Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased ...energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 autosomal dominant) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.
Galaxy And Mass Assembly (GAMA): stellar mass estimates Taylor, Edward N.; Hopkins, Andrew M.; Baldry, Ivan K. ...
Monthly Notices of the Royal Astronomical Society,
December 2011, Letnik:
418, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper describes the first catalogue of photometrically derived stellar mass estimates for intermediate-redshift (z < 0.65; median z= 0.2) galaxies in the Galaxy And Mass Assembly (GAMA) ...spectroscopic redshift survey. These masses, as well as the full set of ancillary stellar population parameters, will be made public as part of GAMA data release 2. Although the GAMA database does include near-infrared (NIR) photometry, we show that the quality of our stellar population synthesis fits is significantly poorer when these NIR data are included. Further, for a large fraction of galaxies, the stellar population parameters inferred from the optical-plus-NIR photometry are formally inconsistent with those inferred from the optical data alone. This may indicate problems in our stellar population library, or NIR data issues, or both; these issues will be addressed for future versions of the catalogue. For now, we have chosen to base our stellar mass estimates on optical photometry only. In light of our decision to ignore the available NIR data, we examine how well stellar mass can be constrained based on optical data alone. We use generic properties of stellar population synthesis models to demonstrate that restframe colour alone is in principle a very good estimator of stellar mass-to-light ratio, M
*/Li
. Further, we use the observed relation between restframe (g−i) and M
*/Li
for real GAMA galaxies to argue that, modulo uncertainties in the stellar evolution models themselves, (g−i) colour can in practice be used to estimate M
*/Li
to an accuracy of ≲0.1 dex (1σ). This 'empirically calibrated' (g−i)-M
*/Li
relation offers a simple and transparent means for estimating galaxies' stellar masses based on minimal data, and so provides a solid basis for other surveys to compare their results to z≲0.4 measurements from GAMA.
An understanding of the role of autophagic processes in the management of cardiac metabolic stress responses is advancing rapidly and progressing beyond a conceptualization of the autophagosome as a ...simple cell recycling depot. The importance of autophagy dysregulation in diabetic cardiomyopathy and in ischemic heart disease - both conditions comprising the majority of cardiac disease burden - has now become apparent. New findings have revealed that specific autophagic processes may operate in the cardiomyocyte, specialized for selective recognition and management of mitochondria and glycogen particles in addition to protein macromolecular structures. Thus mitophagy, glycophagy, and macroautophagy regulatory pathways have become the focus of intensive experimental effort, and delineating the signaling pathways involved in these processes offers potential for targeted therapeutic intervention. Chronically elevated macroautophagic activity in the diabetic myocardium is generally observed in association with structural and functional cardiomyopathy; yet there are also numerous reports of detrimental effect of autophagy suppression in diabetes. Autophagy induction has been identified as a key component of protective mechanisms that can be recruited to support the ischemic heart, but in this setting benefit may be mitigated by adverse downstream autophagic consequences. Recent report of glycophagy upregulation in diabetic cardiomyopathy opens up a novel area of investigation. Similarly, a role for glycogen management in ischemia protection through glycophagy initiation is an exciting prospect under investigation.
We present new limits on an isotropic stochastic gravitational-wave background (GWB) using a six pulsar data set spanning 18 yr of observations from the 2015 European Pulsar Timing Array data ...release. Performing a Bayesian analysis, we fit simultaneously for the intrinsic noise parameters for each pulsar, along with common correlated signals including clock, and Solar system ephemeris errors, obtaining a robust 95 per cent upper limit on the dimensionless strain amplitude A of the background of A < 3.0 × 10−15 at a reference frequency of 1 yr−1 and a spectral index of 13/3, corresponding to a background from inspiralling supermassive black hole binaries, constraining the GW energy density to Ωgw(f)h
2 < 1.1 × 10−9 at 2.8 nHz. We also present limits on the correlated power spectrum at a series of discrete frequencies, and show that our sensitivity to a fiducial isotropic GWB is highest at a frequency of ∼5 × 10−9 Hz. Finally, we discuss the implications of our analysis for the astrophysics of supermassive black hole binaries, and present 95 per cent upper limits on the string tension, Gμ/c
2, characterizing a background produced by a cosmic string network for a set of possible scenarios, and for a stochastic relic GWB. For a Nambu–Goto field theory cosmic string network, we set a limit Gμ/c
2 < 1.3 × 10−7, identical to that set by the Planck Collaboration, when combining Planck and high-ℓ cosmic microwave background data from other experiments. For a stochastic relic background, we set a limit of
$\Omega ^\mathrm{relic}_\mathrm{gw}(f)h^2<1.2 \times 10^{-9}$
, a factor of 9 improvement over the most stringent limits previously set by a pulsar timing array.
The CRISPR-Cas system is a prokaryotic host defense system against genetic elements. The Type III-B CRISPR-Cas system of the bacterium Thermus thermophilus, the TtCmr complex, is composed of six ...different protein subunits (Cmr1-6) and one crRNA with a stoichiometry of Cmr112131445361:crRNA1. The TtCmr complex copurifies with crRNA species of 40 and 46 nt, originating from a distinct subset of CRISPR loci and spacers. The TtCmr complex cleaves the target RNA at multiple sites with 6 nt intervals via a 5′ ruler mechanism. Electron microscopy revealed that the structure of TtCmr resembles a “sea worm” and is composed of a Cmr2-3 heterodimer “tail,” a helical backbone of Cmr4 subunits capped by Cmr5 subunits, and a curled “head” containing Cmr1 and Cmr6. Despite having a backbone of only four Cmr4 subunits and being both longer and narrower, the overall architecture of TtCmr resembles that of Type I Cascade complexes.
•The Cmr complex binds crRNAs (40 and 46 nt) from a subset of CRISPR spacers•The Cmr complex cleaves RNA with a 5′-based ruler mechanism at multiple sites•The stoichiometry of the complex is Cmr112131445361crRNA1•The Cmr complex reveals a “sea worm” shape with similarities to Cascade
Purpose
Many researchers have addressed the potential effects of hyperthermia and dehydration on cognition, often revealing contradictory outcomes. A possible reason for this inconsistency is that ...experiments may have been inadequately designed for such effects. In this study, the impact of hyperthermia, dehydration and their combination on cognition were evaluated in eight young males, after accounting for a range of experimental limitations.
Methods
Passive heating and thermal clamping at two mean body temperatures (36.5, 38.5 °C) were performed under three hydration states (euhydrated, 3 and 5% dehydrated) to assess their effects on difficulty-matched working memory and visual perception tasks, and on a difficulty manipulated perceptual task. Data were analysed according to signal detection theory to isolate changes in response sensitivity, bias and speed.
Results
Neither moderate hyperthermia (
P
= 0.141) nor dehydration (
P
> 0.604) modified response sensitivity, nor did they significantly interact (
P
> 0.698). Therefore, the ability to distinguish correct from incorrect responses was unaffected. Nevertheless, hyperthermia, but not dehydration (
P
= 0.301), reduced the response bias (−0.08 versus 2.2 normothermia;
P
= 0.010) and reaction time (mean reduction 49 ms;
P
< 0.001), eliciting more liberal and faster responses (
P
= 0.010). Response bias was reduced for the memory relative to the perceptual task (
P
= 0.037), and this effect was enhanced during hyperthermia (
P
= 0.031).
Conclusions
These observations imply that, once potentially confounding influences were controlled, moderate hyperthermia, significant dehydration and their combined effects had insufficient impact to impair cognition within the memory and perceptual domains tested. Nonetheless, moderate hyperthermia elicited more liberal and rapid responses.
Chromatin structure has emerged as a key contributor to spatial and temporal control over the initiation of DNA replication. However, despite genome-wide correlations between early replication of ...gene-rich, accessible euchromatin and late replication of gene-poor, inaccessible heterochromatin, a causal relationship between chromatin structure and replication initiation remains elusive. Here, we combined histone gene engineering and whole-genome sequencing in
to determine how perturbing chromatin structure affects replication initiation. We found that most pericentric heterochromatin remains late replicating in
mutants, even though
pericentric heterochromatin is depleted of HP1a, more accessible, and transcriptionally active. These data indicate that HP1a loss, increased chromatin accessibility, and elevated transcription do not result in early replication of heterochromatin. Nevertheless, a small amount of pericentric heterochromatin with increased accessibility replicates earlier in
mutants. Transcription is de-repressed in these regions of advanced replication but not in those regions of the
mutant genome that replicate later, suggesting that transcriptional repression may contribute to late replication. We also explored relationships among chromatin, transcription, and replication in euchromatin by analyzing
mutants. In
the X Chromosome gene expression is up-regulated twofold and replicates earlier in XY males than it does in XX females. We found that
mutation prevents normal male development and abrogates hyperexpression and earlier replication of the male X, consistent with previously established genome-wide correlations between transcription and early replication. In contrast,
females are viable and fertile, indicating that H4K16 modification is dispensable for genome replication and gene expression.
Pest and pathogen losses jeopardise global food security and ever since the 19(th) century Irish famine, potato late blight has exemplified this threat. The causal oomycete pathogen, Phytophthora ...infestans, undergoes major population shifts in agricultural systems via the successive emergence and migration of asexual lineages. The phenotypic and genotypic bases of these selective sweeps are largely unknown but management strategies need to adapt to reflect the changing pathogen population. Here, we used molecular markers to document the emergence of a lineage, termed 13_A2, in the European P. infestans population, and its rapid displacement of other lineages to exceed 75% of the pathogen population across Great Britain in less than three years. We show that isolates of the 13_A2 lineage are among the most aggressive on cultivated potatoes, outcompete other aggressive lineages in the field, and overcome previously effective forms of plant host resistance. Genome analyses of a 13_A2 isolate revealed extensive genetic and expression polymorphisms particularly in effector genes. Copy number variations, gene gains and losses, amino-acid replacements and changes in expression patterns of disease effector genes within the 13_A2 isolate likely contribute to enhanced virulence and aggressiveness to drive this population displacement. Importantly, 13_A2 isolates carry intact and in planta induced Avrblb1, Avrblb2 and Avrvnt1 effector genes that trigger resistance in potato lines carrying the corresponding R immune receptor genes Rpi-blb1, Rpi-blb2, and Rpi-vnt1.1. These findings point towards a strategy for deploying genetic resistance to mitigate the impact of the 13_A2 lineage and illustrate how pathogen population monitoring, combined with genome analysis, informs the management of devastating disease epidemics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A significant fraction of high-harmonic fast-wave (HHFW) power applied to NSTX can be lost to the scrape-off layer (SOL) and deposited in bright and hot spirals on the divertor rather than in the ...core plasma. We show that the HHFW power flows to these spirals along magnetic field lines passing through the SOL in front of the antenna, implying that the HHFW power couples across the entire width of the SOL rather than mostly at the antenna face. This result will help guide future efforts to understand and minimize these edge losses in order to maximize fast-wave heating and current drive.
Mobulid populations are declining on a global scale as a result of both targeted fisheries and indirect anthropogenic threats. In order to implement effective conservation strategies for species of ...this taxa, it is crucial that movement patterns at a range of spatiotemporal scales are defined. To gain insight into such patterns, we deployed a combination of acoustic (n = 21) and satellite (n = 12) tags on reef manta rays Mobula alfredi in the British Indian Ocean Territory Marine Protected Area (BIOT MPA) annually from 2013 through 2016. An extensive array of acoustic receivers (n = 52) were deployed across the archipelago to record the movements of mantas throughout the MPA. Data revealed large individual variation in horizontal movement patterns, ranging from high local site fidelity (<10 km) for up to 3 yr, to large-scale regional movements (>200 km) around the entire MPA. Depth time-series data recorded vertical movement patterns consistent with other epipelagic elasmobranch species, including oscillatory diving and deep dives to greater than 500 m. Though no individuals were directly recorded departing the MPA throughout the study, the gaps in detections and estimated travel speeds documented here indicate that movement of individuals outside of the BIOT MPA cannot be discounted. Collectively, our data suggests that, with effective enforcement, the current size of the BIOT MPA is providing substantial protection to its reef manta ray population. Characterization of movement patterns across ontogenetic classes, however, is required to fully characterize the spatial ecology of this species and ensure protection across all cohorts of the population.
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