Design and Prototype of an Automated Column-Switching HPLC System for Radiometabolite Analysis

Column-switching high performance liquid chromatography (HPLC) is extensively used for the critical analysis of radiolabeled ligands and their metabolites in plasma. However, the lack of streamlined apparatus and consequently varying protocols remain as a challenge among positron emission tomography laboratories. We report here the prototype apparatus and implementation of a fully automated and simplified column-switching procedure to allow for the easy and automated determination of radioligands and their metabolites in up to 5 mL of plasma. The system has been used with conventional UV and coincidence radiation detectors, as well as with a single quadrupole mass spectrometer

An Unexplained 10 Degree - 40 Degree Shift in the Location of Some Diverse Neutral Atom Data at 1 AU

Four different data sets pertaining to the neutral atom environment at 1 AU are presented and discussed. These data sets include neutral solar wind and interstellar neutral atom data from IMAGE/LENA, energetic hydrogen atom data from SOHO/HSTOF and plasma wave data from the magnetometer on ISEE-3. Surprisingly, these data sets are centered between 262 degrees and 292 degrees ecliptic longitude, about 10 degrees - 40 degrees from the upstream interstellar neutral flow direction at 254 degrees resulting from the motion of the Sun relative to the local interstellar cloud. Some possible explanations for this offset, none of which is completely satisfactory, are discussed.Comment: 6 pages, 6 figures, 2 color peer-reviewed paper, in press, COSPAR/WS

Green revolution in Sub-Saharan Africa: Implications of imposed innovation for the wellbeing of rural smallholders

Green Revolution policies are again being pursued to drive agricultural growth and reduce poverty in Sub-Saharan Africa. However conditions have changed since the well-documented successes of the 1960s and 1970s benefited smallholders in southern Asia and beyond. We argue that under contemporary constraints the mechanisms for achieving improvements in the lives of smallholder farmers through such policies are unclear and that both policy rationale and means of governing agricultural innovation are crucial for pro-poor impacts. To critically analyze Rwanda’s Green Revolution policies and impacts from a local perspective, a mixed methods, multidimensional wellbeing approach is applied in rural areas in mountainous western Rwanda. Here Malthusian policy framing has been used to justify imposed rather than ‘‘induced innovation”. The policies involve a substantial transformation for rural farmers from a traditional polyculture system supporting subsistence and local trade to the adoption of modern seed varieties, inputs, and credit in order to specialize in marketable crops and achieve increased production and income. Although policies have been deemed successful in raising yields and conventionally measured poverty rates have fallen over the same period, such trends were found to be quite incongruous with local experiences. Disaggregated results reveal that only a relatively wealthy minority were able to adhere to the enforced modernization and policies appear to be exacerbating landlessness and inequality for poorer rural inhabitants. Negative impacts were evident for the majority of households as subsistence practices were disrupted, poverty exacerbated, local systems of knowledge, trade, and labor were impaired, and land tenure security and autonomy were curtailed. In order to mitigate the effects we recommend that inventive pro-poor forms of tenure and cooperation (none of which preclude improvements to input availability, market linkages, and infrastructure) may provide positive outcomes for rural people, and importantly in Rwanda, for those who have become landless in recent years. We conclude that policies promoting a Green Revolution in Sub-Saharan Africa should not all be considered to be pro-poor or even to be of a similar type, but rather should be the subject of rigorous impact assessment. Such assessment should be based not only on consistent, objective indicators but pay attention to localized impacts on land tenure, agricultural practices, and the wellbeing of socially differentiated people

Effect of betaine supplementation on plasma nitrate/nitrite in exercise-trained men

Background: Betaine, beetroot juice, and supplemental nitrate have recently been reported to improve certain aspects of exercise performance, which may be mechanistically linked to increased nitric oxide. The purpose of the present study was to investigate the effect of betaine supplementation on plasma nitrate/nitrite, a surrogate marker or nitric oxide, in exercise-trained men.Methods: We used three different study designs (acute intake of betaine at 1.25 and 5.00 grams, chronic intake of betaine at 2.5 grams per day for 14 days, and chronic [6 grams of betaine per day for 7 days] followed by acute intake [6 grams]), all involving exercise-trained men, to investigate the effects of orally ingested betaine on plasma nitrate/nitrite. Blood samples were collected before and at 30, 60, 90, and 120 min after ingestion of 1.25 and 5.00 grams of betaine (Study 1); before and after 14 days of betaine supplementation at a dosage of 2.5 grams (Study 2); and before and after 7 days of betaine supplementation at a dosage of 6 grams, followed by acute ingestion of 6 grams and blood measures at 30 and 60 min post ingestion (Study 3).Results: In Study 1, nitrate/nitrite was relatively unaffected and no statistically significant interaction (p = 0.99), dosage (p = 0.69), or time (p = 0.91) effects were noted. Similar findings were noted in Study 2, with no statistically significant interaction (p = 0.57), condition (p = 0.98), or pre/post intervention (p = 0.17) effects noted for nitrate/nitrite. In Study 3, no statistically significant changes were noted in nitrate/nitrite between collection times (p = 0.97).Conclusion: Our data indicate that acute or chronic ingestion of betaine by healthy, exercise-trained men does not impact plasma nitrate/nitrite. These findings suggest that other mechanisms aside from increasing circulating nitric oxide are likely responsible for any performance enhancing effect of betaine supplementation. © 2011 Bloomer et al; licensee BioMed Central Ltd

Folding of cohesin's coiled coil is important for Scc2/4-induced association with chromosomes.

Cohesin's association with and translocation along chromosomal DNAs depend on an ATP hydrolysis cycle driving the association and subsequent release of DNA. This involves DNA being 'clamped' by Scc2 and ATP-dependent engagement of cohesin's Smc1 and Smc3 head domains. Scc2's replacement by Pds5 abrogates cohesin's ATPase and has an important role in halting DNA loop extrusion. The ATPase domains of all SMC proteins are separated from their hinge dimerisation domains by 50-nm-long coiled coils, which have been observed to zip up along their entire length and fold around an elbow, thereby greatly shortening the distance between hinges and ATPase heads. Whether folding exists in vivo or has any physiological importance is not known. We present here a cryo-EM structure of the apo form of cohesin that reveals the structure of folded and zipped-up coils in unprecedented detail and shows that Scc2 can associate with Smc1's ATPase head even when it is fully disengaged from that of Smc3. Using cysteine-specific crosslinking, we show that cohesin's coiled coils are frequently folded in vivo, including when cohesin holds sister chromatids together. Moreover, we describe a mutation (SMC1D588Y) within Smc1's hinge that alters how Scc2 and Pds5 interact with Smc1's hinge and that enables Scc2 to support loading in the absence of its normal partner Scc4. The mutant phenotype of loading without Scc4 is only explicable if loading depends on an association between Scc2/4 and cohesin's hinge, which in turn requires coiled coil folding

Applications and Emerging Trends of Hyaluronic Acid in Tissue Engineering, as a Dermal Filler, and in Osteoarthritis Treatment

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine including scaffolding for tissue engineering, dermatological fillers, and viscosupplementation for osteoarthritis treatment. HA is available in most connective tissues in body fluids such as synovial fluid and the vitreous humor of the eye. HA is responsible for several structural properties of tissues as a component of extracellular matrix (ECM) and is involved in cellular signaling. Degradation of HA is a step-wise process that can occur via enzymatic or non-enzymatic reactions. A reduction in HA mass or molecular weight via degradation or slowing of synthesis affects physical and chemical properties such as tissue volume, viscosity, and elasticity. This review addresses the distribution, turnover, and tissue-specific properties of HA. This information is used as context for considering recent products and strategies for modifying the viscoelastic properties of HA in tissue engineering, as a dermal filler, and in osteoarthritis treatment

Regulation of basal cellular physiology by the homeostatic unfolded protein response

The extensive membrane network of the endoplasmic reticulum (ER) is physically juxtaposed to and functionally entwined with essentially all other cellular compartments. Therefore, the ER must sense diverse and constantly changing physiological inputs so it can adjust its numerous functions to maintain cellular homeostasis. A growing body of new work suggests that the unfolded protein response (UPR), traditionally charged with signaling protein misfolding stress from the ER, has been co-opted for the maintenance of basal cellular homeostasis. Thus, the UPR can be activated, and its output modulated, by signals far outside the realm of protein misfolding. These findings are revealing that the UPR causally contributes to disease not just by its role in protein folding but also through its broad influence on cellular physiology

Corrigendum to "Overview: oxidant and particle photochemical processes above a south-east Asian tropical rainforest (the OP3 project): introduction, rationale, location characteristics and tools" published in Atmos. Chem. Phys., 10, 169–199, 2010

Author(s): Hewitt, CN; Lee, JD; MacKenzie, AR; Barkley, MP; Carslaw, N; Carver, GD; Chappell, NA; Coe, H; Collier, C; Commane, R; Davies, F; Davison, B; DiCarlo, P; Di Marco, CF; Dorsey, JR; Edwards, PM; Evans, MJ; Fowler, D; Furneaux, KL; Gallagher, M; Guenther, A; Heard, DE; Helfter, C; Hopkins, J; Ingham, T; Irwin, M; Jones, C; Karunaharan, A; Langford, B; Lewis, AC; Lim, SF; MacDonald, SM; Mahajan, AS; Malpass, S; McFiggans, G; Mills, G; Misztal, P; Moller, S; Monks, PS; Nemitz, E; Nicolas-Perea, V; Oetjen, H; Oram, DE; Palmer, PI; Phillips, GJ; Pike, R; Plane, JMC; Pugh, T; Pyle, JA; Reeves, CE; Robinson, NH; Stewart, D; Stone, D; Whalley, LK; Yang,

Myc proteins in brain tumor development and maintenance

Myc proteins are often deregulated in human brain tumors, especially in embryonal tumors that affect children. Many observations have shown how alterations of these pleiotropic Myc transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the role of Myc family members (particularly c-myc and Mycn) in tumors like medulloblastoma and glioma and will further discuss how to target stabilization of these proteins for future brain tumor therapies

Linking Employee Stakeholders to Environmental Performance: The Role of Proactive Environmental Strategies and Shared Vision

Drawing on the natural-resource-based view (NRBV), we propose that employee stakeholder integration is linked to environmental performance through firms’ proactive environmental strategies, and that this link is contingent on shared vision. We tested our model with a cross-country and multi-industry sample. In support of our theory, results revealed that firms’ proactive environmental strategies translated employee stakeholder integration into environmental performance. This relationship was pronounced for high levels of shared vision. Our findings demonstrate that shared vision represents a key condition for advancing the corporate greening agenda through proactive environmental strategies. We discuss implications for the CSR and the environmental management literatures, with a particular focus on the NRBV and stakeholder integration debates