From the Rarest to the Most Common: Insights from Progeroid Syndromes into Skin Cancer and Aging

Despite their rarity, diseases of premature aging, or “progeroid” syndromes, have provided important insights into basic mechanisms that may underlie cancer and normal aging. In this review, we highlight these recent developments in Hutchinson—Gilford progeria syndrome (HGPS), Werner syndrome, Bloom syndrome, Cockayne syndrome, trichothiodystrophy, ataxia-telangiectasia, Rothmund–Thomson syndrome, and xeroderma pigmentosum. Though they are caused by different mutations in various genes and often result in quite disparate phenotypes, deciphering the molecular bases of these conditions has served to highlight their underlying basic similarities. Studies of progeroid syndromes, particularly HGPS, the most dramatic form of premature aging, have contributed to our knowledge of fundamental processes of importance to skin biology, including DNA transcription, replication, and repair, genome instability, cellular senescence, and stem-cell differentiation

Formation and Evolution of the Disk System of the Milky Way: [alpha/Fe] Ratios and Kinematics of the SEGUE G-Dwarf Sample

We employ measurements of the [alpha/Fe] ratio derived from low-resolution (R~2000) spectra of 17,277 G-type dwarfs from the SEGUE survey to separate them into likely thin- and thick-disk subsamples. Both subsamples exhibit strong gradients of orbital rotational velocity with metallicity, of opposite signs, -20 to -30 km/s/dex for the thin-disk and +40 to +50 km/s/dex for the thick-disk population. The rotational velocity is uncorrelated with Galactocentric distance for the thin-disk subsample, and exhibits a small trend for the thick-disk subsample. The rotational velocity decreases with distance from the plane for both disk components, with similar slopes (-9.0 {\pm} 1.0 km/s/kpc). Thick-disk stars exhibit a strong trend of orbital eccentricity with metallicity (about -0.2/dex), while the eccentricity does not change with metallicity for the thin-disk subsample. The eccentricity is almost independent of Galactocentric radius for the thin-disk population, while a marginal gradient of the eccentricity with radius exists for the thick-disk population. Both subsamples possess similar positive gradients of eccentricity with distance from the Galactic plane. The shapes of the eccentricity distributions for the thin- and thick-disk populations are independent of distance from the plane, and include no significant numbers of stars with eccentricity above 0.6. Among several contemporary models of disk evolution we consider, radial migration appears to have played an important role in the evolution of the thin-disk population, but possibly less so for the thick disk, relative to the gas-rich merger or disk heating scenarios. We emphasize that more physically realistic models and simulations need to be constructed in order to carry out the detailed quantitative comparisons that our new data enable.Comment: Accepted for publication in ApJ, 18 pages, 12 figures, 2 tables, emulateapj forma

Two Stellar Components in the Halo of the Milky Way

The halo of the Milky Way provides unique elemental abundance and kinematic information on the first objects to form in the Universe, which can be used to tightly constrain models of galaxy formation and evolution. Although the halo was once considered a single component, evidence for its dichotomy has slowly emerged in recent years from inspection of small samples of halo objects. Here we show that the halo is indeed clearly divisible into two broadly overlapping structural components -- an inner and an outer halo -- that exhibit different spatial density profiles, stellar orbits and stellar metallicities (abundances of elements heavier than helium). The inner halo has a modest net prograde rotation, whereas the outer halo exhibits a net retrograde rotation and a peak metallicity one-third that of the inner halo. These properties indicate that the individual halo components probably formed in fundamentally different ways, through successive dissipational (inner) and dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.Comment: Two stand-alone files in manuscript, concatenated together. The first is for the main paper, the second for supplementary information. The version is consistent with the version published in Natur

LAMOST Experiment for Galactic Understanding and Exploration (LEGUE) The survey science plan

We describe the current plans for a spectroscopic survey of millions of stars in the Milky Way galaxy using the Guo Shou Jing Telescope (GSJT, formerly the Large Area Multi-Object Spectroscopic Telescope - LAMOST). The survey will obtain spectra for 2.5 million stars brighter than $r<19$ during dark/grey time, and 5 million stars brighter than $r<17$ or $J<16$ on nights that are moonlit or have low transparency. The survey will begin in fall of 2012, and will run for at least four years. The telescope design constrains the optimal declination range for observations to $10^\circ<\delta<50^\circ$, and site conditions lead to an emphasis on stars in the direction of the Galactic anticenter. The survey is divided into three parts with different target selection strategies: disk, anticenter, and spheroid. The resulting dataset will be used to study the merger history of the Milky Way, the substructure and evolution of the disks, the nature of the first generation of stars through identification of the lowest metallicity stars, and star formation through study of open clusters and the OB associations. Detailed design of the LEGUE survey will be completed after a review of the results of the pilot survey in summer 2012.Comment: 19 pages, 1 figure, accepted for publication in RA

Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: a case study of bats

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. The establishment of new wildlife reservoirs for SARS-CoV-2 would further complicate public health control measures and could lead to wildlife health and conservation impacts. Given the likely bat origin of SARS-CoV-2 and related beta-coronaviruses (β-CoVs), free-ranging bats are a key group of concern for spillover from humans back to wildlife. Here, we review the diversity and natural host range of β-CoVs in bats and examine the risk of humans inadvertently infecting free-ranging bats with SARS-CoV-2. Our review of the global distribution and host range of β-CoV evolutionary lineages suggests that 40+ species of temperate-zone North American bats could be immunologically naïve and susceptible to infection by SARS-CoV-2. We highlight an urgent need to proactively connect the wellbeing of human and wildlife health during the current pandemic and to implement new tools to continue wildlife research while avoiding potentially severe health and conservation impacts of SARS-CoV-2 "spilling back" into free-ranging bat populations

The World's Rediscovered Species: Back from the Brink?

Each year, numerous species thought to have disappeared are rediscovered. Yet, do these rediscoveries represent the return of viable populations or the delayed extinction of doomed species? We document the number, distribution and conservation status of rediscovered amphibian, bird, and mammal species globally. Over the past 122 years, at least 351 species have been rediscovered, most occurring in the tropics. These species, on average, were missing for 61 years before being rediscovered (range of 3–331 years). The number of rediscoveries per year increased over time and the majority of these rediscoveries represent first documentations since their original description. Most rediscovered species have restricted ranges and small populations, and 92% of amphibians, 86% of birds, and 86% of mammals are highly threatened, independent of how long they were missing or when they were rediscovered. Under the current trends of widespread habitat loss, particularly in the tropics, most rediscovered species remain on the brink of extinction

Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: a case study of bats

The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from people to naïve wildlife and other animal populations. The establishment of new wildlife reservoirs for SARS-CoV-2 would further complicate public health control measures and could lead to wildlife health and conservation impacts. Given the likely bat origin of SARS-CoV-2 and related beta-coronaviruses (β-CoVs), free-ranging bats are a key group of concern for spillover from humans back to wildlife. Here, we review the diversity and natural host range of β-CoVs in bats and examine the risk of humans inadvertently infecting free-ranging bats with SARS-CoV-2. Our review of the global distribution and host range of β-CoV evolutionary lineages suggests that 40+ species of temperate-zone North American bats could be immunologically naïve and susceptible to infection by SARS-CoV-2. We highlight an urgent need to proactively connect the wellbeing of human and wildlife health during the current pandemic and to implement new tools to continue wildlife research while avoiding potentially severe health and conservation impacts of SARS-CoV-2 "spilling back" into free-ranging bat populations

Analysis of the Ribonuclease a superfamily of antimicrobial peptides in patients undergoing chronic peritoneal dialysis

Infectious peritonitis is a common complication in patients undergoing chronic peritoneal dialysis (PD), limiting the duration of PD as a modality for renal replacement therapy and increasing patient morbidity and mortality. Antimicrobial peptides (AMPs) serve critical roles in mucosal defense, but their expression and activity during peritonitis are poorly understood. We hypothesized that AMPs belonging to the Ribonuclease (RNase) A Superfamily are present in peritoneal fluid and increase during peritonitis in patients undergoing chronic PD. In the absence of peritonitis, we detected RNase 3, RNase 6, and RNase 7 in cell-free supernatants and viable cells obtained from peritoneal fluid of chronic PD patients. The cellular sources of these RNases were eosinophils (RNase 3), macrophages (RNase 6), and mesothelial cells (RNase 7). During peritonitis, RNase 3 increased 55-fold and RNase 7 levels increased 3-fold on average, whereas RNase 6 levels were unchanged. The areas under the receiver-operating characteristic curves for RNase 3 and RNase 7 were 0.99 (95% confidence interval (CI): 0.96–1.0) and 0.79 (95% CI: 0.64–0.93), respectively, indicating their potential as biomarkers of peritonitis. Discrete omental reservoirs of these RNases were evident in patients with end stage kidney disease prior to PD initiation, and omental RNase 3 reactive cells increased in patients undergoing PD with a history of peritonitis. We propose that constitutive and inducible pools of antimicrobial RNases form a network to shield the peritoneal cavity from microbial invasion in patients undergoing chronic PD