The mitochondrial unfolded protein response: Signaling from the powerhouse

Mitochondria are multifaceted and indispensable organelles required for cell performance. Accordingly, dysfunction to mitochondria can result in cellular decline and possibly the onset of disease. Cells use a variety of means to recover mitochondria and restore homeostasis, including the activation of retrograde pathways such as the mitochondrial unfolded protein response (UPRmt). In this Minireview, we will discuss how cells adapt to mitochondrial stress through UPRmt regulation. Furthermore, we will explore the current repertoire of biological functions that are associated with this essential stress-response pathway

Modelling of the Effects of Stellar Feedback during Star Cluster Formation Using a Hybrid Gas and N-Body Method

Understanding the formation of stellar clusters requires following the interplay between gas and newly formed stars accurately. We therefore couple the magnetohydrodynamics code FLASH to the N-body code ph4 and the stellar evolution code SeBa using the Astrophysical Multipurpose Software Environment (AMUSE) to model stellar dynamics, evolution, and collisional N-body dynamics and the formation of binary and higher-order multiple systems, while implementing stellar feedback in the form of radiation, stellar winds and supernovae in FLASH. We here describe the algorithms used for each of these processes. We denote this integrated package Torch. We then use this novel numerical method to simulate the formation and early evolution of several examples of open clusters of ~1000 stars formed from clouds with a mass range of 10^3-10^5 M_sun. Analyzing the effects of stellar feedback on the gas and stars of the natal clusters, we find that in these examples, the stellar clusters are resilient to disruption, even in the presence of intense feedback. This can even slightly increase the amount of dense, Jeans unstable gas by sweeping up shells; thus, a stellar wind strong enough to trap its own H II region shows modest triggering of star formation. Our clusters are born moderately mass segregated, an effect enhanced by feedback, and retained after the ejection of their natal gas, in agreement with observations.Comment: Accepted to ApJ. 29 pages, 18 figures. Source code at https://bitbucket.org/torch-sf/torch/ and documentation at https://torch-sf.bitbucket.io

Renal Denervation Update From the International Sympathetic Nervous System Summit:JACC State-of-the-Art Review

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications

Strong Carbon Features and a Red Early Color in the Underluminous Type Ia SN 2022xkq

We present optical, infrared, ultraviolet, and radio observations of SN 2022xkq, an underluminous fast-declining type Ia supernova (SN Ia) in NGC 1784 ($\mathrm{D}\approx31$ Mpc), from $<1$ to 180 days after explosion. The high-cadence observations of SN 2022xkq, a photometrically transitional and spectroscopically 91bg-like SN Ia, cover the first days and weeks following explosion which are critical to distinguishing between explosion scenarios. The early light curve of SN 2022xkq has a red early color and exhibits a flux excess which is more prominent in redder bands; this is the first time such a feature has been seen in a transitional/91bg-like SN Ia. We also present 92 optical and 19 near-infrared (NIR) spectra, beginning 0.4 days after explosion in the optical and 2.6 days after explosion in the NIR. SN 2022xkq exhibits a long-lived C I 1.0693 $\mu$m feature which persists until 5 days post-maximum. We also detect C II $\lambda$6580 in the pre-maximum optical spectra. These lines are evidence for unburnt carbon that is difficult to reconcile with the double detonation of a sub-Chandrasekhar mass white dwarf. No existing explosion model can fully explain the photometric and spectroscopic dataset of SN 2022xkq, but the considerable breadth of the observations is ideal for furthering our understanding of the processes which produce faint SNe Ia.Comment: 38 pages, 16 figures, accepted for publication in ApJ, the figure 15 input models and synthetic spectra are now available at https://zenodo.org/record/837925

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated

SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class

We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Determination of quantum numbers for several excited charmed mesons observed in B- -> D*(+)pi(-) pi(-) decays

A four-body amplitude analysis of the B − → D * + π − π − decay is performed, where fractions and relative phases of the various resonances contributing to the decay are measured. Several quasi-model-independent analyses are performed aimed at searching for the presence of new states and establishing the quantum numbers of previously observed charmed meson resonances. In particular the resonance parameters and quantum numbers are determined for the D 1 ( 2420 ) , D 1 ( 2430 ) , D 0 ( 2550 ) , D ∗ 1 ( 2600 ) , D 2 ( 2740 ) and D ∗ 3 ( 2750 ) states. The mixing between the D 1 ( 2420 ) and D 1 ( 2430 ) resonances is studied and the mixing parameters are measured. The dataset corresponds to an integrated luminosity of 4.7     fb − 1 , collected in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV with the LHCb detector

Updated measurement of decay-time-dependent CP asymmetries in D-0 -> K+ K- and D-0 -> pi(+)pi(-) decays

A search for decay-time-dependent charge-parity (CP) asymmetry in D0 \u2192 K+ K 12 and D0 \u2192 \u3c0+ \u3c0 12 decays is performed at the LHCb experiment using proton-proton collision data recorded at a center-of-mass energy of 13 TeV, and corresponding to an integrated luminosity of 5.4 fb^ 121. The D0 mesons are required to originate from semileptonic decays of b hadrons, such that the charge of the muon identifies the flavor of the neutral D meson at production. The asymmetries in the effective decay widths of D0 and anti-D0 mesons are determined to be A_\u393(K+ K 12) = ( 124.3 \ub1 3.6 \ub1 0.5) 7 10^ 124 and A_\u393(\u3c0+ \u3c0 12) = (2.2 \ub1 7.0 \ub1 0.8) 7 10^ 124 , where the uncertainties are statistical and systematic, respectively. The results are consistent with CP symmetry and, when combined with previous LHCb results, yield A_\u393(K+ K 12) = ( 124.4 \ub1 2.3 \ub1 0.6) 7 10^ 124 and A_\u393(\u3c0+ \u3c0 12) = (2.5 \ub1 4.3 \ub1 0.7) 7 10^ 124