Signal transduction and TGF-β superfamily receptors

1996 ◽  
Vol 74 (3) ◽  
pp. 299-314 ◽  
Author(s):  
Steven M. Kolodziejczyk ◽  
Brian K. Hall
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Intracellular Signaling ◽  
Specific Cell ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Wide Range ◽  
Transduction Mechanisms ◽  
Kinase Cascade

The TGF-β superfamily includes a large number of related growth and differentiation factors expressed in virtually all phyla. Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their effects. Candidate receptors fall into two primary groups, termed type I and type II receptors. Both types are serine/threonine kinases. Upon activation by the appropriate ligand, type I and type II receptors physically interact to form hetero-oligomers and subsequently activate intracellular signaling cascades, ultimately regulating gene transcription and expression. In addition, TGF-β binds to a third receptor class, type III, a membrane-anchored proteoglycan lacking the kinase activity typical of signal transducing molecules. Type III receptors appear to regulate ligand availability to type I and type II receptors. Although a number of transduction mechanisms may be available to TGF-β superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G-protein intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene regulation. The myriad responses regulated by TGF-β superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines.Key words: TGF-β superfamily, serine/threonine kinase receptors, G-proteins, Ras, cytoplasmic kinase cascade.

scholarly journals Some characteristics of dynamic spectra of solar bursts

1959 ◽  
Vol 9 ◽  
pp. 188-193 ◽  
Author(s):  
F. T. Haddock
Keyword(s):  
Type I ◽  
Type Ii ◽  
University Of Michigan ◽  
Noise Storm ◽  
Type Iii ◽  
Typical Sequence ◽  
Wide Range ◽  
Time Record ◽  
Solar Bursts ◽  
The University

The sun has been observed daily at the University of Michigan during the last year with three sweep-frequency receivers covering the 100 to 580 Mc/s band three times a second. The output is displayed as an intensity-modulated line on a precision cathode-ray tube that is photographed on a 35-mm film moving about one centimeter per minute, thereby producing a frequency-time record with solar intensities recorded as variations in photographic density. The combination of the film characteristic and the logarithmic response of the IF amplifier permits the recording of a wide range of intensities in greater detail than before. A number of typical radio events associated with solar flares have been obtained; a typical sequence is a short group of intense type III bursts (fast drifts) followed within minutes by a type II burst (slow drifts) lasting 10 to 30 minutes, and followed by a type I noise storm, with or without a continuum increase, continuing for hours or days. The type I event is usually confined to frequencies below about 200 Mc/s, whereas the type III and type II (bursts) have been recorded up to 580 Mc/s.

scholarly journals Tourmaline as a Recorder of Ore-Forming Processes in the Xuebaoding W-Sn-Be Deposit, Sichuan Province, China: Evidence from the Chemical Composition of Tourmaline

Minerals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 438
Author(s):  
Xinxiang Zhu ◽  
Markus B. Raschke ◽  
Yan Liu
Keyword(s):  
Chemical Composition ◽  
Aqueous Fluid ◽  
Sichuan Province ◽  
Coarse Grained ◽  
Gangue Mineral ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Wide Range ◽  
Granite Type

The Xuebaoding W-Sn-Be deposit located in the Songpan-Ganze Orogenic Belt (Sichuan Province, China) is a hydrothermal deposit with less developed pegmatite stage. The deposit is famous for the coarse-grained crystals of beryl, scheelite, cassiterite, apatite, fluorite, muscovite, and others. The orebody is spatially associated with the Pankou and Pukouling granites hosted in Triassic marbles and schists. The highly fractionated granites are peraluminous, Li-Rb-Cs-rich, and related to W-Sn-Be mineralization. The mineralization can chiefly be classified based on the wallrock and mineral assemblages as muscovite and beryl in granite (Zone I), then beryl, cassiterite and muscovite at the transition from granite to triassic strata (Zone II), and the main mineralized veins composed of an assemblage of beryl, cassiterite, scheelite, fluorite, and apatite hosted in metasedimentary rock units of marble and schist (Zone III). Due to the stability of tourmaline over a wide range of temperature and pressure conditions, its compositional variability can reflect the evolution of the ore-forming fluids. Tourmaline is an important gangue mineral in the Xuebaoding deposit and occurs in the late-magmatic to early-hydrothermal stage, and can thus be used as a proxy for the fluid evolution. Three types of tourmalines can be distinguished: tourmaline disseminations within the granite (type I), tourmaline clusters at the margin of the granite (type II), and tourmalines occurring in the mineralized veins (type III). Based on their chemical composition, both type I and II tourmalines belong to the alkali group and to the dravite-schorl solid solution. Type III tourmaline which is higher in X-site vacancy corresponds to foitite and schorl. It is proposed that the weakly zoned type I tourmalines result from an immiscible boron-rich aqueous fluid in the latest stage of granite crystallization, that the type II tourmalines showing skeletal texture directly formed from the undercooled melts, and that type III tourmalines occurring in the mineralized veins formed directly from the magmatic hydrothermal fluids. Both type I and type II tourmalines show similar compositional variations reflecting the highly fractionated Pankou and Pukouling granites. The higher Ca, Mg, and Fe contents of type III tourmaline are buffered by the composition of the metasedimentary host rocks. The decreasing Na content (<0.8 atoms per formula unit (apfu)) and increasing Fe3+/Fe2+ ratios of all tourmaline samples suggest that they precipitated from oxidized, low-salinity fluids. The decreasing trend of Al content from type I (5.60–6.36 apfu) and type II (6.01–6.43 apfu) to type III (5.58–5.87 apfu) tourmalines, and associated decrease in Na, may be caused by the crystallization of albite and muscovite. The combined petrographic, mineralogical, and chemical characteristics of the three types of tourmalines thus reflect the late-magmatic to early-hydrothermal evolution of the ore-forming fluids, and could be used as a geochemical fingerprint for prospecting W-Sn-Be mineralization in the Xuebaoding district.

scholarly journals Transduction and Adaptation Mechanisms in the Cilium or Microvilli of Photoreceptors and Olfactory Receptors From Insects to Humans

2021 ◽  
Vol 15 ◽  
Author(s):  
Fatima Abbas ◽  
Frans Vinberg
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Sensory Neurons ◽  
Electrical Response ◽  
Olfactory Receptors ◽  
Food Sources ◽  
Sensory Cells ◽  
Olfactory Transduction ◽  
Wide Range ◽  
Transduction Mechanisms

Sensing changes in the environment is crucial for survival. Animals from invertebrates to vertebrates use both visual and olfactory stimuli to direct survival behaviors including identification of food sources, finding mates, and predator avoidance. In primary sensory neurons there are signal transduction mechanisms that convert chemical or light signals into an electrical response through ligand binding or photoactivation of a receptor, that can be propagated to the olfactory and visual centers of the brain to create a perception of the odor and visual landscapes surrounding us. The fundamental principles of olfactory and phototransduction pathways within vertebrates are somewhat analogous. Signal transduction in both systems takes place in the ciliary sub-compartments of the sensory cells and relies upon the activation of G protein-coupled receptors (GPCRs) to close cyclic nucleotide-gated (CNG) cation channels in photoreceptors to produce a hyperpolarization of the cell, or in olfactory sensory neurons open CNG channels to produce a depolarization. However, while invertebrate phototransduction also involves GPCRs, invertebrate photoreceptors can be either ciliary and/or microvillar with hyperpolarizing and depolarizing responses to light, respectively. Moreover, olfactory transduction in invertebrates may be a mixture of metabotropic G protein and ionotropic signaling pathways. This review will highlight differences of the visual and olfactory transduction mechanisms between vertebrates and invertebrates, focusing on the implications to the gain of the transduction processes, and how they are modulated to allow detection of small changes in odor concentration and light intensity over a wide range of background stimulus levels.

Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

1984 ◽  
Vol 42 ◽  
pp. 250-251
Author(s):  
G. D. Gagne ◽  
M. F. Miller ◽  
D. A. Peterson
Keyword(s):  
Endoplasmic Reticulum ◽  
Experimental Infection ◽  
Uranyl Acetate ◽  
Type I ◽  
Cellular Injury ◽  
Type Ii ◽  
Tubular Structures ◽  
Type Iii ◽  
Type Iv ◽  
Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

scholarly journals Perforator preservation technologies (PPT) based on a new neuro-interventional classification in endovascular treatment of perforator involving aneurysms (piANs)

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chen Li ◽  
Ao-Fei Liu ◽  
Han-Cheng Qiu ◽  
Xianli Lv ◽  
Ji Zhou ◽  
...  
Keyword(s):  
Endovascular Therapy ◽  
Saccular Aneurysm ◽  
Type I ◽  
Type Ii ◽  
Fusiform Aneurysm ◽  
Type Iii ◽  
Perforating Artery ◽  
Protection Technology ◽  
Perforating Arteries

Abstract Background Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification. Methods The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed. Results Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13–50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence. Conclusions Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

scholarly journals Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

2021 ◽  
Vol 22 (1) ◽  
pp. 429
Author(s):  
Luca Bini ◽  
Domitille Schvartz ◽  
Chiara Carnemolla ◽  
Roberta Besio ◽  
Nadia Garibaldi ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Tandem Mass ◽  
Type Ii ◽  
Type Iii ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Fibrillin 1 ◽  
Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

scholarly journals Brachial supporting structure of Spiriferida (Brachiopoda)

2020 ◽  
pp. 1-15
Author(s):  
Zhiwei Yuan ◽  
Wen Guo ◽  
Dan Lyu ◽  
Yuanlin Sun
Keyword(s):  
Mantle Cavity ◽  
Family Type ◽  
Type I ◽  
Type Ii ◽  
Feeding Apparatus ◽  
Single Family ◽  
Supporting Structure ◽  
Type Iii ◽  
Type Iv ◽  
Evolutionary Lineages

Abstract The filter-feeding organ of some extinct brachiopods is supported by a skeletal apparatus called the brachidium. Although relatively well studied in Atrypida and Athyridida, the brachidial morphology is usually neglected in Spiriferida. To investigate the variations of brachidial morphology in Spiriferida, 65 species belonging to eight superfamilies were analyzed. Based on the presence/absence of the jugal processes and normal/modified primary lamellae of the spiralia, four types of brachidium are recognized. Type-I (with jugal processes) and Type-II (without jugal processes), both having normal primary lamellae, could give rise to each other by losing/re-evolving the jugal processes. Type-III, without jugal processes, originated from Type-II through evolution of the modified lateral-convex primary lamellae, and it subsequently gave rise to Type-IV by evolving the modified medial-convex primary lamellae. The evolution of brachidia within individual evolutionary lineages must be clarified because two or more types can be present within a single family. Type-III and Type-IV are closely associated with the prolongation of the crura, representing innovative modifications of the feeding apparatus in response to possible shift in the position of the mouth towards the anterior, allowing for more efficient feeding on particles entering the mantle cavity from the anterior gape. Meanwhile, the modified primary lamellae adjusted/regulated the feeding currents. The absence of spires in some taxa with Type-IV brachidium might suggest that they developed a similar lophophore to that in some extant brachiopods, which can extend out of the shell.

scholarly journals Mapping of a Yeast G Protein βγ Signaling Interaction

Genetics ◽  
1998 ◽  
Vol 150 (4) ◽  
pp. 1407-1417 ◽  
Author(s):  
Simon J Dowell ◽  
Anne L Bishop ◽  
Susan L Dyos ◽  
Andrew J Brown ◽  
Malcolm S Whiteway
Keyword(s):  
Signal Transduction ◽  
Map Kinase ◽  
G Protein ◽  
Coiled Coil ◽  
Receptor Activation ◽  
Temperature Sensitive ◽  
Hydrophobic Residues ◽  
Map Kinase Cascade ◽  
Kinase Cascade

Abstract The mating pathway of Saccharomyces cerevisiae is widely used as a model system for G protein-coupled receptor-mediated signal transduction. Following receptor activation by the binding of mating pheromones, G protein βγ subunits transmit the signal to a MAP kinase cascade, which involves interaction of Gβ (Ste4p) with the MAP kinase scaffold protein Ste5p. Here, we identify residues in Ste4p required for the interaction with Ste5p. These residues define a new signaling interface close to the Ste20p binding site within the Gβγ coiled-coil. Ste4p mutants defective in the Ste5p interaction interact efficiently with Gpa1p (Gα) and Ste18p (Gγ) but cannot function in signal transduction because cells expressing these mutants are sterile. Ste4 L65S is temperature-sensitive for its interaction with Ste5p, and also for signaling. We have identified a Ste5p mutant (L196A) that displays a synthetic interaction defect with Ste4 L65S, providing strong evidence that Ste4p and Ste5p interact directly in vivo through an interface that involves hydrophobic residues. The correlation between disruption of the Ste4p-Ste5p interaction and sterility confirms the importance of this interaction in signal transduction. Identification of the Gβγ coiled-coil in Ste5p binding may set a precedent for Gβγ-effector interactions in more complex organisms.

scholarly journals Understanding the Evolution and Applications of Intelligent Systems via a Tri-X Intelligence (TI) Model

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1080
Author(s):  
Min Zhao ◽  
Zhenbo Ning ◽  
Baicun Wang ◽  
Chen Peng ◽  
Xingyu Li ◽  
...  
Keyword(s):  
Intelligent Systems ◽  
Intelligent Manufacturing ◽  
Type I ◽  
Type Ii ◽  
Multiple Perspectives ◽  
Ternary Interaction ◽  
Physical Systems ◽  
Type Iii ◽  
Dynamic Level ◽  
Systematic Scheme

The evolution and application of intelligence have been discussed from perspectives of life, control theory and artificial intelligence. However, there has been no consensus on understanding the evolution of intelligence. In this study, we propose a Tri-X Intelligence (TI) model, aimed at providing a comprehensive perspective to understand complex intelligence and the implementation of intelligent systems. In this work, the essence and evolution of intelligent systems (or system intelligentization) are analyzed and discussed from multiple perspectives and at different stages (Type I, Type II and Type III), based on a Tri-X Intelligence model. Elemental intelligence based on scientific effects (e.g., conscious humans, cyber entities and physical objects) is at the primitive level of intelligence (Type I). Integrated intelligence formed by two-element integration (e.g., human-cyber systems and cyber-physical systems) is at the normal level of intelligence (Type II). Complex intelligence formed by ternary-interaction (e.g., a human-cyber-physical system) is at the dynamic level of intelligence (Type III). Representative cases are analyzed to deepen the understanding of intelligent systems and their future implementation, such as in intelligent manufacturing. This work provides a systematic scheme, and technical supports, to understand and develop intelligent systems.

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