Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture

BACKGROUND: Uterine leiomyomas (fibroids) are benign smooth muscle tumors that often contain an excessive extracellular matrix (ECM). In the present study, we investigated the interactions between human uterine leiomyoma (UtLM) cells and uterine leiomyoma-derived fibroblasts (FB), and their importance in cell growth and ECM protein production using a coculture system. RESULTS: We found enhanced cell proliferation, and elevated levels of ECM collagen type I and insulin-like growth factor-binding protein-3 after coculturing. There was also increased secretion of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor-2, and platelet derived growth factor A and B in the media of UtLM cells cocultured with FB. Protein arrays revealed increased phosphorylated receptor tyrosine kinases (RTKs) of the above growth factor ligands, and immunoblots showed elevated levels of the RTK downstream effector, phospho-mitogen activated protein kinase 44/42 in cocultured UtLM cells. There was also increased secretion of transforming growth factor-beta 1 and 3, and immunoprecipitated transforming growth factor-beta receptor I from cocultured UtLM cells showed elevated phosphoserine expression. The downstream effectors phospho-small mothers against decapentaplegic -2 and -3 protein (SMAD) levels were also increased in cocultured UtLM cells. However, none of the above effects were seen in normal myometrial cells cocultured with FB. The soluble factors released by tumor-derived fibroblasts and/or UtLM cells, and activation of the growth factor receptors and their pathways stimulated the proliferation of UtLM cells and enhanced the production of ECM proteins. CONCLUSIONS: These data support the importance of interactions between fibroid tumor cells and ECM fibroblasts in vivo, and the role of growth factors, and ECM proteins in the pathogenesis of uterine fibroids

Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding

Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior

Long-term ecological research in a human-dominated world

Author Posting. © American Institute of Biological Sciences, 2012. This article is posted here by permission of American Institute of Biological Sciences for personal use, not for redistribution. The definitive version was published in BioScience 62 (2012): 342-253, doi:10.1525/bio.2012.62.4.6.The US Long Term Ecological Research (LTER) Network enters its fourth decade with a distinguished record of achievement in ecological science. The value of long-term observations and experiments has never been more important for testing ecological theory and for addressing today's most difficult environmental challenges. The network's potential for tackling emergent continent-scale questions such as cryosphere loss and landscape change is becoming increasingly apparent on the basis of a capacity to combine long-term observations and experimental results with new observatory-based measurements, to study socioecological systems, to advance the use of environmental cyberinfrastructure, to promote environmental science literacy, and to engage with decisionmakers in framing major directions for research. The long-term context of network science, from understanding the past to forecasting the future, provides a valuable perspective for helping to solve many of the crucial environmental problems facing society today.2012-10-0

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Democracy, development and the executive presidency in Sri Lanka

This paper examines the developmental causes and consequences of the shift from a parliamentary to a semi-presidential system in Sri Lanka in 1978, examining its provenance, rationale, and its unfolding trajectory. drawing on a wide range of sources, it set out an argument that the executive presidency was born out of an elite impulse to create a more stable, centralised political structure to resist the welfarist electoral pressures that had taken hold in the post-independence period, and to pursue a market-driven model of economic growth. This strategy succeeded in its early years 197801993, when presidents retained legislative control, maintained a strong personal commitment to market reforms, and cultivated alternative sources of legitimacy. In the absence of these factors, the presidency slipped into crisis over 1994-2004 as resistance to elite-led projects of state reform mounted and as the president lost control of the legislature. Since 2005 the presidency has regained its power, but at the cost of abandoning its original rationale and function as a means to recalibrate the elite/mass power relations to facilitate elite-led reform agendas

Toward a Socialism for the Future, in the Wake of the Demise of the Socialism of the Past

http://deepblue.lib.umich.edu/bitstream/2027.42/51230/1/464.pd

Congenital myasthenic syndrome caused by a frameshift insertion mutation in

Objective: Description of a new variant of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene causing congenital myasthenic syndrome (CMS) in 3 children from 2 unrelated families. Methods: Muscle biopsies, EMG, and whole-exome sequencing were performed. Results: All 3 patients presented with congenital hypotonia, muscle weakness, respiratory insufficiency, head lag, areflexia, and gastrointestinal dysfunction. Genetic analysis identified a homozygous frameshift insertion in the GFPT1 gene (NM_001244710.1: c.686dupC; p.Arg230Ter) that was shared by all 3 patients. In one of the patients, inheritance of the variant was through uniparental disomy (UPD) with maternal origin. Repetitive nerve stimulation and single-fiber EMG was consistent with the clinical diagnosis of CMS with a postjunctional defect. Ultrastructural evaluation of the muscle biopsy from one of the patients showed extremely attenuated postsynaptic folds at neuromuscular junctions and extensive autophagic vacuolar pathology. Conclusions: These results expand on the spectrum of known loss-of-function GFPT1 mutations in CMS12 and in one family demonstrate a novel mode of inheritance due to UPD

1973

Skunks Shoot Back by William Stewart (page 1) The Daily Plan: A Management Factor by Rob McIntyre (2) Teed Off by Samuel Pavadore (3) A Responsible Neighbor by Gerald Moscato (4) Drainage by David Clement (A-1) Fairway Renovation at Baltusrol Golf Club by Joseph R. Flaherty (A-4) Converting to Kentucky Bluegrass Fairways by Thomas Rewinski (A-10) Grooming the Golf Course by Melvin B. Lucas, Jr. (A-12) Turf Diseases of 1972, Controls and Prevention for 1973 by Stanley J. Zontek (A-13) Noncropland Weed Control by John E. Gallagher (A-16) Soil Factors Affecting Arsenic Toxicity by Robert N. Carrow (A-24) The Necessity of Cart Paths and Traffic Regulations by William G. Buchanan (A-27) Herbicides for Turfgrass Areas by John A. Jagschitz (A-29) Perspectives on Lawn Making and Keeping by Robert Schery (A-33) Stadium Turf Maintenance by George P. Toma (A-39) Highway Turfgrass by Robert W. Duell (A-44) Cemetery Maintenance by Martin Stolpe (A-50) Keeping Records by Al Barauskas (A-54) Planning Capital Expenditures by Sherwood A. Moore (A-59) British Golf Course Architecture -Historical Influences- Current Trends by F.W. Hawtree (A-64) Golf Course Architecture in North America By Geoffrey S. Cornish (A-70

US SOLAS Science Report

The article of record may be found at https://doi.org/10.1575/1912/27821The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G).This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

US SOLAS Science Report

The Surface Ocean – Lower Atmosphere Study (SOLAS) (http://www.solas-int.org/) is an international research initiative focused on understanding the key biogeochemical-physical interactions and feedbacks between the ocean and atmosphere that are critical elements of climate and global biogeochemical cycles. Following the release of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016), the Ocean-Atmosphere Interaction Committee (OAIC) was formed as a subcommittee of the Ocean Carbon and Biogeochemistry (OCB) Scientific Steering Committee to coordinate US SOLAS efforts and activities, facilitate interactions among atmospheric and ocean scientists, and strengthen US contributions to international SOLAS. In October 2019, with support from OCB, the OAIC convened an open community workshop, Ocean-Atmosphere Interactions: Scoping directions for new research with the goal of fostering new collaborations and identifying knowledge gaps and high-priority science questions to formulate a US SOLAS Science Plan. Based on presentations and discussions at the workshop, the OAIC and workshop participants have developed this US SOLAS Science Plan. The first part of the workshop and this Science Plan were purposefully designed around the five themes of the SOLAS Decadal Science Plan (2015-2025) (Brévière et al., 2016) to provide a common set of research priorities and ensure a more cohesive US contribution to international SOLAS.This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)