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21.
Background
Dilp8-mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of molting signals. We examined reasons for normal pupation but early pupal death observed in certain cases.Results
Overexpression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via upregulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25- to 30-hour-old pupae. Inhibition of elevated Ras signaling completely rescued early pupal death while post-pupation administration of ecdysone to organisms with elevated Ras signaling in eye discs partially rescued their early pupal death. Unlike the earlier known Dilp8 action in delaying pupation, hyperactivated Ras mediated elevation of pJNK signaling in imaginal discs caused Dilp8 secretion after pupariation. Ectopic expression of certain other transgene causing pupal lethality similarly enhanced pJNK and early pupal Dilp8 levels. Suboptimal ecdysone levels after 8 hours of pupation prevented the early pupal metamorphic changes and caused organismal death.Conclusions
Our results reveal early pupal stage as a novel Dilp8 mediated post-pupariation checkpoint and provide further evidence for interorgan signaling during development, wherein a peripheral tissue influences the CNS driven endocrine function.22.
Ellis RR Flanagan JR Lederman SJ 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1999,125(2):109-114
Visual size illusions have been shown to affect perceived object size but not the aperture of the hand when reaching to those
same objects. Thus, vision for perception is said to be dissociated from vision for action. The present study examines the
effect of visual-position and visual-shape illusions on both the visually perceived center of an object and the position of
a grasp on that object when a balanced lift is required. The results for both experiments show that although the illusions
influence both the perceived and the grasped estimates of the center position, the grasp position is more veridical. This
partial dissociation is discussed in terms of its implications for streams of visual processing.
Received: 17 November 1997 / Accepted: 11 September 1998 相似文献
23.
24.
Miodrag ?oli? Vesna Ili? Milo? D. Pavlovi? Takuya Tamatani Masayuki Miyasaka 《Clinical & developmental immunology》1996,5(1):37-51
The effects of monoclonal antibodies (mAbs) to cell-surface molecules, divalent cations,
and various cell-signaling and metabolic inhibitors on the binding of thymocytes to rat
thymic dendritic cells (TDC) were studied using a rosette assay. It was found that TDC/thymocyte adhesion was stronger and faster at 37°C than at 4°C. Flow cytometric analysis demonstrated that bound thymocytes were predominantly CD4+CD8+ and CD4+CD8-, but in comparison to the phenotype of whole thymocytes, they were enriched in the mature
TCRαβhi subset. The binding of thymocytes to TDC at 37°C was almost completely
dependent on Ca2+ and Mg2+ and partly on an intact cytoskeleton and calmodulin-dependent
protein kinase. The adhesion was independent of new protein synthesis and the activities of protein kinases A and C, tyrosine kinases, as well as phosphotyrosine protein phosphatases. The TDC/thymocyte adhesion at 37°C was partly blocked by anti-LFA-1
(WT.1), anti-CD18 (WT.3), and anti-ICAM-1 (1A29) mAb. MAbs to class II MHC (OX-3 and OX-6), CD4 (W3/25), CD8 (OX-8), and αβTCR (R73) stimulated the adhesion via an LFA-1-dependent pathway, whereas an anti-CD45 mAb (G3C5) stimulated the rosette formation
independently of LFA-1. MAbs to CD2 (OX-34), CD11b (ED7), CD11b/c (OX-42), and class I MHC (OX-18) were without significant effects on the adhesion process. 相似文献
25.
26.
Putney JW 《Pflügers Archiv : European journal of physiology》2005,451(1):29-34
TRPC (canonical transient receptor potential) channels are vertebrate homologs of the Drosophila photoreceptor channel, TRP. Considerable research has been brought to bear on the seven members of this family, especially with regard to their possible role in calcium entry. Unfortunately, the current literature presents a confusing picture, with different laboratories producing widely differing results and interpretations. It appears that ectopically expressed TRPC channels can be activated by phospholipase C products (generally, diacylglycerols), by stimulation of trafficking to the plasma membrane, or by depletion of intracellular Ca2+ stores. Here, I discuss the possibility that these diverse experimental findings arise because TRPC channels can, under both experimental as well as physiological conditions, be activated in three distinct ways, possibly depending on their subunit composition and/or signaling complex environment. The TRPCs may be unique among ion-channel subunit families in being able to participate in the assembly and function of multiple types of physiologically important ion channels. 相似文献
27.
Antonio Porcellini Gianfranco Fenzi E. V. Avvedimento 《Journal of molecular medicine (Berlin, Germany)》1997,75(8):567-575
Thyrotropin is the primary pituitary hor- mone which stimulates the growth and differentiation of thyroid cells. TSH binds
a specific receptor present in the plasma membrane of thyroid cells and signals the G protein transducers, which activate
different effec- tors, mainly adenyl cyclase and phospholipase C. The TSH receptor belongs to a broad class of receptors known
as seven-loop receptors because they contain a long stretch of amino acids which cross the plasma membrane seven times. Mutations
in the TSH receptor gene have been found in hyperfunctioning thyroid adenomas. These mutations are: (a) somatic (present only
in the tumor), (b) dominant (only one copy of the gene is affected), and (c) lead to the constitutive activation of the cAMP
signaling cascade. Most mutations which have been identified occur in the intracellular loop III and in the transmembrane
domain VI. Germline mutations in the same regions of the receptor have been found in congenital nonautoimmune hyperthyroidism.
In addition, germ line mutations have been described in the extracellular domain of the receptor leading to increased TSH
levels. The clinical implications of these findings are discussed.
Received: 15 January 1996 / Accepted: 8 March 1996 相似文献
28.
Vladimir Kenis Eugeniy Melchenko Ilya Mazunin Minna Pekkinen Outi Mäkitie 《American journal of medical genetics. Part A》2021,185(1):112-118
Epiphyseal chondrodysplasia, Miura type (ECDM) is a skeletal dysplasia with tall stature and distinctive skeletal features caused by heterozygous NPR2 pathogenic variants. Only four families have been reported. We present a family with five affected individuals (mother, three sons, and daughter). The mother's phenotype was relatively mild: borderline tall stature and elongated halluces operated during childhood. The children were remarkably more severely affected with tall stature, scoliosis, and elongated toes and fingers leading to suspicion of Marfan syndrome. Progressive valgus deformities (at the hips, knees, and ankles) were the main complaints and necessitated orthopedic investigations and surgery. Radiographs showed coxa valga, scoliosis, multiple pseudoepiphyses of the fingers and toes with uneven elongation of the digits and ankle valgus. The two older brothers underwent osteotomies and guided growth for axial deformities and arthrodesis for elongated halluces. Genetic testing confirmed the clinical diagnosis of ECDM: all affected individuals had a heterozygous c.2647G>A (p.Val883Met) NPR2 variant in a highly conserved region in the carboxyl‐terminal guanylyl cyclase domain. This two‐generation family elucidates the clinical and radiological variability of the disease. These rare cases are important to gain further understanding of the fundamental processes of growth regulation. 相似文献
29.
Dissecting natural killer cell activation pathways through analysis of genetic mutations in human and mouse 总被引:2,自引:1,他引:2
Summary: Natural killer (NK) cell cytotoxicity is mediated by multiple germ line-encoded activating receptors that recognize specific ligands expressed by tumor cells and virally infected cells. These activating receptors are opposed by NK inhibitory receptors, which recognize major histocompatibility complex class I molecules on potential targets, raising the threshold for NK cell activation. Once an abnormal cell has been detected, NK cells are the sentinel source of cytolytic mediators, such as granzymes and perforins, as well as interferon-γ, which can polarize the immune response to a T-helper 1 cell type. Activation signals are transmitted by adhesion-dependent pathways, immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathways, DAP10 ITAM-independent pathways, and by signaling through immunoreceptor tyrosine-based switch motifs. These pathways activate downstream signaling partners to trigger NK cell cytotoxicity. Some of these downstream molecules are unique to the various pathways, and some of these molecules are shared. Because of the complexity of signals involved in NK cell–target cell interaction, the generation of mice with targeted mutations in signaling molecules involved in adhesion, activation, or inhibition is essential for a precise dissection of the mechanisms regulating NK cell effector functions. Here we review recent advances in the genetic analysis of the signaling pathways that mediate NK cell killing. 相似文献
30.