Nuclear Transport: Beginning to Gel?

SummaryThe massive nuclear pore complex mediates nucleocytoplasmic traffic ranging from a single histone to a viral genome. To date, dissecting mechanism has been more an exercise in prediction than biochemical certainty. A recent study combines recombinant proteins with nuclei reconstituted in vitro to test predictions in a startlingly productive manner

Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export

RNA undergoing nuclear export first encounters the basket of the nuclear pore. Two basket proteins, Nup98 and Nup153, are essential for mRNA export, but their molecular partners within the pore are largely unknown. Because the mechanism of RNA export will be in question as long as significant vertebrate pore proteins remain undiscovered, we set out to find their partners. Fragments of Nup98 and Nup153 were used for pulldown experiments from Xenopus egg extracts, which contain abundant disassembled nuclear pores. Strikingly, Nup98 and Nup153 each bound the same four large proteins. Purification and sequence analysis revealed that two are the known vertebrate nucleoporins, Nup96 and Nup107, whereas two mapped to ORFs of unknown function. The genes encoding the novel proteins were cloned, and antibodies were produced. Immunofluorescence reveals them to be new nucleoporins, designated Nup160 and Nup133, which are accessible on the basket side of the pore. Nucleoporins Nup160, Nup133, Nup107, and Nup96 exist as a complex in Xenopus egg extracts and in assembled pores, now termed the Nup160 complex. Sec13 is prominent in Nup98 and Nup153 pulldowns, and we find it to be a member of the Nup160 complex. We have mapped the sites that are required for binding the Nup160 subcomplex, and have found that in Nup98, the binding site is used to tether Nup98 to the nucleus; in Nup153, the binding site targets Nup153 to the nuclear pore. With transfection and in vivo transport assays, we find that specific Nup160 and Nup133 fragments block poly[A]+ RNA export, but not protein import or export. These results demonstrate that two novel vertebrate nucleoporins, Nup160 and Nup133, not only interact with Nup98 and Nup153, but themselves play a role in mRNA export

Psychosocial factors that influence men's help-seeking for cancer symptoms: A systematic synthesis of mixed methods research

Objective Effectiveness of cancer control partly depends upon early identification and treatment. Men appear to be more likely to delay help-seeking for symptoms, resulting in later diagnosis. This review aims to provide a mixed research synthesis of the psychosocial barriers to and facilitators of help-seeking for cancer symptoms among men. Methods Systematic methods were followed, including a predefined research question and search strategy. Searches retrieved 7131 international records from online databases: MEDLINE (n = 3011), PubMed (n = 471), SCOPUS (n = 896), Informit (n = 131), PsychINFO (n = 347), and Web of Science (n = 2275). Forty studies were eligible for inclusion in the review (25 qualitative studies, 11 quantitative studies, and 4 mixed-method studies). Results There was strong observational evidence for several psychosocial barriers to men's help-seeking behaviour: low cancer knowledge and inaccurate symptom interpretation, embarrassment and fear, and conformity to masculine gender role norms. The strongest facilitating factor associated with men's help-seeking behaviour was encouragement and support of spouses and family members. The majority of research was qualitative and used small samples, making generalisations to the wider population difficult. Conclusions Men's help-seeking for cancer symptoms is influenced by several psychosocial factors, which, in part, may be gender-specific. Health promotion initiatives to improve help-seeking behaviour among men should aim to increase cancer knowledge, reduce embarrassment and fear, address social norms deterring timely help-seeking, and acknowledge informal help-seeking with spouses and family members. Increasing the theoretical grounding of research could aid cohesion across the research area and the design of effective health promotion interventions

Facilitating tree-ring dating of historic conifer timbers using Blue Intensity

The Scottish pine network expansion has been an ongoing task since 2006 and funding must be acknowledged to the following projects: EU project ‘Millennium’ (017008-2), Leverhulme Trust project ‘RELiC: Reconstructing 8000 years of Environmental and Landscape change in the Cairngorms (F/00268/BG)’, the Native Oak and Pine project or ‘NOAP’ (Historic Scotland) and the NERC project ‘SCOT2K:Reconstructing 2000 years of Scottish climate from tree rings (NE/K003097/1)’. Further PhD funding for Milos Rydval is acknowledged from The Carnegie Trust.Dendroarchaeology almost exclusively uses ring-width (RW) data for dating historical structures and artefacts. Such data can be used to date tree-ring sequences when regional climate dominates RW variability. However, the signal in RW data can be obscured due to site specific ecological influences (natural and anthropogenic) that impact crossdating success. In this paper, using data from Scotland, we introduce a novel tree-ring parameter (Blue Intensity – BI) and explore its utility for facilitating dendro historical dating of conifer samples. BI is similar to latewood density as they both reflect the combined hemicellulose, cellulose and lignin content in the latewood cell walls of conifer species and the amount of these compounds is strongly controlled, at least for trees growing in temperature limited locations, by late summer temperatures. BI not only expresses a strong climate signal, but is also less impacted by site specific ecological influences. It can be concurrently produced with RW data from images of finely sanded conifer samples but at a significantly reduced cost compared to traditional latewood density. Our study shows that the probability of successfully crossdating historical samples is greatly increased using BI compared to RW. Furthermore, due to the large spatial extent of the summer temperature signal expressed by such data, a sparse multi-species conifer network of long BI chronologies across Europe could be used to date and loosely provenance imported material.PostprintPeer reviewe

Inner/Outer Nuclear Membrane Fusion in Nuclear Pore Assembly: Biochemical Demonstration and Molecular Analysis

The nuclear pore complex (NPC) is characterized by a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel, within which the nuclear pore is built, has little evolutionary precedent. In this report we demonstrate and map the inner/outer nuclear membrane fusion in NPC assembly