The C system of cattle blood groups. 1. Additional factors in the system

Four additional cattle blood group antigenic factors, provisionally termed Fl, F6, F10 and F15, were shown to belong to the C system. Factor Fl appears to be a linear subtype of C"(initially designated F2, or P1B1). It is suggested that future international nomenclature should adopt C", and C"₂ in place of Fl and C . No phenogroup was found to include C" together with C₂ or C₁, but a few phenogroups lack the three factors. Thus C₁, C₂ and C"do not form a closed system within the C system as concluded by Duniec et al. (1973). The effectiveness of the additional factors to uncover the genetic variability of the C system, and to translate phenotypes into genotypes is exemplified in the Charolais breed.     

Factor 420-dependent tyridine nucleotide-linked hydrogenase system of Methanobacterium ruminantium.

Methanobacterium ruminantium was shown to possess a nicotinamide adenine dinucleotide phosphate (NADP)-linked factor 420 (F420)-dependent hydrogenase system. This system was also shown to be present in Methanobacterium strain MOH. The hydrogenase system of M. ruminantium also links directly to F420, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), methyl viologen, and Fe-3 plus. It has a pH optimum of about 8 and an apparent Km for F420 of about 5 x 10-6 M at pH 8 when NADP is the electron acceptor. The F420-NADP oxidoreductase activity is inactive toward nicotinamide adenine dinucleotide (nad) and no NADPH:NAD or FADH2(FMNH2):NAD transhydrogenase system was detected. Neither crude ferredoxin nor boiled crude extract of Clostridium pasteuranum could replace F420 in the NADP-linked hydrogenase reaction of M. ruminantium. Also, neitther F420 nor a curde "ferredoxin" fraction from M. ruminantium extracts could substitute for ferredoxin in the pyruvate-ferredoxin oxidoreductase reaction of C. pasteurianum.     

The C system of cattle blood groups. 2. Partial genetic map of the system

20 cases of irregular inheritance of phenogroups in the C system of cattle blood groups were used to deduce a partial genetic map of this system, taking into consideration the 11 internationally recognized antigenic factors and the 4 additional factors recently described by Grosclaude et al. (1980). This partial map bears resemblance to that established by Bouw et al. (1974) in Dutch cattle.
The operational length of the DNA sequence coding for the C system was estimated to be 0.3 centimorgan, a value which is approximately half of that obtained for the B system by Grosclaude et al. (1979). It is concluded that the phenogroups of the C system, like those of the B system, are controlled by a cluster of loci.     

The C system of cattle blood groups. 2. Partial genetic map of the system

20 cases of irregular inheritance of phenogroups in the C system of cattle blood groups were used to deduce a partial genetic map of this system, taking into consideration the 11 internationally recognized antigenic factors and the 4 additional factors recently described by Grosclaude et al. (1980). This partial map bears resemblance to that established by Bouw et al. (1974) in Dutch cattle. The operational length of the DNA sequence coding for the C system was estimated to be 0.3 centimorgan, a value which is approximately half of that obtained for the B system by Grosclaude et al. (1979). It is concluded that the phenogroups of the C system. like those of the B system, are controlled by a cluster of loci.     

Hybrid dysgenesis in Drosophila melanogaster: influence of temperature on cytotype determination in the P-M system

Summary In Drosophila melanogaster, the P-M system of hybrid dysgenesis is a syndrome of germ line abnormalities, including temperature dependent gonadal dysgenesis (GD sterility), high rates of mutation and male recombination, which occurs in some interstrain hybrids but only from one of the two crosses. In the P-M system, hybrid dysgenesis results from interaction between chromosomally transposable elements of the P element family and a particular extrachromosomal state referred to as the M cytotype. Cytotype (M or P) is known to be determined by the absence or presence of chromosomal factors, but principally with limited cytoplasmic transmission.In a series of experiments in which F1 hybrid females from various P and M strains were submitted to different preadult and ageing temperature treatments, it was found that the cytotype switch is strongly temperature-dependent in the F1 females from M x P but not in the reciprocal cross. In the F1 females from the former cross, a strong M cytotype occurs at a low developmental temperature (18° C) and a weak M cytotype occurs at a high developmental temperature (26.5° C). On the other hand, a high ageing temperature applied after a low developmental temperature switches the cytotype from M to P and reciprocally, a low ageing temperature applied after a high developmental temperature switches the cytotype from P to M.This thermo-reversibility of the extrachromosomal state exists only in the F1 females from M mothers but not in the F1 females from P mothers; this dissymmetrical behavior is discussed in relation to the mechanism proposed by O'Hare and Rubin (1983) which explains cytotype determination by a positive feedback of the regulator of the P transposase on its own level of activity.     

Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells.

Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1----4Glc beta 1----Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of "cascade" reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.     

Functional fragments of a relictual gametophytic self-incompatibility system are associated with the loci determining flower type of the heterostylous outcrosser Fagopyrum esculentum Moench. and the homostylous selfer F. homotropicum ohnishi

Functional fragments of presumably a relictual gametophytic self-incompatibility system (GSI) linked with the loci determining flower type were discovered by genetic analysis of an unilateral pre-zygotic barrier between the short-styled (thrum) morph of a heterostylous cross-pollinated species, Fagopyrum esculentum Moench., and a self-pollinator with homostylous flowers, F. homotropicum Ohnishi (asseccion C9139). The relic genes of GSI were revealed only in interspecific crosses. However, this is a direct experimental confirmation of a hypothesis proposed by Lewis (1954) which combined the heterostyly supergene components (G, P and A) with "pistil" and "pollen" parts of the S-locus of homomorphic self-incompatibility systems (I1 and I2). Also, this result provides strong evidence for the evolution of heterostyly upon the ruins of a gametophytic self-incompatibility system.     

Study of a therapeutic concentrate of factor VIII/vWf prepared in a closed system

An original procedure of preparation in a closed system of high purity Factor VIII concentrate is presented. Starting from cryoprecipitates, this method involves a first step of partial removal of fibrinogen by glycine precipitation (1.6 M) and a second step of Factor VIII concentration by cryoprecipitation. The yield is 16.5% of plasmatic F VIII:C (0.8 mu/ml.). Several batches of concentrates thus prepared are compared "in vitro" to 9 other commercially available concentrates from 8 different manufactories. The results show that most of the characteristics of our concentrate are within the range of specifications of other commercially available high-purity F VIII concentrate: F VIII: C activity (CRTS Lille concentrate: 25-40 U/ml.; other concentrates: 25-50 U/ml) solubility, specific activity (CRTS lille concentrate; 1.0-1.82 U F VIII:C/mg protein and 1.79-4.8 U F VIII: C/mg clottable proteins; other concentrates: 0.53-2.79 U F VIII:C/mg protein an 1.39-4.84 U F VIII:C/mg clottable proteins), isoagglutinin titers (CRTS Lille concentrate: 2-8 anti-A, 0.16 anti-B; other concentrates: 0-64 anti-A, 8-16 anti-B) F VIIIC/F VIII R: Ag ratios (CRTS Lille concentrate: 0.18-0.49; other concentrates: 0.20-0.42). Furthermore F VIII R:Ag electrophoretic mobility studied by crossed immunoelectrophoresis add F VIII R: RCo assays provide evidence that very high molecular weight multimeric forms of F VIII/vWf which support vWf activity are present in our concentrate. "In vivo" study and clinical efficacy in vWd patients confirm these results and show that our concentrate is appropriate for the treatment of patients with F VIII:C or V VIII R:RCo deficiency.     

DNA-directed in vitro synthesis of beta-galactosidase. Studies with purified factors

The phage DNA-directed synthesis of beta-galactosidase has been examined in a system containing the following purified Escherichia coli factors: RNA polymerase; cyclic AMP receptor protein; N10-formyltetrahydrofolate Met-tRNAf transformylase; initiation factors 1, 2, and 3; elongation factors Tu, Ts, and G; release factors 1 and 2; 20 aminoacyl-tRNA synthetases; L factor (Kung, H. F., Spears, C., and Weissbach, H. (1974) J. Biol. Chem. 250, 1556-1562); and Lalpha (Kung, H.-F., Spears, C., and Weissbach, H. (1976) Fed. proc. 35, 1537). Under these conditions, beta-galactosidase synthesis occurs at less than 1% of the rate obtained with unfractionated extracts, which suggested that other required components were lacking. The difficulty in obtaining large amounts of the purified aminoacyl-tRNA synthetases for these studies made it necessary to modify the system. It was possible to conserve many of the purified aminoacyl-tRNA synthetases since at least 13 of them could be replaced by an Ehrlich ascites extract. The ascites extract plus other E. coli purified factors was used as a basic system to search for additional components required for beta-galactosidase synthesis. The present report describes the purification from E. coli extracts of three fractions, called Lbeta, Lgamma, and Ldelta, that are needed to restore enzyme synthesis.     

Cell-mediated suppression of the fifth component of complement in mice.

Suppression of levels of circulating C5 in (C5- C5+)F1 hybrids by administration of (C5- C5-) parental lymphoid cells in the neonatal period has been accomplished with the three strain combinations tested ((SWR X RIII)F1, (A/He x RIII)F1, and (SWR X DBA/1)F1). Suppression was shown to be specific for C5 and not accompanied by reductions of C1, C2, C6, or other major groups of blood proteins. This demonstrated that the C5 reduction was not due to activation of complement (C) with resultant hypercatabolism of C components. When there was a concurrent chronic GVH reaction induced by lymphoid cells administered to offspring of H-2 incompatible parents, there was usually a resultant hypergammaglobulinemia that was also unrelated to the presence or absence of C5 suppression. Effective suppression required preimmunization of either the cell donor, the mother of the F1 hybrids, or both. This suggests that either two cell types or a single cell plus a humoral factor are required for suppression in this system.     

Auxin and Monocot Development

Monocots are known to respond differently to auxinic herbicides; hence, certain herbicides kill broadleaf (i.e., dicot) weeds while leaving lawns (i.e., monocot grasses) intact. In addition, the characters that distinguish monocots from dicots involve structures whose development is controlled by auxin. However, the molecular mechanisms controlling auxin biosynthesis, homeostasis, transport, and signal transduction appear, so far, to be conserved between monocots and dicots, although there are differences in gene copy number and expression leading to diversification in function. This article provides an update on the conservation and diversification of the roles of genes controlling auxin biosynthesis, transport, and signal transduction in root, shoot, and reproductive development in rice and maize.Auxinic herbicides have been used for decades to control dicot weeds in domestic lawns (Fig. 1A), commercial golf courses, and acres of corn, wheat, and barley, yet it is not understand how auxinic herbicides selectively kill dicots and spare monocots (Grossmann 2000; Kelley and Reichers 2007). Monocots, in particular grasses, must perceive or respond differently to exogenous synthetic auxin than dicots. It has been proposed that this selectivity is because of either limited translocation or rapid degradation of exogenous auxin (Gauvrit and Gaillardon 1991; Monaco et al. 2002), altered vascular anatomy (Monaco et al. 2002), or altered perception of auxin in monocots (Kelley and Reichers 2007). To explain these differences, there is a need to further understand the molecular basis of auxin metabolism, transport, and signaling in monocots.Open in a separate windowFigure 1.Differences between monocots and dicots. (A) A dicot weed in a lawn of grasses. Note the difference in morphology of the leaves. (B) Germinating dicot (bean) seedling. Dicots have two cotyledons (cot). Reticulate venation is apparent in the leaves. The stem below the cotyledons is called the hypocotyl (hyp). (C) Germinating monocot (maize) seedling. Monocots have a single cotyledon called the coleoptile (col) in grasses. Parallel venation is apparent in the leaves. The stem below the coleoptile is called the mesocotyl (mes).Auxin, as we have seen in previous articles, plays a major role in vegetative, reproductive, and root development in the model dicot, Arabidopsis. However, monocots have a very different anatomy from dicots (Raven et al. 2005). Many of the characters that distinguish monocots and dicots involve structures whose development is controlled by auxin: (1) As the name implies, monocots have single cotyledons, whereas dicots have two cotyledons (Fig. 1B,C). Auxin transport during embryogenesis may play a role in this difference as cotyledon number defects are often seen in auxin transport mutants (reviewed in Chandler 2008). (2) The vasculature in leaves of dicots is reticulate, whereas the vasculature in monocots is parallel (Fig. 1). Auxin functions in vascular development because many mutants defective in auxin transport, biosynthesis, or signaling have vasculature defects (Scarpella and Meijer 2004). (3) Dicots often produce a primary tap root that produces lateral roots, whereas, in monocots, especially grasses, shoot-borne adventitious roots are the most prominent component of the root system leading to the characteristic fibrous root system (Fig. 2). Auxin induces lateral-root formation in dicots and adventitious root formation in grasses (Hochholdinger and Zimmermann 2008).Open in a separate windowFigure 2.The root system in monocots. (A) Maize seedling showing the primary root (1yR), which has many lateral roots (LR). The seminal roots (SR) are a type of adventitious root produced during embryonic development. Crown roots (CR) are produced from stem tissue. (B) The base of a maize plant showing prop roots (PR), which are adventitious roots produced from basal nodes of the stem later in development.It is not yet clear if auxin controls the differences in morphology seen in dicots versus monocots. However, both conservation and diversification of mechanisms of auxin biosynthesis, homeostasis, transport, and signal transduction have been discovered so far. This article highlights the similarities and the differences in the role of auxin in monocots compared with dicots. First, the genes in each of the pathways are introduced (Part I, Table I) and then the function of these genes in development is discussed with examples from the monocot grasses, maize, and rice (Part II).     

Molecular and Cellular Mechanisms of Lamina-specific Axon Targeting

The specificity of synaptic connections is directly related to the functional integrity of neural circuits. Long-range axon guidance and topographic mapping mechanisms bring axons into spatial proximity of target cells and thus limit the number of potential synaptic partners. Synaptic specificity is then achieved by extracellular short-range guidance cues and cell-surface recognition cues. Neural activity may enhance the precision and strength of specific circuit connections. Here, we focus on one of the final steps of synaptic matchmaking: the targeting of synaptic layers and the mutual recognition of axons and dendrites within these layers.Perception and behavior are critically dependent on synaptic communication between specific neurons. Understanding how neurons achieve such “synaptic specificity” is therefore one of the most fundamental issues in developmental neuroscience. Langley’s notion of “chemical relations” between synaptically connected neurons (Langley 1892) and Sperry’s “chemoaffinity” hypothesis (Sperry 1963) provided a conceptual framework for the development of precise synaptic connections in the central nervous system. Sperry postulated that molecular interactions between neurons and their extracellular environment (including between and amongst axons and dendrites) ensure that connections form only between “appropriate” synaptic partners (Sperry 1963). This hypothesis has been confirmed by experimental work over the last four decades, most importantly by the identification of molecular cues that provide synaptic specificity (see Sanes and Yamagata 2009 for a recent comprehensive review). However, within this broad framework, a number of alternate mechanisms have been shown or proposed to play roles in specific aspects of such targeting processes. Here, we focus on mechanisms that underlie the formation of synaptic layers, a prominent anatomical feature of the visual system as well as many other areas of the CNS.As reviewed previously (O''Leary 2010), the chemoaffinity principle underlies the developmental process of topographic mapping. Indeed, the precision with which neurons preserve the spatial relationships between the visual world and its representation in the brain is remarkable: Across animals ranging from flies to vertebrates, axons that bear signals from adjacent points in visual space invariably choose adjacent targets in the brain (Braitenberg 1967; Lemke and Reber 2005; Sperry 1963). Thus, position-dependent guidance of axons ensures that a visuotopic map develops. However, position in space is just one attribute of a visual stimulus; others include color, brightness, edge detection, and movement. If position in visual space is encoded by localized activation within a two-dimensional field of neurons, then these other features are encoded by local circuits that act both in series and in parallel and are reiterated many times across the field (Fig. 1). These local circuit modules are often envisioned as “columns” that lie orthogonal to the topographic map, with each column corresponding to a pixel in visual space and each level of the column representing a different, specific visual feature within that pixel, such as brightness, color, etc. (Fig. 1). How these columns acquire their laminated structure represents a developmental challenge of extraordinary scale. Although long-range axon guidance and topographic mapping no doubt contribute to restricting the astronomical number of potential synaptic partners, these mechanisms are clearly not sufficient; additional mechanisms must (and do) exist that act on a local scale to provide an additional level of positional information and cell-type-specific “chemoaffinity.”Open in a separate windowFigure 1.Laminae are a fundamental organizing unit of neural circuits. Each column corresponds to a single topographic position (e.g., location on the retina). Within each column, different cell types (shown type A: blue, and type B: red) respond to different features in the visual world, such as motion or luminance. These pixels are repeated many times over and thus cover all of visual space. A simple rule of “Cell type A connects to Layer A, etc.” ensures that functional segregation is maintained in the connections from the retina to the target (parallel processing). Each pixel P1, P2, and P3 connects to a single column (C1, C2, and C3), establishing serial processing. Within each column, there are local circuits that, too, are layer-specific. Thus, laminae ensure functional specificity of both afferent-target connections and local circuit connections.A prominent principle, which guides the formation of connections between specific cell types and is a characteristic feature of CNS architecture, is the concentration of synapses in small areas. These synapse clusters can take the form of planar layers or spherical glomeruli. Although glomeruli are a specialization that appears most prominent in the olfactory system, layers, or laminae, are an almost ubiquitous feature of central nervous system architecture. Indeed, even crude histological stains reveal that axons and dendrites often accumulate in neuropil (cell-body-free areas). Cell-type-specific or single-cell labeling has shown that, within individual neuropil layers, neurites and synapses are not distributed randomly. Rather, synaptic connections arising between neurons with the same or similar functional properties are localized to particular sublaminae that distinguish synapses with different properties (Fig. 1). The structural underpinnings of this functional principle are provided by mechanisms that ensure the lamina-specific branching of the corresponding neurites. How this enormous precision is achieved is the subject of intense investigations in the Drosophila, zebrafish, chick, and mouse visual systems. We will begin by describing three anatomical regions in these model organisms. Then, we will discuss three broad principles of layer-specific targeting in the visual system, namely cell–cell recognition, guidance by matrix cues, and activity-dependent sorting of axon terminals.     

Mitochondrial DNA sequence variation and haplogroup distribution in Chinese patients with LHON and m.14484T>C

Background

Leber hereditary optic neuropathy (LHON, MIM 535000) is one of the most common mitochondrial genetic disorders caused by three primary mtDNA mutations (m.3460G>A, m.11778G>A and m. 14484T>C). The clinical expression of LHON is affected by many additional factors, e.g. mtDNA background, nuclear genes, and environmental factors. Hitherto, there is no comprehensive study of Chinese LHON patients with m.14484T>C.

Methodology/Principal Findings

In this study, we analyzed the mtDNA sequence variations and haplogroup distribution pattern of the largest number of Chinese LHON patients with m.14484T>C to date. We first determined the complete mtDNA sequences in eleven LHON probands with m.14484T>C, to discern the potentially pathogenic mutations that co-segregate with m.14484T>C. We then dissected the matrilineal structure of 52 patients with m.14484T>C (including 14 from unrelated families and 38 sporadic cases) and compared it with the reported Han Chinese from general populations. Complete mtDNA sequencing showed that the eleven matrilines belonged to nine haplogroups including Y2, C4a, M8a, M10a1a, G1a1, G2a1, G2b2, D5a2a1, and D5c. We did not identify putatively pathogenic mutation that was co-segregated with m.14484T>C in these lineages based on the evolutionary analysis. Compared with the reported Han Chinese from general populations, the LHON patients with m.14484T>C had significantly higher frequency of haplogroups C, G, M10, and Y, but a lower frequency of haplogroup F. Intriguingly, we also observed a lower prevalence of F lineages in LHON subjects with m.11778G>A in our previous study, suggesting that this haplogroup may enact similar role during the onset of LHON in the presence of m.14484T>C or m.11778G>A.

Conclusions/Significance

Our current study provided a comprehensive profile regarding the mtDNA variation and background of Chinese patients with LHON and m.14484T>C. Matrilineal background might affect the expression of LHON in Chinese patients with m.14484T>C.     

The effect of the medium on the functional and structural properties of serum albumins. III. Relation between the N-F1-, F1-F2- and F2-E transitions of human serum albumin and temperature and ionic strength

Using fluorescence parameters of tryptophanyl and bound ANS, the acid-induced structural transitions of defatted monomeric human serum albumin were measured as pH-dependences from 6 to 2.5 in the wide range of temperature (10 to 45 degrees C) and ionic strength (from 0.001 to 0.2 M NaCl or 0.067 M Na2SO4). Temperature rise and decrease in ionic strength value result in the splitting of the N-F-transition onto two stages, N-F1 and F1-F2. The N-F1-transition is accompanied by the blue shift of tryptophanyl and ANS fluorescence spectra and increase in the ANS emission yield. The F1-F2-stage is manifested in an additional blue spectral shift and a sharp drop of the ANS emission yield, which is shown to be due to the lowering of albumin affinity for the dye. In the acidic-extension stage (F2-E), the spectra undergo a red shift which means that the nanosecond dipole relaxation of protein groups and bound water becomes faster. In the F2 from, the albumin affinity for ANS is significantly lowered; the association constant of the primary binding site is lower by an order of quantity and two secondary sites are practically disappeared. The complex effect of temperature, ionic strength and pH changes on the properties of ANS-binding sites is considered as a model of possible control influences of these factors upon the albumin transport of amphiphilic anions in organism.     

Neurohypophyseal hormone-responsive renal adenylate cyclase. IV. A random-hit matrix model for coupline in a hormone-sensitive adenylate cyclase system

A "random-hit" matrix model is proposed to account for the dynamic and steady state relationship between occupation of bovine renal medullary membrane receptors by [Lys8]vasopressin (LVP) and neurohypophyseal hormones (NHH) and the associated activation of membrane-bound adenylate cyclase. The model was developed by systematic introduction of specific rules concerning receptor coupling into a general structural model which consists of two square matrices of identical size, one composed of homogeneous R ("receptor") units, the second of homogeneous C ("cyclase") units. R units are either occupied (RO) or unoccupied (RU); C units are either active (CA) or inactive (CI). Hormone molecules are envisioned to "collide" with R units randomly; collision with RU leads to "binding", and occupation is maintained for a characteristic mean occupancy time, TO. In this structure, each R unit has an "interaction field" which consists of the "twin" unit in the "C" matrix, and the 4 nearest neighbor C units surrounding the twin. Occupation of an R unit leads to activation of all CI units in the interaction field of that R; CA units in the interaction field are refractory. Thus binding at a given R may "recruit" a variable number of inactive neighboring C units (5, 4, 3, 2, 1, or 0). The model requires that there be individual coupling delays between the moment of binding at a given R and subsequent activation of CI units (mean coupling delay (Td) approximately 10% To). Activation of C units persists as long as the "parent" R is occupied and is maintained for an additional short time interval (Tp) after RO reverts to RU, corresponding to hormone dissociation from receptor. The model accounts for the following previously demonstrated relations between LVP occupation of receptors and adenylate cyclase activation in bovine renal medullary membranes: 1) the shape of the nonlinear steady state relation between normalized (percentage maximal) receptor occupation (O) and cyclase activation (A), uniformly observed in different membrane preparations: 2) variable hormone concentration-dependent trajectories of approach to the final steady state A:O value (A:Oss) which may be either monophasic or biphasic; 3) the loss of intrinsic adenylate cyclase activity observed in bovine membranes for a series of NHH analogs with progressively diminishing affinity for receptors. The model represents an explicit theory of coupling where a successive series of temporal events are quantitatively related to each other and privide major constraints to any interpretation of the molecular organization of receptors and adenylate cyclase units in membranes. The model excludes a number of mechanistic proposals and suggests a new hypothesis for membrane coupling with features which may be generally applicable to other hormone-sensitive adenylate cyclase systems.     

Schwann Cells: Development and Role in Nerve Repair

Schwann cells develop from the neural crest in a well-defined sequence of events. This involves the formation of the Schwann cell precursor and immature Schwann cells, followed by the generation of the myelin and nonmyelin (Remak) cells of mature nerves. This review describes the signals that control the embryonic phase of this process and the organogenesis of peripheral nerves. We also discuss the phenotypic plasticity retained by mature Schwann cells, and explain why this unusual feature is central to the striking regenerative potential of the peripheral nervous system (PNS).The myelin and nonmyelin (Remak) Schwann cells of adult nerves originate from the neural crest in well-defined developmental steps (Fig. 1). This review focuses on embryonic development (for additional information on myelination, see Salzer 2015). We also discuss how the ability to change between differentiation states, a characteristic attribute of developing cells, is retained by mature Schwann cells, and explain how the ability of Schwann cells to change phenotype in response to injury allows the peripheral nervous system (PNS) to regenerate after damage.Open in a separate windowFigure 1.Main transitions in the Schwann cell precursor (SCP) lineage. The diagram shows both developmental and injury-induced transitions. Black uninterrupted arrows, normal development; red arrows, the Schwann cell injury response; stippled arrows, postrepair reformation of myelin and Remak cells. Embryonic dates (E) refer to mouse development. (Modified from Jessen and Mirsky 2012; reprinted, with permission and with contribution from Y. Poitelon and L. Feltri.)