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At least 793 records · Page 44Linked to original sources

PubMed2002

Sharp genetic breaks among populations of Haptosquilla pulchella (Stomatopoda) indicate limits to larval transport: patterns, causes, and consequences.

To help stem the precipitous decline of coral reef ecosystems world-wide, conservation efforts are focused on establishing interconnected reserve networks to protect threatened populations. Because many coral reef organisms have a planktonic or pelagic larval dispersal phase, it is critical to understand the patterns of ecological connectivity between reserve populations that result from larval dispersal. We used genetics to infer dispersal patterns among 24 Indo-West Pacific populations of the mantis shrimp, Haptosquilla pulchella. Contrary to predictions of high dispersal facilitated by the strong currents of the Indonesian throughflow, mitochondrial DNA sequences from 393 individuals displayed striking patterns of regional genetic differentiation concordant with ocean basins isolated during periods of lowered sea level. Patterns of genetic structuring indicate that although dispersal within geographical regions with semicontiguous coastlines spanning thousands of kilometres may be common, ecologically meaningful connections can be rare among populations separated by as little as 300 km of open ocean. Strong genetic mosaics in a species with high dispersal potential highlight the utility of genetics for identifying regional patterns of genetic connectivity between marine populations and show that the assumption that ocean currents will provide ecological connectivity among marine populations must be empirically tested in the design of marine reserve networks.

Animals↗

PubMed2005

Maximum likelihood haplotyping for general pedigrees.

Haplotype data is valuable in mapping disease-susceptibility genes in the study of Mendelian and complex diseases. We present algorithms for inferring a most likely haplotype configuration for general pedigrees, implemented in the newest version of the genetic linkage analysis system SUPERLINK. In SUPERLINK, genetic linkage analysis problems are represented internally using Bayesian networks. The use of Bayesian networks enables efficient maximum likelihood haplotyping for more complex pedigrees than was previously possible. Furthermore, to support efficient haplotyping for larger pedigrees, we have also incorporated a novel algorithm for determining a better elimination order for the variables of the Bayesian network. The presented optimization algorithm also improves likelihood computations. We present experimental results for the new algorithms on a variety of real and semiartificial data sets, and use our software to evaluate MCMC approximations for haplotyping.

Algorithms↗

PubMed1998

Approaches to the denominator in practice-based epidemiology: a critical overview.

OBJECTIVES: An accurate knowledge of the population at risk is a fundamental requirement for determining rates and making comparisons in epidemiological research. The major obstacle of studying the epidemiology of sentinel practice networks is the determination of population at risk, in this case, the reference population of medical practices. This article is intended to give a brief overview of major denominator approaches used in practice based epidemiology today, to discuss their underlying assumptions, their strengths and limitations. DESIGN: The literature used in this paper was searched from Medline databases of 1970-1997 using the logical expression "denominator and practice". More literature was identified from the references cited in those articles and from research reports that were available to the authors. MAIN RESULTS: There are various approaches to the denominator at different levels of complexity, which were presented akin to the well known "iceberg phenomenon": with only a small portion of the iceberg visible above the surface, inference as to the size of the invisible part may still be made under certain assumptions. Crude numbers of cases may still reflect trends in the true epidemiology of disease and may be useful for time-series analyses. Differences in the number of network participants over time and across region may be controlled for by using the number of sentinel practices as a denominator. The number of consultations is a first step towards a population-based denominator, reflecting characteristics of both patients and the network. The yearly or quarterly contact group is a true person-based denominator, yet disregarding the population not consulting. The population in practices' catchment areas can be either determined from patient lists or estimated using mathematical models. The ideal denominator is the total population in a geographically defined area, though this information can be directly related to medical practices only in very few countries. CONCLUSIONS: Although a person, or ideally a population-based denominator is desirable, even "lower-level" denominators may be suitable for certain research topics. In countries without patient registration, the estimation of incidences and prevalences has many methodological uncertainties that limit the use of sentinel practice systems. Assuming representativeness, valid analytical or time-series studies, however, can still be carried out even if there is very little information on the population at risk covered by particular medical practices.

Bias↗

PubMed2004

SUSTAIN: a network model of category learning.

SUSTAIN (Supervised and Unsupervised STratified Adaptive Incremental Network) is a model of how humans learn categories from examples. SUSTAIN initially assumes a simple category structure. If simple solutions prove inadequate and SUSTAIN is confronted with a surprising event (e.g., it is told that a bat is a mammal instead of a bird), SUSTAIN recruits an additional cluster to represent the surprising event. Newly recruited clusters are available to explain future events and can themselves evolve into prototypes-attractors-rules. SUSTAIN's discovery of category substructure is affected not only by the structure of the world but by the nature of the learning task and the learner's goals. SUSTAIN successfully extends category learning models to studies of inference learning, unsupervised learning, category construction, and contexts in which identification learning is faster than classification learning.

Humans↗

PubMed2005

A century of GH research revisited: from linear models to network complexity.

The history of GH started with the pioneer clinical and anatomical observations of Pierre Marie, who described the symptoms of acromegaly in 1886. Progressively, histochemical and histophysiological methods made it possible to characterize most cell types responsible for normal or pathological pituitary hormone secretion. Although the methods applied were indirect, and hormonal function assigned to each cell type could only be inferred from correlations, the quality of the corresponding studies was such that most of their results proved correct. In the second half of the XXth century, biochemical methods and bioassays led, between 1943 and 1956, to the production from pituitary extracts of highly purified fractions containing somatotropin activity. The subsequent demonstration that hypothalamo-hypophyseal interactions are of a neurohumoral nature permitted isolation of neuropeptides, a new class of neurotransmitters, many of which turned into major therapeutic agents. Subsequent purification of hundreds of neuropeptides, many with hypophysiotropic activity, and mapping of neurons producing them permitted to shift from relatively simple theories, postulating that stimulatory and inhibitory peptides are sufficient to account for the physiological control of pituitary secretion to more complex models. These permitted to understand how complex neuronal networks can produce a fine tuning of multiple combinations of neuropeptides and neurotransmitters, which interact with each other to adapt hormonal secretion to discrete physiological and pathological conditions.

Animals↗

PubMed2026

Multi-omics identification of therapeutic targets of compound sappan decoction in hepatocellular carcinoma.

BACKGROUND: Compound sappan decoction (CSD) is a multi-herbal traditional Chinese medicine formulation with clinical relevance in hepatocellular carcinoma (HCC). However, its therapeutic mechanisms remain unclear. METHODS: Bioactive compounds of CSD were identified and standardized using pharmacological and chemical databases. Potential targets were predicted via multiple target inference platforms. HCC-related genes were curated from comprehensive disease databases. Summary-data-based Mendelian randomization (SMR) was conducted to infer causal relationships between compound targets and HCC risk using large-scale quantitative trait loci (QTL) datasets and HCC genome-wide association study data. Colocalization analysis, protein-protein interaction (PPI) network construction, and GO/KEGG enrichment were performed on SMR-identified targets. Molecular docking evaluated binding affinities of representative compounds to prioritized targets. RESULTS: A total of 784 overlapping genes between predicted CSD targets and HCC-related genes were subjected to SMR analysis. Among these, 22 targets were significantly associated with HCC risk based on transcriptomic or proteomic QTLs and showed colocalization evidence. Notably, four targets (ADRB2, APOE, SYK, and PGF) were supported by both replication in an independent cohort and strong colocalization. These 22 targets were enriched in apoptosis, PI3K-Akt signaling, redox metabolism, and detoxification pathways. PPI analysis revealed central hubs including MMP9, BCL2, CASP1, and MCL1. Molecular docking demonstrated strong binding of APOE to quercetin, PGF to luteolin-7-olate, and SYK to kaempferol. CONCLUSIONS: CSD may exert therapeutic effects on HCC through modulation of genetically validated targets involved in tumor progression, inflammation, and metabolic reprogramming, supporting its potential clinical utility as an adjunctive treatment strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12672-026-04740-8.

Caesalpinia↗

PubMed1977

Response programming, as assessed by reaction time, does not establish commands for particular muscles.

In previous studies, response programming has been inferred from a relation between reaction time and the nature of the response which follows. However, it has not been clear whether this programming process generates commands for specific muscles or abstract timing networks which can be applied to any appropriate muscle group. Experiment 1 employed the Sternberg (1969) additive-factor method to show that muscle selection need not be completed before such programming begins, a conclusion which is inconsistent with the view that this process establishes commands to previously selected muscles. Experiments 2 and 3 provide converging evidence against the muscle-specific view of programming by showing that advance programming of response timing can occur when the response muscle is not specified. A theoretical framework encompassing these and previous results is proposed.

Journal Article↗

PubMedDate not supplied

Hypothesis testing in evolutionary developmental biology: a case study from insect wings.

Developmental data have the potential to give novel insights into morphological evolution. Because developmental data are time-consuming to obtain, support for hypotheses often rests on data from only a few distantly related species. Similarities between these distantly related species are parsimoniously inferred to represent ancestral aspects of development. However, with limited taxon sampling, ancestral similarities in developmental patterning can be difficult to distinguish from similarities that result from convergent co-option of developmental networks, which appears to be common in developmental evolution. Using a case study from insect wings, we discuss how these competing explanations for similarity can be evaluated. Two kinds of developmental data have recently been used to support the hypothesis that insect wings evolved by modification of limb branches that were present in ancestral arthropods. This support rests on the assumption that aspects of wing development in Drosophila, including similarities to crustacean epipod patterning, are ancestral for winged insects. Testing this assumption requires comparisons of wing development in Drosophila and other winged insects. Here we review data that bear on this assumption, including new data on the functions of wingless and decapentaplegic during appendage allocation in the red flour beetle Tribolium castaneum.

Animals↗

PubMed2003

Relationships between conductivity and local topology in heterocyclic polymer networks.

The low frequency complex dielectric relaxation above the glass transition temperature T(g) for a series of well-characterized heterocyclic polymer networks has been analyzed in terms of the electric moduli formalism. It was established that the contribution of ionic conductivity to the electric modulus can be quantitatively separated from the alpha relaxation by using a combination of two Havriliak-Negami (HN) functions. A strong correlation between the mechanisms of both conductivity and segmental mobility was inferred from the similarity of the shape of the HN function for conductivity relaxation to those for the main relaxation. This correlation is further supported by the similarity of the temperature dependencies of the relevant relaxation times corresponding to both processes. The overwhelming contribution of the preexponents D0 in the Arrhenius behavior of the apparent diffusion coefficients can be explained by considering a model implying decreased mean free paths of the diffusing elements and lower activation entropies of diffusion for polymer networks with higher apparent network densities.

Journal Article↗

PubMed2005

Outlines of an "exploding" network of metabolites generated from the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum.

Degradation of the veterinary fluoroquinolone antibiotic enrofloxacin (EFL) was studied with three strains of Gloeophyllum, basidiomycetous fungi thought to produce extracellular hydroxyl radicals. Metabolites generated in a mineral medium were analyzed by combined high-performance liquid chromatography/high-resolution electrospray ionization mass spectrometry. Their origin was inferred from peak doublets representing 12C and 14C isotopomers detected at a defined proportion. From each exact molecular mass, the molecular formula was derived for which the most probable chemical structure was postulated, using for guidance 18 known EFL metabolites. All supernatants provided similar metabolite patterns, with the most comprehensive consisting of 87 compounds. These metabolites belonged to five families headed by EFL, its oxidatively decarboxylated or defluorinated congeners, an isatin-, and an anthranilic acid-type derivative. Metabolites hydroxylated in the aromatic part suggested the formation of three catechols and two oxidizable ortho-aminophenol-type compounds. After oxidation to the respective ortho-quinones or ortho-quinone imines and oxidative ring cleavage at one of three alternative sites, the formation of various cis,cis-muconic acid-type derivatives is likely, one of which could be detected. Anthranilic acid-type compounds provided two additional sites for ortho-aminophenol formation and aromatic ring cleavage. An "exploding" network of diverse EFL congeners produced by Gloeophyllum suggests the broad utility of our model for studying biodegradation.

Basidiomycota↗

PubMed2005

Nebulon: a system for the inference of functional relationships of gene products from the rearrangement of predicted operons.

Since operons are unstable across Prokaryotes, it has been suggested that perhaps they re-combine in a conservative manner. Thus, genes belonging to a given operon in one genome might re-associate in other genomes revealing functional relationships among gene products. We developed a system to build networks of functional relationships of gene products based on their organization into operons in any available genome. The operon predictions are based on inter-genic distances. Our system can use different kinds of thresholds to accept a functional relationship, either related to the prediction of operons, or to the number of non-redundant genomes that support the associations. We also work by shells, meaning that we decide on the number of linking iterations to allow for the complementation of related gene sets. The method shows high reliability benchmarked against knowledge-bases of functional interactions. We also illustrate the use of Nebulon in finding new members of regulons, and of other functional groups of genes. Operon rearrangements produce thousands of high-quality new interactions per prokaryotic genome, and thousands of confirmations per genome to other predictions, making it another important tool for the inference of functional interactions from genomic context.

Bacterial Proteins↗

PubMed1998

Knowledge acquisition, accessibility, and use in person perception and stereotyping: simulation with a recurrent connectionist network.

Connectionist models contrast in many ways with the symbolic models that have traditionally been applied within social psychology. In this article the authors apply an autoassociative connectionist model originally developed by J. L. McClelland and D. E. Rumelhart (1986) to reproduce several well-replicated and theoretically important phenomena related to person perception and stereotyping. These phenomena are exemplar-based inference, group-based stereotyping, the simultaneous application of several stereotypes to generate emergent characteristics, and the effects of recency and frequency of prior exposures on accessibility (the probability of a representation's use). Though many of these phenomena are explained by current theories in social psychology, the simulation contributes to parsimony and theoretical integration by showing that a single, very simple mechanism can generate them all. The model also predicts a new phenomenon--rapid recovery of accessibility after it has declined to zero.

Computer Simulation↗

PubMed1984

Antibodies to synthetic peptides defined by cDNA cloning reveal a network of peptidergic neurons in Aplysia.

We previously isolated and characterized a cDNA clone specifically expressed in neurons R3 to R8 and R14 of the Aplysia abdominal ganglion (Nambu, J.R., R. Taussig, A.C. Mahon, and R.H. Scheller (1983) Cell 35: 47-56). The cDNA nucleotide sequence and the inferred protein amino acid sequence suggest that this gene encodes the precursor for neuroactive peptides used by these cells. Peptides corresponding to three regions of the precursor were synthesized, coupled to a protein carrier, and used to generate antibodies. These antibodies stain a set of cell bodies, R3 to R14, and their processes in the abdominal ganglion; no other cells in the nervous system or the periphery are immunoreactive. R3 to R14 send numerous fine immunoreactive processes into the vascularized sheath that surrounds the ganglion. Each of these cells also has a large axon which exits the ganglion via the branchial nerve and terminates on the heart. In addition, R14 is anatomically distinct from R3 to R13 in that it sends additional immunoreactive processes to the vasculature near the ganglion. Immunoreactive processes and varicosities were observed on the efferent vein of the gill, the abdominal ganglion artery, and the anterior aorta. These data are consistent with previous studies suggesting that one or more neuropeptides released from R3 to R14 function as modulators of cardiovascular physiology.

Abdomen↗

PubMed1984

Ultrastructure of unit fragments of the skeleton of the human erythrocyte membrane.

We have examined fragments of the filamentous network underlying the human erythrocyte membrane by high-resolution electron microscopy. Networks were released from ghosts by extraction with Triton X-100, freed of extraneous proteins in 1.5 M NaCl, and collected by centrifugation onto a sucrose cushion. These preparations contained primarily protein bands 1 + 2 (spectrin), band 4.1 and band 5 (actin). The networks were partially disassembled by incubation at 37 degrees C in 2 mM NaPi (pH 7), which caused the preferential dissociation of spectrin tetramers to dimers. The fragments so generated were fractionated by gel filtration chromatography and visualized by negative staining with uranyl acetate on fenestrated carbon films. Unit complexes, which sedimented at approximately 40S, contained linear filaments approximately 7-8 nm diam from which several slender and convoluted filaments projected. The linear filaments had a mean length of 52 +/- 17 nm and a serrated profile reminiscent of F-actin. They could be decorated in an arrowhead pattern with S1 fragments of muscle heavy meromyosin which, incidentally, displaced the convoluted filaments. Furthermore, the linear filaments nucleated the polymerization of rabbit muscle G-actin, predominantly but not exclusively from the fast-growing ends. On this basis, we have identified the linear filaments as F-actin; we infer that the convoluted filaments are spectrin. Spectrin molecules were usually attached to actin filaments in clusters that showed a preference for the ends of the F-actin. We also observed free globules up to 15 nm diam, usually associated with three spectrin molecules, which also nucleated actin polymerization; these may be simple junctional complexes of spectrin, actin, and band 4.1. In larger ensembles, spectrin tetramers linked actin filaments and/or globules into irregular arrays. Intact networks were an elaboration of the basic pattern manifested by the fragments. Thus, we have provided ultrastructural evidence that the submembrane skeleton is organized, as widely inferred from less direct information, into short actin filaments linked by multiple tetramers of spectrin clustered at sites of association with band 4.1.

Cell Fractionation↗

PubMed1986

Analysis of elastic and surface tension effects in the lung alveolus using finite element methods.

Displacement method finite element theory is used to examine the structural and elastic properties of the constituent network of elastin and collagen of the alveoli that form the mammalian lung. The role of the surface tension of pulmonary surfactant of the lung is also examined using an area-dependent relationship inferred from experimental studies. The pressure-volume (PV) curves of the resulting model are found to compare favourably with measured pressure-volume curves for whole lungs filled with air (surface tension included) and saline (no surface tension effects).

Animals↗

PubMed2004

The genome sequence of the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough.

Desulfovibrio vulgaris Hildenborough is a model organism for studying the energy metabolism of sulfate-reducing bacteria (SRB) and for understanding the economic impacts of SRB, including biocorrosion of metal infrastructure and bioremediation of toxic metal ions. The 3,570,858 base pair (bp) genome sequence reveals a network of novel c-type cytochromes, connecting multiple periplasmic hydrogenases and formate dehydrogenases, as a key feature of its energy metabolism. The relative arrangement of genes encoding enzymes for energy transduction, together with inferred cellular location of the enzymes, provides a basis for proposing an expansion to the 'hydrogen-cycling' model for increasing energy efficiency in this bacterium. Plasmid-encoded functions include modification of cell surface components, nitrogen fixation and a type-III protein secretion system. This genome sequence represents a substantial step toward the elucidation of pathways for reduction (and bioremediation) of pollutants such as uranium and chromium and offers a new starting point for defining this organism's complex anaerobic respiration.

Desulfovibrio vulgaris↗

PubMed1999

Higher-order probabilistic perceptrons as Bayesian inference engines.

An explicit structural connection is established between the Bayes optimal classifier operating on K binary input variables and a corresponding two-layer perceptron having normalized output activities and couplings from input to output units of all orders up to K. With suitable modification of connection weights and biases, such a higher-order probabilistic perceptron should in principle be able to learn the statistics of the classification problem and match the a posteriori probabilities given by Bayes optimal inference. Specific training algorithms are developed that allow this goal to be approximated in a controlled variational sense. An application to the task of discriminating between stable and unstable nuclides in nuclear physics yields network models with predictive performance comparable to the best that has been achieved with conventional multilayer perceptrons containing only pairwise connections.

Journal Article↗

PubMed1997

Reorganization of a novel vimentin-associated protein in 3T3-L1 cells during adipose conversion.

We have found that the antibody A2, a marker for the capsule of steroidogenic lipid droplets, reacts with an intermediate filament-associated protein, P200, in 3T3-L1 preadipocytes. Supporting evidence came from the colocalization pattern of P200 with vimentin in double label experiments. The association of P200 with vimentin was further confirmed by its copurification with vimentin after high salt extraction and colocalization of these two proteins in high salt-extracted and vinblastine-treated cells. In preadipocytes this protein was distributed on the vimentin filament network. At the early stage of adipose conversion, this protein was found to encircle nascent lipid droplets ranging from 0.1 to 0.2 micron, accompanied with a decreased distribution on the vimentin filament system. This infers a possible translocation of P200 from the vimentin filaments to the droplet surface. Meanwhile, the vimentin filaments remained in a normal distribution in the cytoplasm and were apparently not associated with the nascent droplet. The association of vimentin filaments to droplet surfaces became prominent in lipid droplets larger than 0.2 micron, forming a typical vimentin cage. Immunogold staining also confirmed the translocation of P200 immunoreactivity from the droplet surface to the vimentin cage. The relocation of P200 from the cytoplasmic vimentin filaments to the droplet surface prior to the formation of the vimentin cage, as well as the reorganization of this protein in the vimentin cage, suggests a stabilizing role in the lipid droplet formation and an inducing function of this protein in the formation of the vimentin cage.

3T3 Cells↗