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Bacterial ice nucleation proteins (INPs) can cause frost damage to plants by nucleating ice formation at high sub-zero temperatures. Modeling of Pseudomonas borealis INP by AlphaFold suggests that the central domain of 65 tandem sixteen-residue repeats forms a beta-solenoid with arrays of outward-pointing threonines and tyrosines, which may organize water molecules into an ice-like pattern. Here we report that mutating some of these residues in a central segment of P. borealis INP, expressed in Escherichia coli , decreases ice nucleation activity more than the section’s deletion. Insertion of a bulky domain has the same effect, indicating that the continuity of the water-organizing repeats is critical for optimal activity. The ~10 C-terminal coils differ from the other 55 coils in being more basic and lacking water-organizing motifs; deletion of this region eliminates INP activity. We show through sequence modifications how arrays of conserved motifs form the large ice-nucleating surface required for potency. Ice nucleation proteins have the same tandemly arrayed water-organizing motifs seen in some antifreeze proteins, but on a larger scale. The authors show that mutation, interruption, and truncation of these arrays reduce ice nucleation activity indicating that the two protein types share a common mechanism.

William Dobyns, Daniela Pilz and colleagues show that de novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome, a developmental disorder characterized by distinct craniofacial features, ocular colobomata and defects in neuronal migration. Brain malformations are individually rare but collectively common causes of developmental disabilities 1 , 2 , 3 . Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations 4 , 5 . Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect 6 , 7 . Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin–encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations ( ACTB , encoding p.Arg196His, and ACTG1 , encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.

Bringing together leaf trait data spanning 2,548 species and 175 sites we describe, for the first time at global scale, a universal spectrum of leaf economics consisting of key chemical, structural and physiological properties. The spectrum runs from quick to slow return on investments of nutrients and dry mass in leaves, and operates largely independently of growth form, plant functional type or biome. Categories along the spectrum would, in general, describe leaf economic variation at the global scale better than plant functional types, because functional types overlap substantially in their leaf traits. Overall, modulation of leaf traits and trait relationships by climate is surprisingly modest, although some striking and significant patterns can be seen. Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.

Background Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. Methods We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study ( n  = 2,927), and used the PRACTICAL consortium ( n  = 43,737) as a replication sample. Results In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64–0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43–91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91–1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90–0.98), but not with disease grade. Conclusions Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.

We present initial results from a JWST survey of the youngest Galactic core-collapse supernova remnant Cassiopeia A (Cas A), made up of NIRCam and MIRI imaging mosaics that map emission from the main shell, interior, and surrounding circumstellar/interstellar material (CSM/ISM). We also present four exploratory positions of MIRI/MRS IFU spectroscopy that sample ejecta, CSM, and associated dust from representative shocked and unshocked regions. Surprising discoveries include: 1) a web-like network of unshocked ejecta filaments resolved to 0.01 pc scales exhibiting an overall morphology consistent with turbulent mixing of cool, low-entropy matter from the progenitor's oxygen layer with hot, high-entropy matter heated by neutrino interactions and radioactivity, 2) a thick sheet of dust-dominated emission from shocked CSM seen in projection toward the remnant's interior pockmarked with small (approximately one arcsecond) round holes formed by knots of high-velocity ejecta that have pierced through the CSM and driven expanding tangential shocks, 3) dozens of light echoes with angular sizes between 0.1 arcsecond to 1 arcminute reflecting previously unseen fine-scale structure in the ISM. NIRCam observations place new upper limits on infrared emission from the neutron star in Cas A's center and tightly constrain scenarios involving a possible fallback disk. These JWST survey data and initial findings help address unresolved questions about massive star explosions that have broad implications for the formation and evolution of stellar populations, the metal and dust enrichment of galaxies, and the origin of compact remnant objects.

JWST observations of the young Galactic supernova remnant Cassiopeia A revealed an unexpected structure seen as a green emission feature in colored composite MIRI F1130W and F1280W images - hence dubbed the Green Monster - that stretches across the central parts of the remnant in projection. Combining the kinematic information from NIRSpec and MIRI MRS with the multi-wavelength imaging from NIRCam and MIRI, we associate the Green Monster with circumstellar material that was lost during an asymmetric mass-loss phase. MIRI images are dominated by dust emission but its spectra show emission lines from Ne, H and Fe with low radial velocities indicative of a CSM nature. An X-ray analysis of this feature in a companion paper (Vink et al. 2024) supports its CSM nature and detects significant blue shifting, thereby placing the Green Monster on the near side, in front of the Cas A SN remnant. The most striking features of the Green Monster are dozens of almost perfectly circular 1\" - 3\" sized holes, most likely created by interaction between high-velocity SN ejecta material and the CSM. Further investigation is needed to understand whether these holes were formed by small 8000-10500 km/s N-rich ejecta knots that penetrated and advanced out ahead of the remnant's 5000 - 6000 km/s outer blastwave, or by narrow ejecta fingers that protrude into the forward-shocked CSM. The detection of the Green Monster provides further evidence of the highly asymmetric mass-loss that Cas A's progenitor star underwent prior to explosion.

The grand challenges of contemporary fundamental physics---dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem---all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress.

We report new mid-infrared observations of the remarkable object IRAS 15099-5856 using the space telescopes AKARI and Spitzer, which demonstrate the presence of prominent crystalline silicate emission in this bright source. IRAS 15099-5856 has a complex morphology with a bright central compact source (IRS1) surrounded by knots, spurs, and several extended (~4') arc-like filaments. The source is seen only at >= 10 um. The Spitzer MIR spectrum of IRS1 shows prominent emission features from Mg-rich crystalline silicates, strong [Ne II] 12.81 um and several other faint ionic lines. We model the MIR spectrum as thermal emission from dust and compare with the Herbig Be star HD 100546 and the luminous blue variable R71, which show very similar MIR spectra. Molecular line observations reveal two molecular clouds around the source, but no associated dense molecular cores. We suggest that IRS1 is heated by UV radiation from the adjacent O star Muzzio 10 and that its crystalline silicates most likely originated in a mass outflow from the progenitor of the supernova remnant (SNR) MSH 15-52. IRS1, which is embedded in the SNR, could have been shielded from the SN blast wave if the progenitor was in a close binary system with Muzzio 10. If MSH15-52 is a remnant of Type Ib/c supernova (SN Ib/c), as has been previously proposed, this would confirm the binary model for SN Ib/c. IRS1 and the associated structures may be the relics of massive star death, as shaped by the supernova explosion, the pulsar wind and the intense ionizing radiation of the embedded O star.