Context-dependent relationships between the BMPsgbbanddppduring development of theDrosophilawing imaginal disk

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3913-3925 ◽  
Author(s):  
Robert P. Ray ◽  
Kristi A. Wharton
Keyword(s):  
Long Range ◽  
Wing Development ◽  
Type I ◽  
Developmental Context ◽  
Receptor Complexes ◽  
Wing Disk ◽  
Compartment Boundary ◽  
Mutant Phenotypes ◽  
The Relationship ◽  
Single Focus

The Drosophila BMP5/6/7/8 homolog, glass bottom boat (gbb), has been shown to be involved in proliferation and vein patterning in the wing disk. To better understand the roles for gbb in wing development, as well as its relationship with the Drosophila BMP2/4 homolog decapentaplegic (dpp), we have used clonal analysis to define the functional foci of gbb during wing development. Our results show that gbb has both local and long-range functions in the disk that coincide both spatially and functionally with the established functions of dpp, suggesting that both BMPs contribute to the same processes during wing development. Indeed, comparison of the mutant phenotypes of dpp and gbb hypomorphs and null clones shows that both BMPs act locally along the longitudinal and cross veins to affect the process of vein promotion during pupal development, and long-range from a single focus along the A/P compartment boundary to affect the processes of disk proliferation and vein specification during larval development. Moreover, we show that duplications of dpp are able to rescue many of the phenotypes associated with gbb mutants and clones, indicating that the functions of gbb are at least partially redundant with those of dpp. While this relationship is similar to that described for dpp and the BMP screw (scw) in the embryo, we show that the mechanisms underlying both local and long-range functions of gbb and dpp in the wing are different. For the local foci, gbb function is confined to the regions of the veins that require the highest levels of dpp signaling, suggesting that gbb acts to augment dpp signaling in the same way as scw is proposed to do in the embryo. However, unlike scw-dependent signals in the embryo, these gbb signals are not transduced by the Type I receptor saxophone (sax), thus, the cooperativity between gbb and dpp is not achieved by signaling through distinct receptor complexes. For the long-range focus along the A/P compartment boundary, gbb function does not appear to affect the high point of the dpp gradient, but, rather, appears to be required for low points, which is the reciprocal of the relationship between dpp and scw in the embryo. Moreover, these functions of gbb also do not require the Type I receptor sax. Given these results, we conclude that the relationships between gbb and dpp in the wing disk represent novel paradigms for how multiple BMP ligands signal during development, and that signaling by multiple BMPs involves a variety of different inter-ligand relationships that depend on the developmental context in which they act.

The relationship of IGE receptor topography to signaling activity in RBL-2H3 mast cells

1991 ◽  
Vol 49 ◽  
pp. 236-237
Author(s):  
J.R. Pfeiffer ◽  
J.C. Seagrave ◽  
C. Wofsy ◽  
J.M. Oliver
Keyword(s):  
Mast Cells ◽  
Protein A ◽  
Scattered Electron ◽  
Ige Receptor ◽  
Receptor Complexes ◽  
Ige Binding ◽  
Electron Imaging ◽  
Small Clusters ◽  
Relationship Of ◽  
The Relationship

In RBL-2H3 rat leukemic mast cells, crosslinking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor crosslinking also stimulates the redistribution of receptors on the cell surface, a process that can be observed by labeling the anti-IgE with 15 nm protein A-gold particles as described in Stump et al. (1989), followed by back-scattered electron imaging (BEI) in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37“C from a dispersed topography (singlets and doublets; S/D) to distributions dominated sequentially by short chains, small clusters and large aggregates of crosslinked receptors. These patterns can be observed (Figure 1), quantified (Figure 2) and analyzed statistically. Cells incubated with 1 μg/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors as far as chains and small clusters during a 15 min incubation period. At 3 and 10 μg/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates.

Hydrocephalus in Spinal Muscular Atrophy: A Case Report and Review of the Literature

2020 ◽  
Author(s):  
Jeetendra P. Sah ◽  
Aaron W. Abrams ◽  
Geetha Chari ◽  
Craig Linden ◽  
Yaacov Anziska
Keyword(s):  
Spinal Muscular Atrophy ◽  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Muscular Atrophy ◽  
Communicating Hydrocephalus ◽  
Type I ◽  
Review Of The Literature ◽  
Radiographic Findings ◽  
Comprehensive Review ◽  
The Relationship

AbstractIn this article, we reported a case of spinal muscular atrophy (SMA) type I noted to have tetraventricular hydrocephalus with Blake's pouch cyst at 8 months of age following intrathecal nusinersen therapy. The association of hydrocephalus with SMA is rarely reported in the literature. Development of hydrocephalus after intrathecal nusinersen therapy is also reported in some cases, but a cause–effect relationship is not yet established. The aim of this study was to describe the clinical characteristics of a patient with SMA type I and hydrocephalus, to review similar cases reported in the literature, and to explore the relationship between nusinersen therapy and development of hydrocephalus. The clinical presentation and radiographic findings of the patient are described and a comprehensive review of the literature was conducted. The adverse effect of communicating hydrocephalus related to nusinersen therapy is being reported and the authors suggest carefully monitoring for features of hydrocephalus developing during the course of nusinersen therapy.

Introduction to methods of describing the forecast on the risk of failure to the means of transport

2012 ◽  
Vol 30 (1) ◽  
pp. 119-127
Author(s):  
Henryk Tomaszek ◽  
Ryszard Kaleta ◽  
Mariusz Zieja
Keyword(s):  
Long Range ◽  
Failure Rate ◽  
Risk Of Failure ◽  
The Relationship ◽  
Preliminary Description

The paper is an attempt to describe the forecast on the risk of damages resulting from failures to the means of transport. It has been assumed that the product of the probability of failure (fault) occurrence and measures of effects thereof are to be used to estimate the risk. The below presented dependences that describe the risk of damages have been based on the failure rate. With the available literature as the basis, a preliminary description of the probability of a failure (fault) and the level of losses has been proposed. The paper gives dependences on short- and long-range risk forecasts. To determine the relationship for the probability of a failure (fault), the failure rate has been used.

scholarly journals Linkage Disequilibrium in Domestic Sheep

Genetics ◽  
2002 ◽  
Vol 160 (3) ◽  
pp. 1113-1122
Author(s):  
A F McRae ◽  
J C McEwan ◽  
K G Dodds ◽  
T Wilson ◽  
A M Crawford ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Type I Error ◽  
Statistical Significance ◽  
Domestic Sheep ◽  
Type I ◽  
Single Nucleotide ◽  
Microsatellite Genotype ◽  
Marker Distance ◽  
The Relationship ◽  
Two Populations

Abstract The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D′ were also explored. D′ was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D′ may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D′ to determine the true extent of LD.

scholarly journals Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher Agnew ◽  
Pelin Ayaz ◽  
Risa Kashima ◽  
Hanna S. Loving ◽  
Prajakta Ghatpande ◽  
...  
Keyword(s):  
Md Simulations ◽  
Kinase Domain ◽  
Structural Basis ◽  
Type I ◽  
Type Ii ◽  
Exchange Mass Spectrometry ◽  
Receptor Complexes ◽  
Bmp Receptors ◽  
Morphogenetic Protein ◽  
Smad Proteins

AbstractUpon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.

scholarly journals Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carlos G. Acevedo-Rocha ◽  
Aitao Li ◽  
Lorenzo D’Amore ◽  
Sabrina Hoebenreich ◽  
Joaquin Sanchis ◽  
...  
Keyword(s):  
Long Range ◽  
Fitness Landscape ◽  
Conformational Dynamics ◽  
P450 Monooxygenase ◽  
Access Channel ◽  
Long Range Interactions ◽  
Limited Protein ◽  
Dynamics Simulations ◽  
The Relationship ◽  
Single Enzyme

AbstractMultidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.

scholarly journals Relationship Between Incidence of Hyaline Membrane Disease and Maternal Hypertension During Pregnancy

2017 ◽  
Vol 38 (3-4) ◽  
pp. 47
Author(s):  
Lasmida Nazir Nuriman ◽  
Dadang Sjarif Hidajat
Keyword(s):  
Distress Syndrome ◽  
Hyaline Membrane Disease ◽  
Cross Sectional Study ◽  
Type I ◽  
Cross Sectional ◽  
Hypertension In Pregnancy ◽  
Hyaline Membrane ◽  
Neonatal Respiratory Distress ◽  
Maternal Hypertension ◽  
The Relationship

There have been controversies over the eiTect of hypertension in pregnancy on the incidence of type I neonatal respiratory distress syndrome or hyaline membrane disease (HMD). We investigated the relationship between the incidence of HMD and maternal hypertension during pregnancy in 91 infants at 34 weeks gestation or less. This retrospective cross sectional study included all live born babies between May 1, 1994 and April 30, 1995 at Dr. Hasan Sadikin General Hospital, Bandung. Maternal hypertension during pregnancy was diagnosed in 38 mothers of91 infants studied. The incidence of HMD (5%) in the maternal hypertension during pregnancy group was significantly lower than the 62% in the normotensive group (p<0.01). There was a negative correlation between the occurence of HMD and hypertension during pregnancy. We conclude that the risk of developing HMD in infants born to hypertensive mothers is significantly lower than those born to normotensive mothers.

LONG-RANGE CORRELATIONS IN THE PHASE-SHIFTS OF NUMERICAL SIMULATIONS OF BIOCHEMICAL OSCILLATIONS AND IN EXPERIMENTAL CARDIAC RHYTHMS

1999 ◽  
Vol 07 (02) ◽  
pp. 113-130 ◽  
Author(s):  
I. M. DE LA FUENTE ◽  
L. MARTINEZ ◽  
J. M. AGUIRREGABIRIA ◽  
J. VEGUILLAS ◽  
M. IRIARTE
Keyword(s):  
Phase Shift ◽  
Periodic Solutions ◽  
Long Range ◽  
Phase Shifts ◽  
Long Range Correlations ◽  
Rescaled Range ◽  
Biochemical Oscillations ◽  
Phase Shift Data ◽  
Relationship Of ◽  
The Relationship

In biochemical dynamical systems during each transition between periodical behaviors, all metabolic intermediaries of the system oscillate with the same frequency but with different phase-shifts. We have studied the behavior of phase-shift records obtained from random transitions between periodic solutions of a biochemical dynamical system. The phase-shift data were analyzed by means of Hurst's rescaled range method (introduced by Mandelbrot and Wallis). The results show the existence of persistent behavior: each value of the phase-shift depends not only on the recent transitions, but also on previous ones. In this paper, the different kind of periodic solutions were determined by different small values of the control parameter. It was assessed the significance of this results through extensive Monte Carlo simulations as well as quantifying the long-range correlations. We have also applied this type of analysis on cardiac rhythms, showing a clear persistent behavior. The relationship of the results with the cellular persistence phenomena conditioned by the past, widely evidenced in experimental observations, is discussed.

scholarly journals Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 533
Author(s):  
Rania F. Zaarour ◽  
Bilal Azakir ◽  
Edries Y. Hajam ◽  
Husam Nawafleh ◽  
Nagwa A. Zeinelabdin ◽  
...  
Keyword(s):  
Cell Death ◽  
Type I ◽  
Dependent Manner ◽  
Destruction Process ◽  
Tumor Cell Death ◽  
Complex Regulation ◽  
Cancer Immunotherapies ◽  
The Relationship ◽  
Shed Light

Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

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