Collaborative Growth Toward Discovery: Becoming Stronger through Change

The radical act of replacing a traditional OPAC and ILS with a hosted library services platform (LSP) and web-scale discovery (WSD) system creates the impetus for libraries to rethink core workflows and practices. Both of these tools have the potential to greatly improve access to library collections and enhance user experience, but only if the implementation is a collaborative effort between different stakeholders, technical experts and subject librarians, grounded in a thoughtful selection process that emphasizes user needs. Furthermore, because this model removes the traditional OPAC, subject librarians must take on the challenge of understanding the tool and work as partners with backend technical experts as well as the vendor so that they are not left out of providing research assistance as algorithms replace some traditional library skills. Grounded in the literature of collaborative learning and librarian attitudes towards discovery systems, this chapter describe the process of creating a culture of collaboration centered on user needs. Such a model is central to the process of evaluation and implementation of a LSP and a WSD service, particularly in the context of a university with multiple campuses and diverse users. We established a well-structured collaboration model from the systems evaluation phase, and continued to apply the model to the implementation phase. In 2010, the initial solution was to keep a traditional OPAC, and implement WorldCat Local as article discovery tool while doing in-depth user studies and gathering feedback from subject librarians to create a data-driven decision making habit. In 2014, we determined that Alma and Primo should replace the current Voyager ILS and WorldCat Local. The implementation process started in January 2015 and will go live in July 2015. The chapter will share the journey of creating a collaborative model and implementing unified resource management and discovery

Micropropagation of marula, Sclerocarya birrea subsp. caffra (Anarcadiaceae) by axillary bud proliferation and random amplified polymorphic DNA (RAPD) analysis of plantlets

The availability of a rapid vegetative amplification procedure of mass-selected superior trees greatly accelerates the development of a new tree species as a crop. This study outlined the protocol for in vitro propagation of marula nodal explants from marula seedlings. Surface sterilized explants were cultured on Murashige and Skoog media (MS) supplemented with 26 combinations of N6-benzyladenine (BA) and kinetin (KN). Shoots were elongated on MS media supplemented with low BA and KN or BA and Gibberellin A3 (GA3) concentrations. Elongated shoots were rooted on half strength MS media supplemented with indolebutyric acid (IBA) at differing concentrations. MS media supplemented with 4.8 µM BA and 2.4 ìM KN resulted in average 2.5 shoots per responding explant. Moderate shoot elongation was achieved on MS media supplemented with 1.2 µM BA plus 1.0 µM KN. Maximum rooting was observed on half- strength MS media supplemented with 10 µM IBA. Marula plants were acclimatized and established in soil in the growth room at an average micropropagation rate of 0.56 per responding nodal explant. The developed protocol has potential for routine micropropagation of elite Sclerocarya birrea subsp. caffra. Randomly amplified polymorphic DNA (RAPD) analysis scoring 1845 markers showed intraclonal genetic stability between explant parent and micropropagated plants.Key words: Anacardiaceae, axillary bud proliferation, marula, randomly amplified polymorphic DNA (RAPD), somaclonal variation

Expression profiling of ascorbic acid–related transporters in human and mouse eyes

PURPOSE: Ascorbic acid (AsA) is an important antioxidant in the eye. Ascorbic acid is usually transported by sodium-dependent AsA transporters (SVCTs), and dehydroascorbic acid (DHA) by glucose transporters (GLUTs). This study investigates these AsA-related transporters in human compared with mouse eyes. METHODS: Five pairs of human donor eyes and 15 pairs of mouse eyes were collected. Immunofluorescence and in situ hybridization were performed to detect SVCTs and GLUTs expression in the ciliary epithelium, retina, and lens epithelial cells (LECs). These tissues were isolated with laser microdissection followed by extraction of total RNA. Quantitative PCR (qPCR) was performed to examine the mRNA level of SVCTs and GLUTs in human and mouse ocular tissues. RESULTS: Immunofluorescence and in situ hybridization showed SVCT2 and GLUT1 expression in human ciliary epithelium with varied distributions. Sodium-dependent AsA transporter 2 is expressed only in the pigmented epithelium (PE), and GLUT1 is predominately expressed in the nonpigmented epithelium (NPE). However, SVCT2 was not identified in mouse ciliary epithelium, whereas GLUT1 expressed in both PE and NPE. Laser microdissection and qPCR revealed high levels of SVCT2 mRNA in human RPE cells and murine neural retina. Sodium-dependent AsA transporter 1 mRNA could be detected only in human and murine LECs. Glucose transporter 3 and GLUT4 mRNA could not be detected in either the human or mouse ciliary processes or in the lens epithelium. CONCLUSIONS: These fundamental findings indicate AsA transporter expression in eyes of humans is significantly different compared with mice. This may explain why human aqueous and vitreous humors contain higher AsA levels compared with other animals

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Treated Wastewater and Nitrate Transport Beneath Irrigated Fields near Dodge City, Kansas

Use of secondary-treated municipal wastewater for crop irrigation south of Dodge City, Kansas, where the soils are mainly of silty clay loam texture, has raised a concern that it has resulted in high nitrate-nitrogen concentrations (10-50 mg/kg) in the soil and deeper vadose zone, and also in the underlying deep (20-45 m) ground water. The goal of this field-monitoring project was to assess how and under what circumstances nitrogen (N) nutrients under cultivated corn that is irrigated with this treated wastewater can reach the deep ground water of the underlying High Plains aquifer, and what can realistically be done to minimize this problem. We collected 15.2-m-deep cores for physical and chemical properties characterization; installed neutron moisture-probe access tubes and suction lysimeters for periodic measurements; sampled area monitoring, irrigation, and domestic wells; performed dye-tracer experiments to examine soil preferential-flow processes through macropores; and obtained climatic, crop, irrigation, and N-application rate records. These data and additional information were used in the comprehensive Root Zone Water Quality Model (RZWQM2) to identify key parameters and processes that influence N losses in the study area. We demonstrated that nitrate-N transport processes result in significant accumulations of N in the thick vadose zone. We also showed that nitrate-N in the underlying ground water is increasing with time and that the source of the nitrate is from the wastewater applications. RZWQM2 simulations indicated that macropore flow is generated particularly during heavy rainfall events, but during our 2005-06 simulations the total macropore flow was only about 3% of precipitation for one of two investigated sites, whereas it was more than 13% for the other site. Our calibrated model for the two wastewater-irrigated study sites indicated that reducing current levels of corn N fertilization by half or more to the level of 170 kg/ha substantially increases N-use efficiency and achieves near-maximum crop yield. Combining such measures with a crop rotation that includes alfalfa should further reduce the amounts of residual N in the soil, as indicated in one of the study sites that had alfalfa in past crop rotations

Local Cortical Tension by Myosin II Guides 3D Endothelial Cell Branching

SummaryA key feature of angiogenesis is directional control of endothelial cell (EC) morphogenesis and movement [1]. During angiogenic sprouting, endothelial “tip cells” directionally branch from existing vessels in response to biochemical cues such as VEGF or hypoxia and migrate and invade the surrounding extracellular matrix (ECM) in a process that requires ECM remodeling by matrix metalloproteases (MMPs) [2–4]. Tip EC branching is mediated by directional protrusion of subcellular pseudopodial branches [5, 6]. Here, we seek to understand how EC pseudopodial branching is locally regulated to directionally guide angiogenesis. We develop an in vitro 3D EC model system in which migrating ECs display branched pseudopodia morphodynamics similar to those in living zebrafish. Using this system, we find that ECM stiffness and ROCK-mediated myosin II activity inhibit EC pseudopodial branch initiation. Myosin II is dynamically localized to the EC cortex and is partially released under conditions that promote branching. Local depletion of cortical myosin II precedes branch initiation, and initiation can be induced by local inhibition of myosin II activity. Thus, local downregulation of myosin II cortical contraction allows pseudopodium initiation to mediate EC branching and hence guide directional migration and angiogenesis

Building capacity for public and population health research in Africa : the consortium for advanced research training in Africa (CARTA) model

Background: Globally, sub-Saharan Africa bears the greatest burden of disease. Strengthened research capacity to understand the social determinants of health among different African populations is key to addressing the drivers of poor health and developing interventions to improve health outcomes and health systems in the region. Yet, the continent clearly lacks centers of research excellence that can generate a strong evidence base to address the region’s socio-economic and health problems. Objective and program overview: We describe the recently launched Consortium for Advanced Research Training in Africa (CARTA), which brings together a network of nine academic and four research institutions from West, East, Central, and Southern Africa, and select northern universities and training institutes. CARTA’s program of activities comprises two primary, interrelated, and mutually reinforcing objectives: to strengthen research infrastructure and capacity at African universities; and to support doctoral training through the creation of a collaborative doctoral training program in population and public health. The ultimate goal of CARTA is to build local research capacity to understand the determinants of population health and effectively intervene to improve health outcomes and health systems. Conclusions: CARTA’s focus on the local production of networked and high-skilled researchers committed to working in sub-Saharan Africa, and on the concomitant increase in local research and training capacity of African universities and research institutes addresses the inability of existing programs to create a critical mass of well-trained and networked researchers across the continent. The initiative’s goal of strengthening human resources and university-wide systems critical to the success and sustainability of research productivity in public and population health will rejuvenate institutional teaching, research, and administrative systems

Attitudes towards the use and acceptance of eHealth technologies : a case study of older adults living with chronic pain and implications for rural healthcare

Acknowledgements The research described here is supported by the award made by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. MC’s time writing the paper is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) under Theme 8 ‘Vibrant Rural Communities’ of the Food, Land and People Programme (2011–2016). MC is also an Honorary Research Fellow at the Division of Applied Health Sciences, University of Aberdeen. The input of other members of the TOPS research team, Alastair Mort, Fiona Williams, Sophie Corbett, Phil Wilson and Paul MacNamee who contributed to be wider study and discussed preliminary findings reported here with the authors of the paper is acknowledged. We acknowledge the feedback on earlier versions of this paper provided by members of the Trans-Atlantic Rural Research Network, especially Stefanie Doebler and Carmen Hubbard. We also thank Deb Roberts for her comments.Peer reviewedPublisher PD

Validation of Valosin-Containing Protein (VCP) as a Therapeutic Target for Triple Negative Breast Cancer

https://openworks.mdanderson.org/sumexp21/1196/thumbnail.jp

Oestrogen receptor alpha in pulmonary hypertension

Aims Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2+/− mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. Methods and results: By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT+ mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT+ mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. Conclusion: ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression.</p