bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor-β receptors and binding proteoglycans
Authors: Boyd Frederick T. , Cheifetz Sela , Andres Janet , Laiho Marikki , Massagué Joan 
Published: May 2013

ABSTRACT
Transforming growth factors-beta (TGFs-β) are representative of a superfamily whose members were first identified as regulators of morphogenesis and differentiation, and subsequently found to be structurally related. Other members of the family include the activins and inhibins, BMPs, MIS, the DPP-C gene product and Vg-1. When assayed by affinity-labelling techniques, TGFs-β bind to three distinct cell surface proteins which are present on most cells. These proteins are all of relatively low abundance but bind TGFs-β with affinities consistent with the biological potency of the factors. The Type I and Type II binding proteins are glycoproteins with estimated molecular weights of 53 and 73×103Mr, respectively. They both bind TGFS-β significantly better than TGFS-β. The Type I receptor has been identified as the receptor which mediates many of the responses of TGFs-β, based on somatic cell genetic studies of epithelial cell mutants unresponsive to TGFs-β. Betaglycan is the third binding protein present on many, but not all, cell types and is a large proteoglycan (∼280×103Mr) with 100–120 ×103Mr core proteins. A soluble form of this molecule is present in conditioned media of many cell lines and may be derived from the cell surface-associated molecule by cleavage of a small membrane anchor. Betaglycan binds TGFS-β and TGFS-β with similar affinity and this binding is to the core proteins, not the glycosaminoglycan side chains. This molecule may have a function in the localization and delivery or the clearance of activated TGFs-β. The molecular basis of TGFS-β signalling is still largely unknown, but it is possible that one or more of these cell surface molecules signals via a novel mechanism, as the TGFs-β are biologically quite distinct from other factors that act via well-characterized signalling systems.
Growth factors influencing bone development
Authors: Wozney J. M. , Rosen V. , Byrne M. , Celeste A. J. , Moutsatsos I. , Wang E. A. 
Published: May 2013

ABSTRACT
We have approached the study of growth factors affecting cartilage and bone development by investigating those factors present in bone which are able to initiate new cartilage and bone formation in vivo. This has led to the identification and molecular cloning of seven novel human factors which we have named BMP-1 through BMP-7. Six of these molecules are related to each other, and are also distantly related to TGF-β. The presence of one of these molecules, recombinant human BMP-2 (rhBMP-2) is sufficient to produce the complex developmental system of cartilage and bone formation when implanted subcutaneously in a rat assay system. In this model, administration of rhBMP-2 ultimately results in the formation of a piece of trabecular bone, which is filled with mature bone marrow. While our studies demonstrate that rhBMP-2 by itself has the ability to induce cartilage and bone formation in vivo, we find other BMP molecules present along with BMP-2 in our highly purified nonrecombinant bone-inductive material. These results suggest that the bone inductive capacity of bone-derived proteins may reside in the combinatorial or synergistic activities of this set of BMP-2 related molecules.
Structure function relationships in EGF, TGF-α and IGFI
Authors: CAMPBELL IAIN D. , Cooke Robert M. 
Published: May 2013

ABSTRACT
The solution structures of the homologous growth factors hEGF and hTGF-α-, have been determined independently from high resolution nuclear magnetic resonance (NMR) data. A model of the insulin-like growth factor structure based on insulin coordinates (Blundell et al. (1978)Proc natn. Acad. Sci. U.S.A. 75, 180-184), has also been refined using molecular dynamics simulations with NMR-determined restraints. Knowledge of these structures, together with known sequences of other homologous proteins and experiments with site-specific residue changes, allows predictions to be made about growth factor residues which might be involved in the receptor-ligand interfaces.
Regulation of the interaction between smooth muscle myosin and actin
Authors: Trybus Kathleen M. , Warshaw David M. 
Published: May 2013

ABSTRACT
Phosphorylation of the regulatory light chain of smooth muscle myosin efficiently regulates the actin- activated ATPase activity of myosin filaments in solution and actin movement in an in vitro motility assay, independently of thin-filament regulatory proteins. Filaments containing both phosphorylated and dephosphorylated heads move actin at intermediate rates, depending on the relative proportions of the two myosin species. The decrease in velocity can be accounted for by mechanical interactions between phosphorylated heads and ‘weak-binding’ dephosphorylated crossbridges. These results imply that shortening velocity could be modulated in any muscle by varying the relative proportions of two populations of crossbridges with different cycling rates.
MAPs and motors in insect ovaries
Authors: Stebbings Howard , Hunt Cherryl , Anastasi Angela 
Published: May 2013

ABSTRACT
MAPs and microtubule motor proteins from the massive microtubule translocation complexes within the ovaries of hemipteran insects have been identified and characterized. Both classes of proteins have been compared with those of other systems, and the function of both in the insect ovaries is speculated upon.
Self-assembly pathway of nonsarcomeric myosin II
Authors: Cross R. A. , Hodge T. P. , Kendrick-Jones J. 
Published: May 2013

ABSTRACT
Cells need to control the location and timing of actomyosin-dependent force generation, and appear to do so in the first instance by regulating myosin filament self-assembly (Yumura and Fukui, 1985). The mechanism of the self-assembly is little understood. In vitro it is a true self-assembly, which requires a short domain at the C terminus of the myosin molecule. The availability of this domain appears suppressed by the folding of the molecule into a compact, looped state. In vitro, the rate at which these looped molecules unfold turns out to be a key determinant of filament number and filament length.
Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival
Authors: Sendtner Michael , Arakawa Yoshihiro , Stockli Kurt A. , Kreutzberg Georg W. , Thoenen Hans 
Published: May 2013

ABSTRACT
We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities. CNTF is expressed selectively by Schwann cells and astrocytes of the peripheral and central nervous system, respectively, but not by target tissues of the great variety of CNTF-responsive neurons. CNTF mRNA is not detectable by Northern blot or PCR analysis during embryonic development and immediately after birth. However, during the second post-natal week, a more than 30-fold increase in CNTF mRNA and protein occurs in the sciatic nerve. Since the period of low CNTF levels in peripheral nerves coincides with that of high vulnerability of motoneurons (i.e. axonal lesion results in degeneration of motoneuron cell boches), insufficient availability of CNTF may be the reason for the rate of lesion-induced cell death of early post-natal motoneurons. Highly enriched embryonic chick motoneurons in culture are supported at survival rates higher than 60 % by CNTF, even in single cell cultures, indicating that CNTF acts directly on motoneurons. In contrast to CNTF, the members of the neurotrophin gene family (NGF, BDNF and NT-3) do not support the survival of motoneurons in culture. However, aFGF and bFGF show distinct survival activities which are additive to those of CNTF, resulting in the survival of virtually all motoneurons cultured in the presence of CNTF and bFGF.
Coordination of trophic interactions by separate developmental programs in sensory neurons and their target fields
Authors: Davies Alun M. , Larmet Yves , Wright Edwina , Vogel Kristine S. 
Published: May 2013

ABSTRACT
In the developing vertebrate nervous system the survival of sensory neurons becomes dependent on neurotrophic factors when their axons reach their target fields, and the synthesis of nerve growth factor (NGF) by target field cells commences with the arrival of the earliest axons. The timing of NGF synthesis and the onset of neurotrophic factor dependence are not, however, reliant on innervation. NGF synthesis occurs on time in developing target fields in which innervation is prevented, and sensory neurons cultured before innervating their targets become dependent on neurotrophic factors for survival after a certain length of time in culture. The length of time neurons survive in culture before becoming neurotrophic factor-dependent is related to the time they would normally contact their targets in vivo-, populations of neurons that have nearby targets which are innervated early respond to neurotrophic factors before neurons that have more distant targets which are innervated later. The timing of target field innervation is governed not only by the distance axons have to grow but by the rate at which they grow. Axonal growth rate is also regulated in accordance with target distance: neurons with distant targets extend axons faster than neurons with nearby targets. In addition to reviewing evidence for separate developmental programs that control the timing of neurotrophic factor synthesis in the target field and the onset of neurotrophic factor dependence in early sensory neurons, we will consider the mechanisms that might play a role in regulating the survival of neurons during the phase of neurotrophic factor independence.
Growth factors and transcription factors in oligodendrocyte development
Authors: Collarini Ellen J. , Pringle Nigel , Mudhar Hardeep , Stevens Georgina , Kuhn Rainer , Monuki Edwin S. , Lemke Greg , Richardson William D. 
Published: May 2013

ABSTRACT
O-2A progenitor cells, the precursors of oligodendrocytes in the central nervous system (CNS), probably originate in the subventricular germinal zones of the developing CNS, and subsequently migrate away from there to populate the rest of the CNS with oligodendrocytes. We are trying to understand how the O-2A progenitor cells interact with their changing environment as they migrate, and how this influences each stage of their development into mature, myelinating oligodendrocytes. In this article we summarize evidence that platelet-derived growth factor (PDGF) is important for stimulating O-2A progenitor cell proliferation in vivo, and describe our efforts to map the distribution of PDGF and its receptors in the developing rat CNS by in situ hybridization and immunohistochemistry. These studies suggest that, in the CNS, PDGF a-receptor subunits may be restricted to O-2A lineage cells that have started to migrate away from the subventricular zones towards their final destinations. Many neurons express the A and/or B chains of PDGF, and astrocytes express the A chain, but it is not yet clear which of these cell types might be the major source of PDGF for O-2A lineage cells in vivo. O-2A progenitor cells can be purified and maintained in a proliferating state in vitro by culturing in the presence of PDGF and bFGF. Under these conditions, the POU transcription factor SCIP/Tst-1 is expressed at a high level; when oligodendrocyte differentiation is initiated by withdrawing the growth factors, SCIP/Tst-1 mRNA is rapidly down-regulated, followed by a decline in SCIP/Tst-1 protein and sequential activation of myelin-specific genes. These observations suggest that SCIP/Tst-1 may be mechanistically involved in the transition from proliferation to differentiation in the 0-2A lineage. By in situ hybridization, SCIP/Tst-1 appears also to be expressed in developing neurons, so perhaps it fulfils a similar function in several different cell lineages in the CNS.
The contrasting roles of N-CAM and N-cadherin as neurite outgrowthpromoting molecules
Authors: Doherty Patrick , Walsh Frank S. 
Published: May 2013

ABSTRACT
The neural cell adhesion molecule (N-CAM) is a prominent member of the immunoglobulin gene superfamily of recognition molecules. It operates in a calcium-independent manner to promote cell-cell adhesion. Alternative splicing of a single gene generates more than twenty N-CAM isoforms and these can be further modified by the differential addition of complex N- and O-linked carbohydrates. In contrast, N-cadherin is a major calcium-dependent adhesion molecule in the brain; it is not a member of the immunoglobulin gene superfamily and, as far as we know, exists as a single gene product with no evidence of differential post-translational modification. Both molecules are believed to operate through a homophilic binding mechanism and both are expressed at key developmental times in a number of tissues including the brain. Antibody perturbation experiments suggest that both of the above cell adhesion molecules (CAMs) can support neurite outgrowth over complex cellular substrata such as astrocytes and Schwann cells. In the present review we discuss the use of a molecular genetic approach to study the neurite outgrowth-promoting activity of these molecules. Using this approach we have found that both CAMs are potent inducers of neurite outgrowth from a variety of neurons. However, whereas a critical value of N-CAM expression is required for increased neurite outgrowth, with small increases above this value having substantial effects, N-cadherin promotes neurite outgrowth in a highly linear manner. In addition, whereas N-CAM promotes chick retinal ganglion cell (RGC) neurite outgrowth at E6 but not Ell, N-cadherin does so throughout this developmental period. These studies show fundamental differences in neuronal responsiveness to CAMs, and suggest a more dynamic regulation for N-CAM-dependent neurite outgrowth than for N-cadherin-dependent neurite outgrowth.
On the cytomechanics and fluid dynamics of growth cone motility
Authors: Heidemann Steven R. , Lamoureux Phillip , Buxbaum Robert E. 
Published: May 2013

ABSTRACT
Following a brief review of the controversy concerning the physical mechanism of growth cone advance, we present cytomechanical data to support a version of the classic model of growth cone motility. In this model, the growth cone is pulled forward by filopodial tension. Observations of growth cone behavior and axonal guidance suggest that this model should include fluid flow mechanisms as well as the original solid, elastic mechanism. Recent data are reviewed on the similarity of the fluid behavior of cytoplasm and of suspensions of cytoskeletal filaments. The thixotropic behavior of cytoplasm is used to develop a model for lamellipodial protrusion caused by filopodial tension.
Control of microtubule assembly in growth cones
Authors: Gordon-Weeks Phillip R. 
Published: May 2013

ABSTRACT
Growth cones are transient structures present at the tips of growing axons and dendrites (neurites). They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis (reviewed by Dodd and Jessell, 1988). In the last few years it has become apparent that growth cones are also involved in the assembly of the cytoskeleton of the elongating neurite (reviewed by Gordon-Weeks, 1989, 1991). We are particularly interested in the assembly of microtubules in the growth cone and its importance for neurite advance. The microtubules in the neurite are bundled into fascicles, presumably by the cross-linking action of microtubule-associated proteins (MAPs), and on entering the growth cone they splay out like the ribs of a fan with their ‘plus’ ends, the ends at which assembly takes place preferentially, oriented distally. Within the growth cone there is a large pool of assembly competent tubulin that provides subunits for microtubule elongation. Several observations point to the existence of precise mechanisms controlling assembly of this soluble tubulin pool. If the control mechanisms are disrupted the ability of the neurite to advance is severely compromised. We have examined the possibility that MAPs are important components in this control mechanism. Many of the known MAPs are present within growth cones, including MAP IB, MAP 2 and tau. Experiments with neuronal cultures and growth cones isolated as a subcellular fraction from developing rat brain point particularly toward the phosphorylated form of MAP IB as an essential component in the concerted assembly of microtubules at the growth cone and in particular in the bundling of microtubules in the neurite.
The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo
Authors: Ip Y. Tony , Levine Michael , Small Stephen J. 
Published: May 2013

ABSTRACT
The anterior-posterior (A-P) and dorsal-ventral (D-V) axes of the early Drosophila embryo are established by two key maternal morphogens: bicoid (bed) and dorsal (dl), respectively. The bed protein is expressed in a broad concentration gradient along the A-P axis, with peak levels present at the anterior pole, while dl is expressed in a gradient along the D-V axis with peak levels along the ventral surface. The two morphogens are unrelated and their gradients are formed by distinct processes. Nonetheless, we have obtained evidence that they generate sharp on/off stripes of target gene expression through a similar mechanism. Both morphogens establish overlapping patterns of transcriptional activators and repressors in the early embryo. The activators and repressors bind to closely linked sites within short (300 to 500 bp) target promoter elements that have the properties of on/off switches. The activators act in concert with the morphogen to define a broad region where target genes can be initiated. Borders of target gene expression are established by the repressors, resulting in the formation of stripes.
Molecular mechanisms leading to loss of differentiation and gain of invasiveness in epithelial cells
Authors: Birchmeier Walter , Weidner K. Michael , Behrens Jurgen 
Published: May 2013

ABSTRACT
It has been realized for some time that the loss of epithelial differentiation in carcinomas, which is accompanied by higher mobility and invasiveness of the tumor cells, is a consequence of reduced intercellular adhesion. A variety of recent reports have indicated that the primary cause for the ‘scattering’ of the cells in invasive carcinomas is a loss of the integrity of intercellular junctions. Thus, defects in expression or structure of several components of the epithelial adherens junctions (e.g. E-cadherin, a-catenin) can occur, and our increased knowledge about the molecules of the junctions allows an explanation of these defects in molecular terms in some of the cases. Furthermore, tyrosine phosphorylation of junctional components (e.g. p-catenin) appears to play a role in the assembly and disassembly of cell-cell contacts. Some of the effectors of epithelial junction formation are tyrosine protein kinases, e.g. the scatter factor/hepatocyte growth factor receptor c-Met, the FGF receptors and the pp6Osre kinase. The importance of tyrosine phosphorylation in junctions during tumor development is becoming increasingly evident.
Distribution and role of heterotrimeric G proteins in the secretory pathway of polarized epithelial cells
Authors: Stow Jennifer L. , Almeida J. Bruno de 
Published: May 2013

ABSTRACT
The movement of newly synthesized proteins in the constitutive secretory pathway, from their site of synthesis in the endoplasmic reticulum to the cell surface or to intracellular destinations, requires an orderly sequence of transport steps between membrane-bound compartments. Until recently, the trafficking and secretion of proteins through this pathway was thought to occur as a relatively automatic, unregulated series of events. Recent studies show that protein trafficking in the constitutive secretory pathway requires GTP hydrolysis by families of GTP-binding proteins (G proteins), which at multiple steps potentially provide regulation and specificity for protein trafficking. Many monomeric G proteins are known to be localized and functional on membrane compartments in the constitutive secretory pathway. Now, members of the heterotrimeric G protein family have also been localized on intracellular membranes and compartments such as the Golgi complex. We have studied the localization and targeting of Gα subunits to distinct membrane domains in polarized epithelial cells. The distribution of different Gα subunits on very specific membrane domains in cultured epithe-liai cells and in epithelial cells of the kidney cortex, is highly suggestive of roles for these G proteins in intracellular trafficking pathways. One of these G protein subunits, Gαi-3, was localized on Golgi membranes. Studies on LLC-PK 1 cells overexpressing Gαi-3 provided evidence for its functional role in regulating the transport of a constitutively secreted heparan sulfate proteoglycan through the Golgi complex. Inhibition or activation of heterotrimeric G proteins by pertussis toxin or by aluminium fluoride respectively, have provided further evidence for regulation of intracellular transport by pertussis toxin-sensitive G proteins. Although the functions of Golgi-associated G proteins are not yet understood at the molecular level, heterotrimeric G proteins have been implicated in the binding of cytosolic coat proteins and vesicle formation on Golgi membranes. Future studies will elucidate how multiple G proteins, of both the heterotrimeric and monomeric families, are involved in the regulation of Golgi function and protein trafficking in the secretory pathway.
Molecular analysis of the coiled body
Authors: Bohmann Kerstin , Ferreira João , Santama Niovi , Weis Karsten , Lamond Angus I. 
Published: May 2013

ABSTRACT
There is increasing interest in studying how specific metabolic activities within the nucleus are organised into functional domains. The best known example is the nucleolus where rRNA genes are transcribed and rRNA processed and assembled into ribosomal subunits. Other subnuclear domains have been known for many years through morphological studies but are only recently being analysed at the molecular level. Here we focus on an evolutionarily conserved nuclear domain, called the coiled body, which contains splicing snRNPs. We review recent literature on the coiled body and discuss a possible model for its biological function.
Amphiphilic Star Polymers Bearing a Triphenylene Core for Novel Dispersants of Carbon Nanotubes in Polar Media
Authors: Motoyanagi Jin , Matsumoto Tomoyuki , Shiotani Takumi , Miki Sadao , Minoda Masahiko 
Published: May 2013

Abstract
Well-defined six-armed amphiphilic star polymers (TP-C0-PMAPEG)s and (TP-C5-PMAPEG)s bearing a triphenylene core were designed as dispersants of carbon nanotubes, and synthesized via controlled radical polymerization. It was found that these star polymers were capable of forming stable dispersions of single-walled and multiwalled carbon nanotubes in polar media such as MeOH and water.
Control over Flexibility of Entangled Porous Coordination Frameworks by Molecular and Mesoscopic Chemistries
Authors: Furukawa Shuhei , Sakata Yoko , Kitagawa Susumu 
Published: May 2013

Abstract
Entangled porous coordination frameworks, wherein two or more distinct frameworks are catenated over an entire crystal, are known to demonstrate unique structural flexibilities in response to the accommodation of molecules in the voids between the frameworks. In this highlight review, we introduce key functions of entangled frameworks based on two principles of their dynamic features: shearing and displacement. We further describe strategies to control the flexibilities; one is a molecular chemistry approach to functionalize frameworks by chemical modification, and the other is a mesoscopic chemistry approach to change the physical form, in particular, the crystal size.