1,215 research outputs found

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    The headgroup orientation of dimyristoylphosphatidylinositol-4-phosphate in mixed lipid bilayers: a neutron diffraction study

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    AbstractThe trisodium salt of dimyristoylphosphatidylinositol-4-phosphate (DMPI-4P) has been synthesised specifically deuterated at particular sites in the headgroup. These materials have been used in neutron diffraction experiments, which successfully located the position (depth) of each of these deuterated sites to within Ā±0.5 ƅ in a mixed model membrane (a 1:1 molar mixture of DMPI-4P with dimyristoyl-phosphatidylcholine, DMPC, in the LĪ± phase, hydrated to the level of 28 water molecules per lipid molecule). The diffracted intensities were measured at four different D2O/H2O ratios and six orders of diffraction were obtained. These data sets, in conjunction with computer modelling, have been used to determine the orientation of the inositol ring of DMPI-4P, localising each vertical Hā€“H distance to within approximately Ā±0.03 ƅ. The orientation of the inositol ring is found to be one in which the C5 hydroxyl is extended out into the aqueous medium. This is, therefore, the most accessible site for water-borne reagents. This may be significant for the important pathway leading from PI-4P to PI-4,5P2. On the assumption that the P/ODAG bond is orientated parallel to the bilayer normal, these results are consistent with two possible conformations for the portion of the headgroup connecting the diacylglycerol to the inositol ring. Distinction between these two is difficult, but one may be favoured since the other involves close atomā€“atom contacts

    A century-long record of plant evolution reconstructed from a coastal marsh seed bank

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    Evidence is mounting that climate-driven shifts in environmental conditions can elicit organismal evolution, yet there are sparingly few long-term records that document the tempo and progression of responses, particularly for plants capable of transforming ecosystems. In this study, we ā€œresurrectedā€ cohorts of a foundational coastal marsh sedge (Schoenoplectus americanus) from a time-stratified seed bank to reconstruct a century-long record of heritable variation in response to salinity exposure. Common-garden experiments revealed that S. americanus exhibits heritable variation in phenotypic traits and biomass-based measures of salinity tolerance. We found that responses to salinity exposure differed among the revived cohorts, with plants from the early 20th century exhibiting greater salinity tolerance than those from the mid to late 20th century. Fluctuations in salinity tolerance could reflect stochastic variation but a congruent record of genotypic variation points to the alternative possibility that the loss and gain in functionality are driven by selection, with comparisons to historical rainfall and paleosalinity records suggesting that selective pressures vary according to shifting estuarine conditions. Because salinity tolerance in S. americanus is tightly coupled to primary productivity and other vital ecosystem attributes, these findings indicate that organismal evolution merits further consideration as a factor shaping coastal marsh responses to climate change

    Neurogranin in Alzheimerā€™s disease and ageing: a human post-mortem study

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    Neurogranin (Ng), a post-synaptic protein involved in memory formation, has been investigated as a biomarker in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD) and ageing. CSF Ng levels are elevated in AD relative to healthy controls and correlate with cognition; however, few studies have focused on Ng abundance in the brain. Synapse loss in the brain correlates closely with cognitive decline in AD making synaptic biomarkers potentially important for tracking disease progression, but the links between synaptic protein changes in CSF and brain remain incompletely understood. In the current study, Ng abundance was examined in post-mortem human brain tissue across AD, healthy ageing (HA), and mid-life (ML) cohorts. Ng levels were quantified in three brain regions associated with cognitive change found during ageing and neurodegenerative diseases, namely the middle temporal gyrus, primary visual cortex and the posterior hippocampus using immunohistochemistry. To support immunohistochemical analysis, total homogenate and biochemically enriched synaptic fractions from available temporal gyrus tissues were examined by immunoblot. Finally, we examined whether Ng is associated with lifetime cognitive ageing. Ng levels were significantly reduced in AD relative to HA and ML cases across all regions. Additionally Ng was significantly reduced in HA in comparison to ML in the primary visual cortex. Immunoblotting confirms reduced Ng levels in AD cases supporting immunohistochemical results. Interestingly, there was also a significant reduction of synapse-associated Ng in our group who had lifetime cognitive decline in comparison to the group with lifetime cognitive resilience indicating loss of neurogranin in remaining synapses during ageing is associated with cognitive decline. Our findings indicate that increases in CSF Ng reflect loss of brain neurogranin and support the use of CSF Ng as a biomarker of AD and potentially of cognitive decline in healthy ageing

    Understanding the nature of the optically faint radio sources and their connection to the submillimeter population

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    We present a sample of 43 submillimeter sources detected (at >3 sigma), drawn from our program to follow-up optically faint radio sources with SCUBA. These sources already have associated radio and in many cases optical identifications, and many are also detected at 450 microns. We compare these with 12 submillimeter sources drawn from the literature, which were discovered in blank field mapping campaigns, but also have radio detections. We then use this total sample (55 sources) to study and model the evolution of dusty galaxies. A correlation is observed in the sub-mm/radio color-magnitude diagram, which can be modeled by strong luminosity evolution. The selection effects of the radio/optical pre-selection technique are determined from the models, and a corrected redshift distribution is constrained using a range of model assumptions. The temperature/redshift effects on the 450 microns detected subset of our sample are studied in relation to the models, and prospects for improved measurements in the shorter sub-mm wavelength windows (450 microns and 350 microns) are explored.Comment: to appear in ApJ, 19 pages, 9 figure

    Methods for Rapidly Processing Angular Masks of Next-Generation Galaxy Surveys

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    As galaxy surveys become larger and more complex, keeping track of the completeness, magnitude limit, and other survey parameters as a function of direction on the sky becomes an increasingly challenging computational task. For example, typical angular masks of the Sloan Digital Sky Survey contain about N=300,000 distinct spherical polygons. Managing masks with such large numbers of polygons becomes intractably slow, particularly for tasks that run in time O(N^2) with a naive algorithm, such as finding which polygons overlap each other. Here we present a "divide-and-conquer" solution to this challenge: we first split the angular mask into predefined regions called "pixels," such that each polygon is in only one pixel, and then perform further computations, such as checking for overlap, on the polygons within each pixel separately. This reduces O(N^2) tasks to O(N), and also reduces the important task of determining in which polygon(s) a point on the sky lies from O(N) to O(1), resulting in significant computational speedup. Additionally, we present a method to efficiently convert any angular mask to and from the popular HEALPix format. This method can be generically applied to convert to and from any desired spherical pixelization. We have implemented these techniques in a new version of the mangle software package, which is freely available at http://space.mit.edu/home/tegmark/mangle/, along with complete documentation and example applications. These new methods should prove quite useful to the astronomical community, and since mangle is a generic tool for managing angular masks on a sphere, it has the potential to benefit terrestrial mapmaking applications as well.Comment: New version 2.1 of the mangle software now available at http://space.mit.edu/home/tegmark/mangle/ - includes galaxy survey masks and galaxy lists for the latest SDSS data release and the 2dFGRS final data release as well as extensive documentation and examples. 14 pages, 9 figures, matches version accepted by MNRA

    HopScotch - a low-power renewable energy base station network for rural broadband access

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    The provision of adequate broadband access to communities in sparsely populated rural areas has in the past been severely restricted. In this paper, we present a wireless broadband access test bed running in the Scottish Highlands and Islands which is based on a relay network of low-power base stations. Base stations are powered by a combination of renewable sources creating a low cost and scalable solution suitable for community ownership. The use of the 5~GHz bands allows the network to offer large data rates and the testing of ultra high frequency ``white space'' bands allow expansive coverage whilst reducing the number of base stations or required transmission power. We argue that the reliance on renewable power and the intelligent use of frequency bands makes this approach an economic green radio technology which can address the problem of rural broadband access

    Occurrence of liver cirrhosis in England, a cohort study, 1998-2009: a comparison with cancer

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    OBJECTIVES: There is no routine registration of the occurrence of newly diagnosed cases of cirrhosis in the United Kingdom. This study seeks to determine precise estimates and trends of the incidence of cirrhosis in England, and directly compare these figures with those for the 20 most commonly diagnosed cancers in the United Kingdom. METHODS: We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to perform a population-based cohort study. Adult incident cases with a diagnosis of cirrhosis between January 1998 and December 2009 were identified. We described trends in incidence by sex and etiology. We performed a direct standardization to estimate the number of people being newly diagnosed with cirrhosis in 2009, and calculated the change in incidence between 1998 and 2009. RESULTS: A total of 5,118 incident cases of cirrhosis were identified, 57.9% were male. Over the 12-year period, crude incidence increased by 50.6%. Incidence increased for both men and women and all etiology types. We estimated approximately 17,000 people were newly diagnosed with cirrhosis in 2009 in the United Kingdom, greater than that of the fifth most common cancer non-Hodgkin's lymphoma. The percentage change in incidence of cirrhosis between 1998 and 2009 for both men (52.4%) and women (38.3%) was greater than that seen for the top four most commonly diagnosed cancers in the United Kingdom (breast, lung, bowel, and prostate). CONCLUSIONS: The occurrence of cirrhosis increased more than that of the top four cancers during 1998 to 2009 in England. Strategies to monitor and reduce the incidence of this disease are urgently needed
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