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At least 955 records · Page 53Linked to original sources
PubMed2005

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology.

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation.

Journal Article↗
PubMed2004

Update on genome completion and annotations: Protein Information Resource.

The Protein Information Resource (PIR) recently joined the European Bioinformatics Institute (EBI) and Swiss Institute of Bioinformatics (SIB) to establish UniProt--the Universal Protein Resource--which now unifies the PIR, Swiss-Prot and TrEMBL databases. The PIRSF (SuperFamily) classification system is central to the PIR/UniProt functional annotation of proteins, providing classifications of whole proteins into a network structure to reflect their evolutionary relationships. Data integration and associative studies of protein family, function and structure are supported by the iProClass database, which offers value-added descriptions of all UniProt proteins with highly informative links to more than 50 other databases. The PIR system allows consistent, rich and accurate protein annotation for all investigators.

Animals↗
PubMed2004

Recent translational research: microarray expression profiling of breast cancer--beyond classification and prognostic markers?

Genomic expression profiling has greatly improved our ability to subclassify human breast cancers according to shared molecular characteristics and clinical behavior. The logical next question is whether this technology will be similarly useful for identifying the dominant signaling pathways that drive tumor initiation and progression within each breast cancer subtype. A major challenge will be to integrate data generated from the experimental manipulation of model systems with expression profiles obtained from primary tumors. We highlight some recent progress and discuss several obstacles in the use of expression profiling to identify pathway signatures in human breast cancer.

Animals↗
PubMed2024

Identification and analysis of key genes related to efferocytosis in colorectal cancer.

UNLABELLED: The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. BACKGROUND: It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). METHODS: In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. CONCLUSION: Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.

Humans↗
PubMed2025

Transcriptome sequencing reveals regulatory genes associated with neurogenic hearing loss.

Hearing loss is a prevalent condition with a significant impact on individuals' quality of life. However, comprehensive studies investigating the differential gene expression and regulatory mechanisms associated with hearing loss are lacking, particularly in the context of diverse patient samples. In this study, we integrated data from 10 patients across different regions, age groups, and genders, with their data retrieved from a public transcriptome database, to explore the molecular basis of hearing loss. These samples are mainly from fibroblasts and keratinocytes. Through differential gene expression analysis, we identified key genes, including ICAM1, SLC1A1, and CD24, which have already been shown to play important roles in neurogenic hearing loss. Furthermore, we predicted potential transcriptional regulatory factors that may modulate the expression of these genes. Enrichment analysis revealed biological processes and pathways associated with hearing loss, highlighting the involvement of circadian rhythm disruption and other neuro-related disorders. Although our study is limited by the sample size and the absence of larger-scale investigations, the identified genes and regulatory factors provide valuable insights into the molecular mechanisms underlying hearing loss. Further molecular and cellular experiments are necessary to validate these findings and elucidate the precise regulatory mechanisms involved. In conclusion, our study contributes to the understanding of hearing loss pathogenesis and offers potential targets for molecular diagnostics and gene-based therapies. This provides a foundation for further research into personalized approaches to diagnosing and treating hearing loss.

Humans↗
PubMed2006

GRKs and arrestins: regulators of migration and inflammation.

In the immune system, signaling by G protein-coupled receptors (GPCRs) is crucial for the activity of multiple mediators, including chemokines, leukotrienes, and neurotransmitters. GPCR kinases (GRKs) and arrestins control GPCR signaling by mediating desensitization and thus, regulating further signal propagation through G proteins. Recent evidence suggests that the GRK-arrestin desensitization machinery fulfills a vital role in regulating inflammatory processes. First, GRK/arrestin levels in immune cells are dynamically regulated in response to inflammation. Second, in animals with targeted deletion of GRKs or arrestins, the progression of various acute and chronic inflammatory disorders, including autoimmunity and allergy, is profoundly affected. Third, chemokine receptor signaling in vitro is known to be tightly regulated by the GRK/arrestin machinery, and even small changes in GRK/arrestin expression can have a marked effect on cellular responses to chemokines. This review integrates data about the role of GRKs and arrestins in inflammation, with results on the molecular mechanism of action of GRKs/arrestins, and describes the pivotal role of GRKs/arrestins in inflammatory processes, with a special emphasis on regulation of chemokine responsiveness.

Acute Disease↗
PubMed2005

From organ to molecules: steps and consequences.

The classic cardiac research programs revolved around measurable properties such as pressures, work done, vascular blood flow, electrical propagation, and other such parameters that defined the global heart functions in health and decease. Consistently, the first Henry Goldberg Workshop, held in Haifa in 1984, focused on the interactions between cardiac mechanics, electrical activation, perfusion, and metabolism of the whole heart. Questions focused on the macroscale cardiac function and performance. These studies involved engineering science, simulation, and modeling tools that were essential for the understanding of the complex interactions within the cardiac system. Three-dimensional imaging, ventricular structure, fiber mechanics, circulation and cardiovascular flow, electrical propagation, and blood pumping were all major foci of research at that time. However, it was soon obvious that in order to understand organ level characteristics, one must explore the complex cellular and intracellular control mechanisms; these became the foci of our subsequent workshops. Better understanding of organ level performance required integrated studies of organ and tissue structure and function with genetic, molecular, and cellular characteristics, including cellular communication and ionic and molecular signaling. Analysis of the cardiac system thus depends on continuous probing of the heart system with modern measurement techniques and on integrating data and acquired knowledge with analytical models, constantly evolving to match reality.

Heart↗
PubMed2005

Cultural and ethical issues concerning research on American Indian youth.

A study of American Indian youths illustrates competing pressures between research and ethics. A stakeholder-researcher team developed three plans to protect participants. The first allowed participants to skip potentially upsetting interview sections. The second called for participants to skip potentially upsetting interview sections. The second called for participants flagged for abuse or suicidality to receive referrals, emergency 24-hr clinical backup, or both. The third, based on the community's desire to promote service access, included giving participants a list of service resources. Interviewers gave referrals to participants flagged as having mild problems, and reported participants with serious problems to supervisors for clinical backup. Participants seldom chose to skip sections, so data integrity was not compromised. However, participants did have more problems than expected (e.g., 1 in 3 had thought about suicide, 1 in 5 had attempted suicide, and 1 in 4 reported abuse), so service agencies were not equipped to respond. Researchers must accept the competing pressures and find ethically appropriate compromises that will not undermine research integrity.

Adolescent↗
PubMed2006

Sequelae of child sexual abuse: a child and parent assessment.

We present a case example of a 9-year-old, biracial girl and her mother. We integrate data collected from rating scales (e.g., Child Behavior Checklist; Achenbach & Rescorla, 2001), a free response measure (Thematic Apperception Test; Murray, 1943), and a direct observation measure (Parent-Child Interaction Assessment-II; Holigrocki, Kaminski, & Frieswyk, 1999, 2002) and reveal how a child sexual abuse victim's internal representations and symptoms manifest in both an interpersonal context and in the realm of play. We discuss assessment findings regarding how they provide for an idiographic understanding of the child.

Child↗
PubMed1993

The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system.

Electrical coupling between heart muscle cells is mediated by specialised regions of sarcolemmal interaction termed gap junctions. In previous work, we have demonstrated that connexin42, a recently identified gap-junctional protein, is present in the specialised conduction tissues of the avian heart. In the present study, the spatial distribution of the mammalian homologue of this protein, connexin40, was examined using immunofluorescence, confocal scanning laser microscopy and quantitative digital image analysis in order to determine whether a parallel distribution occurs in rat. Connexin40 was detected by immunofluorescence in all main components of the atrioventricular conduction system including the atrioventricular node, atrioventricular bundle, and Purkinje fibres. Quantitation revealed that levels of connexin40 immunofluorescence increased along the axis of atrioventricular conduction, rising over 10-fold between atrioventricular node and atrioventricular bundle and a further 10-fold between atrioventricular bundle and Purkinje fibres. Connexin40 and connexin43, the principal gap-junctional protein of the mammalian heart, were co-localised within atrioventricular nodal tissues and Purkinje fibres. By applying a novel photobleach/double-labelling protocol, it was demonstrated that connexin40 and connexin43 are co-localised in precisely the same Purkinje fibre myocytes. A model, integrating data on the spatial distribution and relative abundance of connexin40 and connexin43 in the heart, proposes how myocyte-type-specific patterns of connexin isform expression account for the electrical continuity of cardiac atrioventricular conduction.

Animals↗
PubMed1997

Work and power output in the hindlimb muscles of Cuban tree frogs Osteopilus septentrionalis during jumping.

It has been suggested that small frogs use a catapult mechanism to amplify muscle power production during the takeoff phase of jumping. This conclusion was based on an apparent discrepancy between the power available from the hindlimb muscles and that required during takeoff. The present study provides integrated data on muscle contractile properties, morphology and jumping performance that support this conclusion. We show here that the predicted power output during takeoff in Cuban tree frogs Osteopilus septentrionalis exceeds that available from the muscles by at least sevenfold. We consider the sartorius muscle as representative of the bulk of the hindlimb muscles of these animals, because this muscle has properties typical of other hindlimb muscles of small frogs. At 25 degrees C, this muscle has a maximum shortening velocity (Vmax) of 8.77 +/- 0.62 L0 s-1 (where L0 is the muscle length yielding maximum isometric force), a maximum isometric force (P0) of 24.1 +/- 2.3 N cm-2 and a maximum isotonic power output of 230 +/- 9.2 W kg-1 of muscle (mean +/- S.E.M.). In contrast, the power required to accelerate the animal in the longest jumps measured (approximately 1.4 m) is more than 800 W kg-1 of total hindlimb muscle. The peak instantaneous power is expected to be twice this value. These estimates are probably conservative because the muscles that probably power jumping make up only 85% of the total hindlimb muscle mass. The total mechanical work required of the muscles is high (up to 60 J kg-1), but is within the work capacities predicted for vertebrate skeletal muscle. Clearly, a substantial portion of this work must be performed and stored prior to takeoff to account for the high power output during jumping. Interestingly, muscle work output during jumping is temperature-dependent, with greater work being produced at higher temperatures. The thermal dependence of work does not follow from simple muscle properties and instead must reflect the interaction between these properties and the other components of the skeletomuscular system during the propulsive phase of the jump.

Animals↗
PubMed2002

Optical high-precision three-dimensional vision-based quality control of manufactured parts by use of synthetic images and knowledge for image-data evaluation and interpretation.

Vision-based evaluation of industrial workpieces can make efficient use of knowledge-based approaches, in particular for quality control, inspection, and accurate-measurement tasks. A possible approach is to compare real images with conceptual (synthetic) images generated by use of standard computer-aided design models, which include tolerances and take the application-specific conditions into account (e.g., the measured-calibration data). Integrated in (industrial) real-life environments, our evaluation methods have been successfully applied to on-line inspection of manufactured parts including sculptured surfaces, using structured light techniques for the reconstruction of three-dimensional shapes. Accuracies in the range 15-50 microm are routinely achieved by use of either isolated images or spatially registered image sequences.

Journal Article↗
PubMed2005

Design and implementation of dynamic near-infrared optical tomographic imaging instrumentation for simultaneous dual-breast measurements.

Dynamic near-infrared optical tomographic measurement instrumentation capable of simultaneous bilateral breast imaging, having a capability of four source wavelengths and 32 source-detector fibers for each breast, is described. The system records dynamic optical data simultaneously from both breasts, while verifying proper optical fiber contact with the tissue through implementation of automatic schemes for evaluating data integrity. Factors influencing system complexity and performance are discussed, and experimental measurements are provided to demonstrate the repeatability of the instrumentation. Considerations in experimental design are presented, as well as techniques for avoiding undesirable measurement artifacts, given the high sensitivity and dynamic range (1:10(9)) of the system. We present exemplary clinical results comparing the measured physiologic response of a healthy individual and of a subject with breast cancer to a Valsalva maneuver.

Algorithms↗
PubMed1990

Multidimensional digital image representations using generalized Kaiser-Bessel window functions.

Inverse problems that require the solution of integral equations are inherent in a number of indirect imaging applications, such as computerized tomography. Numerical solutions based on discretization of the mathematical model of the imaging process, or on discretization of analytic formulas for iterative inversion of the integral equations, require a discrete representation of an underlying continuous image. This paper describes discrete image representations, in n-dimensional space, that are constructed by the superposition of shifted copies of a rotationally symmetric basis function. The basis function is constructed using a generalization of the Kaiser-Bessel window function of digital signal processing. The generalization of the window function involves going from one dimension to a rotationally symmetric function in n dimensions and going from the zero-order modified Bessel function of the standard window to a function involving the modified Bessel function of order m. Three methods are given for the construction, in n-dimensional space, of basis functions having a specified (finite) number of continuous derivatives, and formulas are derived for the Fourier transform, the x-ray transform, the gradient, and the Laplacian of these basis functions. Properties of the new image representations using these basis functions are discussed, primarily in the context of two-dimensional and three-dimensional image reconstruction from line-integral data by iterative inversion of the x-ray transform. Potential applications to three-dimensional image display are also mentioned.

Fourier Analysis↗
PubMed2006

Assessing systems properties of yeast mitochondria through an interaction map of the organelle.

Mitochondria carry out specialized functions; compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarked measures of protein interactions, a network of mitochondria was constructed in their cellular context, including extra-mitochondrial proteins. This network also integrates data from different organisms to expand the known mitochondrial biology beyond the information in the existing databases. Our network brings together annotated and predicted functions into a single framework. This enabled, for the entire system, a survey of mutant phenotypes, gene regulation, evolution, and disease susceptibility. Furthermore, we experimentally validated the localization of several candidate proteins and derived novel functional contexts for hundreds of uncharacterized proteins. Our network thus advances the understanding of the mitochondrial system in yeast and identifies properties of genes underlying human mitochondrial disorders.

Disease Susceptibility↗
PubMed2006

Presence of the BRAF V600E point mutation in morphologically benign appearing thyroid inclusions of cervical lymph nodes.

The biologic nature of morphologically bland-appearing thyroid inclusions in cervical lymph nodes continues to be a controversial topic. The diagnosis of benignity entails a much more conservative clinical approach than does malignancy. Arriving at the correct interpretation, however, can be difficult when only morphologic examination is performed. Incorporating the use of the recently identified BRAF V600E point mutation, a highly specific biomarker for papillary carcinoma of the thyroid, may provide a useful adjunct in assessing the biologic nature of morphologically bland-appearing thyroid inclusions in cervical lymph nodes. In this case report, bland thyroid inclusions were noted in addition to a primary papillary carcinoma of the thyroid and morphologically recognizable cervical lymph node metastasis. Cells from these separate entities were procured by lasercapture microdissection, and the DNA was isolated, amplified, and sequenced. Molecular analysis provided integral data indicating these morphologically bland thyroid inclusions were malignant, findings not readily apparent by morphologic examination alone.

Adult↗
PubMed2002

Online genomics facilities in the new millennium.

The review begins by providing a brief typology of biological databases on the Internet, illustrated by examples of the most influential resources of each kind. We then take an insider look at one typical on-line genomic resource -- the yeast genome database hosted at the Munich Information Center for Protein Sequences (MIPS) -- and explain how and why it has evolved from a basic sequence repository to a multidomain knowledge base. The role of community efforts in curating and annotating genome data is discussed. The crucial role of data integration and interoperability in developing next-generation genomic facilities is underscored.

Animals↗
PubMed2001

Attentional filtering in the design of electronic map displays: a comparison of color coding, intensity coding, and decluttering techniques.

In a series of experiments color coding, intensity coding, and decluttering were compared in order to assess their potential benefits for accessing information from electronic map displays. Participants viewed electronic battlefield maps containing 5 classes of information discriminable by color or intensity, or, in the decluttering condition, displayed or removed entirely by a key press. Participants were asked questions requiring them to focus on objects within a class (objects presented at the same color or intensity) or to integrate data between objects in different classes (objects presented at different colors and intensities). The results suggested that the benefits of color and intensity coding appear to be in segregating the visual field rather than calling attention to the objects presented at a certain color or intensity. Interactivity proved to be a disadvantage; the time cost of information retrieval outweighed the time benefits of presenting less information on the display or even allowing map users to customize their displays. Potential applications of this research include a cost-benefit analysis for the use of 3 attentional filtering techniques and an attempt to quantitatively measure map complexity.

Analysis of Variance↗