37 research outputs found
Circadian oscillations of cytosolic free calcium regulate the Arabidopsis circadian clock
In the last decade, the view of circadian oscillators has expanded from transcriptional feedback to incorporate post-transcriptional, post-translational, metabolic processes and ionic signalling. In plants and animals, there are circadian oscillations in the concentration of cytosolic-free Ca2+ ([Ca2+]cyt), though their purpose has not been fully characterised. We investigated whether circadian oscillations of [Ca2+] cyt regulate the circadian oscillator of Arabidopsis thaliana. We report that in Arabidopsis, [Ca2+]cyt circadian oscillations can regulate circadian clock function through the Ca2+-dependent action of CALMODULIN-LIKE24 (CML24). Genetic analyses demonstrate a linkage
between CML24 and the circadian oscillator, through pathways involving the circadian
oscillator gene TIMING OF CAB2 EXPRESSION1 (TOC1).Supported by BBSRC UK research grants BBSRC BB/D010381/1 (A.N.D.), BB/D017904/1 (F.R.) BB/M00113X/1 (H.J.H.) awarded to (A.A.R.W.), Research Studentship (K.H.) and BBSRC Industrial Case (T.H.). A Swiss Science Foundation Award (PBZHP3-123289) and the Isaac Newton Trust Cambridge (M.C.M.R. and S.A.),
678 the National Science Foundation under Grant No. MCB 0817976 (Y-C.T. and J.B.), a Royal Society Grant RG081257 and Corpus Christi College, Cambridge Junior Research Fellowship (M.J.G.), a Cordenadoria de Apoio ao Ensino Superior Brazil 25681 studentship (C.T.H.), IEF Marrie Curie (Project No. 272186) (M.C.M.R.), a Broodbank Fellowship (M.C.M.R.), a Malaysian Government Studentship (N.I.M-H.)
Diverse perspectives on interdisciplinarity from members of the college of the Royal Society of Canada
Various multiple-disciplinary terms and concepts (although most commonly âinterdisciplinarity,â which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity, represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the worldâs complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demands thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paperâthat interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues
A deimmunised form of the ribotoxin, α-sarcin, lacking CD4+ T cell epitopes and its use as an immunotoxin warhead
Fungal ribotoxins that block protein synthesis can be useful warheads in the context of a targeted immunotoxin. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus that functions by catalytically cleaving a single phosphodiester bond in the sarcinâricin loop of the large ribosomal subunit, thus making the ribosome unrecognisable to elongation factors and leading to inhibition of protein synthesis. Peptide mapping using an ex vivo human T cell assay determined that α-sarcin contained two T cell epitopes; one in the N-terminal 20 amino acids and the other in the C-terminal 20 amino acids. Various mutations were tested individually within each epitope and then in combination to isolate deimmunised α-sarcin variants that had the desired properties of silencing T cell epitopes and retention of the ability to inhibit protein synthesis (equivalent to wild-type, WT α-sarcin). A deimmunised variant (D9T/Q142T) demonstrated a complete lack of T cell activation in in vitro whole protein human T cell assays using peripheral blood mononuclear cells from donors with diverse HLA allotypes. Generation of an immunotoxin by fusion of the D9T/Q142T variant to a single-chain Fv targeting Her2 demonstrated potent cell killing equivalent to a fusion protein comprising the WT α-sarcin. These results represent the first fungal ribotoxin to be deimmunised with the potential to construct a new generation of deimmunised immunotoxin therapeutics.Depto. de BioquĂmica y BiologĂa MolecularFac. de Ciencias QuĂmicasTRUEpu
Fine-scale habitat preference of green sturgeon (Acipenser medirostris) within three spawning locations in the Sacramento River, California
Vast sections of the Sacramento River have been listed as critical habitat by the National Marine Fisheries Service for green sturgeon spawning (Acipenser medirostris), yet spawning is known to occur at only a few specific locations. This study reveals the range of physical habitat variables selected by adult green sturgeon during their spawning period. We integrated fine-scale fish positions, physical habitat characteristics, discharge, bathymetry, and simulated velocity and depth using a 2-dimensional hydraulic model (FaSTMECH). The objective was to create habitat suitability curves for depth, velocity, and substrate type within three known spawning locations over two years. An overall cumulative habitat suitability score was calculated that averaged the depth, velocity, and substrate scores over all fish, sites, and years. A weighted usable area (WUA) index was calculated throughout the sampling periods for each of the three sites. Cumulative results indicate that the microhabitat characteristics most preferred by green sturgeon in these three spawning locations were velocities between 1.0-1.1 m/s, depths of 8-9 m, and gravel and sand substrate. This study provides guidance for those who may in the future want to increase spawning habitat for green sturgeon within the Sacramento River.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis
Hypoplastic left heart is a severe human congenital heart defect characterized by left ventricular hypoplasiawith aortic and mitral valve atresia. A genetic etiology is indicated by an association of the hypoplastic left heart phenotype with terminal 11q deletions that span approximately 20 Mb (distal to FRA11B in 11q23). Here we define the breakpoints in four patients with heart defects in association with distal 11q monosomy and refine the critical region to an approximately 9-Mb region distal to D11S1351. Within this critical region we have identified JAM3, a member of the junction adhesion molecule family, as a strong candidate gene for the cardiac phenotype on the basis that it is expressed during human cardiogenesis in the structures principally affected in hypoplastic left heart
Men at work and at home: managing emotion in telework
Home-based telework is one of the flexible working options available today and is unique in its ability to physically and emotionally blur the boundaries between work and home. This paper explores how men experience working from home, how they construct their identities as workers and as parents in this ambiguous location, and how, as fathers, they manage the emotional work of reconciling family and career in this context. Our findings suggest that in order to manage the emotional aspects of telework men will, at times, focus on either the professional or parental part of their identity in their narratives, and at times attempt to âhave it allâ. We conclude that telework can provide a space where men can adopt emotional discourses and practices traditionally associated with women, and particularly working mothers
Making healthy eating messages more effective: combining integrated marketing communication with the behaviour ecological model
SNOW AS A RESOURCE AND HAZARD IN EARLY-TWENTIETH-CENTURY MINING, SELKIRK MOUNTAINS, BRITISH COLUMBIA
Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy
Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RTâPCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was inversely proportional to serum hCG concentrations (P < 0.001). Stimulation of endometrial epithelial cells with hCG in vitro caused a reduction in CRISP-3 expression (P < 0.01). The measurement of CRISP-3 in endometrium could provide an additional tool in the diagnosis of failing early pregnancy of unknown location. The absence of a local reduction in expression of CRISP-3 in decidualized endometrium of women with EP may be due to reduced exposure to hCG due to the ectopic location of the trophoblast