Recent Decisions

Comments on recent decisions by J. Patrick O\u27Malley, Peter H. Lousberg, David J. Eardley, James M. Corcoran, Jr., Joseph B. Joyce, James E. Murray, Edmund L. White, Berry L. Reece, Jr., A. J. Deutsch, and George N. Tompkins, Jr

The Power of Principled Bayesian Methods in the Study of Stellar Evolution

It takes years of effort employing the best telescopes and in- struments to obtain high-quality stellar photometry, astrometry, and spectroscopy. Stellar evolution models contain the experience of life- times of theoretical calculations and testing. Yet most astronomers fit these valuable models to these precious datasets by eye. We show that a principled Bayesian approach to fitting models to stellar data yields substantially more information over a range of stellar astrophysics. We highlight advances in determining the ages of star clusters, mass ratios of binary stars, limitations in the accuracy of stellar models, post-main-sequence mass loss, and the ages of individual white dwarfs. We also outline a number of unsolved problems that would benefit from principled Bayesian analyses

The Impact of Composition and Morphology on Ionic Conductivity of Silk/Cellulose Bio-Composites Fabricated from Ionic Liquid and Varying Percentages of Coagulation Agents.

Blended biocomposites created from the electrostatic and hydrophobic interactions between polysaccharides and structural proteins exhibit useful and unique properties. However, engineering these biopolymers into applicable forms is challenging due to the coupling of the material’s physicochemical properties to its morphology, and the undertaking that comes with controlling this. In this particular study, numerous properties of the Bombyx mori silk and microcrystalline cellulose biocomposites blended using ionic liquid and regenerated with various coagulation agents were investigated. Specifically, the relationship between the composition of polysaccharide-protein bio-electrolyte membranes and the resulting morphology and ionic conductivity is explored using numerous characterization techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray scattering, atomic force microscopy (AFM) based nanoindentation, and dielectric relaxation spectroscopy (DRS). The results revealed that when silk is the dominating component in the biocomposite, the ionic conductivity is higher, which also correlates with higher β-sheet content. However, when cellulose becomes the dominating component in the biocomposite, this relationship is not observed; instead, cellulose semicrystallinity and mechanical properties dominate the ionic conduction

Spatial definition of the human progesterone receptor-B transcriptional complex.

We report the quaternary structure of core transcriptional complex for the full-length human progesterone receptor-B (PR-B) homodimer with primary coactivator steroid receptor coactivator-2 (SRC-2) and the secondary coactivator p300/CREB-binding protein (CBP). The PR-B homodimer engages one SRC-2 mainly through its activation function 1 (AF1) in N-terminus. SRC-2 is positioned between PR-B and p300 leaving space for direct interaction between PR-B and p300 through PR-B\u27s C-terminal AF2 and its unique AF3. Direct AF3/p300 interaction provides long-desired structural insights into the known functional differences between PR-B and the PR-A isoform lacking AF3. We reveal the contributions of each AF and demonstrate their structural basis in forming the PR-B dimer interface and PR-B/coactivator complex. Comparison of the PR-B/coactivator complex with other steroid receptor (estrogen receptor and androgen receptor) complexes also shows that each receptor has its unique mechanism for recruiting coactivators due to the highly variable N-termini among receptors

TECHNIQUES FOR REARING AND RELEASING NONMIGRATORY CRANES: LESSONS FROM THE MISSISSIPPI SANDHILL CRANE PROGRAM

Captive-reared Mississippi sandhill cranes (Grus canadensis pulla) reared at the Patuxent Wildlife Research Center (patuxent) have been released at the Mississippi Sandhill Crane National Wildlife Refuge (MSCNWR) since 1981. Of 131 birds released through December 1990, 103 were reared by foster parents. The remaining 28 were experimentally hand-reared in 1989 and 1990. After refining release procedures, parent-reared birds have integrated into the wild flock, many have survived, and some have bred. Releases of hand-reared cranes elsewhere in the 1970\u27s were largely unsuccessful. at least in part due to the lack of a lengthy acclimation period. A new hand-rearing protocol holds promise in producing release-worthy birds. The technique employs some features first used in the 1960\u27s (e.g., a costume for the human caretaker and model crane heads used to train chicks to feed). In the mid-1980\u27s, the following features were added: (1) the costumed caretaker was given a visor and feathers, (2) a taxidermic crane head or a hand puppet was held or suspended from the ceiling for use in stimulating chicks to feed, (3) a taxidermic mount of a brooding crane supplied warmth, (4) a full-sized live crane was maintained in an adjacent pen and in visual contact with neonatal young to provide an imprinting model, and (5) a small group of adult (or subadult) cranes was penned adjacent to the outdoor chick pens to provide socialization models. Recent releases of Mississippi sandhill cranes hand-reared according to this protocol and released in Mississippi have had high first-year survival rates. The now-operational technique holds promise for producing large numbers of release-worthy birds

TECHNIQUES FOR REARING AND RELEASING NONMIGRATORY CRANES: LESSONS FROM THE MISSISSIPPI SANDHILL CRANE PROGRAM

Captive-reared Mississippi sandhill cranes (Grus canadensis pulla) reared at the Patuxent Wildlife Research Center (patuxent) have been released at the Mississippi Sandhill Crane National Wildlife Refuge (MSCNWR) since 1981. Of 131 birds released through December 1990, 103 were reared by foster parents. The remaining 28 were experimentally hand-reared in 1989 and 1990. After refining release procedures, parent-reared birds have integrated into the wild flock, many have survived, and some have bred. Releases of hand-reared cranes elsewhere in the 1970\u27s were largely unsuccessful. at least in part due to the lack of a lengthy acclimation period. A new hand-rearing protocol holds promise in producing release-worthy birds. The technique employs some features first used in the 1960\u27s (e.g., a costume for the human caretaker and model crane heads used to train chicks to feed). In the mid-1980\u27s, the following features were added: (1) the costumed caretaker was given a visor and feathers, (2) a taxidermic crane head or a hand puppet was held or suspended from the ceiling for use in stimulating chicks to feed, (3) a taxidermic mount of a brooding crane supplied warmth, (4) a full-sized live crane was maintained in an adjacent pen and in visual contact with neonatal young to provide an imprinting model, and (5) a small group of adult (or subadult) cranes was penned adjacent to the outdoor chick pens to provide socialization models. Recent releases of Mississippi sandhill cranes hand-reared according to this protocol and released in Mississippi have had high first-year survival rates. The now-operational technique holds promise for producing large numbers of release-worthy birds

Lead Compound Development of SRC-3 Inhibitors with Improved Pharmacokinetic Properties and Anticancer Efficacy

Steroid receptor coactivator 3 (SRC-3) is a critical mediator of many intracellular signaling pathways that are crucial for cancer proliferation and metastasis. In this study, we performed structure-activity relationship (SAR) exploration and drug-like optimization of the hit compound SI-2, guided by in vitro/in vivo metabolism studies and cytotoxicity assays. Our efforts led to the discovery of two lead compounds, SI-10 and SI-12. Both compounds exhibit potent cytotoxicity against a panel of human cancer cell lines and demonstrate acceptable pharmacokinetic properties. A biotinylated estrogen response element (ERE) pull-down assay demonstrated that SI-12 could disrupt the recruitment of SRC-3 and p300 in the ER complex. Importantly, SI-10 and SI-12 significantly inhibited tumor growth and metastasis in vivo without appreciable acute toxicity. These results demonstrate the potential of SI-10 and SI-12 as drug candidates for cancer therapy, given their potent SRC-3 inhibition and promising pharmacokinetic and toxicity profiles

A Steroid Receptor Coactivator Stimulator (Mcb-613) Attenuates Adverse Remodeling After Myocardial Infarction

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion of Tsc22d3-expressing macrophages-all of which may limit inflammatory damage. SRC stimulation with MCB-613 (and derivatives) is a potential therapeutic approach for inhibiting cardiac dysfunction after MI

Risk factors and outcomes associated with community-onset and hospital-acquired coinfection in patients hospitalized for coronavirus disease 2019 (COVID-19): A multihospital cohort study

BACKGROUND: We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes. METHODS: In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection. RESULTS: Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P \u3c .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P \u3c .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P \u3c .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P \u3c .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001). CONCLUSION: Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use