131,063 research outputs found
Using seasonal climate forecasting in agriculture: a participatory decision-making approach
No full textFarm Management,
The BAG-1 cochaperone is a negative regulator of p73-dependent transcription.
No full textHigh-level expression of Bcl-2 associated athanogene (BAG-1) protects cancer cells from stress-induced cell death and growth inhibition. These protective effects of BAG-1 are dependent on interactions with the HSC70 and HSP70 chaperones. However, the key stress-response molecules that are regulated by a BAG-1/chaperone mechanism have not been identified. In this study, we investigated the effects of BAG-1 overexpression on the function of p53 family proteins, p53, p63 and p73. Overexpression of BAG-1 isoforms interfered with the transactivating activity of p73 and p63, but had modest and variable effects on p53-dependent transcription. p73 and BAG-1 interacted in intact cells and overexpression of BAG-1 decreased the expression of p73. siRNA-mediated ablation of endogenous BAG-1 increased the activity of a p73-responsive promoter and this was reversed by knock-down of p73. The ability of BAG-1 to modulate p73 activity and expression, and to interact with p73 were dependent on amino acid residues required for the interaction of BAG-1 with HSC70 and HSP70. These results show that BAG-1 inhibits the transactivating functions of p73 and provide new insight into the mechanisms that control the expression of p73. Inhibition of p73 function may be one mechanism that contributes to the pro-survival activity of BAG-
LACK OF STABILITY OF AGGREGATES AFTER THROMBIN-INDUCED REAGGREGATION OF THROMBIN-DEGRANULATED PLATELETS
No full textThe stability of platelet aggregates is influenced by the extent of the release of granule contents; if release is extensive and aggregation is prolonged, deaggregation is difficult to achieve. The relative importance of the contributions of released substances to aggregate stability are not known, although stable thrombin-induced aggregates form in platelet-rich plasma from patients with barely detectable plasma or platelet fibrinogen, and ADP stabilizes thrombin-induced aggregates of platelets from patients with delta storage pool deficiency) which otherwise deaggregate more readily than normal platelets. We degranulated platelets with thrombin (0.9U/ml caused greater than 90% loss of delta and alpha granule contents) and recovered them as individual platelets in fresh medium. The degranulated platelets were reaggregated by thrombin (2U/ml). To prevent continuing effects of thrombin, FPRCH2Cl was added when thrombin-induced aggregation of thrombin-degranulated platelets reached its maximum. EDTA (5mM) or EGTA (5mM) added at maximum aggregation did not deaggregate these platelets, indicating that the stability of these aggregates does not depend on Ca2+ in the medium. Whereas with control platelets a combination of PGE1 (10μM) and chymotrypsin(10 U/ml) was required for deaggregation, with thrombin-degranulated platelets either PGE1 or chymotrypsin alone caused extensive deaggregation. The rate and extent of deaggregation of thrombin-degranulated platelets by a combination of PGE1 and chymotrypsin was greater than with control platelets. Electron microscope gold immunocytochemistry using antihuman fibrinogen IgG, anti-von Willebrand factor and antifibronectin showed a) that fibrinogen in the vacuoles of degranulated platelets was visible at focal points of platelet contact in the aggregates, but that large areas of platelet contact had no fibrinogen detectable between them; and b) in comparison to fibrinogen, little fibronectin or von Willebrand factor (vWf) was detectable in the platelets. Since the linkages between thrombin-degranulated platelets reaggregated by thrombin can be disrupted either by raising cAMP (thus making glycoprotein IIb/IIIa unavailable) or by proteolysis, these linkages are less stable than those formed between normal platelets. It might therefore be expected that platelets that take part in thrombus formation and then recirculate are likely to form less stable thrombi than platelets that have not released their granule contents
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The meaning and relevance of B-cell receptor structure and function in chronic lymphocytic leukemia
No full textThe B-cell receptor (BCR) is of critical importance for normal B cells and for the majority of B-cell malignancies, especially chronic lymphocytic leukemia (CLL). The two major subsets of CLL are biologically distinct, being derived from B cells at different stages of differentiation and carrying unmutated (U-CLL) or mutated (M-CLL) IGHV genes. U-CLL, which has a poorer prognosis, often has relatively conserved (stereotypic) IGHV-HD-HJ sequences, indicative of interaction with large (super)antigens and similar to those in normal naive innate B cells. Conserved sequences are less evident in M-CLL, in keeping with its postfollicular origin. However, both subsets exhibit features of chronic antigen exposure in tissue sites, with local proliferative events, but also downregulation of surface immunoglobulin M but not surface immunoglobulin D, a characteristic of normal anergic B cells. BCR-mediated anergy can spread to other receptors such as CXCR4. Circulating CLL cells retain a shadow of tissue-based events that can reverse over time, but the overall extent of anergy is greater in M-CLL. Despite this stereotypic variety and more genomic complexity, BCR-mediated responses in vitro appear relatively homogeneous in U-CLL, but M-CLL is more heterogeneous. The differential balance between antigen-induced proliferation or anergy is the likely determinant of clinical behavior and possibly of response to kinase inhibitors
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Land use and vegetation change on the Long Mynd
No full textA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyThe plant communities of the Long Mynd plateau are the culmination of over 3000 years of human intervention that largely deforested the uplands, and subsequently maintained the generally treeless heath and grassland communities now extant. The capacity of these communities to respond to directional change is well known, indeed the traditional mode of heathland management, burning, depends on the regenerative capacity of the target species, generally heather (Calluna vulgaris), for its success. However, changes in post WW2 stocking practice; the loss of ponies followed by an increase in the numbers of sheep and a change to them being overwintered on the hill, led to excessive grazing and damage to the heath. This coincided with the spread over the hill by bracken (Pteridium aquilinum) and other changes in the distribution and nature of the vegetation. A sequence of vegetation surveys made by various individuals and organisations over the past 75 years or so has been analysed in an attempt to delineate spatial and temporal changes in the vegetation. This demonstrated the need for a standardised survey methodology to allow consistent monitoring. The analysis showed that bracken had been infiltrating most of the communities from its origins outside the lower limits of the Common as well as from some of the valley sides. Within the last decade, this expansion has apparently been contained in line with the current management plan for control. A survey of 730 quadrats in some 30 stands was made to characterise the variation of the vegetation on the plateau, and to relate it to some of the associated environmental factors. Classification, unconstrained ordination and ordination constrained by the abiotic environmental variables, showed that, a) the strongest trend in the vegetation distinguished water-flushed communities, b) non-wetland communities differentiate between heathland and grassland, c) this trend can be only partly be attributed to the measured abiotic environmental variables, d) the amount of pure Pteridietum [U20] is limited, although much of the heathland and grassland has bracken within it. There are indications that invasion by bracken often correlates with a loss of dominance of Calluna in favour of Deschampsia flexuosa and Vaccinium myrtillus. Difficulties in associating these trends with measured abiotic variables suggests, other factors probably management processes, are critical in driving this trend. Distribution of ‘heathland’ bryophytes was found to be associated more with the structure of their ‘host’ vascular communities rather than with abiotic factors. Finally, this investigation considers the practical implications with regard to the future encouragement of heather and the control of bracken. Cutting rather than burning appears to be the ecologically most suitable method for heather regeneration and bracken control
Fig. 13. A–D, Dictyonema muirae n in Dendroid and Tuboid Graptolites from the Llandovery (Silurian) of the Four Mile Creek Area, New South Wales
No full textFig. 13. A–D, Dictyonema muirae n.sp., respectivelyAM F114763, BF14, AM F114775, F14, holotype AM F114762, F14, and AM F114764, BF14 proximal part of colony attached to pebble of phosphate; E–G, Dictyonema warrisi n.sp., respectively AM F114647, F14, holotype AM F114717, W885 and AM F114647, F14, with stipes more proximal than E; H, Dictyonema sp. 1, AM F11475, F14. Scale bars 1 mm; shading on C indicates badly preserved area.Published as part of <i>Rickards, R.B., Chapman, A.J., Wright, A.J. & Packham, G.H, 2003, Dendroid and Tuboid Graptolites from the Llandovery (Silurian) of the Four Mile Creek Area, New South Wales, pp. 305-330 in Records of the Australian Museum 55 (3)</i> on page 318, DOI: 10.3853/j.0067-1975.55.2003.1387, <a href="http://zenodo.org/record/10092612">http://zenodo.org/record/10092612</a>
- …
