SEARCH · PubMed Health

Results for “Network inference”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

PubMed2006

The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis.

Members of the ATP-binding cassette (ABC) transporters including P-glycoprotein (Pgp/ABCB1), multidrug resistance proteins (MRPs/ABCC) as well as breast cancer resistance protein (BCRP/ABCG2) function as ATP-dependent drug efflux transporters, which form a unique defense network against multiple chemotherapeutic drugs and cellular toxins. Among antitumor agents is the important group of folic acid antimetabolites known as antifolates. Antifolates such as methotrexate (MTX), pemetrexed and raltitrexed exert their cytotoxic activity via potent inhibition of folate-dependent enzymes essential for purine and pyrimidine nucleotide biosynthesis and thereby block DNA replication. Overexpression of MRPs and BCRP confers resistance upon malignant cells to various hydrophilic and lipophilic antifolates. Apart from their central role in mediating resistance to antifolates and other anticancer drugs, MRPs and BCRP have been recently shown to transport naturally occurring reduced folates. This was inferred from various complementary systems as follows: (a) Cell-free systems including ATP-dependent uptake of radiolabeled folate/MTX into purified inside-out membrane vesicles from stable transfectants and/or cells overexpressing these transporters, (b) Decreased accumulation of radiolabeled folate/MTX in cultured tumor cells overexpressing these transporters, as well as (c) In vivo rodent models such as Eisi hyperbillirubinemic rats (EHBR) that hereditarily lack MRP2 in their canalicular membrane and thereby display a bile that is highly deficient in various reduced folate cofactors and MTX, when compared with wild type Sprague-Dawley (SD) rats. In all cases, these folate/antifolate transporters functioned as high capacity, low affinity ATP-driven exporters. While the mechanism of cellular retention of (anti)folates is mediated via (anti)folylpolyglutamylation, certain efflux transporters including MRP5 (ABCC5) and BCRP were shown to transport both mono-, di- as well as triglutamate derivatives of MTX and folic acid. Furthermore, overexpression of MRPs and BCRP has been shown to result in decreased cellular folate pools, whereas loss of ABC transporter expression brought about a significant expansion in the intracellular reduced folate pool. The latter finding has important implications to antifolate-based chemotherapy as an augmented cellular folate pool results in a significant level of resistance to certain antifolates. Hence, the aims of the present review are: (a) To summarize and discuss the cumulative evidence supporting a functional role for various multidrug resistance efflux transporters of the ABC superfamily which mediate resistance to hydrophilic and lipophilic antifolates, (b) To describe and evaluate the recent data suggesting a role for these efflux transporters in regulation of cellular folate homeostasis under folate replete and deplete conditions. Furthermore, novel developments and future perspectives regarding the identification of novel antifolate target proteins and mechanisms of action, as well as rationally designed emerging drug combinations containing antifolates along with receptor tyrosine kinase inhibitors are being discussed.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2005

Earthquake rupture dynamics frozen in exhumed ancient faults.

Most of our knowledge about co-seismic rupture propagation is derived from inversion and interpretation of strong-ground-motion seismograms, laboratory experiments on rock and rock-analogue material, or inferred from theoretical and numerical elastodynamic models. However, additional information on dynamic rupture processes can be provided by direct observation of faults exhumed at the Earth's surface. Pseudotachylytes (solidified friction-induced melts) are the most certain fault-rock indicator of seismicity on ancient faults. Here we show how the asymmetry in distribution and the orientation of pseudotachylyte-filled secondary fractures around an exhumed fault can be used to reconstruct the earthquake rupture directivity, rupture velocity and fracture energy, by comparison with the theoretical dynamic stress field computed around propagating fractures. In particular, the studied natural network of pseudotachylytes is consistent with a dominant propagation direction during repeated seismic events and subsonic rupture propagation close to the Rayleigh wave velocity.

Journal Article↗

PubMed2005

Imaging implicit perception: promise and pitfalls.

The study of implicit perception - perception in the absence of awareness - has a long history. Decades of behavioural work have identified crucial theoretical and methodological issues that must be considered when evaluating claims of implicit perception. Neuroimaging methods provide an important new avenue for illuminating our understanding of perception both with and without awareness, but most imaging experiments have not met the rigorous conditions that the behavioural work has shown are necessary for inferring implicit perception. Here, we review the literature of both behavioural and neuroimaging studies, and note the pitfalls of studying implicit perception as well as the promise that neuroimaging studies have for providing insights about implicit perception when combined with appropriately rigorous behavioural measures of awareness.

Animals↗

PubMed1994

OncoLink: a multimedia oncology information resource on the Internet.

This paper describes OncoLink, the first multimedia World-Wide-Web (WWW) and gopher server focusing on cancer information for both the health care professional and the patient. OncoLink provides an internetworked hypertext and multimedia resource linking people, computers and information together in an easy to use fashion. Our objective in developing OncoLink is to provide comprehensive and timely information about many aspects of oncology for both patients and healthcare providers. Specifically, OncoLink's purposes are: (1) the rapid dissemination of information relevant to treatment of cancer and concomitant problems; (2) education of health care personnel (at all levels) in the field; (3) education of patients and families of patients who have cancer; (4) posting of clinical trials and eligibility criteria; (5) the rapid collection and dissemination of quality, peer-reviewed information pertinent to oncology in general and specific subspecialties; (6) provide a well-organized, frequently updated hypertext system to access other quality cancer information resources on the Internet. OncoLink attempts to provide one-stop shopping for the patient, healthcare provider, researcher or Internet browser searching for cancer-related information. Since its inception on March 7, 1994, OncoLink has averaged more than 36,000 accesses per month from around the world. While also accessible by text-based gopher servers, preliminary observations infer increased use of multimedia and hypertext documents over traditional text-only resources. From the large following of users, it is clear that electronic dissemination of high quality, peer-reviewed cancer information is very popular. We conclude OncoLink is both useful and has wide interest in the international community.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Communication Networks↗

PubMed1998

The variable discharge of cortical neurons: implications for connectivity, computation, and information coding.

Cortical neurons exhibit tremendous variability in the number and temporal distribution of spikes in their discharge patterns. Furthermore, this variability appears to be conserved over large regions of the cerebral cortex, suggesting that it is neither reduced nor expanded from stage to stage within a processing pathway. To investigate the principles underlying such statistical homogeneity, we have analyzed a model of synaptic integration incorporating a highly simplified integrate and fire mechanism with decay. We analyzed a "high-input regime" in which neurons receive hundreds of excitatory synaptic inputs during each interspike interval. To produce a graded response in this regime, the neuron must balance excitation with inhibition. We find that a simple integrate and fire mechanism with balanced excitation and inhibition produces a highly variable interspike interval, consistent with experimental data. Detailed information about the temporal pattern of synaptic inputs cannot be recovered from the pattern of output spikes, and we infer that cortical neurons are unlikely to transmit information in the temporal pattern of spike discharge. Rather, we suggest that quantities are represented as rate codes in ensembles of 50-100 neurons. These column-like ensembles tolerate large fractions of common synaptic input and yet covary only weakly in their spike discharge. We find that an ensemble of 100 neurons provides a reliable estimate of rate in just one interspike interval (10-50 msec). Finally, we derived an expression for the variance of the neural spike count that leads to a stable propagation of signal and noise in networks of neurons-that is, conditions that do not impose an accumulation or diminution of noise. The solution implies that single neurons perform simple algebra resembling averaging, and that more sophisticated computations arise by virtue of the anatomical convergence of novel combinations of inputs to the cortical column from external sources.

Action Potentials↗

PubMed2006

A probabilistic methodology for integrating knowledge and experiments on biological networks.

Biological systems are traditionally studied by focusing on a specific subsystem, building an intuitive model for it, and refining the model using results from carefully designed experiments. Modern experimental techniques provide massive data on the global behavior of biological systems, and systematically using these large datasets for refining existing knowledge is a major challenge. Here we introduce an extended computational framework that combines formalization of existing qualitative models, probabilistic modeling, and integration of high-throughput experimental data. Using our methods, it is possible to interpret genomewide measurements in the context of prior knowledge on the system, to assign statistical meaning to the accuracy of such knowledge, and to learn refined models with improved fit to the experiments. Our model is represented as a probabilistic factor graph, and the framework accommodates partial measurements of diverse biological elements. We study the performance of several probabilistic inference algorithms and show that hidden model variables can be reliably inferred even in the presence of feedback loops and complex logic. We show how to refine prior knowledge on combinatorial regulatory relations using hypothesis testing and derive p-values for learned model features. We test our methodology and algorithms on a simulated model and on two real yeast models. In particular, we use our method to explore uncharacterized relations among regulators in the yeast response to hyper-osmotic shock and in the yeast lysine biosynthesis system. Our integrative approach to the analysis of biological regulation is demonstrated to synergistically combine qualitative and quantitative evidence into concrete biological predictions.

Cell Physiological Phenomena↗

PubMed2004

CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival.

This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir.

ADP-ribosyl Cyclase↗

PubMed2003

Relation between income, air pollution and mortality: a cohort study.

BACKGROUND: Community levels of air pollution have been associated with variability in mortality rates, but previous studies have inferred exposure to pollutants on a citywide basis. We investigated mortality in relation to neighbourhood levels of income and air pollution in an urban area. METHODS: We identified 5228 people in the Hamilton-Burlington area of southern Ontario who had been referred for pulmonary function testing between 1985 and 1999. Nonaccidental deaths that occurred in this group between 1992 and 1999 were ascertained from the Ontario Mortality Registry. Mean household income was estimated by linking the subjects' postal codes with the 1996 census. Mean neighbourhood levels of total suspended particulates and sulfur dioxide were estimated by interpolation from data from a network of sampling stations. We used proportional hazards regression models to compute mortality risk in relation to income and pollutant levels, while adjusting for pulmonary function, body mass index and diagnoses of chronic disease. Household incomes and pollutant levels were each divided into 2 risk categories (low and high) at the median. RESULTS: Mean pollutant levels tended to be higher in lower-income neighbourhoods. Both income and pollutant levels were associated with mortality differences. Compared with people in the most favourable category (higher incomes and lower particulate levels), those with all other income-particulate combinations had a higher risk of death from nonaccidental causes (lower incomes and higher particulate levels: relative risk [RR] 2.62, 95% confidence interval [CI] 1.67-4.13; lower incomes and lower particulate levels: RR 1.82, 95% CI 1.30-2.55; higher incomes and higher particulate levels: RR 1.33, 95% CI 1.12-1.57). Similar results were observed for sulfur dioxide. The relative risk was lower at older ages. INTERPRETATION: Mortality rates varied by neighbourhood of residence in this cohort of people whose lung function was tested. Two of the broader determinants of health--income and air pollution levels--were important correlates of mortality in this population.

Aged↗

PubMed2002

Embryonic assembly of a central pattern generator without sensory input.

Locomotion depends on the integration of sensory information with the activity of central circuitry, which generates patterned discharges in motor nerves to appropriate muscles. Isolated central networks generate fictive locomotor rhythms (recorded in the absence of movement), indicating that the fundamental pattern of motor output depends on the intrinsic connectivity and electrical properties of these central circuits. Sensory inputs are required to modify the pattern of motor activity in response to the actual circumstances of real movement. A central issue for our understanding of how locomotor circuits are specified and assembled is the extent to which sensory inputs are required as such systems develop. Here we describe the effects of eliminating sensory function and structure on the development of the peristaltic motor pattern of Drosophila embryos and larvae. We infer that the circuitry for peristaltic crawling develops in the complete absence of sensory input; however, the integration of this circuitry into actual patterns of locomotion requires additional information from the sensory system. In the absence of sensory inputs, the polarity of movement is deranged, and backward peristaltic waves predominate at the expense of forward peristalsis.

Animals↗

PubMed2002

OILing the way to machine understandable bioinformatics resources.

The complex questions and analyses posed by biologists, as well as the diverse data resources they develop, require the fusion of evidence from different, independently developed, and heterogeneous resources. The web, as an enabler for interoperability, has been an excellent mechanism for data publication and transportation. Successful exchange and integration of information, however, depends on a shared language for communication (a terminology) and a shared understanding of what the data means (an ontology). Without this kind of understanding, semantic heterogeneity remains a problem for both humans and machines. One means of dealing with heterogeneity in bioinformatics resources is through terminology founded upon an ontology. Bioinformatics resources tend to be rich in human readable and understandable annotation, with each resource using its own terminology. These resources are machine readable, but not machine understandable. Ontologies have a role in increasing this machine understanding, reducing the semantic heterogeneity between resources and thus promoting the flexible and reliable interoperation of bioinformatics resources. This paper describes a solution derived from the semantic web [a machine understandable world-wide web (WWW)], the ontology inference layer (OIL), as a solution for semantic bioinformatics resources. The nature of the heterogeneity problems are presented along with a description of how metadata from domain ontologies can be used to alleviate this problem. A companion paper in this issue gives an example of the development of a bio-ontology using OIL.

Algorithms↗

PubMed2002

Which nurseries currently care for ventilated neonates in Illinois and Wisconsin? Implications for the next generation of perinatal regionalization.

We were interested in the extent to which advances in the availability of neonatalogy expertise have provided a centrifugal impetus to perinatal care. Specifically, we wondered where infants who were sick enough to require mechanical ventilation were currently being managed. We surveyed 116 of 140 hospitals in Illinois and Wisconsin that offered obstetric/newborn services in 1998-1999. The 23 Level I nurseries were consistently small, and offered virtually no "advanced" neonatal intensive care unit (NICU) technology. The 16 Level III NICUs were consistently large, offered advanced technology and personnel, and received sick infants from many hospitals in their regional network. The 77 Level II nurseries (two thirds of all hospitals with newborn services) were less consistently characterized. In general, Level II nurseries were a "spoke" (not a hub), and did not offer extracorporeal-membrane oxygenation (ECMO), nitric oxide (NO), or cardiovascular (CV) surgery. However, 19 (25%) of 77 Level II centers self-designated as "Level II+". These were significantly more likely to offer ventilators, percutaneous central venous catheters (PCVCs), total parenteral nutrition (TPN), and surgery. Fifty-three percent (18/34) of all nurseries offering mechanical ventilation self-designated as a Level II or II+, as opposed to Level III. Facile inferences about the appropriate role of Level II centers derived from decades-old data are probably unsupportable. It is time to acknowledge the distinction between the Level II nursery of the past and the newly evolving Level II+ NICUs.

Health Care Surveys↗

PubMed2005

Double dissociation of exteroceptive and interoceptive feedback systems in the orbital and ventromedial prefrontal cortex of humans.

The primate ventral prefrontal cortex contains two densely interconnected subregions: a lateral/orbital cortex processing primarily sensory/exteroceptive information, and a ventromedial cortex processing primarily visceroappetitive/interoceptive information. These regions have major afferents from and efferents to other associative cortices. The organization of these structures leads to an hypothesized role in feedback processing. We use neuroimaging to test this model, defined so far mostly through anatomical studies. Healthy volunteers were trained operantly on a transitive inference task (A>B, B>C ==> A>C) requiring flexible manipulation of feedback to solve. Two groups of subjects learned an arbitrary face hierarchy, one adjacent face pair at a time; each group received either visual/exteroceptive ("XXXX") or visceroappetitive/interoceptive (fruit juice) feedback for correct responses to adjacent face pairs. After task acquisition, the subjects were tested on novel stimulus pairs (i.e., nonadjacent, TEST) derived from the acquired hierarchy. The TEST condition required transitive inference. No feedback was provided during TEST. Brain activity during TEST in the group trained with visual/exteroceptive feedback increased in the orbital prefrontal cortex and decreased in the ventromedial prefrontal cortex. In contrast, brain activity during TEST in the group trained with visceroappetitive/interoceptive feedback decreased in the orbital prefrontal cortex and increased in the ventromedial prefrontal cortex. These results provide functional evidence, consistent with previous anatomical studies, for two major feedback systems in human ventral prefrontal cortex: a lateral system specialized for exteroceptive information and a medial system specialized for interoceptive information. Although highly interconnected, there is a double dissociation of function between these networks in healthy humans.

Adult↗

PubMed1997

Terminal morphology of two branches arising from a single stem-axon of pretectal (PSm) neurons in the common carp.

The induction of postsynaptic structures by presynaptic terminals is suggested in a teleost brain. Neurons in the nucleus pretectalis superficialis pars magnocellularis (PSm) in the common carp are known to send fibers to the corpus mamillare (CM) and the nucleus lateralis valvulae (NLV). Individual axons of PSm neurons bifurcate (or give off an axon collateral), both of which reach the target areas in the CM and NLV. The morphology of horseradish peroxidase-labeled terminals in the CM and NLV appears quite different in light microscopy. Terminals in the CM appear as a fine network of beaded (2-4 microns in diameter) fibers, while those in the NLV are larger (8-12 microns in transverse diameter) and cup-shaped, partially enveloping the soma of individual NLV neurons. In electron microscopy, however, these synapses in the CM and NLV share several ultrastructural similarities. Small (0.2 to 0.4-micron thick, 0.4 to 0.7-micron long) spine-like protrusions arising from dendrites in the CM, and from cell bodies in the NLV, invaginate into the axon terminals, and the synaptic junctions are always formed at the base of the protrusion in both areas. Development of this unusual morphology is inferred to be directed from the presynaptic side. The morphological similarity of the spine-like protrusions to the "spinule," which is thought to be formed in response to synaptic activation, is discussed.

Animals↗

PubMed2004

Population genetic structure and phylogeographical pattern of a relict tree fern, Alsophila spinulosa (Cyatheaceae), inferred from cpDNA atpB- rbcL intergenic spacers.

Sequences of chloroplast DNA (cpDNA) atpB- rbcL intergenic spacers of individuals of a tree fern species, Alsophila spinulosa, collected from ten relict populations distributed in the Hainan and Guangdong provinces, and the Guangxi Zhuang region in southern China, were determined. Sequence length varied from 724 bp to 731 bp, showing length polymorphism, and base composition was with high A+T content between 63.17% and 63.95%. Sequences were neutral in terms of evolution (Tajima's criterion D=-1.01899, P>0.10 and Fu and Li's test D*=-1.39008, P>0.10; F*=-1.49775, P>0.10). A total of 19 haplotypes were identified based on nucleotide variation. High levels of haplotype diversity (h=0.744) and nucleotide diversity (Dij=0.01130) were detected in A. spinulosa, probably associated with its long evolutionary history, which has allowed the accumulation of genetic variation within lineages. Both the minimum spanning network and neighbor-joining trees generated for haplotypes demonstrated that current populations of A. spinulosa existing in Hainan, Guangdong, and Guangxi were subdivided into two geographical groups. An analysis of molecular variance indicated that most of the genetic variation (93.49%, P<0.001) was partitioned among regions. Wright's isolation by distance model was not supported across extant populations. Reduced gene flow by the Qiongzhou Strait and inbreeding may result in the geographical subdivision between the Hainan and Guangdong + Guangxi populations (FST=0.95, Nm=0.03). Within each region, the star-like pattern of phylogeography of haplotypes implied a population expansion process during evolutionary history. Gene genealogies together with coalescent theory provided significant information for uncovering phylogeography of A. spinulosa.

Biological Evolution↗

PubMed2006

Maximum likelihood of phylogenetic networks.

MOTIVATION: Horizontal gene transfer (HGT) is believed to be ubiquitous among bacteria, and plays a major role in their genome diversification as well as their ability to develop resistance to antibiotics. In light of its evolutionary significance and implications for human health, developing accurate and efficient methods for detecting and reconstructing HGT is imperative. RESULTS: In this article we provide a new HGT-oriented likelihood framework for many problems that involve phylogeny-based HGT detection and reconstruction. Beside the formulation of various likelihood criteria, we show that most of these problems are NP-hard, and offer heuristics for efficient and accurate reconstruction of HGT under these criteria. We implemented our heuristics and used them to analyze biological as well as synthetic data. In both cases, our criteria and heuristics exhibited very good performance with respect to identifying the correct number of HGT events as well as inferring their correct location on the species tree. AVAILABILITY: Implementation of the criteria as well as heuristics and hardness proofs are available from the authors upon request. Hardness proofs can also be downloaded at http://www.cs.tau.ac.il/~tamirtul/MLNET/Supp-ML.pdf

Algorithms↗

PubMed1997

The knowledge model of MedFrame/CADIAG-IV.

The medical consultation system MedFrame/CADIAG-IV is a successor of the prior CADIAG projects. It is the result of a complete redesign to account for today's demands on state-of-the-art software. Its knowledge representation and inference process are based on fuzzy set theory and fuzzy logic. Fuzzy sets are used for conversions from measured numeric values and observational data into symbolic ones. Medical relationships between findings, diseases, and therapies, the rules, are represented by fuzzy relations, that express positive or negative associations. Findings, diseases, and therapies are organised in hierarchies.

Artificial Intelligence↗

PubMed1995

[Fate of human fetal dopamine neurons transplanted into rhesus monkey model of Parkinson's disease: a tyrosine hydroxylase immunocytochemical study].

To predicate the value of human fetal substantia nigra transplantation in clinical treatment of Parkinson's disease (PD), dissociated cells of substantia nigra from 8-12 week old abortive human fetus were grafted into the neostriatum of 5 adult rhesus monkeys with hemiparkinsonism induced by unilateral injection of MPTP. At 2, 5 and 12 months after transplanting the monkeys were sacrificed for tyrosine hydroxylase (TH) immunocytochemistry to examine the survival and possible synaptic contact of transplanted dopamine (DA) neurons. Transplanted TH immunoreactive cells took a pattern of patches scattered in the neostriatum. Each of the cell patches consisted of 3-10 cells. The TH immunoreactive fiber network was seen in the neostriatum. Electron microscopic survey revealed that TH+ buttons arising from grafted DA neurons formed symmetric or asymmetric synapses with TH- dendritic shafts/spines, and TH+ dendrites were seen to form synapses with TH- axons of the host. Additionally, there were a few synapses formed by TH+ axonal terminals with negative buttons. The results suggest that DA neurons from 8-12 week old abortive human fetus are able to survive grafting into the neostriatum of monkey, a species phylogenetically very close to human, and to establish reciprocal synaptic connectivity with the host even at 2 months post-transplanting. It is, therefore, inferable that embryonic human DA neurons transplanted into human neostriatum may have the same fate as in monkeys.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Evidence from flagelliform silk cDNA for the structural basis of elasticity and modular nature of spider silks.

Orb-web weaving spiders rely on their aerial nets to entrap flying prey. A key mechanical feature of orb-web design is the high elasticity of the capture spiral. We report the cloning of substantial cDNA for flagelliform gland silk protein, which forms the core fiber of the catching spiral. Like all silks, the flagelliform protein is composed largely of iterated sequences. The dominant repeat of this protein is Gly-Pro-Gly-Gly-X, which can appear up to 63 times in tandem arrays. This motif likely forms Pro2-Gly3 type II beta-turns and the resulting series of concatenated beta-turns are thought to form a beta-spiral. We propose that this spring-like helix is the basis for the elasticity of silk. The variable fifth position of the motif (X) is occupied by a small subset of residues (Ala, Ser, Tyr, Val). Moreover, these X amino acids occur in specific patterns throughout the repeats. This ordered variation strongly suggests that with hydration, the beta-spirals form hydrogen-bonded networks that increase the elasticity of flagelliform silk. The self-assembly of flagelliform protein monomers into silk fibers may be promoted by beta-spiral/beta-spiral interactions. Additionally, the other two motifs in the flagelliform protein, Gly-Gly-X and a spacer that disrupts the glycine-rich regions, may contribute to the alignment of monomers into fibers. The flagelliform protein cDNA was compared to the other members of the spider silk gene family. We show that all spider silk proteins can be characterized as sets of shared structural modules. The occurrence of these modules among the proteins is inconsistent with the phylogenetic relationships inferred from the C-terminal regions. This observation, along with the high level of variation among individual flagelliform protein repeats, but striking lack of such variation in the other silk proteins, suggests that unusual homogenization processes are involved in silk protein evolution.

Amino Acid Sequence↗