13 research outputs found
Light Curves and Colors of the Ejecta from Dimorphos after the DART Impact
On 26 September 2022 the Double Asteroid Redirection Test (DART) spacecraft
impacted Dimorphos, a satellite of the asteroid 65803 Didymos. Because it is a
binary system, it is possible to determine how much the orbit of the satellite
changed, as part of a test of what is necessary to deflect an asteroid that
might threaten Earth with an impact. In nominal cases, pre-impact predictions
of the orbital period reduction ranged from ~8.8 - 17.2 minutes. Here we report
optical observations of Dimorphos before, during and after the impact, from a
network of citizen science telescopes across the world. We find a maximum
brightening of 2.29 0.14 mag upon impact. Didymos fades back to its
pre-impact brightness over the course of 23.7 0.7 days. We estimate lower
limits on the mass contained in the ejecta, which was 0.3 - 0.5% Dimorphos'
mass depending on the dust size. We also observe a reddening of the ejecta upon
impact.Comment: Accepted by Natur
Thermoregulation in free-ranging ground woodpeckers Geocolaptes olivaceus : no evidence of torpor
Heterothermic responses characterised by pronounced hypometabolism and reductions in body temperature (Tb) are one of the most effective ways in which small endotherms can offset the energetic cost of endothermic homeothermy. It remains unclear, therefore, why daily torpor and hibernation are restricted to only a subset of avian lineages. To further our understanding of the phylogenetic distribution of avian torpor, we investigated winter thermoregulation in the southern African ground woodpecker Geocolaptes olivaceus. We considered this species a good candidate for heterothermy, because it is resident year-round in mountainous regions with cold winters and reliant on small ectothermic prey. We recorded Tb patterns in free-ranging individuals and measured Tb and metabolic rates in captive individuals. Neither free-ranging nor captive woodpeckers showed any indication of daily torpor or even shallow rest-phase hypothermia. All birds maintained bimodally distributed Tb characteristic of classic endothemic homeothermy, with a mean rest-phase Tb of 37.9 ± 0.2°C and no data below 37.0°C. The mean circadian amplitude of Tb was 4.2°C, equivalent to approximately twice the expected value. There was some evidence of seasonal acclimatisation in Tb, with a small decrease in rest-phase Tb with the onset of the austral winter. Captive birds showed patterns of resting metabolic rate and Tb consistent with the classic model of endothermic homeothermy. The apparent absence of torpor in G. olivaceus supports the notion that, unlike the case in mammals, many avian taxa that may a priori be expected to benefit from deep heterothermy do not use it.The University of Pretoria and the DST-NRF Centre of Excellence at the Percy FitzPatrick Inst. to AEM.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-048X2018-10-30hj2017Zoology and Entomolog
Data from: Thermoregulation in free-ranging ground woodpeckers Geocolaptes olivaceus: no evidence of torpor
Heterothermic responses characterised by pronounced hypometabolism and reductions in body temperature (Tb) are one of the most effective ways in which small endotherms can offset the energetic cost of endothermic homeothermy. It remains unclear, therefore, why daily torpor and hibernation are restricted to only a subset of avian lineages. To further our understanding of the phylogenetic distribution of avian torpor, we investigated winter thermoregulation in the Southern African ground woodpecker (Geocolaptes olivaceus). We considered this species a good candidate for heterothermy, because it is resident year-round in mountainous regions with cold winters and reliant on small ectothermic prey. We recorded Tb patterns in free-ranging individuals and measured Tb and metabolic rates in captive individuals. Neither free-ranging nor captive woodpeckers showed any indication of daily torpor or even shallow rest-phase hypothermia. All birds maintained bimodally distributed Tb characteristic of classic endothemic homeothermy, with a mean rest-phase Tb of 37.9 ± 0.2 °C and no data below 37.0 °C. The mean circadian amplitude of Tb was 4.2 °C, equivalent to approximately twice the expected value. There was some evidence of seasonal acclimatisation in Tb, with a small decrease in rest-phase Tb with the onset of the austral winter. Captive birds showed patterns of resting metabolic rate and Tb consistent with the classic model of endothermic homeothermy. The apparent absence of torpor in G. olivaceus supports the notion that, unlike the case in mammals, many avian taxa that may a priori be expected to benefit from deep heterothermy do not use it
Ground Woodpecker data - JAB
Lab metabolic rate and air temperature data (sheet 1) and body temperature data for free-ranging individuals (sheet 2
Characterizing the Altered Cellular Proteome Induced by the Stress-Independent Activation of Heat Shock Factor 1
The heat shock response is an evolutionarily conserved, stress-responsive signaling pathway that adapts cellular proteostasis in response to pathologic insult. In metazoans, the heat shock response primarily functions through the posttranslational activation of heat shock factor 1 (HSF1), a stress-responsive transcription factor that induces the expression of cytosolic proteostasis factors including chaperones, cochaperones, and folding enzymes. HSF1 is a potentially attractive therapeutic target to ameliorate pathologic imbalances in cellular proteostasis associated with human disease, although the underlying impact of stress-independent HSF1 activation on cellular proteome composition remains to be defined. Here, we employ a highly controllable, ligand-regulated HSF1 that activates HSF1 to levels compatible with those that could be achieved using selective small molecule HSF1 activators. Using a combination of RNAseq and quantitative proteomics, we define the impact of stress-independent HSF1 activation on the composition of the cellular proteome. We show that stress-independent HSF1 activation selectively remodels cytosolic proteostasis pathways without globally influencing the composition of the cellular proteome. Furthermore, we show that stress-independent HSF1 activation decreases intracellular aggregation of a model polyglutamine-containing protein and reduces the cellular toxicity of environmental toxins like arsenite that disrupt cytosolic proteostasis. Collectively, our results reveal a proteome-level view of stress-independent HSF1 activation, providing a framework to establish therapeutic approaches to correct pathologic imbalances in cellular proteostasis through the selective targeting of HSF1
Broadly Applicable Methodology for the Rapid and Dosable Small Molecule-Mediated Regulation of Transcription Factors in Human Cells
Direct
and selective small molecule control of transcription factor
activity is an appealing avenue for elucidating the cell biology mediated
by transcriptional programs. However, pharmacologic tools to modulate
transcription factor activity are scarce because transcription factors
are not readily amenable to small molecule-mediated regulation. Moreover,
existing genetic approaches to regulate transcription factors often
lead to high nonphysiologic levels of transcriptional activation that
significantly impair our ability to understand the functional implications
of transcription factor activity. Herein, we demonstrate that small
molecule-mediated conformational control of protein degradation is
a generally applicable, chemical biological methodology to obtain
small molecule-regulated transcription factors that modulate transcriptional
responses at physiologic levels in human cells. Our establishment
of this approach allows for the rapid development of genetically encoded,
small molecule-regulated transcription factors to explore the biologic
and therapeutic impact of physiologic levels of transcription factor
activity in cells
Stress-Independent Activation of XBP1s and/or ATF6 Reveals Three Functionally Diverse ER Proteostasis Environments
SummaryThe unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis through the activation of transcription factors such as XBP1s and ATF6. The functional consequences of these transcription factors for ER proteostasis remain poorly defined. Here, we describe methodology that enables orthogonal, small-molecule-mediated activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the same cell independent of stress. We employ transcriptomics and quantitative proteomics to evaluate ER proteostasis network remodeling owing to the XBP1s and/or ATF6 transcriptional programs. Furthermore, we demonstrate that the three ER proteostasis environments accessible by activating XBP1s and/or ATF6 differentially influence the folding, trafficking, and degradation of destabilized ER client proteins without globally affecting the endogenous proteome. Our data reveal how the ER proteostasis network is remodeled by the XBP1s and/or ATF6 transcriptional programs at the molecular level and demonstrate the potential for selective restoration of aberrant ER proteostasis of pathologic, destabilized proteins through arm-selective UPR activation.Video Abstrac
Characterizing the Altered Cellular Proteome Induced by the Stress-Independent Activation of Heat Shock Factor 1
The heat shock response is an evolutionarily
conserved, stress-responsive
signaling pathway that adapts cellular proteostasis in response to
pathologic insult. In metazoans, the heat shock response primarily
functions through the posttranslational activation of heat shock factor
1 (HSF1), a stress-responsive transcription factor that induces the
expression of cytosolic proteostasis factors including chaperones,
cochaperones, and folding enzymes. HSF1 is a potentially attractive
therapeutic target to ameliorate pathologic imbalances in cellular
proteostasis associated with human disease, although the underlying
impact of stress-independent HSF1 activation on cellular proteome
composition remains to be defined. Here, we employ a highly controllable,
ligand-regulated HSF1 that activates HSF1 to levels compatible with
those that could be achieved using selective small molecule HSF1 activators.
Using a combination of RNAseq and quantitative proteomics, we define
the impact of stress-independent HSF1 activation on the composition
of the cellular proteome. We show that stress-independent HSF1 activation
selectively remodels cytosolic proteostasis pathways without globally
influencing the composition of the cellular proteome. Furthermore,
we show that stress-independent HSF1 activation decreases intracellular
aggregation of a model polyglutamine-containing protein and reduces
the cellular toxicity of environmental toxins like arsenite that disrupt
cytosolic proteostasis. Collectively, our results reveal a proteome-level
view of stress-independent HSF1 activation, providing a framework
to establish therapeutic approaches to correct pathologic imbalances
in cellular proteostasis through the selective targeting of HSF1
Characterizing the Altered Cellular Proteome Induced by the Stress-Independent Activation of Heat Shock Factor 1
The heat shock response is an evolutionarily
conserved, stress-responsive
signaling pathway that adapts cellular proteostasis in response to
pathologic insult. In metazoans, the heat shock response primarily
functions through the posttranslational activation of heat shock factor
1 (HSF1), a stress-responsive transcription factor that induces the
expression of cytosolic proteostasis factors including chaperones,
cochaperones, and folding enzymes. HSF1 is a potentially attractive
therapeutic target to ameliorate pathologic imbalances in cellular
proteostasis associated with human disease, although the underlying
impact of stress-independent HSF1 activation on cellular proteome
composition remains to be defined. Here, we employ a highly controllable,
ligand-regulated HSF1 that activates HSF1 to levels compatible with
those that could be achieved using selective small molecule HSF1 activators.
Using a combination of RNAseq and quantitative proteomics, we define
the impact of stress-independent HSF1 activation on the composition
of the cellular proteome. We show that stress-independent HSF1 activation
selectively remodels cytosolic proteostasis pathways without globally
influencing the composition of the cellular proteome. Furthermore,
we show that stress-independent HSF1 activation decreases intracellular
aggregation of a model polyglutamine-containing protein and reduces
the cellular toxicity of environmental toxins like arsenite that disrupt
cytosolic proteostasis. Collectively, our results reveal a proteome-level
view of stress-independent HSF1 activation, providing a framework
to establish therapeutic approaches to correct pathologic imbalances
in cellular proteostasis through the selective targeting of HSF1