The Lantern Vol. 4, No. 3, June 1936

• Dr. Omwake as his Friends See Him: A Letter from Dr. James M. Anders ; An Interview with Dean Kline • George Leslie Omwake, Educator and Churchman • The Story of Ursinus • Way Back When • Editorial: We Look Before and After • Reminiscences of an Ex-Storekeeper\u27s Daughter • The Tale of a Toper, or How the Little Stone Went Rolling • Book Review: May I Present? • Time Out, Please • Youth at the Crossroads • Of Candy Bars and Tears • Reflections • To a Star • It Takes Two to Study the Moonhttps://digitalcommons.ursinus.edu/lantern/1008/thumbnail.jp

Epigenetic reversion of breast carcinoma phenotype is accompanied by DNA sequestration

The importance of microenvironment and context in regulation of tissue-specific genes is finally well established. DNA exposure to, or sequestration from, nucleases can be used to detect differences in higher order chromatin structure in intact cells without disturbing cellular or tissue architecture. To investigate the relationship between chromatin organization and tumor phenotype, we utilized an established 3-D assay where normal and malignant human breast cells can be easily distinguished by the morphology of the structures they make (acinus-like vs tumor-like, respectively). We show that these phenotypes can be distinguished also by sensitivity to AluI digestion where the malignant cells are resistant to digestion relative to non-malignant cells. Reversion of the T4-2 breast cancer cells by either cAMP analogs, or a phospatidylinositol 3-kinase (P13K) inhibitor not only reverted the phenotype, but also the chromatin sensitivity to AluI. By using different cAMP-analogs, we show that the cAMP-induced phenotypic reversion, polarization, and shift in DNA organization act through a cAMP-dependent-protein-kinase A-coupled signaling pathway. Importantly, inhibitory antibody to fibronectin also reverted the malignant phenotype, polarized the acini, and changed chromatin sequestration. These experiments show not only that modifying the tumor microenvironment can alter the organization of tumor cells but also that architecture of the tissues and the global chromatin organization are coupled and yet highly plastic

The Lantern Vol. 4, No. 3, June 1936

• Dr. Omwake as his Friends See Him: A Letter from Dr. James M. Anders ; An Interview with Dean Kline • George Leslie Omwake, Educator and Churchman • The Story of Ursinus • Way Back When • Editorial: We Look Before and After • Reminiscences of an Ex-Storekeeper\u27s Daughter • The Tale of a Toper, or How the Little Stone Went Rolling • Book Review: May I Present? • Time Out, Please • Youth at the Crossroads • Of Candy Bars and Tears • Reflections • To a Star • It Takes Two to Study the Moonhttps://digitalcommons.ursinus.edu/lantern/1008/thumbnail.jp

Diverse specificity of cellulosome attachment to the bacterial cell surface

This work was supported by the EU FP7 programme under the WallTraC project (grant No. 263916) and by projects PTDC/BIA-MIC/5947/2014, RECI/BBB-BEP/0124/2012 and EXPL/BIA-MIC/1176/2012 supported by Fundacao para a Ciencia e Tecnologia (FCT-MCTES). The Research Unit UCIBIO (Unidade de Ciencias Biomoleculares Aplicadas) is financed by national funds from FCT/MCTES EC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). We thank the European Synchrotron Radiation Facility (Grenoble, France), Soleil (Saint-Aubin, France) and Diamond Light Source (Harwell, UK) for data collection and the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement No. 283570, proposal number: Biostruct-X_ 4399) for funding.During the course of evolution, the cellulosome, one of Nature's most intricate multi-enzyme complexes, has been continuously fine-tuned to efficiently deconstruct recalcitrant carbohydrates. To facilitate the uptake of released sugars, anaerobic bacteria use highly ordered protein-protein interactions to recruit these nanomachines to the cell surface. Dockerin modules located within a non-catalytic macromolecular scaffold, whose primary role is to assemble cellulosomal enzymatic subunits, bind cohesin modules of cell envelope proteins, thereby anchoring the cellulosome onto the bacterial cell. Here we have elucidated the unique molecular mechanisms used by anaerobic bacteria for cellulosome cellular attachment. The structure and biochemical analysis of five cohesin-dockerin complexes revealed that cell surface dockerins contain two cohesin-binding interfaces, which can present different or identical specificities. In contrast to the current static model, we propose that dockerins utilize multivalent modes of cohesin recognition to recruit cellulosomes to the cell surface, a mechanism that maximises substrate access while facilitating complex assembly.publishersversionpublishe

Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

In the mammary gland, epithelial cells are embedded in a ‘soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for β-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of β-casein expression required both laminin signalling and a ‘soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of β-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues' unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis

Evidence-based planning and costing palliative care services for children : novel multi-method epidemiological and economic exemplar

Background: Children’s palliative care is a relatively new clinical specialty. Its nature is multi-dimensional and its delivery necessarily multi-professional. Numerous diverse public and not-for-profit organisations typically provide services and support. Because services are not centrally coordinated, they are provided in a manner that is inconsistent and incoherent. Since the first children’s hospice opened in 1982, the epidemiology of life-limiting conditions has changed with more children living longer, and many requiring transfer to adult services. Very little is known about the number of children living within any given geographical locality, costs of care, or experiences of children with ongoing palliative care needs and their families. We integrated evidence, and undertook and used novel methodological epidemiological work to develop the first evidence-based and costed commissioning exemplar. Methods: Multi-method epidemiological and economic exemplar from a health and not-for-profit organisation perspective, to estimate numbers of children under 19 years with life-limiting conditions, cost current services, determine child/parent care preferences, and cost choice of end-of-life care at home. Results: The exemplar locality (North Wales) had important gaps in service provision and the clinical network. The estimated annual total cost of current children’s palliative care was about £5.5 million; average annual care cost per child was £22,771 using 2007 prevalence estimates and £2,437- £11,045 using new 2012/13 population-based prevalence estimates. Using population-based prevalence, we estimate 2271 children with a life-limiting condition in the general exemplar population and around 501 children per year with ongoing palliative care needs in contact with hospital services. Around 24 children with a wide range of life-limiting conditions require end-of-life care per year. Choice of end-of-life care at home was requested, which is not currently universally available. We estimated a minimum (based on 1 week of end-of-life care) additional cost of £336,000 per year to provide end-of-life support at home. Were end-of-life care to span 4 weeks, the total annual additional costs increases to £536,500 (2010/11 prices). Conclusions: Findings make a significant contribution to population-based needs assessment and commissioning methodology in children’s palliative care. Further work is needed to determine with greater precision which children in the total population require access to services and when. Half of children who died 2002-7 did not have conditions that met the globally used children's palliative care condition categories, which need revision in light of findings

Identification of Fluorescent Compounds with Non-Specific Binding Property via High Throughput Live Cell Microscopy

10.1371/journal.pone.0028802PLoS ONE71

Strengthening research capacity through the medical education partnership initiative: the Mozambique experience

BACKGROUND: Since Mozambique’s independence, the major emphasis of its higher educational institutions has been on didactic education. Because of fiscal and human resource constraints, basic and applied research activities have been relatively modest in scope, and priorities have often been set primarily by external collaborators. These factors have compromised the scope and the relevance of locally conducted research and have limited the impact of Mozambique’s universities as major catalysts for national development. CASE DESCRIPTION: We developed a multi-institutional partnership to undertake a comprehensive analysis of the research environment at Mozambique’s major public universities to identify factors that have served as barriers to the development of a robust research enterprise. Based on this analysis, we developed a multifaceted plan to reduce the impact of these barriers and to enhance research capacity within Mozambique. INTERVENTIONS: On the basis of our needs assessment, we have implemented a number of major initiatives within participating institutions to facilitate basic and applied research activities. These have included specialized training programmes, a reorganization of the research administration infrastructure, the development of multiple collaborative research projects that have emphasized local research priorities and a substantial investment in bioinformatics. We have established a research support centre that provides grant development and management services to Mozambique’s public universities and have developed an independent Institutional Review Board for the review of research involving human research subjects. Multiple research projects involving both communicable and non-communicable diseases have been developed and substantial external research support has been obtained to undertake these projects. A sizable investment in biomedical informatics has enhanced both connectivity and access to digital reference material. Active engagement with relevant entities within the Government of Mozambique has aligned institutional development with national priorities. CONCLUSIONS: Although multiple challenges remain, over the past 3 years significant progress has been made towards establishing conditions within which a broad range of basic, translational and clinical and public health research can be undertaken. Ongoing development of this research enterprise will enhance capacity to address critical locally relevant research questions and will leverage resources to accelerate the development of Mozambique’s national universities

Variation in carbon and nitrogen concentrations among peatland categories at the global scale

Publisher Copyright: © 2022 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.Peatlands account for 15 to 30% of the world's soil carbon (C) stock and are important controls over global nitrogen (N) cycles. However, C and N concentrations are known to vary among peatlands contributing to the uncertainty of global C inventories, but there are few global studies that relate peatland classification to peat chemistry. We analyzed 436 peat cores sampled in 24 countries across six continents and measured C, N, and organic matter (OM) content at three depths down to 70 cm. Sites were distinguished between northern (387) and tropical (49) peatlands and assigned to one of six distinct broadly recognized peatland categories that vary primarily along a pH gradient. Peat C and N concentrations, OM content, and C:N ratios differed significantly among peatland categories, but few differences in chemistry with depth were found within each category. Across all peatlands C and N concentrations in the 10-20 cm layer, were 440 ± 85.1 g kg-1 and 13.9 ± 7.4 g kg-1, with an average C:N ratio of 30.1 ± 20.8. Among peatland categories, median C concentrations were highest in bogs, poor fens and tropical swamps (446-532 g kg-1) and lowest in intermediate and extremely rich fens (375-414 g kg-1). The C:OM ratio in peat was similar across most peatland categories, except in deeper samples from ombrotrophic tropical peat swamps that were higher than other peatlands categories. Peat N concentrations and C:N ratios varied approximately two-fold among peatland categories and N concentrations tended to be higher (and C:N lower) in intermediate fens compared with other peatland types. This study reports on a unique data set and demonstrates that differences in peat C and OM concentrations among broadly classified peatland categories are predictable, which can aid future studies that use land cover assessments to refine global peatland C and N stocks.Peer reviewe