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At least 829 records · Page 46Linked to original sources

PubMed2007

Internet-enabled high-resolution brain mapping and virtual microscopy.

Virtual microscopy involves the conversion of histological sections mounted on glass microscope slides to high-resolution digital images. Virtual microscopy offers several advantages over traditional microscopy, including remote viewing and data sharing, annotation, and various forms of data mining. We describe a method utilizing virtual microscopy for generation of internet-enabled, high-resolution brain maps and atlases. Virtual microscopy-based digital brain atlases have resolutions approaching 100,000 dpi, which exceeds by three or more orders of magnitude resolutions obtainable in conventional print atlases, MRI, and flat-bed scanning. Virtual microscopy-based digital brain atlases are superior to conventional print atlases in five respects: (1) resolution, (2) annotation, (3) interaction, (4) data integration, and (5) data mining. Implementation of virtual microscopy-based digital brain atlases is located at BrainMaps.org, which is based on more than 10 million megapixels (35 terabytes) of scanned images of serial sections of primate and non-primate brains with a resolution of 0.46 microm/pixel (55,000 dpi). The method can be replicated by labs seeking to increase accessibility and sharing of neuroanatomical data. Online tools offer the possibility of visualizing and exploring completely digitized sections of brains at a sub-neuronal level and can facilitate large-scale connectional tracing, histochemical, and stereological analyses.

Animals↗

PubMed2006

Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia).

Chronic fibromyalgia (FM) pain is prevalent (estimated as high as 13%), predominantly affects women, and is associated with a variety of focal pain conditions. Ongoing FM pain is referred to deep tissues and is described as widespread but usually is maximally located within a restricted region such as the shoulders. Palpation of deep tissues reveals an enhanced nociceptive sensitivity that is not restricted to regions of clinical pain. Similarly, psychophysical testing reveals allodynia and hyperalgesia for cutaneous stimulation at locations beyond regions of clinical pain referral. The combination of widely distributed clinical pain and generalized hypersensitivity is highly disabling, but no satisfactory treatment is regularly prescribed. A thorough understanding of mechanisms will likely be required to develop and document adequate therapies. The generalized hypersensitivity associated with FM has focused considerable interest on central (CNS) mechanisms for the disorder. These include central sensitization, central disinhibition and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis. However, the central effects associated with FM can be produced by a peripheral source of pain. Chronic nociceptive input induces central sensitization, magnifying pain, and it activates the HPA and the sympathetic nervous system. Chronic sympathetic activation indirectly sensitizes peripheral nociceptors and sets up a vicious cycle. Thus, it appears that central mechanisms of FM pain are dependent on abnormal peripheral input(s) for development and maintenance of this condition. A substantial literature defines peripheral-CNS-peripheral interactions that are integral to FM pain. These reciprocal actions and related phenomena of relevance to FM pain are reviewed here, leading to suggestions for testing of therapeutic approaches.

Chronic Disease↗

PubMed2026

Digital healthcare solutions in preoperative care: A systematic review.

OBJECTIVE: Active participation in preoperative anesthesia preparation is crucial to ensure safe and efficient care. Compliance with preoperative instructions improves clinical outcomes, enhances patient satisfaction and optimizes use of healthcare resources. As digital communication becomes increasingly integrated into healthcare, interactive digital tools such as smartphone applications and Short Message Service (SMS) reminders may offer a valuable means of engaging patients in their own care. In this review, we evaluated the role of digital tools in guiding patients during their preoperative care pathway for anesthesia. METHODS: Following registration (CRD420250655119), we conducted a systematic review of studies evaluating the use of smartphone applications or SMS reminders designed to support preoperative preparation for anesthesia or procedural sedation in adult patients undergoing elective procedures. The primary outcome was compliance with preoperative instructions. Secondary outcomes included rate of late cancellations, patient satisfaction and cost-effectiveness. Studies were eligible if they reported at least one of these outcomes. RESULTS: Ten studies (1 RCT and 9 observational studies), including 11501 participants, were identified. Compliance with preoperative instructions was assessed in 8 studies, most of which reported higher compliance in patients receiving digital interventions across multiple instruction domains, although statistical significance was not consistently observed. Evidence suggested a beneficial effect on reducing late cancellations and improving patient satisfaction. However, results varied across study designs, and data on cost-effectiveness were limited. CONCLUSIONS: Digital tools for preoperative anesthesia guidance were associated with higher compliance and showed potential reduction of late cancellations and increase of patient satisfaction. However, the current evidence is predominantly observational and heterogeneous, limiting the strength of conclusions. PRACTICAL IMPLICATIONS: With healthcare systems under pressure, digital technologies may offer a scalable and patient-centered care solution to support preoperative anesthesia preparation. Nonetheless, further high-quality research is needed to evaluate their long-term clinical, economic and equity implications.

Humans↗

PubMed2026

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗

PubMed2026

Charting host structural variations in cervical cancer by long-read sequencing pinpoints a functional deletion in PIAS1.

Host structural variations (SVs) are critical in cancer development but their landscape and interaction with HPV integration in cervical carcinogenesis remain unclear. In this study, we performed Nanopore long-read sequencing on five HPV-positive cervical cancer tissues and two cell lines to profile host SVs. We identified thousands of SVs and statistically demonstrated their significant enrichment in genomic windows ±25 to ±50 kb from HPV integration sites. Cross-sample analysis revealed 60 shared SVs, including a recurrent deletion within the PIAS1 gene. Multi-omics integration (Hi-C, H3K27ac ChIP-seq, and TCGA data) showed that this deletion is associated with reduced PIAS1 expression, disruption of local topologically associating domains, advanced pathological tumor stage, and poorer overall survival. Functional assays confirmed that PIAS1 deficiency inhibits cervical cancer cell proliferation and migration. Our findings identify a PIAS1 deletion as a candidate driver event, and underscore the pivotal role of host genomic instability in HPV-associated oncogenesis.

Cervical cancer↗

PubMed1996

Nitroprusside ameliorates lung allograft reperfusion injury.

BACKGROUND: Nitric oxide is believed to play a critical role in the maintenance of vascular integrity through its interaction with neutrophils, platelets, and cellular components of the vessel wall. It has been reported that endogenous nitric oxide level was depressed after ischemia, reperfusion, or both. Furthermore, exogenous as well as endogenous nitric oxide decreases reperfusion-induced vascular dysfunction. We hypothesized that nitroprusside, a potent nitric oxide donor, might enhance lung preservation and reduce posttransplantation lung allograft dysfunction. METHODS: Ten dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction, 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity and wet-to-dry weight ratio were assessed. Group 1 (n = 5) animals received no nitroprusside. In group 2 (n = 5), the donor lung received nitroprusside in the flush solution (10 mg/L) and recipient animals received 0.2 mg/kg just before reperfusion as well as a continuous infusion (0.11 +/- 0.01 mg.kg-1. h-1) during the assessment period. RESULTS: Superior gas exchange and hemodynamics were noted in lungs receiving nitroprusside. Although allograft myeloperoxidase activity and the total amount of fluid suctioned from the allograft were significantly reduced in group 2, protein levels in bronchoalveolar lavage fluid were not statistically different. CONCLUSIONS: Nitroprusside administration in the flush solution and during reperfusion improves lung allograft function and blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. Nitroprusside reduces lung allograft reperfusion injury.

Animals↗

PubMed1994

Automated detection and tracking of individual and clustered cell surface low density lipoprotein receptor molecules.

We have developed a technique to detect, recognize, and track each individual low density lipoprotein receptor (LDL-R) molecule and small receptor clusters on the surface of human skin fibroblasts. Molecular recognition and high precision (30 nm) simultaneous automatic tracking of all of the individual receptors in the cell surface population utilize quantitative time-lapse low light level digital video fluorescence microscopy analyzed by purpose-designed algorithms executed on an image processing work station. The LDL-Rs are labeled with the biologically active, fluorescent LDL derivative dil-LDL. Individual LDL-Rs and unresolved small clusters are identified by measuring the fluorescence power radiated by the sub-resolution fluorescent spots in the image; identification of single particles is ascertained by four independent techniques. An automated tracking routine was developed to track simultaneously, and without user intervention, a multitude of fluorescent particles through a sequence of hundreds of time-lapse image frames. The limitations on tracking precision were found to depend on the signal-to-noise ratio of the tracked particle image and mechanical drift of the microscope system. We describe the methods involved in (i) time-lapse acquisition of the low-light level images, (ii) simultaneous automated tracking of the fluorescent diffraction limited punctate images, (iii) localizing particles with high precision and limitations, and (iv) detecting and identifying single and clustered LDL-Rs. These methods are generally applicable and provide a powerful tool to visualize and measure dynamics and interactions of individual integral membrane proteins on living cell surfaces.

Algorithms↗

PubMed1996

A tethered adhesive particle model of two-dimensional elasticity and its application to the erythrocyte membrane.

A new model of two-dimensional elasticity with application to the erythrocyte membrane is proposed. The system consists of a planar array of self-adhesive particles attached to nearest neighbors with flexible tethers. Stretching from the equilibrium dimension is resisted because force is required to dissociate the particle clusters and to decrease the distribution entropy. Release of the external force is accompanied by a contraction as thermal diffusion randomizes the particles and allows interparticle attachments to form again. Analysis of membrane thermodynamics and mechanics under the two-state particle assumption results in a shear softening stress-strain relation. The shear modulus is found proportional to the square root of the surface density of particles, the interparticle adhesive energy, and is inversely proportional to the tether length. Applied to the erythrocyte membrane under the assumption that band 3 tetramer represents the particle and spectrin the tether, the shear modulus predicted corresponds to the measured value when the interparticle adhesive energy is approximately 4.0-5.9 kT, where kT is the Boltzmann constant multiplied by the temperature. This model suggests a mechanism wherein erythrocyte membrane deformability depends on integral protein homomultimeric interactions and can be modulated from the external surface.

Adhesiveness↗

PubMedDate not supplied

Ionic ligand interactions with the intracellular loop of the sodium-calcium exchanger. Modulation by ATP.

In the last decade, there has been a large increase in the study of the Na(+)/Ca(2+) exchanger due to its implications in physiological and pathophysiological processes at the cell and organ levels. Key areas of these studies have been molecular biology, regulation and physiology-pathophysiology of the exchanger. There are three main types of regulation that take place at the large intracellular loop of the Na(+)/Ca(2+) exchanger: (i) ionic (sodium inactivation, calcium regulation and proton inhibition), (ii) metabolic (ATP as phosphoryl group donor), and (iii) genetic (alternative splicing). This review analyzes the most recent data on the mutual interactions of regulatory ionic ligands (Ca(2+), Na(+), H(+)) and how they are secondarily modulated by MgATP, emphasizing the importance of the binding of Ca(2+) to its regulatory site as an essential requirement for the exchange function. Intracellular protons and sodium inhibit the Na(+)/Ca(2+) exchanger by reducing the apparent affinity of the Ca(i)-regulatory site for Ca(2+). Although the metabolic pathways are different in the mammalian heart (membrane lipids) and squid nerve cells (soluble cytosolic regulatory protein), the final mechanism for the protective effect of MgATP is the same: a reduction of Na(i)(+)-H(i)(+) binding affinities facilitating the attachment of Ca(2+) to its regulatory site. Kinetic models, which partially analyzed some of these ionic and metabolic interactions, can be integrated into a single scheme where the Ca(i)-regulatory site plays a central role.

Adenosine Triphosphate↗

PubMed2005

Computational correlates of consciousness.

Over the past few years numerous proposals have appeared that attempt to characterize consciousness in terms of what could be called its computational correlates: Principles of information processing with which to characterize the differences between conscious and unconscious processing. Proposed computational correlates include architectural specialization (such as the involvement of specific regions of the brain in conscious processing), properties of representations (such as their stability in time or their strength), and properties of specific processes (such as resonance, synchrony, interactivity, or information integration). In exactly the same way as one can engage in a search for the neural correlates of consciousness, one can thus search for the computational correlates of consciousness. The most direct way of doing is to contrast models of conscious versus unconscious information processing. In this paper, I review these developments and illustrate how computational modeling of specific cognitive processes can be useful in exploring and in formulating putative computational principles through which to capture the differences between conscious and unconscious cognition. What can be gained from such approaches to the problem of consciousness is an understanding of the function it plays in information processing and of the mechanisms that subtend it. Here, I suggest that the central function of consciousness is to make it possible for cognitive agents to exert flexible, adaptive control over behavior. From this perspective, consciousness is best characterized as involving (1) a graded continuum defined over quality of representation, such that availability to consciousness and to cognitive control correlates with properties of representation, and (2) the implication of systems of meta-representations.

Cognition↗

PubMed2000

The integration of SPR biosensors with mass spectrometry: possible applications for proteome analysis.

The successful integration of biospecific interaction analysis based on surface plasmon resonance and mass spectrometry produces a powerful technique that couples the benefits of sensitive affinity capture and characterization of binding events with the ability to characterize interacting molecules. A variety of biosensors has been used to capture proteins and peptides biospecifically on sensor surfaces, with subsequent analysis using mass spectrometry. Applying this type of analysis to proteomic studies could lead to ligand and protein-complex identification, and might provide clues leading to the identification of pathways.

Amino Acid Sequence↗

PubMed2000

Evidence for a paracrine role of adrenomedullin in the physiological resetting of aldosterone secretion by rat adrenal zona glomerulosa.

Adrenomedullin (ADM) has been recently found to directly inhibit agonist-stimulated aldosterone secretion by dispersed zona glomerulosa (ZG) cells and to stimulate basal catecholamine release by adrenomedullary fragments. In light of the fact that catecholamines enhance aldosterone secretion acting in a paracrine manner, we have investigated whether these two effects of ADM may interact when the integrity of the adrenal gland is preserved. ADM increased basal aldosterone output by adrenal slices containing a core of adrenal medulla, and the effect was blocked by the beta-adrenoceptor antagonist l-alprenolol. In contrast, ADM evoked a moderate inhibition of K(+)-stimulated aldosterone production, and the blockade was complete in the presence of l-alprenolol. The in vivo bolus injection of ADM did not affect plasma aldosterone concentration (PAC) in rats under basal conditions. Conversely, when rat ZG secretory function was enhanced (by sodium restriction or infusion with angiotensin-II [ANG-II]) or depressed (by sodium loading or infusion with the angiotensin-converting enzyme inhibitor captopril), ADM evoked a sizeable decrease or increase in PAC, respectively. The prolonged infusion with the ADM receptor antagonist ADM(22-52) caused a further enhancement of PAC in sodium-restricted or ANG-II-treated rats, and a further moderate decrease of it in sodium-loaded or captopril-administered animals. RIA showed that ADM plasma concentration did not exceed a concentration of 10(-11) M in any group of animals. Under basal conditions, ADM adrenal content was 1.2-2.0 pmol/g, which may give rise to local concentrations higher than 10(-8) M (i.e. well above the minimal effective ones in vitro). ADM adrenal concentration was markedly increased (from two-fold to three-fold) by both ZG stimulatory and suppressive treatments. Collectively, our findings suggest that in vivo 1) ADM, in addition to directly inhibit aldosterone secretion, may enhance it indirectly by eliciting catecholamine release, the two actions annulling each other under basal conditions; 2) under conditions leading to enhanced aldosterone secretion, the direct inhibitory effect of ADM prevails over the indirect stimulatory one, and the reverse occurs when aldosterone secretion is decreased; and 3) the modulatory action of ADM on the aldosterone secretion has a physiological relevance, endogenous ADM being locally synthesized in adrenals.

Adrenomedullin↗

PubMed1996

Mutual sensitization of ATP and GTP in driving F-actin on the surface-fixed H-meromyosin.

Using an in vitro motility assay on acto-H-meromyosin, we studied the sliding velocity of an actin filament driven by two kinds of H-meromyosin heads: H-meromyosin head with ATP bound (fast motor) and with GTP bound (slow motor). We found a significant increase in the sliding velocity owing to the coexistence of the fast motor and the slow motor. This phenomenon may give an important suggestion with regard to the integration over multiple interactions of H-meromyosin heads along the actin filament.

Actins↗

PubMed1999

Age-related attenuation of stimulated cortical acetylcholine release in basal forebrain-lesioned rats.

In vivo microdialysis was used to measure the effects of partial deafferentation of cortical cholinergic inputs on acetylcholine efflux in young (four to seven months) and aged (24-28 months) male F344/BNNIA rats. Partial deafferentation was produced by bilateral infusions of the immunotoxin 192 immunoglobulin G-saporin (0.56 microg/1.0 microl) or its vehicle solution into the ventral pallidum/substantia innominata region of the basal forebrain. The lesion produced comparable (65%) decreases in basal cortical acetylcholine efflux in young and aged rats. Presentation of a complex environmental stimulus (exposure to darkness/palatable food), in conjunction with the systemic administration of the benzodiazepine receptor weak inverse agonist ZK 93 426, increased cortical acetylcholine efflux in young shams, aged shams and young lesioned rats, but not in aged lesioned rats. Administration of the benzodiazepine receptor partial inverse agonist FG 7142, in the absence of the environmental stimulus, comparably stimulated cortical acetylcholine efflux in young and aged sham rats. FG 7142-induced increases in acetylcholine efflux were attenuated by approximately 50% following partial deafferentation in both young and aged rats. These results suggests that, under certain conditions, ageing potently interacts with the integrity of the cortical cholinergic afferent system. The effects of ageing on cortical cholinergic function may be most potently revealed by experiments assessing age-related limitations in the responsiveness of a partially deafferented cholinergic system to certain behavioral and/or pharmacological stimuli.

Acetylcholine↗

PubMed1994

The acute phase response: general aspects.

The acute phase response in a given individual represents the integrated sum of multiple, separately regulated changes. Although many of these changes commonly occur together in affected individuals, clinical experience indicates that not all of them occur in all individuals, indicating that they must be individually regulated. For example, febrile patients may have normal blood levels of CRP and vice versa, leukocytosis does not always accompany other acute phase phenomena, and many instances of discordance between levels of the various acute phase proteins are seen. Cytokines function as part of a complex regulatory network, a signalling language in which information is conveyed to cells by combinations, and perhaps sequence, of intercellular messenger molecules. The effects of combinations of cytokines are complex. To use a somewhat crude simile, individual cytokines can be thought of as words which bear informational content and which may, on occasion, communicate a complete message. More commonly, however, the actual messages received by cells probably resemble sentences, in which combinations and sequences of words convey information. Currently available data suggest that hepatocytes receive a complex mixture of humoral or paracrine signals during the acute phase response. These are integrated by multiple interacting signal transducing mechanisms to cause finely regulated changes in plasma protein synthesis. Regulation largely occurs by transcriptional control, but post-transcriptional mechanisms, including translational regulation, may also participate. Both the extracellular and intracellular mechanisms that mediate the response of the hepatocyte to inflammatory stimuli appear to be highly complex and involve multiple overlapping, concurrent and parallel pathways. Enough is known at present to conclude that IL-6 is a major participant in these plasma protein changes. Regulation of non-hepatocyte acute phase phenomena has not been delineated as thoroughly, but clearly involves a number of inflammation-associated cytokines.

Acute-Phase Proteins↗

PubMed2001

A neuron-glia signalling network in the active brain.

Glial cells are active partners of neurons in processing information and synaptic integration. They receive coded signals from synapses and elaborate modulatory responses. The active properties of glia, including long-range signalling and regulated transmitter release, are beginning to be elucidated. Recent insights suggest that the active brain should no longer be regarded as a circuitry of neuronal contacts, but as an integrated network of interactive neurons and glia.

Action Potentials↗

PubMedDate not supplied

Estrogen and progesterone receptors: an overview from the year 2000.

Our current understanding of the steroid/thyroid superfamily of ligand-dependent nuclear transcription factors now involves specific domains for steroid ligand binding, receptor homo- and heterodimer formation, the association of transcription mediators or adaptors that activate, repress, or integrate competing influences, interaction with the hormone response element, transcription modulation based on the components of the transcriptional complex, and intracellular trafficking. Various ligands, including selective hormone receptor modulators, interact with transcriptional mediators in both ligand- and tissue-specific manners, thus multiplying the variety and complexity of interactions substantially. Transcriptional mediators, selective hormone receptor modulators, and varying isoforms of nuclear receptors and their tissue-specific interactions will be a major focus of research in the future. This symposium assembles many of the investigators presently elucidating our understanding of nuclear receptors as we move into the next millennium.

Animals↗

PubMed2002

bZIP transcription factors in Arabidopsis.

In plants, basic region/leucine zipper motif (bZIP) transcription factors regulate processes including pathogen defence, light and stress signalling, seed maturation and flower development. The Arabidopsis genome sequence contains 75 distinct members of the bZIP family, of which approximately 50 are not described in the literature. Using common domains, the AtbZIP family can be subdivided into ten groups. Here, we review the available data on bZIP functions in the context of subgroup membership and discuss the interacting proteins. This integration is essential for a complete functional characterization of bZIP transcription factors in plants, and to identify functional redundancies among AtbZIP factors.

Arabidopsis↗