The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

A WC/WO star exploding within an expanding carbon-oxygen-neon nebula.

The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars2,3, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion4. Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients5-8. Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.

Restoration of energy homeostasis by SIRT6 extends healthy lifespan.

Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.

iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.

We report the discovery of a multiply imaged, gravitationally lensed type Ia supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was identified because the light from the stellar explosion was magnified more than 50 times by the curvature of space around matter in an intervening galaxy. We used high-spatial-resolution observations to resolve four images of the lensed supernova, approximately 0.3 arc seconds from the center of the foreground galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is typical in other studies of extragalactic gravitational lensing. The large magnification and symmetric image configuration imply close alignment between the lines of sight to the supernova and to the lens. The relative magnifications of the four images provide evidence for substructures in the lensing galaxy.

RGS2 expression predicts amyloid-ß sensitivity, MCI and Alzheimer's disease: genome-wide transcriptomic profiling and bioinformatics data mining.

Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-ß (Aß) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aß in AD pathology have been raised as Aß is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aß neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aß plaques. Here, we applied genome-wide transcriptomic profiling of lymphoblastoid cells lines (LCLs) from healthy individuals and AD patients for identifying genes that predict sensitivity to Aß. Real-time PCR validation identified 3.78-fold lower expression of RGS2 (regulator of G-protein signaling 2; P=0.0085) in LCLs from healthy individuals exhibiting high vs low Aß sensitivity. Furthermore, RGS2 showed 3.3-fold lower expression (P=0.0008) in AD LCLs compared with controls. Notably, RGS2 expression in AD LCLs correlated with the patients' cognitive function. Lower RGS2 expression levels were also discovered in published expression data sets from postmortem AD brain tissues as well as in mild cognitive impairment and AD blood samples compared with controls. In conclusion, Aß sensitivity phenotyping followed by transcriptomic profiling and published patient data mining identified reduced peripheral and brain expression levels of RGS2, a key regulator of G-protein-coupled receptor signaling and neuronal plasticity. RGS2 is suggested as a novel AD biomarker (alongside other genes) toward early AD detection and future disease modifying therapeutics.

A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind.

The explosive fate of massive Wolf-Rayet stars (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections. Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 10(12) centimetres, as expected for some WRSs. The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions.

An outburst from a massive star 40 days before a supernova explosion.

Some observations suggest that very massive stars experience extreme mass-loss episodes shortly before they explode as supernovae, as do several models. Establishing a causal connection between these mass-loss episodes and the final explosion would provide a novel way to study pre-supernova massive-star evolution. Here we report observations of a mass-loss event detected 40 days before the explosion of the type IIn supernova SN 2010mc (also known as PTF 10tel). Our photometric and spectroscopic data suggest that this event is a result of an energetic outburst, radiating at least 6 × 10(47) erg of energy and releasing about 10(-2) solar masses of material at typical velocities of 2,000 km s(-1). The temporal proximity of the mass-loss outburst and the supernova explosion implies a causal connection between them. Moreover, we find that the outburst luminosity and velocity are consistent with the predictions of the wave-driven pulsation model, and disfavour alternative suggestions.

Mutation R120G in alphaB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function.

alphaB-crystallin, a member of the small heat shock protein family, possesses chaperone-like function. Recently, it has been shown that a missense mutation in alphaB-crystallin, R120G, is genetically linked to a desmin-related myopathy as well as to cataracts [Vicart, P., Caron, A., Guicheney, P., Li, A., Prevost, M.-C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.-M., et al. (1998) Nat. Genet. 20, 92-95]. By using alpha-lactalbumin, alcohol dehydrogenase, and insulin as target proteins, in vitro assays indicated that R120G alphaB-crystallin had reduced or completely lost chaperone-like function. The addition of R120G alphaB-crystallin to unfolding alpha-lactalbumin enhanced the kinetics and extent of its aggregation. R120G alphaB-crystallin became entangled with unfolding alpha-lactalbumin and was a major portion of the resulting insoluble pellet. Similarly, incubation of R120G alphaB-crystallin with alcohol dehydrogenase and insulin also resulted in the presence of R120G alphaB-crystallin in the insoluble pellets. Far and near UV CD indicate that R120G alphaB-crystallin has decreased beta-sheet secondary structure and an altered aromatic residue environment compared with wild-type alphaB-crystallin. The apparent molecular mass of R120G alphaB-crystallin, as determined by gel filtration chromatography, is 1.4 MDa, which is more than twice the molecular mass of wild-type alphaB-crystallin (650 kDa). Images obtained from cryoelectron microscopy indicate that R120G alphaB-crystallin possesses an irregular quaternary structure with an absence of a clear central cavity. The results of this study show, through biochemical analysis, that an altered structure and defective chaperone-like function of alphaB-crystallin are associated with a point mutation that leads to a desmin-related myopathy and cataracts.

Mutation of alpha B-crystallin: effects on chaperone-like activity.

A recent paper by Plater et al. [20], showed that the mutation of a single phenylalanine residue F27R in mouse alpha B completely abolished the chaperone-like property of alpha-crystallin when assayed with insulin at 25 degrees C or with gamma-crystallin at 66 degrees C. We have produced the same mutation as well as some additional mutations in human alpha B-crystallin. Our data suggest that the F27R mutation effected the thermal stability of alpha B-crystallin making it unstable at temperatures > or = 60 degrees C. In agreement with the published work, at these temperatures the F27R human recombinant alpha B-crystallin does not protect the target protein from aggregation. When assayed with insulin or alpha-lactalbumin at 25 or 37 degrees C, however, there were no differences in the protective abilities between the native alpha B-crystallin or the F27R mutated human alpha B-crystallin. Several other multiple mutations involving proline residues were also produced. These mutations did not effect the chaperone-like properties of human alpha B-crystallin, but some of them did effect the native molecular weight size as judged by gel filtration chromatography.