Forecasting Distributional Responses of Limber Pine to Climate Change at Management-Relevant Scales in Rocky Mountain National Park

Resource managers at parks and other protected areas are increasingly expected to factor climate change explicitly into their decision making frameworks. However, most protected areas are small relative to the geographic ranges of species being managed, so forecasts need to consider local adaptation and community dynamics that are correlated with climate and affect distributions inside protected area boundaries. Additionally, niche theory suggests that species\u27 physiological capacities to respond to climate change may be underestimated when forecasts fail to consider the full breadth of climates occupied by the species rangewide. Here, using correlative species distribution models that contrast estimates of climatic sensitivity inferred from the two spatial extents, we quantify the response of limber pine (Pinus flexilis) to climate change in Rocky Mountain National Park (Colorado, USA). Models are trained locally within the park where limber pine is the community dominant tree species, a distinct structural-compositional vegetation class of interest to managers, and also rangewide, as suggested by niche theory. Model forecasts through 2100 under two representative concentration pathways (RCP 4.5 and 8.5 W/m2) show that the distribution of limber pine in the park is expected to move upslope in elevation, but changes in total and core patch area remain highly uncertain. Most of this uncertainty is biological, as magnitudes of projected change are considerably more variable between the two spatial extents used in model training than they are between RCPs, and novel future climates only affect local model predictions associated with RCP 8.5 after 2091. Combined, these results illustrate the importance of accounting for unknowns in species\u27 climatic sensitivities when forecasting distributional scenarios that are used to inform management decisions. We discuss how our results for limber pine may be interpreted in the context of climate change vulnerability and used to help guide adaptive management

Comparing shades of darkness: trolling victims’ experiences on social media vs. online gaming

Although there is ample literature available on toxicity in games, as there is regarding trolling on social media, there are few to no cross-platform studies on toxicity and trolling. In other words, the extant literature focuses on one platform at a time instead of comparing and contrasting them. The present work aims to rectify this gap by analyzing interviews from a larger study of 22 self-proclaimed victims of in-game trolling to not only determine whether social media or gaming communities are considered more toxic but also to explore how definitions of the word ‘trolling’ change depending on the platform in question. We found that while definitions of in-game trolling behavior focused on behavioral styles of trolling (e.g., throwing one’s avatar into enemy fire to disadvantage one’s team, and blocking other players’ avatars’ movement), social media trolling is defined by more sinister actions such as misinformation spreading and ‘canceling’ other users. We also found that gaming is perceived as generally more toxic than social media, often due to company policies or lack thereof. Practical and theoretical implications for the study of toxicity in all online communities – gaming or social-media based – are discussed

Genes Encoding the T-Cell Antigen Receptor

The search for the elusive and controversial T-cell antigen receptor is over. It is now clear that gene complexes for both alpha and beta chains are distinct from those for immunoglobulin genes. They are, however, related to Ig genes as well as to other class I and class II major histocompatibility complex (MHC) gene products. Therefore, they belong to the immunoglobulin super gene family

The Elephant in the Room: Too Much Medicine in Musculoskeletal Practice

Too much medicine burdens health care systems and deprives societies of resources. Overcoming too much medicine requires stakeholders (patients, clinicians, educators, health care funders, media, policy makers, industry, insurers, politicians, etc) to appropriately prioritize low-risk, cost-effective care over higher-risk and more expensive care of equal clinical effectiveness. Professional bodies, government agencies, clinicians, and patients must collaborate to discuss and synthesize the available evidence, share decisions, and translate knowledge. We do not underestimate the challenge of the task. Reducing the harm of medicalizing normality and avoiding the temptation to provide too much medicine in current musculoskeletal practice depend on all of us. © 2020 Journal of Orthopaedic & Sports Physical Therapy

The magic bullet: Creating Indium-111 bombesin targeting vectors for use in diagnostic imaging of prostate and breast cancer [abstract]

Abstract only availableBackground: According to the American Cancer Society, over 68,000 men and women will die from prostate and breast cancer in this year alone. Prostate, breast and other cancers have been shown to express the BB2 receptor. For the past decade the Hoffman laboratory has been synthesizing radiopharmaceutical conjugates based on the Bombesin (BBN) peptide (Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2) that target the BB2 receptor for diagnosis and treatment of cancer. The radioconjugates are composed of a bombesin targeting vector, linking group, chelation moiety and a radioactive metal. One focus of our group is to investigate the efficacy of new Bombesin Targeting Vectors (BTV) which are derivatives of the BBN peptide. In the sixth position of the BTV is a D-phenylalanine amino acid. Our hypothesis is that the D-phenylalanine is responsible for significantly reducing kidney retention. Reduction of kidney retention is crucial for clinical radiotherapeutic applications because the kidney is often the dose limiting organ. In order to understand the structure function relationship of the D-phenylalanine in the BTV targeting vectors, we synthesized and evaluated the BTV peptide with the L-phenylalanine in the sixth position to determine what effect the stereochemistry has upon the in vitro receptor binding and in vivo pharmacokinetic properties of the peptide. Methods: The peptides were synthesized using solid phase peptide synthesis, purified using RP-HPLC, and characterized using electrospray mass spectrometry. Radiolabeling of the peptides was performed using 111InCl3. In vitro cell binding assays and internalization and efflux studies were performed using the PC-3 human cancer cell line. In vivo pharmacokinetic studies were performed using CF-1 mice. Micro-SPECT (single photon emission computed tomography) imaging studies were performed in PC-3 SCID mice. Results: In vivo pharmacokinetic studies at 15 min post-injection gave 39.85 ± 5.07 %ID/g in the BB2 receptor expressing mouse pancreas for the L-Phe-BTV radioconjugate compared to 10.30 ± 0.34 for the D-Phe-BTV. Surprisingly, the kidney clearance for both radioconjugates was statistically identical. Conclusion: Incorporation of the L-Phe instead of the D-Phe into the sixth position of the BTV had no statistically significant effect upon the renal clearance of the radioconjugate. However, the change in stereochemistry from the L to the D-form had significant effects upon the in vivo uptake and retention of the radioconjugate. Further investigations will be conducted to understand the mechanism responsible for the difference in uptake and retention of the two Bombesin radioconjugates

Chemical Abundances of the Leo II Dwarf Galaxy

We use previously-published moderate-resolution spectra in combination with stellar atmosphere models to derive the first measured chemical abundance ratios in the Leo II dSph galaxy. We find that for spectra with SNR > 24, we are able to measure abundances from weak Ti, Fe and Mg lines located near the calcium infrared triplet (CaT). We also quantify and discuss discrepancies between the metallicities measured from Fe I lines and those estimated from the CaT features. We find that while the most metal-poor ([Fe/H] <-2.0]) Leo II stars have Ca and Ti abundance ratios similar to those of Galactic globular clusters, the more metal-rich stars show a gradual decline of Ti, Mg and Ca abundance ratio with increasing metallicity. Finding these trends in this distant and apparently dynamically stable dSph galaxy supports the hypothesis that the slow chemical enrichment histories of the dSph galaxies is universal, independent of any interaction with the Milky Way. Combining our spectroscopic abundances with published broadband photometry and updated isochrones, we are able to approximate stellar ages for our bright RGB stars to a relative precision of 2-3 Gyr. While the derived age-metallicity relationship of Leo II hints at some amount of slow enrichment, the data are still statistically consistent with no enrichment over the history of Leo II.Comment: Accepted to A

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV-visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

EGFR-targeted semiconducting polymer nanoparticles for photoacoustic imaging

Semiconducting polymer nanoparticles (SPN), formulated from organic semiconducting polymers and lipids, show promise as exogenous contrast agents for photoacoustic imaging (PAI). To fully realise the potential of this class of nanoparticles for imaging and therapeutic applications, a broad range of active targeting strategies, where ligands specific to receptors on the target cells are displayed on the SPN surface, are urgently needed. In addition, effective strategies for quantifying the level of surface modification are also needed to support development of ligand-targeted SPN. In this paper, we have developed methods to prepare SPN bearing peptides targeted to Epidermal Growth Factor Receptors (EGFR), which are overexpressed at the surface of a wide variety of cancer cell types. In addition to fully characterising these targeted nanoparticles by standard methods (UV–visible, photoacoustic absorption, dynamic light scattering, zeta potential and SEM), we have developed a powerful new NMR method to determine the degree of conjugation and the number of targeting peptides attached to the SPN. Preliminary in vitro experiments with the colorectal cancer cell line LIM1215 indicated that the EGFR-targeting peptide conjugated SPN were either ineffective in delivering the SPN to the cells, or that the targeting peptide itself destabilised the formulation. This in reinforces the need for effective characterisation techniques to measure the surface accessibility of targeting ligands attached to nanoparticles

Neutrophils are Mediators of Metastatic Prostate Cancer Progression in Bone

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis of PCa in vitro and in vivo, such that neutrophil depletion in bone metastasis models enhanced BM-PCa growth. Neutrophil-mediated PCa killing was found to be mediated by suppression of STAT5, a transcription factor shown to promote PCa progression. However, as the tumor progressed in bone over time, neutrophils from late-stage bone tumors failed to elicit cytotoxic effector responses to PCa. These findings are the first to demonstrate that bone-resident neutrophils inhibit PCa and that BM-PCa are able to progress via evasion of neutrophil-mediated killing. Enhancing neutrophil cytotoxicity in bone may present a novel therapeutic option for bone metastatic prostate cancer