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At least 487 records · Page 27Linked to original sources
PubMed2005

Culture of melanoma cells in 3-dimensional architectures results in impaired immunorecognition by cytotoxic T lymphocytes specific for Melan-A/MART-1 tumor-associated antigen.

OBJECTIVE: To assess the effects of the culture of melanoma cells in 3-dimensional (3D) architectures on their immunorecognition by cytotoxic T lymphocytes (CTLs) specific for tumor-associated antigens. SUMMARY BACKGROUND DATA: Growth in 3D architectures has been shown to promote the resistance of cancers to treatment with drugs, cytokines, or irradiation, thereby potentially playing an important role in tumor expansion. We investigated the effects of 3D culture on the recognition of melanoma cells by antigen-specific HLA class I-restricted CTLs. METHODS: Culture of HBL melanoma cells expressing Melan-A/Mart-1 tumor-associated antigen and HLA-A0201 on poly-2-hydroxyethyl methacrylate (polyHEMA)-coated plates resulted in the generation of aggregates of 400- to 500-microm diameters containing on average 30,000 cells and characterized by slower proliferation, as compared with monolayer (2-dimensional) cultures. HLA-A0201 restricted Melan-A/Mart-127-35-specific CTL clones were used to evaluate tumor cell immunorecognition measured as specific IFN-gamma production. Comparative gene and protein expression in 2D and 3D cultures was studied by real-time PCR and flow cytometry, respectively. Overall differences in gene expression profiles between 2D and 3D cultures were evaluated by high-density oligonucleotide array hybridization. RESULTS: HLA-A0201 restricted Melan-A/Mart-127-35 specific CTL clones produced high amounts of IFN-gamma upon short-term (4-24 hours) coincubation with HBL cells cultured in 2D but not in 3D, thus suggesting altered antigen recognition. Indeed, Melan-A/Mart-1 expression, at both gene and protein levels, was significantly decreased in 3D as compared with 2D cultures. Concomitantly, a parallel decrease of HLA class I molecule expression was also observed. Differential gene profiling studies on HBL cells showed an increased expression of genes encoding molecules involved in intercellular adhesion, such as junctional adhesion molecule 2 and cadherin-like 1 (>20- and 8-fold up-regulated, respectively) in 3D as compared with 2D cultures. CONCLUSIONS: Taken together, our data suggest that mere growth of melanoma cells in 3D architectures, in the absence of immunoselective pressure, may result in defective recognition by tumor-associated antigen-specific CTL.

Analysis of Variance↗
PubMed2026

Shared genetic architecture of obesity and gastroesophageal reflux disease.

Obesity is identified as a risk factor of gastroesophageal reflux disease (GERD). This study aims to elucidate the shared genetic architecture of obesity-related phenotypes and GERD. Based on the publicly available genome-wide association studies' datasets, this genome-wide pleiotropic association study was conducted with various genetic approaches (including linkage disequilibrium score regression, high-definition likelihood inference for genetic correlations, pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation, Bayesian colocalization, summary-based Mendelian randomization, and multi-marker analysis of genomic annotation analysis) sequentially to unravel the genetic associations from single-nucleotide polymorphism to gene levels, and to reveal the underlying shared genetic architecture between obesity-related phenotypes and GERD. This study discovered shared genetic mechanisms between GERD and several obesity-related phenotypes, including arm fat percentage (left), arm fat percentage (right), leg fat percentage (left), leg fat percentage (right), trunk fat percentage, waist-to-hip ratio, and body mass index. Significant genetic correlations were observed by linkage disequilibrium score regression and high-definition likelihood inference for genetic correlations, with multiple associated pleiotropic loci and their mapped genes identified by pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation, Bayesian colocalization, summary-based Mendelian randomization, and multi-marker analysis of genomic annotation analysis. Additionally, several brain tissues were identified to be linked to both obesity and GERD by multi-marker analysis of genomic annotation. This research provided strong evidence of genetic correlations and brought novel insights into the underlying genetic connections and shared genetic architectures of obesity and GERD.

Humans↗
PubMed2005

Examining the architecture of cellular computing through a comparative study with a computer.

The computer and the cell both use information embedded in simple coding, the binary software code and the quadruple genomic code, respectively, to support system operations. A comparative examination of their system architecture as well as their information storage and utilization schemes is performed. On top of the code, both systems display a modular, multi-layered architecture, which, in the case of a computer, arises from human engineering efforts through a combination of hardware implementation and software abstraction. Using the computer as a reference system, a simplistic mapping of the architectural components between the two is easily detected. This comparison also reveals that a cell abolishes the software-hardware barrier through genomic encoding for the constituents of the biochemical network, a cell's "hardware" equivalent to the computer central processing unit (CPU). The information loading (gene expression) process acts as a major determinant of the encoded constituent's abundance, which, in turn, often determines the "bandwidth" of a biochemical pathway. Cellular processes are implemented in biochemical pathways in parallel manners. In a computer, on the other hand, the software provides only instructions and data for the CPU. A process represents just sequentially ordered actions by the CPU and only virtual parallelism can be implemented through CPU time-sharing. Whereas process management in a computer may simply mean job scheduling, coordinating pathway bandwidth through the gene expression machinery represents a major process management scheme in a cell. In summary, a cell can be viewed as a super-parallel computer, which computes through controlled hardware composition. While we have, at best, a very fragmented understanding of cellular operation, we have a thorough understanding of the computer throughout the engineering process. The potential utilization of this knowledge to the benefit of systems biology is discussed.

Cell Physiological Phenomena↗
PubMed2006

Division of labour and colony efficiency in social insects: effects of interactions between genetic architecture, colony kin structure and rate of perturbations.

The efficiency of social insect colonies critically depends on their ability to efficiently allocate workers to the various tasks which need to be performed. While numerous models have investigated the mechanisms allowing an efficient colony response to external changes in the environment and internal perturbations, little attention has been devoted to the genetic architecture underlying task specialization. We used artificial evolution to compare the performances of three simple genetic architectures underlying within-colony variation in response thresholds of workers to five tasks. In the 'deterministic mapping' system, the thresholds of individuals for each of the five tasks is strictly genetically determined. In the second genetic architecture ('probabilistic mapping'), the genes only influence the probability of engaging in one of the tasks. Finally, in the 'dynamic mapping' system, the propensity of workers to engage in one of the five tasks depends not only on their own genotype, but also on the behavioural phenotypes of other colony members. We found that the deterministic mapping system performed well only when colonies consisted of unrelated individuals and were not subjected to perturbations in task allocation. The probabilistic mapping system performed well for colonies of related and unrelated individuals when there were no perturbations. Finally, the dynamic mapping system performed well under all conditions and was much more efficient than the two other mapping systems when there were perturbations. Overall, our simulations reveal that the type of mapping between genotype and individual behaviour greatly influences the dynamics of task specialization and colony productivity. Our simulations also reveal complex interactions between the mode of mapping, level of within-colony relatedness and risk of colony perturbations.

Animals↗
PubMed1992

Modelling mechanically stable muscle architectures.

This paper presents a planar architectural model for an activated skeletal muscle, with mechanical equilibrium throughout the muscle belly. The model can predict the shape of the muscle fibres and tendinous sheets as well as the internal pressure distribution in the central longitudinal plane (perpendicular to the tendinous sheets) of uni- and bipennate muscle bellies. Mechanically stable solutions for muscle architectures were calculated by equating the pressure developed by curved muscle fibres with the pressure under a curved tendinous sheet. The pressure distribution under a tendinous sheet is determined by its tension, its curvature and the tensile stress of the attached muscle fibres. Dissections showed a good resemblance of the architecture of embalmed muscles with those from our simulations. Calculated maximum pressures are in the same order of magnitude as pressure measurements from the literature. Our model predicts that intramuscular blood flow can be blocked during sustained contraction, as several experimental studies have indeed demonstrated. The volume fractions of muscle fibres and interfibre space in the muscle belly were also calculated. The planar models predict a too low volume fraction for the muscle fibres (about 45% for the bipennate models with a straight central aponeurosis, and about 60% for the simulated unipennate muscle). It is discussed how, in a real muscle, this volume problem can be solved by a special three-dimensional arrangement of muscle fibres in combination with varying widths of the tendinous sheets.

Animals↗
PubMed2005

Relating connectional architecture to grey matter function using diffusion imaging.

Understanding brain function in terms of connectional architecture is a major goal of neuroimaging. However, direct investigation of the influence of brain circuitry on function has been hindered by the lack of a technique for exploring anatomical connectivity in the in vivo brain. Recent advances in magnetic resonance diffusion imaging have given scientists access to data relating to local white matter architecture and, for the first time, have raised the possibility of in vivo investigations into brain circuitry. This review investigates whether diffusion imaging may be used to identify regions of grey matter that are distinct in their connectional architecture, and whether these connectional differences are reflected either in local cytoarchitecture or in local grey matter function. Establishing a direct relationship between regional boundaries based on diffusion imaging and borders between regions that perform different functions would not only be of great significance when interpreting functional results, but would also provide a first step towards the validation of diffusion-based anatomical connectivity studies.

Brain↗
PubMed2004

Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes.

Recent analysis of genome rearrangements in human and mouse genomes revealed evidence for more rearrangements than thought previously and shed light on previously unknown features of mammalian evolution, like breakpoint reuse and numerous microrearrangements. However, two-way analysis cannot reveal the genomic architecture of ancestral mammals or assign rearrangement events to different lineages. Thus, the "original synteny" problem introduced by Nadeau and Sankoff previously, remains unsolved, as at least three mammalian genomes are required to derive the ancestral mammalian karyotype. We show that availability of the rat genome allows one to reconstruct a putative genomic architecture of the ancestral murid rodent genome. This reconstruction suggests that this ancestral genome retained many previously postulated chromosome associations in the placental ancestor and reveals others that were beyond the resolution of cytogenetic, radiation hybrid mapping, and chromosome painting techniques. Three-way analysis of rearrangements leads to a reliable reconstruction of the genomic architecture of specific regions in the murid ancestor, including the X chromosome, and for the first time allows one to assign major rearrangement events to one of human, mouse, and rat lineages. Our analysis implies that the rate of rearrangements is much higher in murid rodents than in the human lineage and confirms the existence of rearrangement hot-spots in all three lineages.

Algorithms↗
PubMed2004

Serial segmental duplications during primate evolution result in complex human genome architecture.

The human genome is particularly rich in low-copy repeats (LCRs) or segmental duplications (5%-10%), and this characteristic likely distinguishes us from lower mammals such as rodents. How and why the complex human genome architecture consisting of multiple LCRs has evolved remains an open question. Using molecular and computational analyses of human and primate genomic regions, we analyzed the structure and evolution of LCRs that resulted in complex architectural features of the human genome in proximal 17p. We found that multiple LCRs of different origins are situated adjacent to one another, whereas each LCR changed at different time points between >25 to 3-7 million years ago (Mya) during primate evolution. Evolutionary studies in primates suggested communication between the LCRs by gene conversion. The DNA transposable element MER1-Charlie3 and retroviral ERVL elements were identified at the breakpoint of the t(4;19) chromosome translocation in Gorilla gorilla, suggesting a potential role for transpositions in evolution of the primate genome. Thus, a series of consecutive segmental duplication events during primate evolution resulted in complex genome architecture in proximal 17p. Some of the more recent events led to the formation of novel genes that in human are expressed primarily in the brain. Our observations support the contention that serial segmental duplication events might have orchestrated primate evolution by the generation of novel fusion/fission genes as well as potentially by genomic inversions associated with decreased recombination rates facilitating gene divergence.

Animals↗
PubMed2002

CDART: protein homology by domain architecture.

The Conserved Domain Architecture Retrieval Tool (CDART) performs similarity searches of the NCBI Entrez Protein Database based on domain architecture, defined as the sequential order of conserved domains in proteins. The algorithm finds protein similarities across significant evolutionary distances using sensitive protein domain profiles rather than by direct sequence similarity. Proteins similar to a query protein are grouped and scored by architecture. Relying on domain profiles allows CDART to be fast, and, because it relies on annotated functional domains, informative. Domain profiles are derived from several collections of domain definitions that include functional annotation. Searches can be further refined by taxonomy and by selecting domains of interest. CDART is available at http://www.ncbi.nlm.nih.gov/Structure/lexington/lexington.cgi.

BRCA1 Protein↗
PubMed2004

Comparative architectures of mammalian and chicken genomes reveal highly variable rates of genomic rearrangements across different lineages.

Molecular evolution studies are usually based on the analysis of individual genes and thus reflect only small-range variations in genomic sequences. A complementary approach is to study the evolutionary history of rearrangements in entire genomes based on the analysis of gene orders. The progress in whole genome sequencing provides an unprecedented level of detailed sequence data to infer genome rearrangements through comparative approaches. The comparative analysis of recently sequenced rodent genomes with the human genome revealed evidence for a larger number of rearrangements than previously thought and led to the reconstruction of the putative genomic architecture of the murid rodent ancestor, while the architecture of the ancestral mammalian genome and the rate of rearrangements in the human lineage remained unknown. Sequencing the chicken genome provides an opportunity to reconstruct the architecture of the ancestral mammalian genome by using chicken as an outgroup. Our analysis reveals a very low rate of rearrangements and, in particular, interchromosomal rearrangements in chicken, in the early mammalian ancestor, or in both. The suggested number of interchromosomal rearrangements between the mammalian ancestor and chicken, during an estimated 500 million years of evolution, only slightly exceeds the number of interchromosomal rearrangements that happened in the mouse lineage, over the course of about 87 million years.

Animals↗
PubMed2005

Interaction of auxin and ERECTA in elaborating Arabidopsis inflorescence architecture revealed by the activation tagging of a new member of the YUCCA family putative flavin monooxygenases.

The aboveground body of higher plants has a modular structure of repeating units, or phytomers. As such, the position, size, and shape of the individual phytomer dictate the plant architecture. The Arabidopsis (Arabidopsis thaliana) ERECTA (ER) gene regulates the inflorescence architecture by affecting elongation of the internode and pedicels, as well as the shape of lateral organs. A large-scale activation-tagging genetic screen was conducted in Arabidopsis to identify novel genes and pathways that interact with the ER locus. A dominant mutant, super1-D, was isolated as a nearly complete suppressor of a partial loss-of-function allele er-103. We found that SUPER1 encodes YUCCA5, a novel member of the YUCCA family of flavin monooxygenases. The activation tagging of YUCCA5 conferred increased levels of free indole acetic acid, increased auxin response, and mild phenotypic characteristics of auxin overproducers, such as elongated hypocotyls, epinastic cotyledons, and narrow leaves. Both genetic and cellular analyses indicate that auxin and the ER pathway regulate cell division and cell expansion in a largely independent but overlapping manner during elaboration of inflorescence architecture.

Amino Acid Sequence↗
PubMed2001

Phosphate availability regulates root system architecture in Arabidopsis.

Plant root systems are highly plastic in their development and can adapt their architecture in response to the prevailing environmental conditions. One important parameter is the availability of phosphate, which is highly immobile in soil such that the arrangement of roots within the soil will profoundly affect the ability of the plant to acquire this essential nutrient. Consistent with this, the availability of phosphate was found to have a marked effect on the root system architecture of Arabidopsis. Low phosphate availability favored lateral root growth over primary root growth, through increased lateral root density and length, and reduced primary root growth mediated by reduced cell elongation. The ability of the root system to respond to phosphate availability was found to be independent of sucrose supply and auxin signaling. In contrast, shoot phosphate status was found to influence the root system architecture response to phosphate availability.

Arabidopsis↗
PubMed2002

KNAT1 and ERECTA regulate inflorescence architecture in Arabidopsis.

Plant architecture is dictated by morphogenetic factors that specify the number and symmetry of lateral organs as well as their positions relative to the primary axis. Mutants defective in the patterning of leaves and floral organs have provided new insights on the signaling pathways involved, but there is comparatively little information regarding aspects of the patterning of stems, which play a dominant role in architecture. To this end, we have characterized five alleles of the brevipedicellus mutant of Arabidopsis, which exhibits reduced internode and pedicel lengths, bends at nodes, and downward-oriented flowers and siliques. Bends in stems correlate with a loss of chlorenchyma tissue at the node adjacent to lateral organs and in the abaxial regions of pedicels. A stripe of achlorophyllous tissue extends basipetally from each node and is positioned over the vasculature that services the corresponding lateral organ. Map-based cloning and complementation studies revealed that a null mutation in the KNAT1 homeobox gene is responsible for these pleiotropic phenotypes. Our observation that wild-type Arabidopsis plants also downregulate chlorenchyma development adjacent to lateral organs leads us to propose that KNAT1 and ERECTA are required to restrict the action of an asymmetrically localized, vasculature-associated chlorenchyma repressor at the nodes. Our data indicate that it is feasible to alter the architecture of ornamental and crop plants by manipulating these genetically defined pathways.

Alleles↗
PubMed2005

Minimal-memory bit-vector architecture for computational mathematical morphology using subspace projections.

Computational mathematical morphology (CMM) is a nonlinear filter representation particularly amenable to real-time image processing. A windowed, translation-invariant filter is represented by a set of less-than-or-equal decisions that are executed by a parallel arrangement of comparators. In the state-of-the-art implementation, each pixel value of a windowed observation is indexed into separate lookup tables to retrieve a set of bit vectors which are "anded" together to produce a bit vector with a unique nonzero bit. The position of that bit is used to look up a filter value in a table. The number of stored bit vectors is proportional to the number of image gray levels. An architecture for CMM is presented that uses a minimal number of bit vectors so that required memory is less sensitive to the number of gray levels. The number of pixels in the observation window is the dimension of the image space. In the proposed architecure, basis elements are projected to subspaces of the image space and only bit vectors unique to each subspace are stored. Each projection corresponds to a subspace partition. Filter memory is greatly reduced by using intermediate lookup tables to map observations to unique bit vectors. We investigate two possible projection strategies: A fixed, singleton architecture, in which each subspace is one dimension, and a minimal architecture, in which a large number of subspace projections are searched for, one with minimal memory. Insensitivity to the number of gray levels is demonstrated through simulated, random-image space tessellations. We also present memory savings in a digital photocopier application.

Algorithms↗
PubMed2005

A new architecture for digital stochastic pulse-mode neurons based on the voting circuit.

This paper presents a new kind of architecture for artificial digital neurons based on the voting circuit, which may be considered an improved version of those presented in literature. Stochastic pulse modulation has been used, where the values of the neuron's inputs are coded in terms of bit probabilities. The resulting activation function closely resembles the logistic sigmoid, with a transition slope that can be selected at the architectural level with no additional hardware requirements. The proposed neuron architecture has been simulated in software. Simulation results confirm that the neuron features a sigmoid transfer characteristic similar to that of conventional voting circuits. The resource occupation of the neuron, as obtained from implementation on reconfigurable platforms, has been estimated to be significantly lower than previous implementations. The theoretical analysis of the neuron's behavior is also presented.

Algorithms↗
PubMed2006

Control architecture for human-robot integration: application to a robotic wheelchair.

Completely autonomous performance of a mobile robot within noncontrolled and dynamic environments is not possible yet due to different reasons including environment uncertainty, sensor/software robustness, limited robotic abilities, etc. But in assistant applications in which a human is always present, she/he can make up for the lack of robot autonomy by helping it when needed. In this paper, the authors propose human-robot integration as a mechanism to augment/improve the robot autonomy in daily scenarios. Through the human-robot-integration concept, the authors take a further step in the typical human-robot relation, since they consider her/him as a constituent part of the human-robot system, which takes full advantage of the sum of their abilities. In order to materialize this human integration into the system, they present a control architecture, called architecture for human-robot integration, which enables her/him from a high decisional level, i.e., deliberating a plan, to a physical low level, i.e., opening a door. The presented control architecture has been implemented to test the human-robot integration on a real robotic application. In particular, several real experiences have been conducted on a robotic wheelchair aimed to provide mobility to elderly people.

Artificial Intelligence↗
PubMedDate not supplied

A network architecture supporting consistent rich behavior in collaborative interactive applications.

Network architectures for collaborative virtual reality have traditionally been dominated by client-server and peer-to-peer approaches, with peer-to-peer strategies typically being favored where minimizing latency is a priority, and client-server where consistency is key. With increasingly sophisticated behavior models and the demand for better support for haptics, we argue that neither approach provides sufficient support for these scenarios and, thus, a hybrid architecture is required. We discuss the relative performance of different distribution strategies in the face of real network conditions and illustrate the problems they face. Finally, we present an architecture that successfully meets many of these challenges and demonstrate its use in a distributed virtual prototyping application which supports simultaneous collaboration for assembly, maintenance, and training applications utilizing haptics.

Communication↗
PubMed2006

Repeat protein architectures predicted by a continuum representation of fold space.

It is an open question whether nature has utilized all possible protein folds. For a simple protein architecture, the helical repeats, we report a method to address this question based on a mapping between the set of repetitive curves and a space of parameters specifying the curve. The exploration of the parameter space for a particular architecture enables a systematic exploration of the fold space for that protein architecture. In a planar subspace of the parameter space of helical repeats we have identified points corresponding to both naturally occurring folds and potential folds not observed so far.

Algorithms↗