scholarly journals Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jie Li ◽  
Guijun Shang ◽  
Yu-Ju Chen ◽  
Chad A Brautigam ◽  
Jen Liou ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Ternary Complexes ◽  
Common Mechanism ◽  
Dimeric Complex ◽  
Receptor Complexes ◽  
Extracellular Region ◽  
Atomic Interactions ◽  
Close Proximity ◽  
The Common ◽  
Tetrameric Assembly

RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands.

STUDY OF PEDIATRIC INJURIES: PATTERNS AND OUTCOME

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Yasir. B. Elshambaty
Keyword(s):  
School Level ◽  
Common Mechanism ◽  
Injury Patterns ◽  
Severe Injuries ◽  
Injured Child ◽  
Cross Sectional ◽  
Pediatric Injuries ◽  
Pediatric Injury ◽  
The Common ◽  
Structured Questionnaire

Purpose this study aims to show the patterns and outcome of pediatric injury among those living in Albaha region in Saudi Arabia Methods this is a cross-sectional descriptive household-based study, included children between 0-17 years old both male and female. The data were collected with structured questionnaire between 20 Nov – 20 Dec 2018 and  analyzed with SPSS version 25 Results the total of participants was 257 injured child. 199(77.4%) are male and 58(22.6%) are female. About 44%of them were injured at pre-school level and 56% were traumatized at school age. The least incidence of injury occurred in those less than 2 yrs and higher incidence in those between 3-10 yrs old. The most common mechanism of injury was falling from height. The most affected group age by RTA accidents was 11-17 yrs old. Approximately 83% of the injured children required hospital management. Only one third of the injuries were  associated complications. The most common injured anatomic part was the upper limb and the least affected part was the spine. Only 5% of the injuries were associated with a disability and the common was loss of organ or part of it. Paralysis occurred in less than 1% and head injury resulted in disabilities more than 1%. Conclusion the vast majority of the injuries in our participants are not serious. The severe injuries were associated with RTA-related trauma. Most of injuries due to falling from height are not serious. We recommend not to allow the children to drive cars. Keywords: pediatric injuries; injury patterns; household.

scholarly journals Evidence for biological shaping of hair ice

2015 ◽  
Vol 12 (14) ◽  
pp. 4261-4273 ◽  
Author(s):  
D. Hofmann ◽  
G. Preuss ◽  
C. Mätzler
Keyword(s):  
Organic Matter ◽  
Dead Wood ◽  
Complex Mixture ◽  
Fulvic Acids ◽  
Common Mechanism ◽  
Ice Growth ◽  
Physical Chemical ◽  
Broad Leaf ◽  
The Common

Abstract. An unusual ice type, called hair ice, grows on the surface of dead wood of broad-leaf trees at temperatures slightly below 0 °C. We describe this phenomenon and present physical, chemical, and biological investigations to gain insight in the properties and processes related to hair ice. Tests revealed that the biological activity of a winter-active fungus is required in the wood for enabling the growth of hair ice. We confirmed the fungus hypothesis originally suggested by Wegener (1918) by reproducing hair ice on wood samples. Treatment by heat and fungicide suppresses the formation of hair ice. Fruiting bodies of Asco- and Basidiomycota are identified on hair-ice-carrying wood. One species, Exidiopsis effusa (Ee), was present on all investigated samples. Both hair-ice-producing wood samples and those with killed fungus show essentially the same temperature variation, indicating that the heat produced by fungal metabolism is very small, that the freezing rate is not influenced by the fungus activity, and that ice segregation is the common mechanism of ice growth on the wood surface. The fungus plays the role of shaping the ice hairs and preventing them from recrystallisation. Melted hair ice indicates the presence of organic matter. Chemical analyses show a complex mixture of several thousand CHO(N,S) compounds similar to fulvic acids in dissolved organic matter (DOM). The evaluation reveals decomposed lignin as being the main constituent. Further work is needed to clarify its role in hair-ice growth and to identify the recrystallisation inhibitor.

scholarly journals Cytokine Imbalance as a Common Mechanism in Both Psoriasis and Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Yong Tan ◽  
Qiu Qi ◽  
Cheng Lu ◽  
Xuyan Niu ◽  
Yanping Bai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanism ◽  
Mononuclear Cells ◽  
Mitogen Activated Protein Kinase ◽  
Common Mechanism ◽  
New Paradigm ◽  
Peripheral Blood Mononuclear ◽  
The Common ◽  
Common Pathogenesis ◽  
Cytokine Imbalance

Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism. In total, 120 and 212 DEGs were identified in PS and RA, respectively, and 31 shared DEGs were identified. Bioinformatics analysis indicated that the cytokine imbalance relevant to key molecules (such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), colony-stimulating factor 3 (CSF3), interleukin- (IL-) 6, and interferon gene (IFNG)) and canonical signaling pathways (such as the complement system, antigen presentation, macropinocytosis signaling, nuclear factor-kappa B (NF-κB) signaling, and IL-17 signaling) was responsible for the common comprehensive mechanism of PS and RA. Our findings provide a better understanding of the pathogenesis of PS and RA, suggesting potential strategies for treating and preventing both diseases. This study may also provide a new paradigm for illuminating the common pathogenesis of different diseases.

scholarly journals Role of Klotho in Chronic Calcineurin Inhibitor Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Kang Luo ◽  
Sun Woo Lim ◽  
Yi Quan ◽  
Sheng Cui ◽  
Yoo Jin Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Calcineurin Inhibitor ◽  
Calcineurin Inhibitors ◽  
Common Mechanism ◽  
Protective Mechanism ◽  
Klotho Protein ◽  
The Common ◽  
And Oxidative Stress

Calcineurin inhibitors (CNIs) are the most popular immunosuppressants in organ transplantation, but nephrotoxicity is a major concern. The common mechanism underlying chronic CNI nephropathy is oxidative stress, and the process of chronic CNI nephropathy is similar to that of aging. Current studies provide evidence that antiaging Klotho protein plays an important role in protecting against oxidative stress, and its signaling is a target for preventing oxidative stress-induced aging process. In this review, we focus on the association between Klotho and oxidative stress and the protective mechanism of action of Klotho against oxidative stress in chronic CNI nephropathy. In addition, we discuss the delivery strategy for Klotho in CNI-induced nephropathy.

Mouse macrophage development in the absence of the common γ chain: defining receptor complexes responsible for IL-4 and IL-13 signaling

1997 ◽  
Vol 27 (7) ◽  
pp. 1762-1768 ◽  
Author(s):  
Åsa Andersson ◽  
Susanne M. Grunewald ◽  
Albert Duschl ◽  
Alain Fischer ◽  
James P. Disanto
Keyword(s):  
Mouse Macrophage ◽  
Receptor Complexes ◽  
The Common

Mechanical determinants of left ventricular relaxation in isovolumically beating hearts

1995 ◽  
Vol 268 (1) ◽  
pp. H170-H177 ◽  
Author(s):  
A. H. Tobias ◽  
B. K. Slinker ◽  
R. D. Kirkpatrick ◽  
K. B. Campbell
Keyword(s):  
Muscle Length ◽  
Wall Stress ◽  
Left Ventricular ◽  
Common Mechanism ◽  
Ventricular Relaxation ◽  
Time Period ◽  
Relaxation Experiments ◽  
The Common ◽  
Lv Volume ◽  
Developed Pressure

Both pressure and volume have been proposed to determine the speed of left ventricular (LV) relaxation, but their relative importance is not known. Accordingly, we used isolated, buffer-perfused, isovolumically beating ferret hearts to study the effects of maximal developed pressure (Pdmax) and LV volume (V) on the speed of LV relaxation. Experiments were performed at 30 degrees C, and the hearts were paced at a baseline interbeat interval (BI) of 800 ms. Pdmax was varied independently of V by use of seven BI (75 to 133% of baseline BI), which resulted in test beats that developed a range of Pdmax due to varying degrees of restitution. Pdmax was also varied by setting V at five levels (80 to 120% of baseline V) during the test beats. Speed of relaxation was quantified as the time period of pressure decay from 75 to 25% Pdmax (T75–25). Data were analyzed by multiple linear regression. Increases in both Pdmax and V independently prolonged T75-25, and T75–25 was 1.45 times more sensitive to Pdmax than to V. However, when Pdmax and V were combined to estimate maximal wall stress (sigma max), the effects of Pdmax and V, as well as relative circumferential muscle length (estimated by V1/3), were not important determinants, and T75–25 depended on sigma max alone. Thus we conclude that 1) Pdmax and V are both determinants of the speed of LV relaxation and that Pdmax is approximately 1.5 times more important than V, and 2) the effects of Pdmax and V on relaxation act via the common mechanism of sigma max.

scholarly journals The material-weight illusion disappears or inverts in objects made of two materials

2019 ◽  
Vol 121 (3) ◽  
pp. 996-1010 ◽  
Author(s):  
Vivian C. Paulun ◽  
Gavin Buckingham ◽  
Melvyn A. Goodale ◽  
Roland W. Fleming
Keyword(s):  
Bayesian Inference ◽  
Weight Distribution ◽  
Weight Perception ◽  
Sensory Information ◽  
Common Mechanism ◽  
Potential Candidate ◽  
Bayesian Integration ◽  
The Common ◽  
Weight Illusion

The material-weight illusion (MWI) occurs when an object that looks heavy (e.g., stone) and one that looks light (e.g., Styrofoam) have the same mass. When such stimuli are lifted, the heavier-looking object feels lighter than the lighter-looking object, presumably because well-learned priors about the density of different materials are violated. We examined whether a similar illusion occurs when a certain weight distribution is expected (such as the metal end of a hammer being heavier), but weight is uniformly distributed. In experiment 1, participants lifted bipartite objects that appeared to be made of two materials (combinations of stone, Styrofoam, and wood) but were manipulated to have a uniform weight distribution. Most participants experienced an inverted MWI (i.e., the heavier-looking side felt heavier), suggesting an integration of incoming sensory information with density priors. However, a replication of the classic MWI was found when the objects appeared to be uniformly made of just one of the materials ( experiment 2). Both illusions seemed to be independent of the forces used when the objects were lifted. When lifting bipartite objects but asked to judge the weight of the whole object, participants experienced no illusion ( experiment 3). In experiment 4, we investigated weight perception in objects with a nonuniform weight distribution and again found evidence for an integration of prior and sensory information. Taken together, our seemingly contradictory results challenge most theories about the MWI. However, Bayesian integration of competing density priors with the likelihood of incoming sensory information may explain the opposing illusions. NEW & NOTEWORTHY We report a novel weight illusion that contradicts all current explanations of the material-weight illusion: When lifting an object composed of two materials, the heavier-looking side feels heavier, even when the true weight distribution is uniform. The opposite (classic) illusion is found when the same materials are lifted in two separate objects. Identifying the common mechanism underlying both illusions will have implications for perception more generally. A potential candidate is Bayesian inference with competing priors.

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