Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt ...activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.
Stellar mergers are common Kochanek, C. S; Adams, Scott M; Belczynski, Krzysztof
Monthly notices of the Royal Astronomical Society,
09/2014, Letnik:
443, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The observed Galactic rate of stellar mergers or the initiation of common envelope phases brighter than M
V
= −3 (M
I
= −4) is of the order of ∼0.5 (0.3) yr−1 with 90 per cent confidence ...statistical uncertainties of 0.24–1.1 (0.14–0.65) and factor of ∼2 systematic uncertainties. The (peak) luminosity function is roughly
$\text{d}N/\text{d} L \propto L^{-1.4\pm 0.3}$
, so the rates for events more luminous than V1309 Sco (M
V
≃ −7 mag) or V838 Mon (M
V
≃ −10 mag) are lower at r ∼ 0.1 and ∼0.03/year, respectively. The peak luminosity is a steep function of progenitor mass, L ∝ M
2 − 3. This very roughly parallels the scaling of luminosity with mass on the main sequence, but the transients are ∼2000–4000 times more luminous at peak. Combining these, the mass function of the progenitors, dN/dM ∝ M
−2.0 ± 0.8, is consistent with the initial mass function, albeit with broad uncertainties. These observational results are also broadly consistent with the estimates of binary population synthesis models. While extragalactic variability surveys can better define the rates and properties of the high-luminosity events, systematic, moderate depth (I ≳ 16 mag) surveys of the Galactic plane are needed to characterize the low-luminosity events. The existing Galactic samples are only ∼20 per cent complete, and Galactic surveys are (at best!) reaching a typical magnitude limit of ≲ 13 mag.
Abstract Background Computed tomography (CT) pulmonary angiography use has increased dramatically, raising concerns for patient safety. Adherence to recommendations and guidelines may protect ...patients. We measured adherence to the recommendations of Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) investigators for evaluation of suspected pulmonary embolism and the rate of potential false-positive pulmonary embolism diagnoses when recommendations of PIOPED II investigators were not followed. Methods We used a structured record review to identify 3500 consecutive CT pulmonary angiograms performed to investigate suspected pulmonary embolism in 2 urban emergency departments, calculating the revised Geneva score (RGS) to classify patients as “pulmonary embolism unlikely” (RGS ≤ 10) or “pulmonary embolism likely” (RGS > 10). CT pulmonary angiograms were concordant with PIOPED II investigator recommendations if pulmonary embolism was likely or pulmonary embolism was unlikely and a highly sensitive D-dimer test result was positive. We independently reviewed 482 CT pulmonary angiograms to measure the rate of potential false-positive pulmonary embolism diagnoses. Results A total of 1592 of 3500 CT pulmonary angiograms (45.5%) followed the recommendations of PIOPED II investigators. The remaining 1908 CT pulmonary angiograms were performed on patients with an RGS ≤ 10 without a D-dimer test (n = 1588) or after a negative D-dimer test result (n = 320). The overall rate of pulmonary embolism was 9.7%. Potential false-positive diagnoses of pulmonary embolism occurred in 2 of 3 patients with an RGS ≤ 10 and a negative D-dimer test result. Conclusions Nonadherence to recommendations for CT pulmonary angiography is common and exposes patients to increased risks, including potential false-positive diagnoses of pulmonary embolism.
Research summary
Several of the largest U.S. police departments reported a sharp increase in officer resignations following massive public protests directed at policing in the summer of 2020. Yet, to ...date, no study has rigorously assessed the impact of the George Floyd protests on police resignations. We fill this void using 60 months of employment data from a large police department in the western United States. Bayesian structural time‐series modeling shows that voluntary resignations increased by 279% relative to the synthetic control, and the model predicts that resignations will continue at an elevated level. However, retirements and involuntary separations were not significantly affected during the study period.
Policy implications
A retention crisis may diminish police departments’ operational capacity to carry out their expected responsibilities. Criminal justice stakeholders must be prepared to confront workforce decline and increased voluntary turnover. Proactive efforts to improve organizational justice for sworn personnel can moderate officer perceptions of public hostility.
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human ...and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.
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► We determined mRNA expression signatures of skeletal muscle atrophy in humans ► Muscle atrophy signatures negatively correlated with the signature of ursolic acid ► Ursolic acid reduced muscle atrophy and induced muscle hypertrophy in mice ► Although ursolic acid increased skeletal muscle mass, it reduced adiposity
Abstract
We present a systematic study of the most luminous (
M
IR
Vega magnitudes brighter than −14) infrared (IR) transients discovered by the
SPitzer
InfraRed Intensive Transients Survey (SPIRITS) ...between 2014 and 2018 in nearby galaxies (
D
< 35 Mpc). The sample consists of nine events that span peak IR luminosities of
M
4.5,peak
between −14 and −18.2, show IR colors between 0.2 < (3.6–4.5) < 3.0, and fade on timescales between 55 days <
t
fade
< 480 days. The two reddest events (
A
V
> 12) show multiple, luminous IR outbursts over several years and have directly detected, massive progenitors in archival imaging. With analyses of extensive, multiwavelength follow-up, we suggest the following possible classifications: five obscured core-collapse supernovae (CCSNe), two erupting massive stars, one luminous red nova, and one intermediate-luminosity red transient. We define a control sample of all optically discovered transients recovered in SPIRITS galaxies and satisfying the same selection criteria. The control sample consists of eight CCSNe and one Type Iax SN. We find that 7 of the 13 CCSNe in the SPIRITS sample have lower bounds on their extinction of 2 <
A
V
< 8. We estimate a nominal fraction of CCSNe in nearby galaxies that are missed by optical surveys as high as
(90% confidence). This study suggests that a significant fraction of CCSNe may be heavily obscured by dust and therefore undercounted in the census of nearby CCSNe from optical searches.
Activating transcription factor 4 (ATF4) is a multifunctional transcription regulatory protein in the basic leucine zipper superfamily. ATF4 can be expressed in most if not all mammalian cell types, ...and it can participate in a variety of cellular responses to specific environmental stresses, intracellular derangements, or growth factors. Because ATF4 is involved in a wide range of biological processes, its roles in human health and disease are not yet fully understood. Much of our current knowledge about ATF4 comes from investigations in cultured cell models, where ATF4 was originally characterized and where further investigations continue to provide new insights. ATF4 is also an increasingly prominent topic of in vivo investigations in fully differentiated mammalian cell types, where our current understanding of ATF4 is less complete. Here, we review some important high-level concepts and questions concerning the basic biology of ATF4. We then discuss current knowledge and emerging questions about the in vivo role of ATF4 in one fully differentiated cell type, mammalian skeletal muscle fibers.
The detonation of a helium shell on a white dwarf (WD) has been proposed as a possible explosion triggering mechanism for SNe Ia. Here, we report ZTF 18aaqeasu (SN 2018byg/ATLAS 18pqq), a peculiar ...Type I supernova, consistent with being a helium-shell double-detonation. With a rise time of 18 days from explosion, the transient reached a peak absolute magnitude of MR −18.2 mag, exhibiting a light curve akin to sub-luminous SN 1991bg-like SNe Ia, albeit with an unusually steep increase in brightness within a week from explosion. Spectra taken near peak light exhibit prominent Si absorption features together with an unusually red color (g − r 2 mag) arising from nearly complete line blanketing of flux blueward of 5000 . This behavior is unlike any previously observed thermonuclear transient. Nebular phase spectra taken at and after 30 days from peak light reveal evidence of a thermonuclear detonation event dominated by Fe-group nucleosynthesis. We show that the peculiar properties of ZTF 18aaqeasu are consistent with the detonation of a massive ( 0.15 ) helium shell on a sub-Chandrasekhar mass ( 0.75 ) WD after including mixing of 0.2 of material in the outer ejecta. These observations provide evidence of a likely rare class of thermonuclear supernovae arising from detonations of massive helium shells.
How do public expectations of police use-of-force align with the strict professional and legal guidelines under which police officers train and operate? This is a largely unexamined but salient ...question in the use-of-force literature and is important given the ongoing public discourse regarding police use-of-force, community standards, and perceived gaps between the two. This study focuses on two main research questions: Are substantial portions of the public predisposed to disapprove of legally reasonable police use-of-force? If so, what are the principal correlates of those disapproving attitudes? We analyze responses (n = 20,781) to General Social Survey (GSS) questions from 1990 through 2018 entailing police use-of-force scenarios that are prima facie legally reasonable. We find a substantial proportion of GSS respondents have expressed their disapproval of legally reasonable, justifiable police uses-of-force over the entire period, and such disapproval has increased over time. Causes and policy implications of this misalignment are discussed.
Skeletal muscle atrophy proceeds through a complex molecular signaling network that is just beginning to be understood. Here, we discuss examples of recently identified molecular mechanisms of muscle ...atrophy and how they highlight an immense need and opportunity for focused biochemical investigations and further unbiased discovery work.
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