A risk profile for identifying community-dwelling elderly with a highrisk of recurrent falling: results of a 3-year prospective study

Introduction: The aim of the prospective study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling. Materials and methods: The study was designed as a 3-year prospective cohort study. A total of 1365 community-dwelling persons, aged 65 years and older, of the population-based Longitudinal Aging Study Amsterdam participated in the study. During an interview in 1995/1996, physical, cognitive, emotional and social aspects of functioning were assessed. A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly. Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up. Results: The incidence of recurrent falls at the 3-year follow-up point was 24.9% in women and 24.4% in men. Of the respondents, 5.5% reported a total of 87 fractures that resulted from a fall, including 20 hip fractures, 21 wrist fractures and seven humerus fractures. Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers (11.9% vs. 3.4%; OR: 3.8; 95% CI: 2.3-6.1). Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling: two or more previous falls, dizziness, functional limitations, weak grip strength, low body weight, fear of falling, the presence of dogs/cats in the household, a high educational level, drinking 18 or more alcoholic consumptions per week and two interaction terms (high educationx18 or more alcohol consumptions per week and two or more previous falls x fear of falling) (AUC=0.71). Discussion: At a cut-off point of 5 on the total risk score (range 0-30), the model predicted recurrent falling with a sensitivity of 59% and a specificity of 71%. At a cut-off point of 10, the sensitivity and specificity were 31% and 92%, respectively. A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity

African sleeping sickness is a disease found in sub-Saharan Africa that is caused by the single-celled parasite Trypanosoma brucei. The drugs used widely now to treat infections are 50 years old and notable for their toxicity, emphasizing the need for development of new therapeutics. In the search for potential drug targets, researchers typically focus on enzymes or proteins that are essential to the survival of the infectious agent while being distinct enough from the host to avoid accidental targeting of the host enzyme. This work describes our research on one such trypanosome enzyme, hexokinase, which is a protein that the parasite requires to make energy. Here we describe the results of our search for inhibitors of the parasite enzyme. By screening 220,223 compounds for anti-hexokinase activity, we have identified new inhibitors of the parasite enzyme. Some of these are toxic to trypanosomes while having no effect on mammalian cells, suggesting that they may hold promise for the development of new anti-parasitic compounds

Integrated genetic map and genetic analysis of a region associated with root traits on the short arm of rye chromosome 1 in bread wheat

A rye–wheat centric chromosome translocation 1RS.1BL has been widely used in wheat breeding programs around the world. Increased yield of translocation lines was probably a consequence of increased root biomass. In an effort to map loci-controlling root characteristics, homoeologous recombinants of 1RS with 1BS were used to generate a consensus genetic map comprised of 20 phenotypic and molecular markers, with an average spacing of 2.5 cM. Physically, all recombination events were located in the distal 40% of the arms. A total of 68 recombinants was used and recombination breakpoints were aligned and ordered over map intervals with all the markers, integrated together in a genetic map. This approach enabled dissection of genetic components of quantitative traits, such as root traits, present on 1S. To validate our hypothesis, phenotyping of 45-day-old wheat roots was performed in five lines including three recombinants representative of the entire short arm along with bread wheat parents ‘Pavon 76’ and Pavon 1RS.1BL. Individual root characteristics were ranked and the genotypic rank sums were subjected to Quade analysis to compare the overall rooting ability of the genotypes. It appears that the terminal 15% of the rye 1RS arm carries gene(s) for greater rooting ability in wheat

Dynamics of dental evolution in ornithopod dinosaurs.

Ornithopods were key herbivorous dinosaurs in Mesozoic terrestrial ecosystems, with a variety of tooth morphologies. Several clades, especially the 'duck-billed' hadrosaurids, became hugely diverse and abundant almost worldwide. Yet their evolutionary dynamics have been disputed, particularly whether they diversified in response to events in plant evolution. Here we focus on their remarkable dietary adaptations, using tooth and jaw characters to examine changes in dental disparity and evolutionary rate. Ornithopods explored different areas of dental morphospace throughout their evolution, showing a long-term expansion. There were four major evolutionary rate increases, the first among basal iguanodontians in the Middle-Late Jurassic, and the three others among the Hadrosauridae, above and below the split of their two major clades, in the middle of the Late Cretaceous. These evolutionary bursts do not correspond to times of plant diversification, including the radiation of the flowering plants, and suggest that dental innovation rather than coevolution with major plant clades was a major driver in ornithopod evolution

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

hElp3 Directly Modulates the Expression of HSP70 Gene in HeLa Cells via HAT Activity

Human Elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. However, there are only a few studies focusing on its target gene characterization in vivo. We studied the effect of down-regulation of the human elongation protein 3 (hELP3) on the expression of HSP70 through antisense strategy. Transfecting antisense plasmid p1107 into HeLa cells highly suppressed hELP3 expression, and substantially reduced expression of HSP70 mRNA and protein. Furthermore, chromatin immunoprecipitation assay (ChIP Assay) revealed that hElp3 participates in the transcription elongation of HSPA1A in HeLa cells. Finally, complementation and ChIP Assay in yeast showed that hElp3 can not only complement the growth and slow activation of HSP70 (SSA3) gene transcription, but also directly regulates the transcription of SSA3. On the contrary, these functions are lost when the HAT domain is deleted from hElp3. These data suggest that hElp3 can regulate the transcription of HSP70 gene, and the HAT domain of hElp3 is essential for this function. These findings now provide novel insights and evidence of the functions of hELP3 in human cells