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PubMed1991

Gastric potential difference measurements. The gastric mucosal integrity and function studied with a new method for measurement of the electric potential difference across the stomach wall.

PD--the electric potential difference across the gastric mucosa--is a variable used to describe the gastric mucosal integrity and function. A new, reliable, and easily applied method for gastric PD measurements corrected for the disturbing liquid junction potentials between gastric juice and the PD measuring probe is presented. PD is measured with the gastric lumen negative, and a numeric reduction in PD is used as an expression of an injured mucosal condition. A reduced gastric PD is found along with a reduced gastric mucosal blood flow after intravenous indomethacin in anesthetized dogs. Increasing the FFA/albumin ratios in mini-pigs causes vasoconstriction and PD reduction. Short hypoxia and selective gastric ischemia cause a reversible PD reduction and no morphologic changes in anesthetized dogs, but ischemia for 1 h causes more permanent changes in PD, pH, and morphology. This damage can be reduced by allopurinol pretreatment, possibly due to the inhibition of oxygen-derived free radical formation. Gastric PD and pH were measured in volunteers and duodenal ulcer patients during Stroop's color word conflict test, in which mental stress causes sympathetic activation. A PD reduction and a pH increase were found along with stress induction, thereby indicating an influence of mental stress on stomach mucosal function. It is concluded that gastric PD measurement may be useful in ulcer pathogenetic research, and a sufficient gastric mucosal blood flow is stressed as being important for the mucosal defense.

Animals↗

PubMed1996

The fission yeast pmk1+ gene encodes a novel mitogen-activated protein kinase homolog which regulates cell integrity and functions coordinately with the protein kinase C pathway.

We have isolated a gene, pmk1+, a third mitogen-activated protein kinase (MAPK) gene homolog from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence shows the most homology (63 to 65% identity) to those of budding yeast Saccharomyces Mpk1 and Candida Mkc1. The Pmk1 protein contains phosphorylated tyrosines, and the level of tyrosine phosphorylation was increased in the dsp1 mutant which lacks an attenuating phosphatase for Pmk1. The level of tyrosine phosphorylation appears constant during hypotonic or heat shock treatment. The cells with pmk1 deleted (delta pmk1) are viable but show various defective phenotypes, including cell wall weakness, abnormal cell shape, a cytokinesis defect, and altered sensitivities to cations, such as hypersensitivity to potassium and resistance to sodium. Consistent with a high degree of conservation of amino acid sequence, multicopy plasmids containing the MPK1 gene rescued the defective phenotypes of the delta pmk1 mutant. The frog MAPK gene also suppressed the pmk1 disruptant. The results of genetic analysis indicated that Pmk1 lies on a novel MAPK pathway which does not overlap functionally with the other two MAPK pathways, the Spk1-dependent mating signal pathway and Sty1/Spc1/Phh1-dependent stress-sensing pathway. In Saccharomyces cerevisiae, Mpk1 is involved in cell wall integrity and functions downstream of the protein kinase C homolog. In contrast, in S. pombe, Pmk1 may not act in a linear manner with respect to fission yeast protein kinase C homologs. Interestingly, however, these two pathways are not independent; instead, they regulate cell integrity in a coordinate manner.

Amino Acid Sequence↗

PubMed1984

Quantitative evaluation of the human spermatozoal motility and acrosome reaction in infertile oligozoospermic and fertile euspermic men.

Idiopathic oligozoospermia is one of the most important problems in Andrology, but up to now it is poorly understood because the often routine conventional semen parameters, unquestionably are not directly related to the evaluation of the morphological and functional integrity that determines the spermatozoan fertilizing capacity. A non complex strategy was designed to determine the presence of alterations in the functional integrity of the spermatozoa from infertile men with idiopathic oligozoospermia and from euspermic fertile men, by the quantitative analysis of the spermatozoan motility and the acrosome reaction. There was a lower percentage of acrosome reacted spermatozoa within the semen of the infertile men, accompanied with a significant decrease in the motility percentage, sperm velocity and motility index in comparison with semen from fertile men. These data strongly support a possible detrimental structural and functional integrity of the spermatozoa from the oligozoospermic men.

Acrosome↗

PubMed1990

Morphological evolution of subterranean mammals: integrating structural, functional, and ecological perspectives.

The widely recognized convergence of subterranean mammals offers unique opportunities for the study of patterns, causes and consequences of morphological integration. For example, behavioral and biomechanical observations have revealed a diversity of digging modes among subterranean mammals. In rodents, scratch-digging and chisel-tooth digging, alone or combined, are widespread. This dual nature of the digging apparatus must be understood to avoid erroneous assessments of specializations based on forelimb modifications only. Additionally, bulldozing and disposal of loose soil is performed by head-lifting, by means of the forelimbs, or with the hindlimbs. Insectivores are known to resort to scratch-digging, sand-swimming, or to a unique system known as humeral rotation. Semi-fossorial species among rodents and insectivores are scratch-diggers. In contrast, fully subterranean taxa show further specializations for scratch-digging and/or resort to some of the other digging modes. The ecological correlates of these morphological trends are still poorly known; work in geomyids suggests that scratch-digging specializations are efficient in friable soils, whereas tooth-digging allows the utilization of a much broader spectrum of soil types. This indicates that alternative pathways of morphological specialization are not equivalent in their ecological potentialities. Important morphological features, such as incisor procumbency among tooth-diggers, are shown to be constrained by structural, allometric, and mechanical factors. In geomyids, the same procumbent morphologies may be acquired as a byproduct of size increases, by means of adaptive shifts independent from size, or by a combination of both. Thus, geometric similarity may not be indicative of functional similarity. Further constraints result from the integration of different functions. For instance, it is suggested that mastication imposes limitations upon potential modifications of jaw morphology for tooth-digging. Scratch-digging appears to be less constrained by locomotion, but the effects of integration of various functions in fore- and hind-limbs are largely unexplored. Multiple approaches, combining behavioral, functional, ecological, structural, and phylogenetic data, are necessary for the study of morphological evolution among subterranean mammals.

Animals↗

PubMed2026

TNFα-induced endothelial extracellular vesicles regulate astrocyte function: an integrated transcriptomic and proteomic study.

Endothelial cells and astrocytes are critical structural and functional components of the blood-brain barrier. In many neuroinflammatory diseases, endothelial cells are among the first to respond to inflammatory stimuli and release extracellular vesicles (EVs). However, whether inflammatory stimulation alters EV RNA cargo and subsequently regulates astrocyte function remains unclear. In this study, we performed integrated RNA sequencing and proteomic analyses to investigate the effects of TNFα-stimulated endothelial EVs on astrocytes. RNA profiling revealed significant alterations in EV cargo after TNFα stimulation, including 867 upregulated and 577 downregulated mRNAs, 317 upregulated and 15 downregulated lncRNAs, and 88 upregulated and 62 downregulated miRNAs. The results of functional enrichment analysis suggested that altered EV RNAs may primarily promote inflammatory responses, cell migration, and RNA splicing in astrocytes while reducing their regulatory effects on neuronal projection and calcium homeostasis. Further integrative analysis of EV RNAs and astrocytic proteomics revealed key overlapping targets, including upregulated expression of ICAM1, SOD2, TFPI2, and TNFAIP8, whereas NFKBIA expression was consistently decreased. Network analysis revealed NF-κB as the central regulatory node. Reduced levels of EV-derived NFKBIA mRNA were associated with decreased IκBα protein levels in astrocytes, which promoted NF-κB activation and inflammatory cytokine release. Finally, overexpression of IκBα in astrocytes significantly attenuated TNFα EV-induced IL-1β and IL-6 secretion. Collectively, these findings demonstrate that TNFα-stimulated endothelial EVs coordinately regulate astrocyte function through mRNA, lncRNA, and miRNA cargo and that the IκBα/NF-κB axis may be a key mechanism underlying endothelial EV-mediated inflammatory disruption of the blood-brain barrier.

Astrocytes↗

PubMed2004

TRIP-Br links E2F to novel functions in the regulation of cyclin E expression during cell cycle progression and in the maintenance of genomic stability.

The TRIP-Br family of transcriptional regulators (TRIP-Br1 and TRIP-Br2) has been proposed to function at E2F-responsive promoters to integrate regulatory signals provided by PHD zinc finger- and/or bromodomain-containing transcription factors. To characterize the TRIP-Br "integrator" function(s), we have employed decoy peptides (*Br1 and *Br2) to antagonize the interaction between TRIP-Br1 or TRIP-Br2 and the PHD zinc finger and/or bromodomain of other transcription factors. Antagonism of the TRIP-Br integrator function elicits anti-proliferative effects through the transcriptional downregulation of a subset of E2F-responsive genes in vivo, and induces aberrant cyclin E accumulation, leading to Geminin deregulation and caspase-3-independent cellular sub-diploidization. The observed cyclin E deregulation is attributed to the downregulation of Fbxw7, which encodes the Fbw7 receptor subunit of the SCF(FBW7) ubiquitin ligase (E3) responsible for targeting cyclin E for proteolysis. Fbxw7 is identified herein as an E2F-responsive and TRIP-Br coregulated gene. Our results demonstrate a physiologic role for TRIP-Br in coupling E2F to novel functions in the regulation of cyclin E expression during cell cycle progression to ensure the proper execution of DNA replication and the maintenance of genomic stability.

Caspase 3↗

PubMed2005

Molecular dissection of ARP1 regions required for nuclear migration and cell wall integrity checkpoint functions in Saccharomyces cerevisiae.

The dynactin complex is one of the components required for the regulation of the cell wall integrity checkpoint, which ensures the completion of cell wall remodeling before mitosis. The core of the dynactin complex is a backbone filament composed of monomers of an actin-related protein, Arp1, which is also involved in nuclear migration. To examine the molecular basis for the dual functions of the dynactin core subunit Arp1p in yeast, we constructed 32 mutated arp1 alleles. We assessed the effects of the mutations on cell wall integrity checkpoint and nuclear migration functions and identified four categories of mutants: 1) those showing no change from the wild type; 2) those resulting in a defective cell wall integrity checkpoint but normal nuclear migration; 3) those with a normal cell wall integrity checkpoint but defective nuclear migration; and 4) those defective in both the cell wall integrity checkpoint and nuclear migration functions. Our results show a separation of the two functions in the molecular structure of Arp1p and indicate that a local surface region of Arp1p is important in maintaining the cell wall integrity checkpoint function.

Alleles↗

PubMed2004

Contexts and catalysts: a resolution of the localization and integration of function in the brain.

There has been a historical tension between theories of brain function emphasizing regional specialization and those focusing on integration across regions. This tension continues despite the pervasive use of functional neuroimaging, which enables testing of these theories in the human brain. There are instances of agreement, where regions thought to be critical for a given behavior (e.g., Broca's area and language production) do become more active when a person engages in that behavior. However, a number of disconcerting results have also been found. These include activation in areas not thought to be important for the behavior, and lack of activation in regions thought to be critical for particular behaviors based on studies of the damaged brain. A recently proposed Neural Context hypothesis of brain function provides a mechanism that can reconcile these apparently disparate findings. The hypothesis states that the functional relevance of a brain area depends on the status of other connected areas i.e., the context within which the region is operating. A region can participate in several behaviors through variations in its interactions with other areas. It is possible that certain critical nodes serve as Behavioural Catalysts, enabling the transition between behavioral states, without differential alterations in the measured activity. By virtue of its anatomical connections, an area could facilitate a shift in functional connectivity between one set of regions to another. An imaging study on the changing interregional interactions involving the hippocampus in learning and awareness serves as an example of neural context. In this case, the hippocampus may serve to catalyze the transition to awareness.

Animals↗

PubMed2025

An integrated anatomical, functional and evolutionary view of the Drosophila olfactory system.

The Drosophila melanogaster olfactory system is one of the most intensively studied parts of the nervous system in any animal. Composed of ~60 independent olfactory neuron classes, with several associated hygrosensory and thermosensory pathways, it has been subject to diverse types of experimental analyses. However, synthesizing the available data is limited by the incompleteness and inconsistent nomenclature found in the literature. In this work, we first "complete" the peripheral sensory map through the identification of a previously uncharacterized antennal sensory neuron population expressing Or46aB, and the definition of an exceptional "hybrid" olfactory neuron class comprising functional Or and Ir receptors. Second, we survey developmental, anatomical, connectomic, functional and evolutionary studies to generate an integrated dataset of these sensory neuron pathways - and associated visualizations - creating an unprecedented comprehensive resource. Third, we illustrate the utility of the dataset to reveal relationships between different organizational properties of this sensory system, and the new questions these stimulate. These examples emphasize the power of this resource to promote further understanding of the construction, function and evolution of these neural circuits.

Journal Article↗

PubMed2004

Functional informatics: convergence and integration of automation and bioinformatics.

The biopharmaceutical industry is currently being presented with opportunities to improve research and business efficiency via automation and the integration of various systems. In the examples discussed, industrial high-throughput screening systems are integrated with functional tools and bioinformatics to facilitate target and biomarker identification and validation. These integrative functional approaches generate value-added opportunities by leveraging available automation and information technologies into new applications that are broadly applicable to different types of projects, and by improving the overall research and development and business efficiency via the integration of various systems.

Automation↗

PubMed1991

Integral excitation functions for natKr + p up to 116 MeV and optimization of the production of 81Rb for (81m)Kr generators.

Effective cross-sections for the production of 79,81,81m,82m,83,84,84m,86Rb, (77,79,85m)Kr and 77,82Br in the bombardment of natKr with protons were measured from threshold up to 116 MeV. Thick-target production-rate curves based on the measured integral excitation functions were also derived for 81,82m,83,84,86Rb, and the optimum incident energy for the production of 81Rb/(81m)Kr, as a function of the target thickness in MeV, was determined. Geometry-dependent hybrid-model calculations performed by means of the computer code ALICE/85/300 were found to be in good agreement with the experimental results as well as the derived thick-target production-rate curves.

Krypton Radioisotopes↗

PubMed1983

Membrane integration and function of the three F0 subunits of the ATP synthase of Escherichia coli K12.

Integration into the cytoplasmic membrane and function of the three F0 subunits, a, b and c, of the membrane-bound ATP synthase of Escherichia coli K12 were analysed in situations where synthesis of only one or two types of subunits was possible. This was achieved by combined use of atp mutations and plasmids carrying and expressing one or two of the atp genes coding for ATP synthase subunits. AU three F0 subunits were found to be required for the establishment of efficient H+ conduction. Subunits a and b individually as well as together were found to bind F1 ATPase to the membrane while subunit c did not. The ATPase activity bound to either of these single subunits, or in pairwise combinations, was not inhibited by N,N'-dicyclohexylcarbodiimide. Also ATP-dependent H+ translocation was not catalysed unless all three F0 subunits were present in the membrane. The integration into the membrane of the subunits a and b was independent of the presence of other ATP synthase subunits.

Bacterial Proton-Translocating ATPases↗

PubMed2004

Motor evoked potential monitoring for spinal cord and brain stem surgery.

Intraoperative Neurophysiology (ION) has established itself as one of the means by which modern neurosurgery can improve surgical results while minimizing morbidity. The advent of motor evoked potential (MEP) monitoring represents a landmark in this recent progress. ION consists of monitoring (the continuous "on-line" assessment of the functional integrity of neural pathways) and mapping (the functional identification and preservation of anatomically ambiguous nervous tissue) techniques. In this chapter we have attempted to critically review the evolution of MEP use during monitoring and mapping techniques for neurosurgical procedures in the brainstem and the spinal cord, providing the neurophysiological theoretical background and practical aspects of clinical applications. According to the experience from our and other groups involved in ION, we suggest the following: 1) ION is mandatory whenever neurological complications are expected as predicted by a known pathophysiological mechanism. It is therefore advisable to perform ION when dealing with brain stem and intramedullary spinal cord lesions. 2) MEP monitoring after transcranial electrical stimulation is today a feasible and reliable technique for use under general anesthesia. MEP monitoring is the most appropriate technique to assess the functional integrity of descending motor pathways in the brainstem and, foremost, in the spinal cord. 3) Mapping of the corticospinal tract at the level of the cerebral peduncle as well as mapping of the VII, IX-X and XII cranial nerve motor nuclei on the floor of the fourth ventricle is of great value with which to identify "safe entry zones" into the brainstem. 4) Other techniques, although safe and feasible, still lack rigorous validation in terms of prognostic value and correlation with the postoperative neurological outcome. These techniques include mapping of the corticospinal tract within the spinal cord and monitoring of the corticobulbar tracts. These techniques, however, are expected to open new perspectives in the near future.

Adult↗

PubMed2001

Instanton solutions in the problem of wrinkled flame-front dynamics.

The statistics of the slopes of wrinkling flames propagating through an infinitely wide channel is investigated by the quantum-field-theory methods. We dwell on the WKB approximation in the functional integral, which is analogous to the Wyld functional integral in turbulence. The main contribution to statistics is due to a coupled field-force configuration. This configuration is related to a kink between metastable exact pole solutions of the Sivashinsky equation. These kinks are responsible for both the formation of new cusps and the rapid power-law acceleration of the mean flame front. The problem of asymptotic stability of the solutions is discussed.

Journal Article↗

PubMed2003

Integrating leprosy control into general health service in a war situation: the level after 5 years in eastern Congo.

South Kivu Province of the Democratic Republic of Congo, plagued by a turbulent civil war, started a process of integrating leprosy into general health services in 1995. A questionnaire survey was carried out in September 2000 to assess the level of structural and functional integration, after 5 years of the integration process, in nine of its 14 health districts. The survey revealed that a total of 76 clinic nurses remained of those trained in leprosy since 1993. In all, 33-6% of the total 226 health facilities had a trained nurse, but according to the district supervisors who filled the questionnaires, nurses in only 28.3% of health facilities could diagnose leprosy. Less than 40% of the total 226 health facilities were structurally integrated with MDT and other leprosy services. Functionally, the clinic nurses were involved in dispensing MDT drugs and keeping leprosy records in 90.8 and 81.6%, respectively, of the integrated facilities, and diagnostic activities in 43.7%. The degree of involvement put health facilities into four grades of functional integration: 1) fully-functional integrated, 2) semi-functional integrated, 3) semi-integrated (structural but not functional), 4) not integrated (vertical). On this scale, 80% of 107 health facilities reported by the supervisors had some form of integration and 20% were not integrated. Treatment activities were significantly more functionally integrated than the diagnostic and POD activities, which require more skills. The presence of a trained nurse in a health facility made no significant difference to the involvement of clinic nurses in dispensing MDT drugs and performing POD activities, but significantly affected their performance of diagnostic activities and records keeping. The endemic districts had higher levels of structural integration, were not more likely to be functionally integrated. The levels of structural integration after 5 years are considered low in South Kivu Province, and reflect the significant negative effect of civil conflicts on integration of leprosy programmes in Africa.

Delivery of Health Care, Integrated↗

PubMedDate not supplied

Primary health care teams. Opportunities and challenges in evaluation of service delivery innovations.

Quality of service and corporate productivity may be improved when employees are formed into semi-autonomous teams that are empowered to be innovative in service and are rewarded for attaining performance goals. This article describes the planned staffing and implementation strategies for three models of primary health care teams (HCTs) in a managed care organization (MCO). Implementation of each model focussed on (1) changes to primary care staffing mix (structural integration of roles) and (2) development of teamwork (functional integration of roles). Evidence from other industries suggests that the planned changes to structural and functional integration of existing primary care delivery models could improve system productivity, patient satisfaction, clinical quality, and employee morale. Retrospective evaluations of whether the planned improvements were achieved, and whether these achievements can be attributed to changes in staffing mix or teamwork, are now being conducted. Opportunities and limitations in conducting these retrospective evaluations are discussed, particularly with reference to use of existing data sources. The article concludes with recommendations for evaluation of natural experiments in primary care redesign.

Efficiency, Organizational↗

PubMed1997

Effect of pH and buffering condition on dMPV of three types of platelet concentrates.

Normal platelets display a log normal size distribution pattern when analysed by an automated cell counter. Considerable changes in the platelet size distribution occurs during collection, processing and storage. This is easily monitored by the variation seen in the cellular indices or size distribution patterns. Platelet activation leads to a shift to the right whereas discoid/spheric conversion and microvesiculation/fragmentation are associated to shift to the left. Therefore changes in cellular indices are of value in assessing the dynamic shape changes and aggregation/disaggregation that platelet undergo during storage. We describe here an objective method for measuring platelet functional integrity based on cell counting. Our procedure is simple and based on the measurement of difference (d) of MPV before and after the addition of platelet samples to EDTA (4 ml dry dipotassium EDTA tube), incubating at 22 degrees C for a period of 1 h (for optimisation of shape changes and disaggregation) before counting. Since the platelet functional activity/aggregation states are pH-dependent we have investigated the effect of buffering condition on the functional integrity measured by dMPV. Both the standard and buffered EDTA exposure procedures appear to be suited for monitoring platelet functional integrity/aggregation and activation states but the standard EDTA protocol eliminates the need for pH determination hence is our preferred diagnostic tool, for platelet functional integrity and aggregation states.

Blood Platelets↗

PubMed1997

MedWeaver: integrating decision support, literature searching, and Web exploration using the UMLS Metathesaurus.

Integrating functions from disparate and widely-distributed information systems has been an interest of the medical informatics community for some time. Barriers to progress have included the lack of network-accessible information sources, inadequate methods for inter-system messaging, and lack of vocabulary translation services. With the advent of the World Wide Web (WWW) and the evolution of the National Library of Medicine's Unified Medical Language System (UMLS), it is now possible to develop applications that integrate functions from diverse, distributed systems. In this paper we describe one such system, MedWeaver, a WWW application that integrates functions from a decision support application (DXplain), a literature searching system (WebMedline), and a clinical Web searching system (CliniWeb) using the UMLS Metathesaurus for vocabulary translation. This system demonstrates how application developers can design systems around anticipated clinical information needs and then draw together the needed content and functionality from diverse sources.

Computer Communication Networks↗