Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction ...program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.
Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to ...drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ∼40% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration.
A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern ...of G614 increase at multiple geographic levels: national, regional, and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to a higher titer as pseudotyped virions. In infected individuals, G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, but not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus and support continuing surveillance of Spike mutations to aid with development of immunological interventions.
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•A SARS-CoV-2 variant with Spike G614 has replaced D614 as the dominant pandemic form•The consistent increase of G614 at regional levels may indicate a fitness advantage•G614 is associated with lower RT PCR Cts, suggestive of higher viral loads in patients•The G614 variant grows to higher titers as pseudotyped virions
Korber et al. present evidence that there are now more SARS-CoV-2 viruses circulating in the human population globally that have the G614 form of the Spike protein versus the D614 form that was originally identified from the first human cases in Wuhan, China. Follow-up studies show that patients infected with G614 shed more viral nucleic acid compared with those with D614, and G614-bearing viruses show significantly higher infectious titers in vitro than their D614 counterparts.
We describe the photometric calibration and stellar classification methods used by the Stellar Classification Project to produce the Kepler Input Catalog (KIC). The KIC is a catalog containing ...photometric and physical data for sources in the Kepler mission field of view; it is used by the mission to select optimal targets. Four of the visible-light (g, r, i, z) magnitudes used in the KIC are tied to Sloan Digital Sky Survey magnitudes; the fifth (D51) is an AB magnitude calibrated to be consistent with Castelli & Kurucz (CK) model atmosphere fluxes. We derived atmospheric extinction corrections from hourly observations of secondary standard fields within the Kepler field of view. For these filters and extinction estimates, repeatability of absolute photometry for stars brighter than magnitude 15 is typically 2%. We estimated stellar parameters {T eff, log (g), log (Z), E B -- V } using Bayesian posterior probability maximization to match observed colors to CK stellar atmosphere models. We applied Bayesian priors describing the distribution of solar-neighborhood stars in the color-magnitude diagram, in log (Z), and in height above the galactic plane. Several comparisons with samples of stars classified by other means indicate that for 4500 K <=T eff <= 6500 K, our classifications are reliable within about ?200 K and 0.4 dex in log (g) for dwarfs, with somewhat larger log (g) uncertainties for giants. It is difficult to assess the reliability of our log (Z) estimates, but there is reason to suspect that it is poor, particularly at extreme T eff. Comparisons between the CK models and observed colors are generally satisfactory with some exceptions, notably for stars cooler than 4500 K. Of great importance for the Kepler mission, for T eff <= 5400 K, comparison with asteroseismic results shows that the distinction between main-sequence stars and giants is reliable with about 98% confidence. Larger errors in log (g) occur for warmer stars, for which our filter set provides inadequate gravity diagnostics. The KIC is available through the MAST data archive.
Twilight is characterised by changes in both quantity ("irradiance") and quality ("colour") of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their ...behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.
Most organisms use internal biological clocks to match behavioural and physiological processes to specific phases of the day-night cycle. Central to this is the synchronisation of internal processes ...across multiple organ systems. Environmental desynchrony (e.g. shift work) profoundly impacts human health, increasing cardiovascular disease and diabetes risk, yet the underlying mechanisms remain unclear. Here, we characterise the impact of desynchrony between the internal clock and the external light-dark (LD) cycle on mammalian physiology. We reveal that even under stable LD environments, phase misalignment has a profound effect, with decreased metabolic efficiency and disrupted cardiac function including prolonged QT interval duration. Importantly, physiological dysfunction is not driven by disrupted core clock function, nor by an internal desynchrony between organs, but rather the altered phase relationship between the internal clockwork and the external environment. We suggest phase misalignment as a major driver of pathologies associated with shift work, chronotype and social jetlag.The misalignment between internal circadian rhythm and the day-night cycle can be caused by genetic, behavioural and environmental factors, and may have a profound impact on human physiology. Here West et al. show that desynchrony between the internal clock and the external environment alter metabolic parameters and cardiac function in mice.
We report the first confirmation of a hot Jupiter discovered by the Transiting Exoplanet Survey Satellite (TESS) mission: HD 202772A b. The transit signal was detected in the data from TESS Sector 1, ...and was confirmed to be of planetary origin through radial velocity (RV) measurements. HD 202772A b is orbiting a mildly evolved star with a period of 3.3 days. With an apparent magnitude of V = 8.3, the star is among the brightest and most massive known to host a hot Jupiter. Based on the 27 days of TESS photometry and RV data from the CHIRON, HARPS, and Tillinghast Reflector Echelle Spectrograph, the planet has a mass of and radius of , making it an inflated gas giant. HD 202772A b is a rare example of a transiting hot Jupiter around a quickly evolving star. It is also one of the most strongly irradiated hot Jupiters currently known.
Transiting Exoplanet Survey Satellite (TESS) observations have revealed a compact multiplanet system around the sixth-magnitude star HR 858 (TIC 178155732, TOI 396), located 32 pc away. Three ...planets, each about twice the size of Earth, transit this slightly evolved, late F-type star, which is also a member of a visual binary. Two of the planets may be in mean motion resonance. We analyze the TESS observations, using novel methods to model and remove instrumental systematic errors, and combine these data with follow-up observations taken from a suite of ground-based telescopes to characterize the planetary system. The HR 858 planets are enticing targets for precise radial velocity observations, secondary eclipse spectroscopy, and measurements of the Rossiter-McLaughlin effect.
The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing ...information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.
•We trace 97 million years of bromeliad adaptation, biogeography, and species diversification.•We use these data to test an integrative model for bromeliad evolution.•Patterns of correlated and ...contingent evolution are consistent with this model.•Diversification rates are significantly higher in epiphytic, tank-forming, bird-pollinated, and montane lineages.•86% Of bromeliad species richness reflects six major adaptive radiations in different areas.
We present an integrative model predicting associations among epiphytism, the tank habit, entangling seeds, C3 vs. CAM photosynthesis, avian pollinators, life in fertile, moist montane habitats, and net rates of species diversification in the monocot family Bromeliaceae. We test these predictions by relating evolutionary shifts in form, physiology, and ecology to time and ancestral distributions, quantifying patterns of correlated and contingent evolution among pairs of traits and analyzing the apparent impact of individual traits on rates of net species diversification and geographic expansion beyond the ancestral Guayana Shield. All predicted patterns of correlated evolution were significant, and the temporal and spatial associations of phenotypic shifts with orogenies generally accorded with predictions. Net rates of species diversification were most closely coupled to life in fertile, moist, geographically extensive cordilleras, with additional significant ties to epiphytism, avian pollination, and the tank habit. The highest rates of net diversification were seen in the bromelioid tank-epiphytic clade (Dcrown=1.05My−1), associated primarily with the Serra do Mar and nearby ranges of coastal Brazil, and in the core tillandsioids (Dcrown=0.67My−1), associated primarily with the Andes and Central America. Six large-scale adaptive radiations and accompanying pulses of speciation account for 86% of total species richness in the family. This study is among the first to test a priori hypotheses about the relationships among phylogeny, phenotypic evolution, geographic spread, and net species diversification, and to argue for causality to flow from functional diversity to spatial expansion to species diversity.
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