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PubMed2006

MANET: tracing evolution of protein architecture in metabolic networks.

BACKGROUND: Cellular metabolism can be characterized by networks of enzymatic reactions and transport processes capable of supporting cellular life. Our aim is to find evolutionary patterns and processes embedded in the architecture and function of modern metabolism, using information derived from structural genomics. DESCRIPTION: The Molecular Ancestry Network (MANET) project traces evolution of protein architecture in biomolecular networks. We describe metabolic MANET, a database that links information in the Structural Classification of Proteins (SCOP), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and phylogenetic reconstructions depicting the evolution of protein fold architecture. Metabolic MANET literally 'paints' the ancestries of enzymes derived from rooted phylogenomic trees directly onto over one hundred metabolic subnetworks, enabling the study of evolutionary patterns at global and local levels. An initial analysis of painted subnetworks reveals widespread enzymatic recruitment and an early origin of amino acid metabolism. CONCLUSION: MANET maps evolutionary relationships directly and globally onto biological networks, and can generate and test hypotheses related to evolution of metabolism. We anticipate its use in the study of other networks, such as signaling and other protein-protein interaction networks.

Computer Graphics↗
PubMed2006

Flexible promoter architecture requirements for coactivator recruitment.

BACKGROUND: The spatial organization of transcription factor binding sites in regulatory DNA, and the composition of intersite sequences, influences the assembly of the multiprotein complexes that regulate RNA polymerase recruitment and thereby affects transcription. We have developed a genetic approach to investigate how reporter gene transcription is affected by varying the spacing between transcription factor binding sites. We characterized the components of promoter architecture that govern the yeast transcription factors Cbf1 and Met31/32, which bind independently, but collaboratively recruit the coactivator Met4. RESULTS: A Cbf1 binding site was required upstream of a Met31/32 binding site for full reporter gene expression. Distance constraints on coactivator recruitment were more flexible than those for cooperatively binding transcription factors. Distances from 18 to 50 bp between binding sites support efficient recruitment of Met4, with only slight modulation by helical phasing. Intriguingly, we found that certain sequences located between the binding sites abolished gene expression. CONCLUSION: These results yield insight to the influence of both binding site architecture and local DNA flexibility on gene expression, and can be used to refine computational predictions of gene expression from promoter sequences. In addition, our approach can be applied to survey promoter architecture requirements for arbitrary combinations of transcription factor binding sites.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2006

The complete chloroplast DNA sequence of the green alga Oltmannsiellopsis viridis reveals a distinctive quadripartite architecture in the chloroplast genome of early diverging ulvophytes.

BACKGROUND: The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. The basal position of the Prasinophyceae has been well documented, but the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae is currently debated. The four complete chloroplast DNA (cpDNA) sequences presently available for representatives of these classes have revealed extensive variability in overall structure, gene content, intron composition and gene order. The chloroplast genome of Pseudendoclonium (Ulvophyceae), in particular, is characterized by an atypical quadripartite architecture that deviates from the ancestral type by a large inverted repeat (IR) featuring an inverted rRNA operon and a small single-copy (SSC) region containing 14 genes normally found in the large single-copy (LSC) region. To gain insights into the nature of the events that led to the reorganization of the chloroplast genome in the Ulvophyceae, we have determined the complete cpDNA sequence of Oltmannsiellopsis viridis, a representative of a distinct, early diverging lineage. RESULTS: The 151,933 bp IR-containing genome of Oltmannsiellopsis differs considerably from Pseudendoclonium and other chlorophyte cpDNAs in intron content and gene order, but shares close similarities with its ulvophyte homologue at the levels of quadripartite architecture, gene content and gene density. Oltmannsiellopsis cpDNA encodes 105 genes, contains five group I introns, and features many short dispersed repeats. As in Pseudendoclonium cpDNA, the rRNA genes in the IR are transcribed toward the single copy region featuring the genes typically found in the ancestral LSC region, and the opposite single copy region harbours genes characteristic of both the ancestral SSC and LSC regions. The 52 genes that were transferred from the ancestral LSC to SSC region include 12 of those observed in Pseudendoclonium cpDNA. Surprisingly, the overall gene organization of Oltmannsiellopsis cpDNA more closely resembles that of Chlorella (Trebouxiophyceae) cpDNA. CONCLUSION: The chloroplast genome of the last common ancestor of Oltmannsiellopsis and Pseudendoclonium contained a minimum of 108 genes, carried only a few group I introns, and featured a distinctive quadripartite architecture. Numerous changes were experienced by the chloroplast genome in the lineages leading to Oltmannsiellopsis and Pseudendoclonium. Our comparative analyses of chlorophyte cpDNAs support the notion that the Ulvophyceae is sister to the Chlorophyceae.

Base Sequence↗
PubMed2006

Quantitative analysis of the epithelial lining architecture in radicular cysts and odontogenic keratocysts.

BACKGROUND: This paper describes a quantitative analysis of the cyst lining architecture in radicular cysts (of inflammatory aetiology) and odontogenic keratocysts (thought to be developmental or neoplastic) including its 2 counterparts: solitary and associated with the Basal Cell Naevus Syndrome (BCNS). METHODS: Epithelial linings from 150 images (from 9 radicular cysts, 13 solitary keratocysts and 8 BCNS keratocysts) were segmented into theoretical cells using a semi-automated partition based on the intensity of the haematoxylin stain which defined exclusive areas relative to each detected nucleus. Various morphometrical parameters were extracted from these "cells" and epithelial layer membership was computed using a systematic clustering routine. RESULTS: Statistically significant differences were observed across the 3 cyst types both at the morphological and architectural levels of the lining. Case-wise discrimination between radicular cysts and keratocyst was highly accurate (with an error of just 3.3%). However, the odontogenic keratocyst subtypes could not be reliably separated into the original classes, achieving discrimination rates slightly above random allocations (60%). CONCLUSION: The methodology presented is able to provide new measures of epithelial architecture and may help to characterise and compare tissue spatial organisation as well as provide useful procedures for automating certain aspects of histopathological diagnosis.

Journal Article↗
PubMedDate not supplied

Arden/J: an architecture for MLM execution on the Java platform.

The Arden Syntax was introduced more than 10 years ago, but it is still not in widespread use. One reason might be that for each particular architecture and information system, a different Arden Syntax compiler must be written as well as a program for the runtime execution of the medical logic modules (MLMs). The authors have designed and implemented an architecture that increases the portability of Arden Syntax rules, using the Java platform. The portability to a target information system is achieved by the addition of appropriate adapter components, which they call mappers. These mappers are dynamically selected using explicit and implicit elements of MLMs. Furthermore, they can help translate data from the clinical information system representation into the representation needed by an MLM. This was validated by an experiment in two clinical units. Also, the authors propose a convention to name signals that trigger other MLMs (called intermediate states) so that they remain unique to each institution. The authors implemented this architecture in their clinical system and in an XML-based medical record application that has been used experimentally in their urology and nephrology departments. The Tetrasys company that provided the medical record was able to incorporate their runtime without modifications, and typical MLM execution time was less than 1 sec.

Decision Support Systems, Clinical↗
PubMed2006

Dynamic tables: an architecture for managing evolving, heterogeneous biomedical data in relational database management systems.

Data sparsity and schema evolution issues affecting clinical informatics and bioinformatics communities have led to the adoption of vertical or object-attribute-value-based database schemas to overcome limitations posed when using conventional relational database technology. This paper explores these issues and discusses why biomedical data are difficult to model using conventional relational techniques. The authors propose a solution to these obstacles based on a relational database engine using a sparse, column-store architecture. The authors provide benchmarks comparing the performance of queries and schema-modification operations using three different strategies: (1) the standard conventional relational design; (2) past approaches used by biomedical informatics researchers; and (3) their sparse, column-store architecture. The performance results show that their architecture is a promising technique for storing and processing many types of data that are not handled well by the other two semantic data models.

Computational Biology↗
PubMed2003

Training-specific muscle architecture adaptation after 5-wk training in athletes.

PURPOSE: This study examined changes in the muscle size, muscle architecture, strength, and sprint/jump performances of concurrently training athletes during 5 wk of "altered" resistance training (RT). METHODS: Eight female and 15 male athletes performed 4 wk of sprint, jump, and resistance training in addition to their sports training (standardization) before adopting one of three different programs for 5 wk: 1) squat lift training (SQ, N = 8) with sprint/jump training; 2) forward hack squat training (FHS, N = 7) with sprint/jump training; or 3) sprint/jump training only (SJ, N = 8). Muscle size, fascicle angle, and fascicle length of the vastus lateralis (VL) and rectus femoris (RF) muscles (using ultrasound procedures) as well as 20-m sprint run, vertical jump, and strength performance changes were examined. RESULTS: A small increase in VL fascicle angle in SQ and FHS was statistically different to the decrease in SJ subjects (P < 0.05 at distal, P < 0.1 at proximal). VL fascicle length increased for SJ only (P < 0.05 at distal, P < 0.1 at proximal) and increased in RF in SQ subjects (P < 0.05). Muscle thickness of VL and RF increased in all training groups (P < 0.05) but only at proximal sites. There were no between-group differences in squat, forward hack squat, or isokinetic strength performances, or in sprint or jump performances, despite improvements in some of the tests across the groups. CONCLUSIONS: Significant muscle size and architectural adaptations can occur in concurrently training athletes in response to a 5-wk training program. These adaptations were possibly associated with the force and velocity characteristics of the training exercises but not the movement patterns. Factors other than, or in addition to, muscle architecture must mediate changes in strength, sprint, and jump performance.

Adaptation, Physiological↗
PubMed2001

Muscle architecture of the elongated nose in the Asian elephant (Elephas maximus).

The architecture of the M. caninus in the elongated nose was examined in the Asian elephant (Elephas maximus). The following complicated musculature of the M. caninus was observed in the proximal and distal regions of the nose: (1) Proximal region: In the superficial layer, the longitudinal bundles are confirmed in the dorsal part, and the obliquely-oriented ones in the ventral part. In the middle layer, some bundles run ventro-distally, while other ones represent longitudinally-oriented running. The deep layer consists of complicated architecture of many bundles. Some muscle bundles run medio-laterally, while the others extend proximo-distally in this space. (2) Distal region: In the dorsal part of the M. caninus, the bundles run at deep-superficial direction, while in the ventral part the bundles are longitudinally arranged. The bundles run at lateral direction near the septum of the nasal conduits. The N. facialis and N. infraorbitalis send many branches in the lateral area of the M. caninus in the trunk. This muscle architecture of multi-oriented bundles and well-developed innervation to them suggest that they enable the elongated nose to act as a refined manipulator in the Asian elephant.

Animals↗
PubMed2004

Parathyroid cells cultured in collagen matrix retain calcium responsiveness: importance of three-dimensional tissue architecture.

UNLABELLED: Primary cultures of bovine parathyroid cells rapidly lose calcium responsiveness. Here, we show that bovine parathyroid cells grown in collagen coalesce into an organoid ("pseudogland") with stable calcium responsiveness. These findings also illustrate the importance of 3-D cellular architecture in parathyroid gland function. INTRODUCTION: The ability of extracellular calcium to suppress parathyroid hormone (PTH) secretion is quickly lost in primary monolayer cultures of bovine parathyroid cells. This has been attributed to a decrease in the expression of the cell surface calcium-sensing receptor (CaR), but other factors, including normal cell-to-cell interaction, may be critical. Here we describe a novel system for culturing bovine parathyroid cells that promotes re-formation of a three-dimensional (3-D) cellular architecture and re-establishment of calcium responsiveness. MATERIALS AND METHODS: Dispersed bovine parathyroid cells were cultured as monolayers or were mixed with type I collagen and placed in culture plates. CaR mRNA and the calcium regulation of PTH secretion were measured over a period of several weeks in parathyroid cells cultured both in collagen matrix and as monolayers. Calcium regulation of PTH mRNA was also investigated. RESULTS AND CONCLUSIONS: Within 1-2 weeks in collagen culture, parathyroid cells coalesced into a small mass approximately 1-2 mm in size (referred to as a pseudogland). Suppression of PTH secretion by high calcium was blunted at 1 day in collagen, but returned within 1 week, and was retained through 3 weeks; the calcium set point (1.05 +/- 0.04 mM) was similar to that reported for freshly dispersed cells. PTH mRNA was also suppressed by increasing extracellular calcium. CaR mRNA expression was decreased at 1 day in collagen and increased with time in culture, although never reaching the level found in dispersed cells. In bovine parathyroid cells cultured as monolayers, however, suppression of PTH by calcium was observed only at day 1 in culture. CaR mRNA content fell by 70% at day 1 but remained stable thereafter. Thus, a total loss of calcium responsiveness in monolayers was observed despite significant residual expression of CaR, suggesting that loss of the calcium response cannot be attributed solely to decreased CaR. In summary, the pseudogland model illustrates the importance of the 3-D cellular architecture in parathyroid gland function and provides a useful model in which to investigate calcium-mediated control of parathyroid gland functions, especially those requiring extended treatment.

Animals↗
PubMed2002

ACTIVE-EYES: an adaptive pixel-by-pixel image-segmentation sensor architecture for high-dynamic-range hyperspectral imaging.

The ACTIVE-EYES (adaptive control for thermal imagers via electro-optic elements to yield an enhanced sensor) architecture, an adaptive image-segmentation and processing architecture, based on digital micromirror (DMD) array technology, is described. The concept provides efficient front-end processing of multispectral image data by adaptively segmenting and routing portions of the scene data concurrently to an imager and a spectrometer. The goal is to provide a large reduction in the amount of data required to be sensed in a multispectral imager by means of preprocessing the data to extract the most useful spatial and spectral information during detection. The DMD array provides the flexibility to perform a wide range of spatial and spectral analyses on the scene data. The spatial and spectral processing for different portions of the input scene can be tailored in real time to achieve a variety of preprocessing functions. Since the detected intensity of individual pixels may be controlled, the spatial image can be analyzed with gain varied on a pixel-by-pixel basis to enhance dynamic range. Coarse or fine spectral resolution can be achieved in the spectrometer by use of dynamically controllable or addressable dispersion elements. An experimental prototype, which demonstrated the segmentation between an imager and a grating spectrometer, was demonstrated and shown to achieve programmable pixelated intensity control. An information theoretic analysis of the dynamic-range control aspect was conducted to predict the performance enhancements that might be achieved with this architecture. The results indicate that, with a properly configured algorithm, the concept achieves the greatest relative information recovery from a detected image when the scene is made up of a relatively large area of moderate-dynamic-range pixels and a relatively smaller area of strong pixels that would tend to saturate a conventional sensor.

Journal Article↗
PubMed2002

Relative performance of filled and feedhorn-coupled focal-plane architectures.

Modern far-infrared and submillimeter instruments require large-format arrays. We consider the relative performance of filled-array (bare pixel) and feedhorn-coupled architectures for bolometer focal planes. Based on typical array parameters, we quantify the relative observing speeds and comment on the merits of the different architectures. Filled arrays can provide higher mapping speed (by a factor of as much as 3.5) and simpler observing modes at the expense of reduced sensitivity for pointed observations, increased detector numbers, and greater vulnerability to stray light and electromagnetic interference. Taking advantage of the filled-array architecture requires strongly background-limited detectors. At millimeter wavelengths, filled arrays must be surrounded by a sufficiently cold enclosure to minimize the background power from the instrument itself.

Journal Article↗
PubMed2005

Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy.

The recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets alpha and delta cells resided at the periphery of the beta-cell core. However, human islets were markedly different in that alpha, beta, and delta cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of alpha, beta, and delta cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets.

Animals↗
PubMed2003

Neural architectures for robot intelligence.

We argue that direct experimental approaches to elucidate the architecture of higher brains may benefit from insights gained from exploring the possibilities and limits of artificial control architectures for robot systems. We present some of our recent work that has been motivated by that view and that is centered around the study of various aspects of hand actions since these are intimately linked with many higher cognitive abilities. As examples, we report on the development of a modular system for the recognition of continuous hand postures based on neural nets, the use of vision and tactile sensing for guiding prehensile movements of a multifingered hand, and the recognition and use of hand gestures for robot teaching. Regarding the issue of learning, we propose to view real-world learning from the perspective of data-mining and to focus more strongly on the imitation of observed actions instead of purely reinforcement-based exploration. As a concrete example of such an effort we report on the status of an ongoing project in our laboratory in which a robot equipped with an attention system with a neurally inspired architecture is taught actions by using hand gestures in conjunction with speech commands. We point out some of the lessons learnt from this system, and discuss how systems of this kind can contribute to the study of issues at the junction between natural and artificial cognitive systems.

Action Potentials↗
PubMed2004

Functions of sleep architecture and the concept of protective fields.

This article focuses on the function of human sleep architecture and, where it adjoins, on the ultradian rhythm of NREM and REM cycles. In healthy adult human sleep, NREM and REM sleep succeed each other in 90-110 min intervals. This ultradian pattern of NREM/REM succession is cyclical. Sleep architecture relates to the shifting between sleep stages of varying sleep intensity and arousal thresholds. It has been found to follow a typical but non-cyclical pattern throughout the night. In the first third of the night, light sleep alternates predominantly with slow wave sleep (SWS). As sleep progresses, the amount of SWS typically decreases and REM sleep increases. In the last third of the night, light sleep almost exclusively alternates with REM sleep. The author postulates that one function of the non-cyclical succession of sleep stages is the erection and maintenance of a protective field around the sleeper. A protective field is to be understood as an area of relative safety, minimizing the chances for an intruder to enter the field without detection. The frequent shifts between sleep phases with low and high arousal thresholds allow a periodic screening of the sleep environment for danger signals. The relevant literature on sleep architecture, ultradian rhythms and its determinants is reviewed and the implications of the concept of protective fields are discussed.

Activity Cycles↗
PubMed2005

The genetic architecture of sucrose responsiveness in the honeybee (Apis mellifera L.).

One of the best examples of a natural behavioral syndrome is the pollen-hoarding syndrome in honeybees that ties together multiple behavioral phenotypes, ranging from foraging behavior to behavioral ontogeny and learning performance. A central behavioral factor is the bees' responsiveness to sucrose, measured as their proboscis extension reflex. This study examines the genetics of this trait in diploid worker and haploid male honeybees (drones) to learn more about the genetic architecture of the overall behavioral syndrome, using original strains selected for pollen-hoarding behavior. We show that a significant proportion of the phenotypic variability is determined by genotype in males and workers. Second, our data present overwhelming evidence for pleiotropic effects of previously identified quantitative trait loci for foraging behavior (pln-QTL) and epistatic interactions among them. Furthermore, we report on three genomic QTL scans (two reciprocal worker backcrosses and one drone hybrid population) derived from our selection strains. We present at least one significant and two putative new QTL directly affecting the sucrose response of honeybees. Thus, this study demonstrates the modular genetic architecture of behavioral syndromes in general, and elucidates the genetic architecture of the pollen-hoarding behavioral syndrome in particular. Understanding this behavioral syndrome is important for understanding the division of labor in social insects and social evolution itself.

Animals↗
PubMed2004

Nuclear architecture and gene expression in the quest for novel therapeutics.

The architecture of the cell nucleus has long been a matter of debate, and is still not completely understood yet. However, much progress has been made in the last few years, gradually unraveling nuclear infrastructure and its importance of the regulation of key genetic events. It is now established that the readout of genetic information and its faithful duplication are not only affected by regulatory sequences in the genome, but also by their localization in the three-dimensional context and their relative position to functional subcompartments in the nucleus. Understanding how nuclear architecture and function are related and depend on each other has great potential to open up novel ways for the development of therapeutic agents. It is the purpose of this review to shed light on the role of nuclear architecture in regulating gene expression, and suggest that interfering with specific protein-protein interactions of transcription factors might provide new approaches to drug development.

Animals↗
PubMed1998

Mechanical significance of obliquely striated architecture in nematode muscle.

In certain invertebrate muscles, adjacent narrow columns of sarcomeres are displaced along the fiber axis, providing an obliquely striated myofilament pattern in certain section planes. Although this architecture is described in many phyla and has been the subject of much discussion (1-12), its mechanical significance has yet to be resolved. In nematodes, where ultrastructural details of the obliquely striated muscle have long been known (12-19), another unique and prominent feature is the attachment of every sarcomere to the plasmalemma and basal lamina via dense bodies (Z-disc analogs). Unfortunately, the importance of this feature to the transmission of the contractile force to the cuticle is not understood outside the Caenorhabditis elegans literature: it was overlooked in recent reviews covering obliquely striated muscle (9-11). Here we consider transmission of force and oblique striation together. We compare the contractile architecture in C. elegans with that in the more complex muscle type of larger nematodes. Both types are designed to transmit the force of contraction laterally to the cuticle rather than longitudinally to the muscle ends. In the second type, folding of the contractile structure around an inward extension of the basal lamina enables a higher number of sarcomeres to be linked to cuticle per unit length. We suggest that the mechanical significance of the oblique arrangement of sarcomeres in both types is that it distributes the force application sites of the sarcomeres more evenly over the basal lamina and cuticle. With this muscle architecture, smooth bending of the nematode body tube would be possible, and kinking would be prevented.

Actin Cytoskeleton↗
PubMed2004

Determination of muscle architecture and fiber characteristics of the superficial and deep digital flexor muscles in the forelimbs of adult horses.

OBJECTIVE: To provide a quantitative description of the architecture of superficial digital flexor (SDF) and deep digital flexor (DDF) muscles in adult horses to predict muscle-tendon behavior and estimate muscle forces. SAMPLE POPULATION: 7 forelimb specimens from 7 adult Thoroughbreds. PROCEDURE: Muscle and tendon lengths and volumes were measured from 6 fixed forelimbs. After processing, fiber bundle and sarcomere lengths were measured. Optimal fascicle lengths and muscle length-to-fascicle length, muscle length-to-free tendon length, and fascicle length-to-tendon length ratios were calculated, as were tendon and muscle physiologic cross-sectional areas (PCSAs). Pennation angles were measured in 1 embalmed specimen. RESULTS: The SDF optimal fascicle lengths were uniformly short (mean +/- SD, 0.8 +/- 0.1 cm), whereas DDF lengths ranged from 0.9 +/- 0.2 cm to 10.8 +/- 1.6 cm. The DDF humeral head had 3 architectural subunits, each receiving a separate median nerve branch, suggestive of neuromuscular compartmentalization. Pennation angles were small (10 degrees to 25 degrees). The PCSAs of the SDF and DDF muscle were 234 +/- 51 cm2 and 259 +/- 30 cm2, with estimated forces of 4,982 +/- 1148 N and 5,520 +/- 544 N, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The SDF muscle appears to provide strong tendinous support with little muscle fascicular shortening and fatigue-resistance properties. The DDF muscle combines passive and dynamic functions with larger tension development and higher shortening velocities during digital motion. Architectural parameters are useful for estimation of forces and have implications for analysis of muscle-tendon function, surgical procedures involving muscle-tendon lengthening, and biomechanical modeling.

Age Factors↗