Respiration and photosynthesis in cones of Norway spruce (Picea abies (L.) Karst.)

Summary Dark respiration and photosynthetic carbon dioxide refixation in purple and green Picea abies cones were investigated from budbreak to cone maturity. The rate of dark respiration per unit dry weight and CO₂ refixation capacity decreased during cone maturation. At the beginning of the growing season, photosynthetic CO₂ refixation could reduce the amount of CO₂ released by respiration in green and purple cones by 50% and 40%, respectively. The seasonal performance of the components of the cone carbon balance was calculated using information on the seasonal course of respiration, refixation capacity and the light response curves of cone photosynthesis, as well as the actual light and temperature regime in the field. The daily gain of CO₂ refixation reached 28%–34% of respiration in green and 22%–26% in purple cones during the first month of their growth, but decreased later in the season. Over the entire growth period refixation reduced carbon costs of cone production in both cone colour polymorphs by 16%–17%.     

After the strike: using facilitation in a residency training program

Methods of alternative dispute resolution, including facilitation, can be used to identify and resolve areas of conflict. Facilitation was used by the University of Saskatchewan''s Department of Family Medicine (Saskatoon division) after the strike by residents in July and August 1995 so as to allow optimal use of the remaining educational time. Through facilitation, experiences of the strike and areas of potential conflict were explored. Participants had a broad range of responses to the strike. Specific coping strategies were developed to deal with identified concerns. Although outcomes were not measured formally, levels of trust improved and collegial relationships were restored. Because so many changes occur in health care and medical education, conflict inevitably arises. Facilitation offers one way of dealing with change constructively, thereby making possible the optimal use of educational time.     

Corner detection in curvilinear dot grouping

Corners, or discontinuities in orientation, are one of the most salient and useful properties of contours. But how sensitive are we in detecting them, and what does this sensitivity imply about the processes by which corners can be detected. In this paper we address both of these questions, starting with the observation that changing the samplign phase of a curve changes the geometry of its discrete trace, or the set of discrete (retinotopic) points onto which the curve projects. This motivates our stimuli — dotted curves —and our experimental design: if curves are represented by dots, the placement of the dots effects whether or not corners are perceived. Specifically, we present quantitative data on sensitivity to discontinuities as a function of dot phase, and address its theoretical explanation within a two-stage model of orientation selection. Curvature plays a key role in this model, and, finally, the model and experimental data are brought together by showing that a very coarse approximation to change in curvature (or differences in local curvature estimates) is sufficent to account for the psychophysical data on sensitivity to discontinuities.     

Cyclosporin A versus methotrexate, followed by rescue with folinic acid as prophylaxis of acute graft-versus-host disease after bone marrow transplantation

Fifty-seven patients undergoing bone marrow transplantation were randomly assigned to receive either cyclosporin A (CsA, n = 26) or methotrexate, followed by rescue with folinic acid (MTX + FA, n = 31) as prophylaxis for graft-versus-host disease (GVHD). All patients but one receiving CsA had evidence of sustained engraftment, and there was no difference between the two groups on the day in which marrow engraftment was documented. Oropharyngeal mucositis was of similar incidence and severity in the two groups. In contrast, patients receiving CsA showed higher renal and hepatic toxicity rates than those treated with MTX + FA. Severe-to-moderate acute GVHD (grades II-IV) was documented in 12 patients receiving CsA and in 12 treated with MTX + FA. The cumulative incidence of this complication was similar in both groups (46.1% and 38.7%). Similarly, there was no difference in the incidence of chronic GVHD. The leukemic relapse rates were also comparable, as well as the estimated probability of survival, which was 55% in patients treated with MTX + FA and 41% in those who were given CsA. We conclude that MTX + FA is as effective as CsA in the prevention of GVHD, with the additional advantage of reduced renal and hepatic toxicities.     

The role of cellular iron deficiency in controlling iron export

BackgroundIron export via the transport protein ferroportin (Fpn) plays a critical role in the regulation of dietary iron absorption and iron recycling in macrophages. Fpn plasma membrane expression is controlled by the hepatic iron-regulated hormone hepcidin in response to high iron availability and inflammation. Hepcidin binds to the central cavity of the Fpn transporter to block iron export either directly or by inducing Fpn internalization and lysosomal degradation. Here, we investigated whether iron deficiency affects Fpn protein turnover.MethodsWe ectopically expressed Fpn in HeLa cells and used cycloheximide chase experiments to study basal and hepcidin-induced Fpn degradation under extracellular and intracellular iron deficiency.Conclusions/General significanceWe show that iron deficiency does not affect basal Fpn turnover but causes a significant delay in hepcidin-induced degradation when cytosolic iron levels are low. These data have important mechanistic implications supporting the hypothesis that iron export is required for efficient targeting of Fpn by hepcidin. Additionally, we show that Fpn degradation is not involved in protecting cells from intracellular iron deficiency.     

Endogenous retroviruses promote homeostatic and inflammatory responses to the microbiota

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Clues to the etiology of autoimmune diseases through analysis of immunoglobulin genes

The role of autoantibodies in the etiology of autoimmune diseases remains unclear. However, an examination of the sequences of these autoantibodies can be informative. Antibody sequences that violate constraints normally imposed during ontogeny and during development point to a failure of regulation. The existence of clonally related sequences indicates that production of these antibodies may frequently be driven by self-antigen. A better understanding of the mechanisms that normally constrain the composition of the antibody repertoire and of the nature of the inciting and/or driving antigens may yield new insights into both the pathogenesis and potential treatment of these crippling diseases.     

Synthesis,biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral phosphorothioate linkages

Bicyclic oxazaphospholidine monomers were used to prepare a series of phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with control of the chirality of each of the PS linkages within the 10-base gap. The stereoselectivity was determined to be 98% for each coupling. The objective of this work was to study how PS chirality influences biophysical and biological properties of the ASO including binding affinity (T_m), nuclease stability, activity in vitro and in vivo, RNase H activation and cleavage patterns (both human and E. coli) in a gapmer context. Compounds that had nine or more Sp-linkages in the gap were found to be poorly active in vitro, while compounds with uniform Rp-gaps exhibited activity very similar to that of the stereo-random parent ASOs. Conversely, when tested in vivo, the full Rp-gap compound was found to be quickly metabolized resulting in low activity. A total of 31 ASOs were prepared with control of the PS chirally of each linkage within the gap in an attempt to identify favorable Rp/Sp positions. We conclude that a mix of Rp and Sp is required to achieve a balance between good activity and nuclease stability.