Macrophages come to mind as keys to cognitive decline

Cognitive impairment, an underappreciated consequence of hypertension, is linked to cerebral arteriolar disease through poorly defined mechanisms. A study by Faraco et al. in this issue of the JCI points to perturbations of neurovascular unit coupling caused by perivascular macrophages (PVMs) as a cause of hypertension-related cognitive impairment. Angiotensin II (Ang II) was shown to activate PVMs, causing them to produce superoxide and thereby alter the proper functioning of the adjacent arterioles. Faraco and colleagues also show that disruption of the blood-brain barrier occurs in hypertension, allowing circulating Ang II to access PVMs. This study provides important new insight into the role of inflammatory cells in the genesis of vascular dementia

Least-squares methods for identifying biochemical regulatory networks from noisy measurements

<b>Background</b>: We consider the problem of identifying the dynamic interactions in biochemical networks from noisy experimental data. Typically, approaches for solving this problem make use of an estimation algorithm such as the well-known linear Least-Squares (LS) estimation technique. We demonstrate that when time-series measurements are corrupted by white noise and/or drift noise, more accurate and reliable identification of network interactions can be achieved by employing an estimation algorithm known as Constrained Total Least Squares (CTLS). The Total Least Squares (TLS) technique is a generalised least squares method to solve an overdetermined set of equations whose coefficients are noisy. The CTLS is a natural extension of TLS to the case where the noise components of the coefficients are correlated, as is usually the case with time-series measurements of concentrations and expression profiles in gene networks. <b>Results</b>: The superior performance of the CTLS method in identifying network interactions is demonstrated on three examples: a genetic network containing four genes, a network describing p53 activity and <i>mdm2</i> messenger RNA interactions, and a recently proposed kinetic model for interleukin (IL)-6 and (IL)-12b messenger RNA expression as a function of ATF3 and NF-κB promoter binding. For the first example, the CTLS significantly reduces the errors in the estimation of the Jacobian for the gene network. For the second, the CTLS reduces the errors from the measurements that are corrupted by white noise and the effect of neglected kinetics. For the third, it allows the correct identification, from noisy data, of the negative regulation of (IL)-6 and (IL)-12b by ATF3. <b>Conclusion</b>: The significant improvements in performance demonstrated by the CTLS method under the wide range of conditions tested here, including different levels and types of measurement noise and different numbers of data points, suggests that its application will enable more accurate and reliable identification and modelling of biochemical networks

Chemical signatures of the Anthropocene in the Clyde Estuary, UK: sediment hosted Pb, 207/206 Pb, Total Petroleum Hydrocarbons (TPH), Polyaromatic Hydrocarbon (PAH) and Polychlorinated Bipheny (PCB) pollution records

The sediment concentrations of total petroleum hydrocarbons (TPHs), polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), Pb and 207/206Pb isotope ratios were measured in seven cores from the middle Clyde estuary (Scotland, UK) with an aim of tracking the late Anthropocene. Concentrations of TPHs ranged from 34 to 4386 mg kg−1, total PAHs from 19 to 16 163 μg kg−1 and total PCBs between less than 4.3 to 1217 μg kg−1. Inventories, distributions and isomeric ratios of the organic pollutants were used to reconstruct pollutant histories. Pre-Industrial Revolution and modern non-polluted sediments were characterized by low TPH and PAH values as well as high relative abundance of biogenic-sourced phenanthrene and naphthalene. The increasing industrialization of the Clyde gave rise to elevated PAH concentrations and PAH isomeric ratios characteristic of both grass/wood/coal and petroleum and combustion (specifically petroleum combustion). Overall, PAHs had the longest history of any of the organic contaminants. Increasing TPH concentrations and a concomitant decline in PAHs mirrored the lessening of coal use and increasing reliance on petroleum fuels from about the 1950s. Thereafter, declining hydrocarbon pollution was followed by the onset (1950s), peak (1965–1977) and decline (post-1980s) in total PCB concentrations. Lead concentrations ranged from 6 to 631 mg kg−1, while 207/206Pb isotope ratios spanned 0.838–0.876, indicative of various proportions of ‘background’, British ore/coal and Broken Hill type petrol/industrial lead. A chronology was established using published Pb isotope data for aerosol-derived Pb and applied to the cores

Validation of a model of regulation in the tryptophan operon against multiple experiment data using global optimisation

This paper is concerned with validating a mathematical model of regulation in the tryptophan operon using global optimization. Although a number of models for this biochemical network are proposed, in many cases only qualitative agreement between the model output and experimental data was demonstrated, since very little information is currently available to guide the selection of parameter values for the models. This paper presents a model validating method using both multiple experimental data and global optimization

A_4 Symmetry and Lepton Masses and Mixing

Stimulated by Ma's idea which explains the tribimaximal neutrino mixing by assuming an A_4 flavor symmetry, a lepton mass matrix model is investigated. A Frogatt-Nielsen type model is assumed, and the flavor structures of the masses and mixing are caused by the VEVs of SU(2)_L-singlet scalars \phi_i^u and \phi_i^d (i=1,2,3), which are assigned to {\bf 3} and ({\bf 1}, {\bf 1}',{\bf 1}'') of A_4, respectively.Comment: 13 pages including 1 table, errors in Sec.7 correcte

Mineral resource information in support of national, regional and local planning : Gloucestershire (comprising Gloucestershire and South Gloucestershire)

This report is one of a series prepared by the British Geological Survey for various administrative areas in England for the Office of the Deputy Prime Minister’s research project Mineral Resource Information in Support of National, Regional and Local Planning. The accompanying map relates to the county of Gloucestershire, comprising Gloucestershire and South Gloucestershire, and delineates the mineral resources of current, or potential, economic interest in the area and the sites where minerals are or have been worked. It also relates these to national planning designations, which may represent constraints on the extraction of minerals. Three major elements of information are presented: • the geological distribution and importance of mineral resources; • the extent of mineral planning permissions and the location of current mineral workings; and • the extent of selected, nationally-designated planning constraints. This wide range of information, much of which is scattered and not always available in a consistent and convenient form, is presented on a digitally-generated summary map on the scale of 1:100 000. This scale is convenient for the overall display of the data and allows for a legible topographic base on which to depict the information. However, all the data are held digitally at larger scales using a Geographical Information System (GIS), which allows easy revision, updating and customisation of the information together with its possible integration with other datasets. The information will form part of a Summary of the Mineral Resources of the South West Region. The purpose of the work is to assist all interested parties involved in the preparation and review of development plans, both in relation to the extraction of minerals and the protection of mineral resources from sterilisation. It provides a knowledge base, in a consistent format, on the nature and extent of mineral resources and the environmental constraints, which may affect their extraction. An important objective is to provide baseline data for the long term. The results may also provide a starting point for discussions on specific planning proposals for mineral extraction or on proposals, which may sterilise resources. It is anticipated that the maps and report will also provide valuable background data for a much wider audience, including the different sectors of the minerals industry, other agencies and authorities (e.g. The Planning Inspectorate Agency, the Environment Agency, the Countryside Agency and English Nature), environmental interests and the general public. Basic mineral resource information is essential to support mineral exploration and development activities, for resource management and land-use planning, and to establish baseline data for environmental impact studies and environmental guidelines. It also enables a more sustainable pattern and standard of development to be achieved by valuing mineral resources as national assets. The mineral resources covered are sand and gravel, bedrock sand, crushed rock aggregate, building stone, hydrocarbons, and coal

Mineral resource information in support of national, regional and local planning : Suffolk

This report is one of a series prepared by the British Geological Survey for various administrative areas in England for the Office of the Deputy Prime Minister's research project Mineral Resource Information in Support of National, Regional and Local Planning. The accompanying map relates to the county of Suffolk and delineates the mineral resources of current, or potential, economic interest in the area and the sites where minerals are or have been worked. It also relates these to national planning designations, which may represent constraints on the extraction of minerals. Three major elements of information are presented: • the geological distribution and importance of mineral resources; • the extent of mineral planning permissions and the location of current mineral workings, and • the extent of selected, nationally-designated planning constraints. This wide range of information, much of which is scattered and not always available in a consistent and convenient form, is presented on a digitally-generated summary map on the scale of 1:100 000. This scale is convenient for the overall display of the data and allows for a legible topographic base on which to depict the information. However, all the data are held digitally at larger scales using a Geographical Information System (GIS), which allows easy revision, updating and customisation of the information together with its possible integration with other datasets. The information will form part of a Summary of the Mineral Resources of the East of England Region. The purpose of the work is to assist all interested parties involved in the preparation and review of development plans, both in relation to the extraction of minerals and the protection of mineral resources from sterilisation. It provides a knowledge base, in a consistent format, on the nature and extent of mineral resources and the environmental constraints, which may affect their extraction. An important objective is to provide baseline data for the long term. The results may also provide a starting point for discussions on specific planning proposals for mineral extraction or on proposals, which may sterilise resources. It is anticipated that the maps and report will also provide valuable background data for a much wider audience, including the different sectors of the minerals industry, other agencies and authorities (e.g. The Planning Inspectorate Agency, the Environment Agency, the Countryside Agency and English Nature), environmental interests and the general public. Basic mineral resource information is essential to support mineral exploration and development activities, for resource management and land-use planning, and to establish baseline data for environmental impact studies and environmental guidelines. It also enables a more sustainable pattern and standard of development to be achieved by valuing mineral resources as national assets. The mineral resources covered are sand and gravel, brick clay, hydrocarbons, building stone, chalk and peat

Effects of interleukin-1β Inhibition on blood pressure, incident hypertension, and residual inflammatory risk

While hypertension and inflammation are physiologically inter-related, the effect of therapies that specifically target inflammation on blood pressure is uncertain. The recent CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) afforded the opportunity to test whether IL (interleukin)-1β inhibition would reduce blood pressure, prevent incident hypertension, and modify relationships between hypertension and cardiovascular events. CANTOS randomized 10 061 patients with prior myocardial infarction and hsCRP (high sensitivity C-reactive protein) ≥2 mg/L to canakinumab 50 mg, 150 mg, 300 mg, or placebo. A total of 9549 trial participants had blood pressure recordings during follow-up; of these, 80% had a preexisting diagnosis of hypertension. In patients without baseline hypertension, rates of incident hypertension were 23.4, 26.6, and 28.1 per 100-person years for the lowest to highest baseline tertiles of hsCRP (P>0.2). In all participants random allocation to canakinumab did not reduce blood pressure (P>0.2) or incident hypertension during the follow-up period (hazard ratio, 0.96 [0.85–1.08], P>0.2). IL-1β inhibition with canakinumab reduces major adverse cardiovascular event rates. These analyses suggest that the mechanisms underlying this benefit are not related to changes in blood pressure or incident hypertension

S_3 Symmetry and Neutrino Masses and Mixings

Based on a universal seesaw mass matrix model with three scalars \phi_i, and by assuming an S_3 flavor symmetry for the Yukawa interactions, the lepton masses and mixings are investigated systematically. In order to understand the observed neutrino mixing, the charged leptons (e, \mu, \tau) are regarded as the 3 elements (e_1, e_2, e_3) of S_3, while the neutrino mass-eigenstates are regarded as the irreducible representation (\nu_\eta, \nu_\sigma, \nu_\pi) of S_3, where (\nu_\pi, \nu_\eta) and \nu_\sigma are a doublet and a singlet, respectively, which are composed of the 3 elements (\nu_1, \nu_2, \nu_3) of S_3.Comment: 16 pages, no figure, version to appear in EPJ-

Direct amplification of nodD from community DNA reveals the genetic diversity of Rhizobium leguminosarum in soil

Sequences of nodD, a gene found only in rhizobia, were amplified from total community DNA isolated from a pasture soil. The polymerase chain reaction (PCR) primers used, Y5 and Y6, match nodD from Rhizobium leguminosarum biovar trifolii, R. leguminosarum biovar viciae and Sinorhizobium meliloti. The PCR product was cloned and yielded 68 clones that were identified by restriction pattern as derived from biovar trifolii [11 restriction fragment length polymorphism (RFLP) types] and 15 clones identified as viciae (seven RFLP types). These identifications were confirmed by sequencing. There were no clones related to S. meliloti nodD. For comparison, 122 strains were isolated from nodules of white clover (Trifolium repens) growing at the field site, and 134 from nodules on trap plants of T. repens inoculated with the soil. The nodule isolates were of four nodD RFLP types, with 77% being of a single type. All four of these patterns were also found among the clones from soil DNA, and the same type was the most abundant, although it made up only 34% of the trifolii-like clones. We conclude that clover selects specific genotypes from the available soil population, and that R. leguminosarum biovar trifolii was approximately five times more abundant than biovar viciae in this pasture soil, whereas S. meliloti was rare