Long term metabolic arrest and recovery of HEK293 spheroids involves NF-κB signaling and sustained JNK activation

2006 ◽  
Vol 206 (2) ◽  
pp. 526-536 ◽  
Author(s):  
Graham D. Jack ◽  
E. Andrew Mead ◽  
James F. Garst ◽  
M. Carla Cabrera ◽  
Andrea M. DeSantis ◽  
...  
Keyword(s):  
Metabolic Arrest ◽  
Jnk Activation

scholarly journals Increasing intracellular trehalose is sufficient to confer desiccation tolerance toSaccharomyces cerevisiae

2015 ◽  
Vol 112 (19) ◽  
pp. 6122-6127 ◽  
Author(s):  
Hugo Tapia ◽  
Lindsey Young ◽  
Douglas Fox ◽  
Carolyn R. Bertozzi ◽  
Douglas Koshland
Keyword(s):  
Desiccation Tolerance ◽  
Protein Misfolding ◽  
De Novo ◽  
Metabolic Effects ◽  
The Media ◽  
Metabolic Arrest ◽  
Induced Tolerance ◽  
High Level ◽  
Protein Misfolding And Aggregation

Diverse organisms capable of surviving desiccation, termed anhydrobiotes, include species from bacteria, yeast, plants, and invertebrates. However, most organisms are sensitive to desiccation, likely due to an assortment of different stresses such as protein misfolding and aggregation, hyperosmotic stress, membrane fracturing, and changes in cell volume and shape leading to an overcrowded cytoplasm and metabolic arrest. The exact stress(es) that cause lethality in desiccation-sensitive organisms and how the lethal stresses are mitigated in desiccation-tolerant organisms remain poorly understood. The presence of trehalose in anhydrobiotes has been strongly correlated with desiccation tolerance. In the yeastSaccharomyces cerevisiae, trehalose is essential for survival after long-term desiccation. Here, we establish that the elevation of intracellular trehalose in dividing yeast by its import from the media converts yeast from extreme desiccation sensitivity to a high level of desiccation tolerance. This trehalose-induced tolerance is independent of utilization of trehalose as an energy source, de novo synthesis of other stress effectors, or the metabolic effects of trehalose biosynthetic intermediates, indicating that a chemical property of trehalose is directly responsible for desiccation tolerance. Finally, we demonstrate that elevated intracellular maltose can also make dividing yeast tolerant to short-term desiccation, indicating that other disaccharides have stress effector activity. However, trehalose is much more effective than maltose at conferring tolerance to long-term desiccation. The effectiveness and sufficiency of trehalose as an antagonizer of desiccation-induced damage in yeast emphasizes its potential to confer desiccation tolerance to otherwise sensitive organisms.

Is long-term hypoxia met by the Pasteur effect in roots of wheat seedlings?

1994 ◽  
Vol 102 ◽  
pp. 407-412 ◽  
Author(s):  
G. Albrecht ◽  
E.-M. Wiedenroth
Keyword(s):  
Hypoxia Tolerance ◽  
Soluble Carbohydrates ◽  
Low Oxygen ◽  
Wheat Roots ◽  
Wheat Seedlings ◽  
Pasteur Effect ◽  
Metabolic Arrest ◽  
Oxygen Shortage ◽  
Anaerobic Environment

SynopsisIt has been argued, whether or not the Pasteur effect occurs in plant tissues as a response to long-term hypoxia. To study this question roots of wheat seedlings (Triticum aestivum L. cv. Alcedo) were analysed following acclimation to oxygen shortage by a prior 6-d-cultivation in a nitrogen-flushed nutrient solution. A Pasteur Quotient of approximately one suggested the absence of a significant Pasteur effect. This conclusion was supported by finding an accumulation of soluble carbohydrates.A progressive adaptation of hypoxically pretreated wheat roots was indicated by measurements under low oxygen tension of 2 kPa, when half of the produced carbon dioxide was generated by fermentation (Gas exchange Quotient, GQ≈2.1) with no apparent increase in the glycolytic substrate flux. The remaining oxygen uptake was even higher in hypoxically grown roots than in the aerobically grown control specimens. When whole seedlings were placed in oxygen-free conditions for 2 h, roots of seedlings pretreated hypoxically suffered a 50% loss in the concentration of ATP, while 90% of the ATP was lost in roots transferred from an aerated solution directly into an anaerobic environment. This was interpreted as an improvement in hypoxia tolerance by minimising the fermentation rate (low PQ) but in particular the ATP requirements by metabolic arrest strategies.

scholarly journals Interleukin-4 Synergizes With Raf-1 to Promote Long-Term Proliferation and Activation of c-jun N-terminal Kinase

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3694-3702 ◽  
Author(s):  
Megan K. Levings ◽  
Darrell C. Bessette ◽  
John W. Schrader
Keyword(s):  
Protein Kinase ◽  
Cellular Growth ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 4 ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Erk Activity ◽  
Increased Activity

Abstract This report shows that interleukin-4 (IL-4), which plays a key role in regulating immune responses, fails to support cellular growth. We investigated whether this failure of IL-4 to promote growth was because of its unique inability to activate the Ras/Raf/Erk pathway. Consistent with other reports, expression in Ba/F3, a factor-dependent hematopoietic cell line, of either activated Q61KN-Ras or a hormone-inducible activated Raf-1, resulted in suppression of apoptosis but not in long-term growth. However, in the presence of IL-4, Ba/F3 cells that expressed either Q61KN-Ras or activated Raf-1 grew continuously at a rate comparable with that stimulated by IL-3. Investigation of the biochemical events associated with the stimulation of long-term growth showed that, as expected, the presence of activated Raf-1 resulted in an increased activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) but not of c-jun N-terminal kinase/stress-activated protein kinase (JNK). However, surprisingly, if IL-4 was present, cells expressing active Raf-1 exhibited increases in JNK activity. These observations point to a novel mechanism for JNK activation involving synergy between Raf-1 and pathways activated by IL-4 and suggest that in hematopoietic cells proliferation is correlated not only with “mitogen activated” ERK activity, but also with JNK activity.

scholarly journals Interleukin-4 Synergizes With Raf-1 to Promote Long-Term Proliferation and Activation of c-jun N-terminal Kinase

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3694-3702 ◽  
Author(s):  
Megan K. Levings ◽  
Darrell C. Bessette ◽  
John W. Schrader
Keyword(s):  
Protein Kinase ◽  
Cellular Growth ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 4 ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Erk Activity ◽  
Increased Activity

This report shows that interleukin-4 (IL-4), which plays a key role in regulating immune responses, fails to support cellular growth. We investigated whether this failure of IL-4 to promote growth was because of its unique inability to activate the Ras/Raf/Erk pathway. Consistent with other reports, expression in Ba/F3, a factor-dependent hematopoietic cell line, of either activated Q61KN-Ras or a hormone-inducible activated Raf-1, resulted in suppression of apoptosis but not in long-term growth. However, in the presence of IL-4, Ba/F3 cells that expressed either Q61KN-Ras or activated Raf-1 grew continuously at a rate comparable with that stimulated by IL-3. Investigation of the biochemical events associated with the stimulation of long-term growth showed that, as expected, the presence of activated Raf-1 resulted in an increased activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) but not of c-jun N-terminal kinase/stress-activated protein kinase (JNK). However, surprisingly, if IL-4 was present, cells expressing active Raf-1 exhibited increases in JNK activity. These observations point to a novel mechanism for JNK activation involving synergy between Raf-1 and pathways activated by IL-4 and suggest that in hematopoietic cells proliferation is correlated not only with “mitogen activated” ERK activity, but also with JNK activity.

Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis
Keyword(s):  
Mental Health ◽  
Mental Disease ◽  
Brain Disorders ◽  
Social Stressors ◽  
Labor Education ◽  
Mental Diseases ◽  
Long Term Follow Up ◽  
Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Brief summary of Kleť photographic search programme for minor planets

1999 ◽  
Vol 173 ◽  
pp. 189-192
Author(s):  
J. Tichá ◽  
M. Tichý ◽  
Z. Moravec
Keyword(s):  
Ccd Camera ◽  
Minor Planet ◽  
Minor Planets ◽  
Main Belt

AbstractA long-term photographic search programme for minor planets was begun at the Kleť Observatory at the end of seventies using a 0.63-m Maksutov telescope, but with insufficient respect for long-arc follow-up astrometry. More than two thousand provisional designations were given to new Kleť discoveries. Since 1993 targeted follow-up astrometry of Kleť candidates has been performed with a 0.57-m reflector equipped with a CCD camera, and reliable orbits for many previous Kleť discoveries have been determined. The photographic programme results in more than 350 numbered minor planets credited to Kleť, one of the world's most prolific discovery sites. Nearly 50 per cent of them were numbered as a consequence of CCD follow-up observations since 1994.This brief summary describes the results of this Kleť photographic minor planet survey between 1977 and 1996. The majority of the Kleť photographic discoveries are main belt asteroids, but two Amor type asteroids and one Trojan have been found.

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