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At least 919 records · Page 51Linked to original sources
PubMed2001

A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation.

A group of 16-kDa proteins, synthesized and secreted by rat pancreatic acinar cells and composed of pancreatic stone protein (PSP/reg) and isoforms of pancreatitis-associated protein (PAP), show structural homologies, including conserved amino acid sequences, cysteine residues, and highly sensitive N-terminal trypsin cleavage sites, as well as conserved functional responses in conditions of pancreatic stress. Trypsin activation of recombinant stress proteins or counterparts contained in rat pancreatic juice (PSP/reg, PAP I and PAP III) resulted in conversion of 16-kDa soluble proteins into 14-kDa soluble isoforms (pancreatic thread protein and pancreatitis-associated thread protein, respectively) that rapidly polymerize into insoluble sedimenting structures. Activated thread proteins show long lived resistance to a wide spectrum of proteases contained in pancreatic juice, including serine proteases and metalloproteinases. In contrast, PAP II, following activation with trypsin or pancreatic juice, does not form insoluble structures and is rapidly digested by pancreatic proteases. Scanning and transmission electron microscopy indicate that activated thread proteins polymerize into highly organized fibrillar structures with helical configurations. Through bundling, branching, and extension processes, these fibrillar structures form dense matrices that span large topological surfaces. These findings suggest that PSP/reg and PAP I and III isoforms consist of a family of highly regulated soluble secretory stress proteins, which, upon trypsin activation, convert into a family of insoluble helical thread proteins. Dense extracellular matrices, composed of helical thread proteins organized into higher ordered matrix structures, may serve physiological functions within luminal compartments in the exocrine pancreas.

Amino Acid Sequence↗
PubMed2004

Effects of brood manipulation costs on optimal sex allocation in social hymenoptera.

In eusocial Hymenoptera, queens and workers are in conflict over optimal sex allocation. Sex ratio theory, while generating predictions on the extent of this conflict under a wide range of conditions, has largely neglected the fact that worker control of investment almost certainly requires the manipulation of brood sex ratio. This manipulation is likely to incur costs, for example, if workers eliminate male larvae or rear more females as sexuals rather than workers. In this article, we present a model of sex ratio evolution under worker control that incorporates costs of brood manipulation. We assume cost to be a continuous, increasing function of the magnitude of sex ratio manipulation. We demonstrate that costs counterselect sex ratio biasing, which leads to less female-biased population sex ratios than expected on the basis of relatedness asymmetry. Furthermore, differently shaped cost functions lead to different equilibria of manipulation at the colony level. While linear and accelerating cost functions generate monomorphic equilibria, decelerating costs lead to a process of evolutionary branching and hence split sex ratios.

Animals↗
PubMed2003

A computational pipeline for protein structure prediction and analysis at genome scale.

MOTIVATION: Experimental techniques alone cannot keep up with the production rate of protein sequences, while computational techniques for protein structure predictions have matured to such a level to provide reliable structural characterization of proteins at large scale. Integration of multiple computational tools for protein structure prediction can complement experimental techniques. RESULTS: We present an automated pipeline for protein structure prediction. The centerpiece of the pipeline is our threading-based protein structure prediction system PROSPECT. The pipeline consists of a dozen tools for identification of protein domains and signal peptide, protein triage to determine the protein type (membrane or globular), protein fold recognition, generation of atomic structural models, prediction result validation, etc. Different processing and prediction branches are determined automatically by a prediction pipeline manager based on identified characteristics of the protein. The pipeline has been implemented to run in a heterogeneous computational environment as a client/server system with a web interface. Genome-scale applications on Caenorhabditis elegans, Pyrococcus furiosus and three cyanobacterial genomes are presented. AVAILABILITY: The pipeline is available at http://compbio.ornl.gov/proteinpipeline/

Algorithms↗
PubMed2002

Human secreted attractin disrupts neurite formation in differentiating cortical neural cells in vitro.

Mutations at the Atrn locus that encodes a transmembrane protein with a large ectodomain are responsible for a juvenile-onset neurodegeneration manifest as hypomyelination and cerebral vacuole development in several rodent species. In addition to a membrane isoform, the human Atm locus generates by alternative splicing a secreted form corresponding to the entire ectodomain that then circulates at high concentration in the periphery, released in part by activated T lymphocytes. We report here that the secreted form mRNA is downregulated throughout representative discrete regions of the human brain while membrane attractin mRNA is well represented, resulting in the apparent absence of secreted attractin protein in cerebrospinal fluid (CSF). Transcription of attractin secreted form mRNA is strongly downregulated upon differentiation of a human cortical neuron-derived cell line (HCN-1A) to a mature neuron phenotype in response to nerve growth factor. Recombinant secreted attractin disrupts neurite formation by differentiated HCN-1A cells, resulting in higher levels of branching with shorter processes. This effect is duplicated by anti-attractin and by human serum but not by human serum depleted of attractin or by CSF We propose that inappropriate expression of secreted attractin in the CNS blocks membrane attractin function and that its presence, either by leakage from the periphery, aberrant transcription, or release from inflammatory foci may affect neuron extracellular interactions leading to neurodegeneration in the human.

Animals↗
PubMed1986

Genetic and environmental control of crown development in Picea sitchensis and its relation to stem wood production.

Differences in stem wood production were found among four clones of Picea sitchensis (Bong.) Carr. at both an agricultural and a forest site. Clonal rankings were not consistent between the sites. Four variables were identified that may influence stem wood production, foliage amount, total aboveground production per unit foliage, proportional allocation of production to new foliage and to branch wood thickening. Comparison of clonal performance between sites showed that stem wood production could be influenced by differences in each of these variables. The four variables were themselves determined by components of crown structure, these were (i) production of new branches from the main stem, (ii) the numbers and lengths of branchlets supported on branches from the main stem, (iii) foliage production per unit branchlet length and foliage longevity, and (iv) branch wood thickening per unit branch length. These components varied both among clones and between sites. Branch production from the mainstem varied among clones, and for some clones it varied substantially between sites. In some clones branch production was positively correlated with mainstem height increment. There were differences among clones in the way that branchlet production varied between the agricultural and forest sites. In the absence of needle fall, foliage weight/branch length varied threefold among clones, but for each clone, varied little between sites. Branch wood weight/branch length was generally greater when foliage weight/branch length was large, but total branch wood increment/tree was strongly influenced by total branch length. The dynamics of crown development and its relation to stem wood production are discussed with reference to (i) the importance of needle longevity, (ii) the importance of tallness and narrowness of crowns and (iii) the importance of branch thickening, a process that competes with stem growth in the utilization of photosynthate. It is concluded that although each of these factors may be important, none singly accounts for the observed differences in stem wood production among genotypes and the way these change in response to the environment.

Journal Article↗
PubMed2001

A differentiation switch for genetically modified hepatocytes.

The hepatocyte growth factor (HGF) receptor mediates a two-sided response-cell proliferation and differentiation. This process, defined as "branching morphogenesis," involves cell scatter and redistribution to form ramified hollow tubules within the extracellular matrix, and protection from apoptosis. We have fused the intracellular domain of the HGF receptor (HGFR) with three FK506-binding protein (FKBP) domains and a membrane-targeting signal. This molecule (FKBP-HGFR) dimerizes after administration of a bifunctional ligand specific for FKBP domains. We show that, in mouse hepatocyte progenitors, FKBP-HGFR dimerization elicits the differentiative side of the HGF response, including cell scatter, morphogenesis, and protection from apoptosis. Surprisingly, FKBP-HGFR does not induce cell proliferation. We could correlate the segregation of the differentiative response with a distinctive signaling kinetic of FKBP-HGFR: a) reduced and prolonged tyrosine kinase activation; and b) low early peak of MAP kinase activation (a log lower than the peak induced by the wild-type receptor), followed by a sustained activation over 6 h. These data show that the biological response triggered by the HGFR can be dissected on the basis of the quantitative signaling profile, and that FKBP-HGFR may be used to control selectively the differentiation of hepatocytes, without promoting cell expansion.

Animals↗
PubMed2004

Virus particles produced by the herpes simplex virus type 1 alkaline nuclease null mutant ambUL12 contain abnormal genomes.

Open reading frame UL12 of herpes simplex virus type 1 (HSV-1) encodes an alkaline nuclease that has previously been implicated in processing the complex, branched, viral DNA replication intermediates and allowing egress of DNA-containing capsids from the nucleus. This report describes experiments using the HSV-1 UL12 null mutant ambUL12, which aim to explain the approximately 200- to 1000-fold decrease in the yield of infectious virus, compared with wild-type (wt) HSV-1, from non-complementing cells. A detailed examination revealed that both DNA replication and encapsidation were affected in ambUL12-infected cells, resulting in an approximately 15- to 20-fold reduction in the amount of packaged DNA. In contrast to previous reports, the absence of UL12 function did not greatly impair capsid release into the cytoplasm, and virus particles were readily detected in the supernatant medium from ambUL12-infected cells. The released virus, however, exhibited much higher particle/p.f.u. ratios than wt HSV-1, and this made a further important contribution to the overall reduction in yield. Gel analyses of packaged ambUL12 and wt DNAs revealed the presence of structural abnormalities. The DNA obtained from extracellular ambUL12 virions was non-infectious in transfection assays, and both ambUL12 DNA and virus particles exerted a dominant inhibitory effect on the growth of wt virus. These results suggest that ambUL12 virions produced in non-complementing cells have a greatly reduced ability to initiate new cycles of infection, and that this defect results from the encapsidation of abnormal genomes.

Animals↗
PubMed1994

The fate of inflorescence meristems is controlled by developing fruits in Arabidopsis.

The relationship between fruit development and the proliferative capacities of inflorescence meristems has been examined in Arabidopsis thaliana. In the wild-type Landsberg erecta (Ler) line, flower production ceases coordinately on all inflorescence branches by a process we have designated global proliferative arrest (GPA). Morphological studies indicate that GPA involves a cessation of proliferative activity at the meristems, but a retention of the structural characteristics of the proliferating meristems. GPA does not occur in the male-sterile (ms1-1) line, nor in wild-type Ler when fruits are surgically removed. In these cases, inflorescence meristems continue to proliferate, ultimately terminating by a different process, designated terminal differentiation, in which disruptions in patterning at the apex are followed by the loss of the inflorescence meristem. We present an argument that GPA is mediated by a specific communication system between inflorescence meristems and developing fruits. Analysis of reduced-fertility mutants provided evidence that GPA is dependent on seed development specifically. Mutations conferring hormone deficiency or insensitivity did not disrupt the correlative interactions leading to GPA.

Arabidopsis↗
PubMed2002

Life cycle emission distributions within the economy: implications for life cycle impact assessment.

Refinements of methods for life cycle impact assessment (LCIA) are directed at removing unjustified simplifications and quantifying and reducing uncertainties in results. The amount of uncertainty reduction that is actually achieved through LCIA method refinement depends on the structure of the life cycle inventory model. We investigate the general structure of inventory models using an economic input/output (I/O) life cycle assessment model of the U.S. economy. In particular, we study the results of applying a streamlining algorithm to the I/O LCA model. The streamlining algorithm retains only those "branches" of the process tree that are jointly required to account for a specified fraction of the total impacts upstream of each point in the tree. We examine the implications of these "tree pruning" results for site-informed LCIA. Percentiles are presented for U.S. commodities and several important pollutants, for the share of total upstream emissions contributed by the set of processes in each supply tier, that is, each set of processes that directly supply inputs to another set of processes Capturing at least 90% of the total direct plus upstream emissions for criteria air pollutants and toxic releases for at least 75% of the commodities in the U.S. economy requires full modeling of direct emissions plus the first five supply tiers. The requirements for capturing a high percentage (e.g., >80%) of total emissions vary widely across products or commodities. To capture more than 60% of total emissions for more than half of all commodities requires models with more than 4,000 process instances. To well characterize the total impacts of products, life cycle impact assessment methods must characterize foreground process impacts in a site-informed way and mean impacts of far-removed processes in an unbiased way.

Air Pollutants↗
PubMed2006

Expanded polyglutamines impair synaptic transmission and ubiquitin-proteasome system in Caenorhabditis elegans.

Polyglutamine (polyQ) expansion in many proteins, including huntingtin and ataxin-3, is pathogenic and responsible for neuronal dysfunction and degeneration. Although at least nine neurodegenerative diseases are caused by expanded polyQ, the pathogenesis of these diseases is still not well understood. In the present study, we used Caenorhabditis elegans to study the molecular mechanism of polyQ-mediated toxicity. We expressed full-length and truncated ataxin-3 with different lengths of polyQ in the nervous system of C. elegans. We show that expanded polyQ interrupts synaptic transmission, and induces swelling and aberrant branching of neuronal processes. Using an ubiquitinated fluorescence reporter construct, we also showed that polyQ aggregates impair the ubiquitin-proteasome system in C. elegans. These results may provide information for further understanding the pathogenesis of polyQ diseases.

Animals↗
PubMed1993

Cell and oxygen flow in arterioles controlling capillary perfusion.

Measurements of hemodynamic and oxygen transport characteristics in the arterioles that control capillary perfusion in striated muscle were used to compare oxygen flow into adjacent capillary networks. Observations were made in arterioles arising consecutively (branches 1-3 and the last branch) from a single transverse arteriole. During maximal dilation [after 5 min of exposure to superfusate with 10(-4) M adenosine (ADO)], mean cell flow into branches decreased significantly with increasing axial distance along the transverse arteriole, from 8.47 +/- 2.43 x 10(3) (SE) cells/s in branch 1 to 5.56 +/- 2.14 x 10(3), 3.21 +/- 1.30 x 10(3), and 4.00 +/- 1.33 x 10(3) cells/s in successive branches. During control, cell fluxes were not significantly different by position (2.21 +/- 1.12, 1.31 +/- 0.42, 0.97 +/- 0.31, and 1.23 +/- 0.40 cells/s in branches 1, 2, and 3 and the last branch, respectively). Branch diameters during ADO were not significantly different by position (26.2 +/- 2.9, 24.5 +/- 1.4, 22.0 +/- 2.8, and 26.7 +/- 2.7 microns, respectively). Hemoglobin saturations during ADO were not different (59.6 +/- 2.2, 60.6 +/- 2.3, 60.3 +/- 2.3, and 61.0 +/- 2.3%, respectively), whereas mean oxygen flow into branch 1 significantly exceeded that into branches 2 and 3 and the last branch (1.40 +/- 0.40 vs. 0.60 +/- 0.17, 0.53 +/- 0.22, and 0.66 +/- 0.22 pl/min, respectively). During control, oxygen flows were not significantly different between branches. Thus, both cell and oxygen flow into these arterioles vary in a systematic way dependent on their relative branch position; regulatory processes serve to make oxygen supply more uniform.

Adenosine↗
PubMed1989

Innervation of vascular and cardiac muscle of Aplysia by multimodal motoneuron L7.

1. The cardiovascular system of Aplysia has proven to be a useful preparation for study of the neural control of circulation. To better understand the neural integration of function in this system, we have attempted to gain a more complete picture of its morphology and innervation patterns, with particular emphasis on the abdominal aorta and heart. 2. The vasoconstrictor muscle fibers of the abdominal aorta were found by dye injection to be extensively branched, with many processes that are less than 1 micron in diameter. Because of the wide spacing between individual muscle fibers, these fine processes, which have relatively few contractile filaments, may be required to mediate the electrical coupling that is observed between muscle cells. 3. L7, an identified cell in the abdominal ganglion, had been shown by others to be an excitatory motoneuron for the gill, the siphon, and the sheath-contracting muscles of the pleuroabdominal connectives, and also to excite the gill motoneurons in the branchial ganglion (5, 43, 56). We have found that this multimodal motoneuron also directly excites the auricle of the heart and the vasoconstrictor muscle of the abdominal aorta. 4. The excitatory effect of L7 on the abdominal aorta interacts synergistically with that produced by the other known excitatory inputs to that structure, the LBVc vasoconstrictor motoneurons. 5. The abdominal aorta is also richly innervated by axons immunoreactive for serotonin and for the neuropeptide FMRFamide. Serotonin inhibits the contractions of the aorta elicited by firing either L7 or the LBVC cells. In contrast, FMRFamide selectively inhibits the contractions elicited by the LBVC cells. 6. Our results suggest that a significant amount of the functional integration of the cardiovascular and respiratory systems is achieved by the use of a motoneuron common to both systems, and that there is likely to be extensive peripheral inhibitory modulation of the vasoconstrictor inputs to the abdominal aorta.

Animals↗
PubMed1999

Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation.

Embryonic metanephroi, differentiating into the adult kidney, have come to be a generally accepted model system for organogenesis. Nephrogenesis implies a highly controlled series of morphogenetic and differentiation events that starts with reciprocal inductive interactions between two different primordial tissues and leads, in one of two mainstream processes, to the formation of mesenchymal condensations and aggregates. These go through the intricate process of mesenchyme-to-epithelium transition by which epithelial cell polarization is initiated, and they continue to differentiate into the highly specialized epithelial cell populations of the nephron. Each step along the developmental metanephrogenic pathway is initiated and organized by signaling molecules that are locally secreted polypeptides encoded by different gene families and regulated by transcription factors. Nephrogenesis proceeds from the deep to the outer cortex, and it is directed by a second, entirely different developmental process, the ductal branching of the ureteric bud-derived collecting tubule. Both systems, the nephrogenic (mesenchymal) and the ductogenic (ureteric), undergo a repeat series of inductive signaling that serves to organize the architecture and differentiated cell functions in a cascade of developmental gene programs. The aim of this review is to present a coherent picture of principles and mechanisms in embryonic renal epithelia.

Animals↗
PubMed2006

Uncinatectomy: a novel surgical option for the management of intraductal papillary mucinous tumors of the pancreas.

An intraductal papillary mucinous tumor (IPMT) is a rare cystic lesion of the pancreas, comprising only 1% of all pancreatic exocrine neoplasms. The prognosis for these lesions is typically favorable as compared with invasive ductal carcinomas. Nevertheless, the management of IPMTs involves surgical resection due to their malignant potential. When located in the pancreatic head, the conventional treatment for IPMT is pancreatoduodenectomy. Some authors have advocated limited pancreatectomy for low-grade IPMTs of the pancreas, thereby decreasing the morbidity of more extensive resection. In this report, we describe our technique of minimal pancreatectomy, whereby the uncinate process and associated branch duct were completely extirpated while preserving remainder of the pancreatic head, duodenum, and pancreatic ducts. The case presented underscores the feasibility and advantages of minimal pancreatic resection in the management of such tumors.

Carcinoma, Pancreatic Ductal↗
PubMed1996

Combination warp-matching method for stereotactic neurosurgery.

Digital image warping is a growing branch of image processing that deals with geometric transformation techniques. A geometric transformation is an operating that redefines the spatial relationship between points in an image. Physically based modeling is a field strongly attracting research interest in recent years. A physically based model includes physical characteristics of things being modeled and specifies their behavior via mathematical equations. This paper presents a warp-matching method and a general non-rigid body representation suitable for physically based modeling of deformations of heterogeneous objects. The main aim is to develop a new heterogeneous warping technique to correct for distortion in medical data sets.

Humans↗
PubMed2001

Vascular endothelial cell growth factor-driven endothelial tube formation is mediated by vascular endothelial cell growth factor receptor-2, a kinase insert domain-containing receptor.

Vascular endothelial cell growth factor (VEGF) binds to 2 related receptor tyrosine kinases, known as kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase (Flt-1). The KDR has been shown to mediate VEGF-stimulated endothelial cell mitogenesis, migration, and permeability. The Flt-1 receptor has been suggested to mediate VEGF-stimulated endothelial branching morphogenesis, a process whereby endothelial cells, in the presence of a 3D milieu composed of extracellular matrix components and a mixture of growth factors, undergo a morphological transition into a tubular network with many lumina. In the present study, we have used 2 independent endothelial cell tube formation models and highly selective VEGF mutants for the KDR and Flt-1 receptors. We demonstrate that KDR, not Flt-1, stimulation is responsible for the induction of endothelial tubulogenesis. In addition, we demonstrate a modulatory role for Flt-1 in VEGF-mediated tube formation. We also report that VEGF-driven endothelial tube formation is inhibited by selective inhibitors of mitogen-activated protein kinase activation and p38 protein kinase.

Blood Vessels↗
PubMed2004

Stage-specific markers define early steps of procambium development in Arabidopsis leaves and correlate termination of vein formation with mesophyll differentiation.

During leaf development, ground meristem cells along continuous lines undergo coordinated oriented cell divisions and differentiate to form procambial cells, the precursors of all vascular cells. The molecular genetic dissection of early procambial development suffers from the lack of easily identifiable markers, especially of cell states preceding procambium formation. In this study, we have identified and characterized three reporter gene expression markers that reflect three distinct preprocambial stages, as well as one marker whose expression seems to be perfectly congruent with the appearance of procambial cells. All four markers are invariably expressed in continuous domains connected to pre-existing vasculature and their expression profiles reveal a common spatiotemporal pattern of early vein formation. We observed progressive extension of vascular strands at the preprocambial stage, suggesting that veins are initiated as freely ending preprocambial domains and that network formation occurs through subsequent fusion of these domains. Consistent with this interpretation, we demonstrate that veins are generally not programmed to become freely ending or interconnected network elements. Instead, we found that the progressive extension of preprocambial domains can be interrupted experimentally and that this leads to less complex vein patterns consisting of fewer vein orders, in which even lower-order veins become freely ending. Mesophyll differentiation turned out to be strictly correlated with the termination of preprocambial domain extension. These findings suggest that Arabidopsis vein pattern is not inherently determinate, but arises through reiterative initiation of new preprocambial branches until this process becomes terminated by the differentiation of mesophyll.

Arabidopsis↗
PubMed2004

Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the Drosophila trachea.

The migration of cellular extensions is guided by signals from tissues with which they contact. Many axon guidance molecules regulate growth cone migration by directly regulating actin cytoskeletal dynamics. Secreted morphogens control global patterns of cell fate decisions during organogenesis through transcriptional regulation, and constitute another class of guidance molecules. We have investigated the guidance roles of the morphogens Hedgehog and Decapentaplegic during directed outgrowth of cytoplasmic extensions in the Drosophila trachea. A subset of tracheal terminal cells adheres to the internal surface of the epidermis and elongates cytoplasmic processes called terminal branches. Hedgehog promotes terminal branch spreading and its extension over the posterior compartment of the epidermis. Decapentaplegic, which is expressed at the onset of terminal branching, restricts dorsal extension of the terminal branch and ensures its monopolar growth. Orthogonal expression of Hedgehog and Decapentaplegic in the epidermis instructs monopolar extension of the terminal branch along the posterior compartment, thereby matching the pattern of airway growth with that of the epidermis.

Adaptor Proteins, Signal Transducing↗