scholarly journals Threshold concentration and random collision determine the growth of the huntingtin inclusion from a stable core

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sen Pei ◽  
Theresa C. Swayne ◽  
Jeffrey F. Morris ◽  
Lesley Emtage
Keyword(s):  
Inclusion Bodies ◽  
Physical Nature ◽  
Living Cells ◽  
Threshold Concentration ◽  
Rich Mixture ◽  
Unfolded Protein ◽  
New Material ◽  
Stable Core ◽  
The Relationship

AbstractThe processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases but poorly characterized in living cells. In S. cerevisiae, inclusions formed by mutant huntingtin (mHtt) have some characteristics of biomolecular condensates but the physical nature and growth mechanisms of inclusion bodies remain unclear. We have probed the relationship between concentration and inclusion growth in vivo and find that growth of mHtt inclusions in living cells is triggered at a cytoplasmic threshold concentration, while reduction in cytoplasmic mHtt causes inclusions to shrink. The growth rate is consistent with incorporation of new material through collision and coalescence. A small remnant of the inclusion is relatively long-lasting, suggesting that it contains a core that is structurally distinct, and which may serve to nucleate it. These observations support a model in which aggregative particles are incorporated by random collision into a phase-separated condensate composed of a particle-rich mixture.

scholarly journals Threshold concentration and random collision determine the growth of the phase-separated huntingtin inclusion from a stable core

2020 ◽  
Author(s):  
Sen Pei ◽  
Theresa C. Swayne ◽  
Jeffrey F. Morris ◽  
Lesley Emtage
Keyword(s):  
Growth Rate ◽  
Confocal Microscopy ◽  
Neurodegenerative Diseases ◽  
Inclusion Bodies ◽  
Threshold Concentration ◽  
Mutant Huntingtin ◽  
Unfolded Protein ◽  
Stable Core ◽  
The Relationship

AbstractThe processes underlying formation and growth of unfolded protein inclusions are relevant to neurodegenerative diseases. In S. cerevisiae, inclusion bodies formed by mutant huntingtin have characteristics of phase-separated compartments: they are mobile, ovoid, and the contents are diffusible. We have used molecular genetics and quantitative confocal microscopy to probe the relationship between concentration and inclusion growth in vivo. Our analysis and modeling of the growth of mutant huntingtin inclusion bodies (mHtt IBs) suggests that there is a cytoplasmic threshold concentration that triggers the formation of an IB, regardless of proteasome capacity, and that reduction in cytoplasmic mHtt causes IBs to shrink. These findings confirm that the IB is a phase-separated compartment that continuously exchanges material with the cytoplasm. The growth rate of the IB is most consistent with a model in which material is incorporated through collision with the IB. A small remnant of the IB is relatively long-lasting, suggesting that the IB contains a core that is structurally distinct, and which may serve to nucleate it.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin?

1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston
Keyword(s):  
Platelet Count ◽  
Background Concentration ◽  
Serum Concentrations ◽  
Bone Marrow Depression ◽  
Serial Sampling ◽  
Control Serum ◽  
Platelet Release ◽  
Highly Correlated ◽  
The Relationship

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Dose Requirement for Replacement Therapy in Hemophilia A

1979 ◽  
Vol 42 (03) ◽  
pp. 825-831 ◽  
Author(s):  
Jean-Pierre Allain
Keyword(s):  
Clinical Effect ◽  
Hemophilia A ◽  
Clinical Results ◽  
Severe Hemophilia ◽  
Dose Requirement ◽  
Viii Level ◽  
The Relationship ◽  
In Vivo Recovery ◽  
Different Doses

SummaryIn order to determine the correlation between different doses of F. VIII and their clinical effect,. 70 children with severe hemophilia A were studied after treatment with single doses of cryoprecipitate. The relationship between plasma F. VIII levels or doses calculated in u/ kg of body weight and clinical results followed an exponential curve. Plasma F. VIII levels of 0.35 and 0.53 u/ml corresponded to 95 and 99% satisfactory treatment, respectively. Similar clinical results were obtained with 20 and 31 u/kg. When the in vivo recovery of F. VIII after lyophilized cryoprecipitate was 0.015 u/ml for each u/kg injected, plasma F. VIII levels of 0.30 and 0.47 u/ml respectively were achieved. Since home treatment is largely based on single infusions of F. VIII, it is suggested that moderate and severe hemorrhages be treated with a dose which will provide a plasma F. VIII level of 0.5 u/ml.

Shall I trust you? From child human-robot interaction to trusting relationships

2019 ◽  
Author(s):  
Cinzia Di Dio ◽  
Federico Manzi ◽  
Giulia Peretti ◽  
Angelo Cangelosi ◽  
Paul L. Harris ◽  
...  
Keyword(s):  
Behavioral Pattern ◽  
Human Robot Interaction ◽  
School Age Children ◽  
Social Relevance ◽  
Robot Interaction ◽  
Cognitive Correlates ◽  
The Social ◽  
The Relationship

Studying trust within human-robot interaction is of great importance given the social relevance of robotic agents in a variety of contexts. We investigated the acquisition, loss and restoration of trust when preschool and school-age children played with either a human or a humanoid robot in-vivo. The relationship between trust and the quality of attachment relationships, Theory of Mind, and executive function skills was also investigated. No differences were found in children’s trust in the play-partner as a function of agency (human or robot). Nevertheless, 3-years-olds showed a trend toward trusting the human more than the robot, while 7-years-olds displayed the reverse behavioral pattern, thus highlighting the developing interplay between affective and cognitive correlates of trust.

scholarly journals Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

2002 ◽  
Vol 39 (3) ◽  
pp. 203-210 ◽  
Author(s):  
John R Burnett ◽  
Samuel D Vasikaran
Keyword(s):  
Cardiovascular Disease ◽  
Bone Density ◽  
Vascular Calcification ◽  
Cholesterol Biosynthesis ◽  
Hormone Replacement ◽  
Plasma Lipid ◽  
Clinical Effects ◽  
Cardiovascular Morbidity And Mortality ◽  
The Relationship

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals Actin and Microtubules Differently Contribute to Vacuolar Targeting Specificity during the Export from the ER

Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 299
Author(s):  
Monica De Caroli ◽  
Fabrizio Barozzi ◽  
Luciana Renna ◽  
Gabriella Piro ◽  
Gian-Pietro Di Sansebastiano
Keyword(s):  
Spatial Targeting ◽  
Traffic Regulation ◽  
Emergent Features ◽  
Vacuolar Sorting ◽  
Er Export ◽  
Golgi Network ◽  
Relationship Of ◽  
The Relationship ◽  
Fine Tune

Plants rely on both actin and microtubule cytoskeletons to fine-tune sorting and spatial targeting of membranes during cell growth and stress adaptation. Considerable advances have been made in recent years in the comprehension of the relationship between the trans-Golgi network/early endosome (TGN/EE) and cytoskeletons, but studies have mainly focused on the transport to and from the plasma membrane. We address here the relationship of the cytoskeleton with different endoplasmic reticulum (ER) export mechanisms toward vacuoles. These emergent features of the plant endomembrane traffic are explored with an in vivo approach, providing clues on the traffic regulation at different levels beyond known proteins’ functions and interactions. We show how traffic of vacuolar markers, characterized by different vacuolar sorting determinants, diverges at the export from the ER, clearly involving different components of the cytoskeleton.

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