Pharmacological Evidence Suggests That the Lysozyme/PACAP Receptor of \u3cem\u3eTetrahymena thermophila\u3c/em\u3e is a Polycation Receptor

Pituitary adenylate cyclase activating polypeptide (PACAP) is a peptide hormone that exists in two biologically active forms: PACAP-38 and PACAP-27. Several types of PACAP receptors have been characterized, and these have been classified into three families: the VPAC1, the VPAC2, and the PAC1 receptors. In this study, we used in vivo behavioral assays along with pharmacological inhibitors to investigate the behavior of the lysozyme/PACAP receptor in Tetrahymena. This receptor behaves like a PAC1 receptor in some respects; however, PACAP 6-38 serves as an agonist, rather than an antagonist, for this receptor. These results are consistent with the existence of a generalized polycation receptor rather than a PACAP-specific receptor

The Initial Mass Function of Low-Mass Stars and Brown Dwarfs in Young Clusters

We have obtained images of the Trapezium Cluster (140" x 140"; 0.3 pc x 0.3 pc) with the Hubble Space Telescope Near-Infrared Camera and Multi-Object Spectrometer (NICMOS). Combining these data with new ground-based K-band spectra (R=800) and existing spectral types and photometry and the models of D'Antona & Mazzitelli, we find that the distributions of ages of comparable samples of stars in the Trapezium, rho Oph, and IC 348 indicate median ages of \~0.4 Myr for the first two regions and ~1-2 Myr for the latter. The low-mass IMFs in these sites of clustered star formation are similar over a wide range of stellar densities and other environmental conditions. With current data, we cannot rule out modest variations in the substellar mass functions among these clusters. We then make the best estimate of the true form of the IMF in the Trapezium by using the evolutionary models of Baraffe et al. and an empirically adjusted temperature scale and compare this mass function to recent results for the Pleiades and the field. All of these data are consistent with an IMF that is flat or rises slowly from the substellar regime to about 0.6 Msun, and then rolls over into a power law that continues from about 1 Msun to higher masses with a slope similar to or somewhat larger than the Salpeter value of 1.35. For the Trapezium, this behavior holds from our completeness limit of ~0.02 Msun and probably, after a modest completeness correction, even from 0.01-0.02 Msun. These data include ~50 likely brown dwarfs. We test the predictions of theories of the IMF against various properties of the observed IMF.Comment: 34 pages, 13 figures, for color image see http://cfa-www.harvard.edu/~kluhman/trap/colorimage.jp

Beyond the Bandwagon: Curating Cultural Memory at Milner Library

Archival and manuscript materials record human experience; they document how people have lived, worked, interacted, and thought about the world. These unique or rare materials make visible the experience and impact of individuals and organizations within their respective cultural, geographical, historical, local, and educational milieu. By exploring such documents and objects, patrons can see and investigate these relationships firsthand. Primary sources form the bedrock of humanistic research, personal inquiry, and engaged teaching. With this volume, we invite you to explore the unique and rare materials housed in Milner Library’s Special Collections and Dr. Jo Ann Rayfield University Archives as well as the services that bring them to life for readers worldwide. Contributed essays from scholars and collection stewards highlight how a small sample of these rich collections facilitate teaching and learning within the Illinois State University community and beyond.https://ir.library.illinoisstate.edu/mlp/1032/thumbnail.jp

Multisite Qualitative Study of Primary Care Physicians’ and Midlevel Providers’ Self-Reported Practices and Perceptions About Maintaining Cognitive Health

IntroductionTo facilitate national efforts to maintain cognitive health through public health practice, the Healthy Brain Initiative recommended examining diverse groups to identify stakeholder perspectives on cognitive health. In response, the Healthy Aging Research Network (HAN), funded by the Centers for Disease Control and Prevention (CDC), coordinated projects to document the perspectives of older adults, caregivers of people with dementia, and primary care providers (PCPs) on maintaining cognitive health. Our objective was to describe PCPs’ perceptions and practices regarding cognitive health.MethodsHAN researchers conducted 10 focus groups and 3 interviews with physicians (N = 28) and advanced practice providers (N = 21) in Colorado, Texas, and North Carolina from June 2007 to November 2008. Data were transcribed and coded axially.ResultsPCPs reported addressing cognitive health with patients only indirectly in the context of physical health or in response to observed functional changes and patient or family requests. Some providers felt evidence on the efficacy of preventive strategies for cognitive health was insufficient, but many reported suggesting activities such as games and social interaction when queried by patients. PCPs identified barriers to talking with patients about cognitive health such as lack of time and patient reactions to recommendations.ConclusionCommunicating new evidence on cognitive health and engaging older adults in making lasting lifestyle changes recommended by PCPs and others may be practical ways in which public health practitioners can partner with PCPs to address cognitive health in health care settings

Adapting international clinical trials during COVID-19 and beyond

Background: The COVID-19 pandemic and resulting restrictions, particularly travel restrictions, have had significant impact on the conduct of global clinical trials. Our clinical trials programme, which relied on in-person visits for training, monitoring and capacity building across nine low- and middle-income countries, had to adapt to those unprecedented operational challenges. We report the adaptation of our working model with a focus on the operational areas of training, monitoring and cross-site collaboration. The new working model: Adaptations include changing training strategies from in-person site visits with three or four team members to a multi-pronged virtual approach, with generic online training for good clinical practice, the development of a library of study-specific training videos, and interactive virtual training sessions, including practical laboratory-focused training sessions. We also report changes from in-person monitoring to remote monitoring as well as the development of a more localized network of clinical trial monitors to support hybrid models with in-person and remote monitoring depending on identified risks at each site. We established a virtual network across different trial and study sites with the objective to further build capacity for good clinical practice–compliant antimalarial trials and foster cross-country and cross-study site collaboration. Conclusion: The forced adaptation of these new strategies has come with advantages that we did not envisage initially. This includes improved, more frequent engagement through the established network with opportunities for increased south-to-south support and a substantially reduced carbon footprint and budget savings. Our new approach is challenging for study sites with limited prior experience but this can be overcome with hybrid models. Capacity building for laboratory-based work remains difficult using a virtual environment. The changes to our working model are likely to last, even after the end of the pandemic, providing a more sustainable and equitable approach to our research

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey : baryon acoustic oscillations in the Data Releases 10 and 11 Galaxy samples

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations (BAO) in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released DR9 and DR10 samples. Assuming a concordance Λ cold dark matter (ΛCDM) cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = (1264 ± 25 Mpc)(rd/rd,fid) at z = 0.32 and DV = (2056 ± 20 Mpc)(rd/rd,fid) at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = (1421 ± 20 Mpc)(rd/rd,fid) and H = (96.8 ± 3.4 km s−1 Mpc−1)(rd,fid/rd). Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant.Publisher PDFPeer reviewe

Introductory programming: a systematic literature review

As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research

Differences in risk factors for three types of stroke: UK prospective study and meta-analyses

OBJECTIVE: To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. METHODS: A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999-2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies. RESULTS: After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke. CONCLUSION: Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke

Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland

Mactinin, a fragment of cytoskeletal α-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

<p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-α, interleukin (IL)-1α and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein α-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1α, IL-1β and TNF-α, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p