Thermal physiological traits in tropical lowland amphibians: Vulnerability to climate warming and cooling

Climate change is affecting biodiversity and ecosystem function worldwide, and the lowland tropics are of special concern because organisms living in this region experience temperatures that are close to their upper thermal limits. However, it remains unclear how and whether tropical lowland species will be able to cope with the predicted pace of climate warming. Additionally, there is growing interest in examining how quickly thermal physiological traits have evolved across taxa, and whether thermal physiological traits are evolutionarily conserved or labile. We measured critical thermal maximum (CTmax) and minimum (CTmin) in 56 species of lowland Amazonian frogs to determine the extent of phylogenetic conservatism in tolerance to heat and cold, and to predict species’ vulnerability to climate change. The species we studied live in sympatry and represent ~65% of the known alpha diversity at our study site. Given that critical thermal limits may have evolved differently in response to different temperature constraints, we tested whether CTmax and CTmin exhibit different rates of evolutionary change. Measuring both critical thermal traits allowed us to estimate species’ thermal breadth and infer their potential to respond to abrupt changes in temperature (warming and cooling). Additionally, we assessed the contribution of life history traits and found that both critical thermal traits were correlated with species’ body size and microhabitat use. Specifically, small direct-developing frogs in the Strabomantidae family appear to be at highest risk of thermal stress while tree frogs (Hylidae) and narrow mouthed frogs (Microhylidae) tolerate higher temperatures. While CTmax and CTmin had considerable variation within and among families, both critical thermal traits exhibited similar rates of evolutionary change. Our results suggest that 4% of lowland rainforest frogs assessed will experience temperatures exceeding their CTmax, 25% might be moderately affected and 70% are unlikely to experience pronounced heat stress under a hypothetical 3°C temperature increase

The intertwined history of non-human primate health and human medicine at the Smithsonian's national Zoo and conservation Biology Institute

In April 2020, the Bronx Zoo made a headline-grabbing announcement: one of their tigers tested positive for COVID-19, a striking example of zoos as microcosms of human health and medicine. Indeed, many diseases and health problems experienced by zoo animals are found in, and frequently linked to, humans. Furthermore, the veterinary care they receive often incorporates knowledge, tools and treatments used in human health care. Here, we analyse these developments across the history of non-human primate health at the Smithsonian's National Zoo and Conservation Biology Institute (NZP), one of the oldest zoos in the United States. From NZP's opening in 1891, we distinguish five historical time periods within its first century based on how animal health was described, treated and understood. Concentrating on descriptions of primates in annual Smithsonian reports, we see notable changes in NZP activities focused on housing and environment (1889–1900), disease diagnosis and prevention (1901–1916), human–animal connections (1917–1940), research and collaboration (1941–1973) and conservation (1974–1989). We relate these shifts to concurrent medical events and trends in the United States, and interpret NZP's history in a broader scientific and societal context leading to a ‘One Health’ approach to animal care and welfare today.Output Status: Forthcoming/Available Onlin

Beyond the Planar Limit in ABJM

In this article we consider gauge theories with a U(N)X U(N) gauge group. We provide, for the first time, a complete set of operators built from scalar fields that are in the bi fundamental of the two groups. Our operators diagonalize the two point function of the free field theory at all orders in 1/N. We then use this basis to investigate non-planar anomalous dimensions in the ABJM theory. We show that the dilatation operator reduces to a set of decoupled harmonic oscillators, signaling integrability in a nonplanar large N limit.Comment: v2: minor revisison

ABJM Dibaryon Spectroscopy

We extend the proposal for a detailed map between wrapped D-branes in Anti-de Sitter space and baryon-like operators in the associated dual conformal field theory provided in hep-th/0202150 to the recently formulated AdS_4 \times CP^3/ABJM correspondence. In this example, the role of the dibaryon operator of the 3-dimensional CFT is played by a D4-brane wrapping a CP^2 \subset CP^3. This topologically stable D-brane in the AdS_4 \times CP^3 is nothing but one-half of the maximal giant graviton on CP^3.Comment: 26 page

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA

Symbiotic organs shaped by distinct modes of genome evolution in cephalopods.

Microbes have been critical drivers of evolutionary innovation in animals. To understand the processes that influence the origin of specialized symbiotic organs, we report the sequencing and analysis of the genome of Euprymna scolopes, a model cephalopod with richly characterized host-microbe interactions. We identified large-scale genomic reorganization shared between E. scolopes and Octopus bimaculoides and posit that this reorganization has contributed to the evolution of cephalopod complexity. To reveal genomic signatures of host-symbiont interactions, we focused on two specialized organs of E. scolopes: the light organ, which harbors a monoculture of Vibrio fischeri, and the accessory nidamental gland (ANG), a reproductive organ containing a bacterial consortium. Our findings suggest that the two symbiotic organs within E. scolopes originated by different evolutionary mechanisms. Transcripts expressed in these microbe-associated tissues displayed their own unique signatures in both coding sequences and the surrounding regulatory regions. Compared with other tissues, the light organ showed an abundance of genes associated with immunity and mediating light, whereas the ANG was enriched in orphan genes known only from E. scolopes Together, these analyses provide evidence for different patterns of genomic evolution of symbiotic organs within a single host

Optimising platelet secretomes to deliver robust tissue specific regeneration

Promoting cell proliferation is the cornerstone of most tissue regeneration therapies. As platelet‐based applications promote cell division and can be customised for tissue‐specific efficacy, this makes them strong candidates for developing novel regenerative therapies. Therefore, the aim of this study was to determine if platelet releasate could be optimised to promote cellular proliferation and differentiation of specific tissues. Growth factors in platelet releasate were profiled for physiological and supra‐physiological platelet concentrations. We analysed the effect of physiological and supra‐physiological releasate on C2C12 skeletal myoblasts, H9C2 rat cardiomyocytes, human dermal fibroblasts (HDF), HaCaT keratinocytes and chondrocytes. Cellular proliferation and differentiation were assessed through proliferation assays, mRNA and protein expression. We show that supra‐physiological releasate is not simply a concentrated version of physiological releasate. Physiological releasate promoted C2C12, HDF and chondrocyte proliferation with no effect on H9C2 or HaCaT cells. Supra‐physiological releasate induced stronger proliferation in C2C12 and HDF cells compared to physiological releasate. Importantly, supra‐physiological releasate induced proliferation of H9C2 cells. The proliferative effects of skeletal and cardiac muscle cells were in part driven by VEGFα. Furthermore, supra‐physiological releasate induced differentiation of H9C2 and C2C12, HDF and keratinocyte differentiation. This study provides insights into the ability of releasate to promote muscle, heart, skin and cartilage cell proliferation and differentiation and highlights the importance of optimising releasate composition for tissue‐specific regeneration

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

457 KEYNOTE-495/KeyImPaCT: interim analysis of a randomized, biomarker-directed, phase 2 trial of pembrolizumab-based combination therapy for non–small cell lung cancer (NSCLC)

BackgroundT-cell–inflamed gene expression profile (TcellinfGEP) and tumor mutational burden (TMB) are clinically validated biomarkers that independently predict pembrolizumab response. This study investigated prospective TcellinfGEP and TMB assessment in evaluating first-line pembrolizumab-based combination therapies; the different treatment combinations evaluated may provide insight into the unique biology of each biomarker subgroup.MethodsKEYNOTE-495/KeyImPaCT is a group-sequential, adaptively randomized, multisite, open-label, phase 2 study investigating first-line pembrolizumab plus the VEGF/FGFR inhibitor lenvatinib, CTLA-4 inhibitor quavonlimab (MK-1308), or LAG-3 inhibitor favezelimab (MK-4280) in patients with advanced NSCLC. DNA and RNA were extracted from tumor tissue to determine TcellinfGEP and TMB; patients were assigned to one of four biomarker-defined subgroups (TcellinfGEPlowTMBlow, TcellinfGEPlowTMBhigh, TcellinfGEPhighTMBlow, TcellinfGEPhighTMBhigh) and randomly assigned 1:1:1 to receive pembrolizumab (200mg IV Q3W)+lenvatinib (20mg oral QD), pembrolizumab+quavonlimab (75mg IV Q6W), or pembrolizumab+favezelimab (200mg [n=30] or 800mg [n=34] Q3W; the initial prespecified dose was 200mg but changed to 800mg based on emerging data). The primary end point was investigator-assessed ORR per RECIST v1.1. Multiple interim analyses will be performed until the prespecified clinical signal is observed. The first interim analysis for each combination therapy occurred after ≥10 patients had ≥12 weeks of follow-up.ResultsAt the data cutoff (January 11, 2021), 208 patients were treated (pembrolizumab+lenvatinib, n=72; pembrolizumab+quavonlimab, n=72; pembrolizumab+favezelimab 200mg, n=30; pembrolizumab+favezelimab 800mg, n=34). The overall assay success rate for testing and determining TcellinfGEP and TMB was 94%. In patients treated with pembrolizumab+lenvatinib, pembrolizumab+quavonlimab, or pembrolizumab+favezelimab, ORRs were generally highest in the TcellinfGEPhighTMBhigh subgroup (table 1); response rates were similar across combinations within this subgroup. ORR was low across combinations within the TcellinfGEPlowTMBlow subgroup. Treatment-related adverse events (TRAEs) occurred in 88%, 65%, 57%, and 59% of patients in the pembrolizumab+lenvatinib, pembrolizumab+quavonlimab, pembrolizumab+favezelimab 200mg and pembrolizumab+favezelimab 800mg arms, respectively. Consistent with the known TRAEs of these agents, most TRAEs were grade 1 or 2 in severity except in the pembrolizumab+lenvatinib arm (grade 3–5, 63%). Three deaths from TRAEs occurred (pembrolizumab+lenvatinib [n=2], brain hemorrhage and myocardial infarction; pembrolizumab+favezelimab 800 mg [n=1], pneumonitis).Abstract 457 Table 1Confirmed ORR by Therapy and Biomarker StatusConclusionsThese data demonstrate the feasibility and clinical usefulness of prospective TcellinfGEP and TMB assessment to study the clinical activity of three first-line pembrolizumab-based combination therapies in patients with advanced NSCLC. Although sample sizes were small, the TcellinfGEPhighTMBhigh subgroup demonstrated the best response among the biomarker subgroups for all three combination therapies; further validation is needed to determine additional signals and may be addressed as more mature data become available.AcknowledgementsJeanne Fahey, PhD, of Merck & Co., Inc., Kenilworth, New Jersey, USA, provided critical review of the abstract. Elisha Dettman PhD, Mark Ayers MS, and Andrey Loboda PhD of Merck & Co., Inc., Kenilworth, New Jersey, USA, provided critical review of study translational data. Medical writing and/or editorial assistance was provided by Shane Walton, PhD, and Lei Bai, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials.gov, NCT03516981Ethics ApprovalThe study protocol and all amendments were approved by the relevant institutional review board or ethics committee at each study site. All patients provided written informed consent to participate in the clinical trial