Ancient and modern genomes unravel the evolutionary history of the rhinoceros family.

Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (∼16 million years ago [mya]) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines.

A high internal heat flux and large core in a warm Neptune exoplanet.

Interactions between exoplanetary atmospheres and internal properties have long been proposed to be drivers of the inflation mechanisms of gaseous planets and apparent atmospheric chemical disequilibrium conditions1. However, transmission spectra of exoplanets have been limited in their ability to observationally confirm these theories owing to the limited wavelength coverage of the Hubble Space Telescope (HST) and inferences of single molecules, mostly H2O (ref. 2). In this work, we present the panchromatic transmission spectrum of the approximately 750 K, low-density, Neptune-sized exoplanet WASP-107b using a combination of HST Wide Field Camera 3 (WFC3) and JWST Near-Infrared Camera (NIRCam) and Mid-Infrared Instrument (MIRI). From this spectrum, we detect spectroscopic features resulting from H2O (21σ), CH4 (5σ), CO (7σ), CO2 (29σ), SO2 (9σ) and NH3 (6σ). The presence of these molecules enables constraints on the atmospheric metal enrichment (M/H is 10-18× solar3), vertical mixing strength (log10Kzz = 8.4-9.0 cm2 s-1) and internal temperature (>345 K). The high internal temperature is suggestive of tidally driven inflation4 acting on a Neptune-like internal structure, which can naturally explain the large radius and low density of the planet. These findings suggest that eccentricity-driven tidal heating is a critical process governing atmospheric chemistry and interior-structure inferences for most of the cool (<1,000 K) super-Earth-to-Saturn-mass exoplanet population.

SO2, silicate clouds, but no CH4 detected in a warm Neptune.

WASP-107b is a warm (approximately 740 K) transiting planet with a Neptune-like mass of roughly 30.5 M⊕ and Jupiter-like radius of about 0.94 RJ (refs. 1,2), whose extended atmosphere is eroding3. Previous observations showed evidence for water vapour and a thick, high-altitude condensate layer in the atmosphere of WASP-107b (refs. 4,5). Recently, photochemically produced sulfur dioxide (SO2) was detected in the atmosphere of a hot (about 1,200 K) Saturn-mass planet from transmission spectroscopy near 4.05 µm (refs. 6,7), but for temperatures below about 1,000 K, sulfur is predicted to preferably form sulfur allotropes instead of SO2 (refs. 8-10). Here we report the 9σ detection of two fundamental vibration bands of SO2, at 7.35 µm and 8.69 µm, in the transmission spectrum of WASP-107b using the Mid-Infrared Instrument (MIRI) of JWST. This discovery establishes WASP-107b as the second irradiated exoplanet with confirmed photochemistry, extending the temperature range of exoplanets exhibiting detected photochemistry from about 1,200 K down to about 740 K. Furthermore, our spectral analysis reveals the presence of silicate clouds, which are strongly favoured (around 7σ) over simpler cloud set-ups. Furthermore, water is detected (around 12σ) but methane is not. These findings provide evidence of disequilibrium chemistry and indicate a dynamically active atmosphere with a super-solar metallicity.

Sulfur dioxide in the mid-infrared transmission spectrum of WASP-39b.

The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1-3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1-10 ppm)4-9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 µm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 µm in the 5-12-µm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5-25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 µm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1-8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.

Thermal emission from the Earth-sized exoplanet TRAPPIST-1 b using JWST.

The TRAPPIST-1 system is remarkable for its seven planets that are similar in size, mass, density and stellar heating to the rocky planets Venus, Earth and Mars in the Solar System1. All the TRAPPIST-1 planets have been observed with transmission spectroscopy using the Hubble or Spitzer space telescopes, but no atmospheric features have been detected or strongly constrained2-5. TRAPPIST-1 b is the closest planet to the M-dwarf star of the system, and it receives four times as much radiation as Earth receives from the Sun. This relatively large amount of stellar heating suggests that its thermal emission may be measurable. Here we present photometric secondary eclipse observations of the Earth-sized exoplanet TRAPPIST-1 b using the F1500W filter of the mid-infrared instrument on the James Webb Space Telescope (JWST). We detect the secondary eclipses in five separate observations with 8.7σ confidence when all data are combined. These measurements are most consistent with re-radiation of the incident flux of the TRAPPIST-1 star from only the dayside hemisphere of the planet. The most straightforward interpretation is that there is little or no planetary atmosphere redistributing radiation from the host star and also no detectable atmospheric absorption of carbon dioxide (CO2) or other species.

Single-cell spatial landscapes of the lung tumour immune microenvironment.

Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution1-9. Most clinical strategies rely on histopathological stratification of tumour subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm2 tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.

A reflective, metal-rich atmosphere for GJ 1214b from its JWST phase curve.

There are no planets intermediate in size between Earth and Neptune in our Solar System, yet these objects are found around a substantial fraction of other stars1. Population statistics show that close-in planets in this size range bifurcate into two classes on the basis of their radii2,3. It is proposed that the group with larger radii (referred to as 'sub-Neptunes') is distinguished by having hydrogen-dominated atmospheres that are a few percent of the total mass of the planets4. GJ 1214b is an archetype sub-Neptune that has been observed extensively using transmission spectroscopy to test this hypothesis5-14. However, the measured spectra are featureless, and thus inconclusive, due to the presence of high-altitude aerosols in the planet's atmosphere. Here we report a spectroscopic thermal phase curve of GJ 1214b obtained with the James Webb Space Telescope (JWST) in the mid-infrared. The dayside and nightside spectra (average brightness temperatures of 553 ± 9 and 437 ± 19 K, respectively) each show more than 3σ evidence of absorption features, with H2O as the most likely cause in both. The measured global thermal emission implies that GJ 1214b's Bond albedo is 0.51 ± 0.06. Comparison between the spectroscopic phase curve data and three-dimensional models of GJ 1214b reveal a planet with a high metallicity atmosphere blanketed by a thick and highly reflective layer of clouds or haze.

X-ray polarization evidence for a 200-year-old flare of Sgr A.

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A* (Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei1. Reflection of X-rays from Sgr A* by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years2. The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A* are consistent with the reflection scenario3-5. If this interpretation is correct, the reflected continuum emission should be polarized6. Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of -48° ± 11°. The polarization angle is consistent with Sgr A* being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A* was briefly comparable to that of a Seyfert galaxy.

15NH3 in the atmosphere of a cool brown dwarf.

Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical1,2. Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios3. However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity4. Isotope ratios, such as deuterium to hydrogen and 14N/15N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System5-7. For exoplanets, only a handful of constraints on 12C/13C exist, pointing to the accretion of 13C-rich ice from beyond the CO iceline of the disks8,9. Here we report on the mid-infrared detection of the 14NH3 and 15NH3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14N/15N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15N isotope10, we expect that 15NH3 will be detectable in several cold, wide-separation exoplanets.

Polarized blazar X-rays imply particle acceleration in shocks.

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization-the only range available until now-probe extended regions of the jet containing particles that left the acceleration site days to years earlier1-3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock.

Immune Checkpoint Blockade across the Cancer Care Continuum.

Four studies recently reported in the New England Journal of Medicine highlight advances in treatment with immune checkpoint blockade across the cancer care continuum. These findings demonstrate efficacy of these agents in the treatment of early and late-stage disease, as monotherapy or in combination, and in addition to-or in place of-standard front-line therapy.

A Late Pleistocene coastal ecosystem in French Guiana was hyperdiverse relative to today.

Warmer temperatures and higher sea level than today characterized the Last Interglacial interval [Pleistocene, 128 to 116 thousand years ago (ka)]. This period is a remarkable deep-time analog for temperature and sea-level conditions as projected for 2100 AD, yet there has been no evidence of fossil assemblages in the equatorial Atlantic. Here, we report foraminifer, metazoan (mollusks, bony fish, bryozoans, decapods, and sharks among others), and plant communities of coastal tropical marine and mangrove affinities, dating precisely from a ca. 130 to 115 ka time interval near the Equator, at Kourou, in French Guiana. These communities include ca. 230 recent species, some being endangered today and/or first recorded as fossils. The hyperdiverse Kourou mollusk assemblage suggests stronger affinities between Guianese and Caribbean coastal waters by the Last Interglacial than today, questioning the structuring role of the Amazon Plume on tropical Western Atlantic communities at the time. Grassland-dominated pollen, phytoliths, and charcoals from younger deposits in the same sections attest to a marine retreat and dryer conditions during the onset of the last glacial (ca. 110 to 50 ka), with a savanna-dominated landscape and episodes of fire. Charcoals from the last millennia suggest human presence in a mosaic of modern-like continental habitats. Our results provide key information about the ecology and biogeography of pristine Pleistocene tropical coastal ecosystems, especially relevant regarding the-widely anthropogenic-ongoing global warming.

Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production. In the respiratory tract of neonates with severe RSV-induced acute bronchiolitis, RSV-infected nBreg cell frequencies correlated with increased viral load and decreased blood memory Th1 cell frequencies. Thus, the frequency of nBreg cells is predictive of the severity of acute bronchiolitis disease and nBreg cell activity may constitute an early-life host response that favors microbial pathogenesis.

B cells and tertiary lymphoid structures promote immunotherapy response.

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.

H2A.Z is involved in premature aging and DSB repair initiation in muscle fibers.

Histone variants are key epigenetic players, but their functional and physiological roles remain poorly understood. Here, we show that depletion of the histone variant H2A.Z in mouse skeletal muscle causes oxidative stress, oxidation of proteins, accumulation of DNA damages, and both neuromuscular junction and mitochondria lesions that consequently lead to premature muscle aging and reduced life span. Investigation of the molecular mechanisms involved shows that H2A.Z is required to initiate DNA double strand break repair by recruiting Ku80 at DNA lesions. This is achieved via specific interactions of Ku80 vWA domain with H2A.Z. Taken as a whole, our data reveal that H2A.Z containing nucleosomes act as a molecular platform to bring together the proteins required to initiate and process DNA double strand break repair.

An eosimiid primate of South Asian affinities in the Paleogene of Western Amazonia and the origin of New World monkeys.

Recent fossil discoveries in Western Amazonia revealed that two distinct anthropoid primate clades of African origin colonized South America near the Eocene/Oligocene transition (ca. 34 Ma). Here, we describe a diminutive fossil primate from Brazilian Amazonia and suggest that, surprisingly, a third clade of anthropoids was involved in the Paleogene colonization of South America by primates. This new taxon, Ashaninkacebus simpsoni gen. et sp. nov., has strong dental affinities with Asian African stem anthropoids: the Eosimiiformes. Morphology-based phylogenetic analyses of early Old World anthropoids and extinct and extant New World monkeys (platyrrhines) support relationships of both Ashaninkacebus and Amamria (late middle Eocene, North Africa) to the South Asian Eosimiidae. Afro-Arabia, then a mega island, played the role of a biogeographic stopover between South Asia and South America for anthropoid primates and hystricognathous rodents. The earliest primates from South America bear little adaptive resemblance to later Oligocene-early Miocene platyrrhine monkeys, and the scarcity of available paleontological data precludes elucidating firmly their affinities with or within Platyrrhini. Nonetheless, these data shed light on some of their life history traits, revealing a particularly small body size and a diet consisting primarily of insects and possibly fruit, which would have increased their chances of survival on a natural floating island during this extraordinary over-water trip to South America from Africa. Divergence-time estimates between Old and New World taxa indicate that the transatlantic dispersal(s) could source in the intense flooding events associated with the late middle Eocene climatic optimum (ca. 40.5 Ma) in Western Africa.

Tethering of hexokinase 2 to mitochondria promotes resistance of liver cancer cells to natural killer cell cytotoxicity.

Hexokinases (HKs) control the first step of glucose catabolism. A switch of expression from liver HK (glucokinase, GCK) to the tumor isoenzyme HK2 is observed in hepatocellular carcinoma progression. Our prior work revealed that HK isoenzyme switch in hepatocytes not only regulates hepatic metabolic functions but also modulates innate immunity and sensitivity to Natural Killer (NK) cell cytotoxicity. This study investigates the impact of HK2 expression and its mitochondrial binding on the resistance of human liver cancer cells to NK-cell-induced cytolysis. We have shown that HK2 expression induces resistance to NK cell cytotoxicity in a process requiring mitochondrial binding of HK2. Neither HK2 nor GCK expression affects target cells' ability to activate NK cells. In contrast, mitochondrial binding of HK2 reduces effector caspase 3/7 activity both at baseline and upon NK-cell activation. Furthermore, HK2 tethering to mitochondria enhances their resistance to cytochrome c release triggered by tBID. These findings indicate that HK2 mitochondrial binding in liver cancer cells is an intrinsic resistance factor to cytolysis and an escape mechanism from immune surveillance.

FHL1 is a major host factor for chikungunya virus infection.

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o'nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery-Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore,  CHIKV infection  is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.

Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress.

The hypoxia response pathway enables adaptation to oxygen deprivation. It is mediated by hypoxia-inducible factors (HIF), which promote metabolic reprogramming, erythropoiesis, angiogenesis and tissue remodeling. This led to the successful development of HIF-inducing drugs for treating anemia and some of these molecules are now in clinic. However, elevated levels of HIFs are frequently associated with tumor growth, poor prognosis, and drug resistance in various cancers, including hepatocellular carcinoma (HCC). Consequently, there are concerns regarding the recommendation of HIF-inducing drugs in certain clinical situations. Here, we analyzed the effects of two HIF-inducing drugs, Molidustat and Roxadustat, in the well-characterized HCC cell line Huh7. These drugs increased HIF-1α and HIF-2α protein levels which both participate in inducing hypoxia response genes such as BNIP3, SERPINE1, LDHA or EPO. Combined transcriptomics, proteomics and metabolomics showed that Molidustat increased the expression of glycolytic enzymes, while the mitochondrial network was fragmented and cellular respiration decreased. This metabolic remodeling was associated with a reduced proliferation and a lower demand for pyrimidine supply, but an increased ability of cells to convert pyruvate to lactate. This was accompanied by a higher resistance to the inhibition of mitochondrial respiration by antimycin A, a phenotype confirmed in Roxadustat-treated Huh7 cells and Molidustat-treated hepatoblastoma cells (Huh6 and HepG2). Overall, this study shows that HIF-inducing drugs increase the metabolic resilience of liver cancer cells to metabolic stressors, arguing for careful monitoring of patients treated with HIF-inducing drugs, especially when they are at risk of liver cancer.

Covalent Transition Metal Borosilicides: Reaction Pathways in Molten Salts for Water Oxidation Electrocatalysis.

The properties of transition metal borides and silicides are intimately linked to the covalent character of the chemical bonds within their crystal structures. Bringing boron and silicon together within metal borosilicides can then engender different competing covalent networks and complex charge distributions. This situation results in unique structures and atomic environments, which can impact charge transport and catalytic properties. Metal borosilicides, however, hold the status of unusual exotic species, difficult to synthesize and with poor knowledge of their properties. Our strategy consists of developing a redox pathway to synthesize transition metal borosilicides in inorganic molten salts as high-temperature solvents. By studying the formation of Ni6Si2B, Co4.75Si2B, Fe5SiB2, and Mn5SiB2 with in situ X-ray diffraction, we highlight how new reaction routes, maintaining covalent structural building blocks, draw a general scheme of their formation. This pathway is driven by the covalence of the chemical bonds within the boron coordination framework. Next, we demonstrate high efficiency for water oxidation electrocatalysis, especially for Ni6Si2B. We ascribe the strongly increased resistance to corrosion, high stability, and electrocatalytic activity of the Ni6Si2B-derived material to three factors: (1) the two entangled boron and silicon covalent networks; (2) the ability to codope with boron and silicon an in situ generated catalytic layer; and (3) a rare electron enrichment of the transition metal by back-donation from boron atoms, previously unknown within this compound family. With this work, we then unveil a new chemical dimension for Earth-abundant water oxidation electrocatalysts by bringing to light a new family of materials.