in the tension band of the cross section than in the compression band; this may reflect the higher strains induced in the tension band compared with the compression band within the mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference between the loaded side and the unloaded contralateral control side decreased with increasing loading frequency. Whether this reflects the length of exposure to the tracer or specific frequency effects cannot be determined by this set of experiments. These in vivo experimental results corroborate those of previous ex vivo and in vitro studies, Strain-related differences in tracer distribution provide support for the hypothesis that load-induced fluid flow plays a regulatory role in processes associated with functional adaptation.