Maternal high-fat diet induces hyperproliferation and alters Pten/Akt signaling in prostates of offspring

Developing recommendations for prostate cancer prevention requires identification of modifiable risk factors. Maternal exposure to high-fat diet (HFD) initiates a broad array of second-generation adult disorders in murine models and humans. Here, we investigate whether maternal HFD in mice affects incidence of prostate hyperplasia in offspring. Using three independent assays, we demonstrate that maternal HFD is sufficient to initiate prostate hyperproliferation in adult male offspring. HFD-exposed prostate tissues do not increase in size, but instead concomitantly up-regulate apoptosis. Maternal HFD-induced phenotypes are focally present in young adult subjects and greatly exacerbated in aged subjects. HFD-exposed prostate tissues additionally exhibit increased levels of activated Akt and deactivated Pten. Taken together, we conclude that maternal HFD diet is a candidate modifiable risk factor for prostate cancer initiation in later life

Statistics of convective cloud turbulence from a comprehensive turbulence retrieval method for radar observations

Turbulent mixing processes are important in determining the evolution of convective clouds,and the production of convective precipitation. However, the exact nature of these impacts remains uncertain due to limited observations. Model simulations show that assumptions made in parametrizing turbulence can have a marked effect on the characteristics of simulated clouds. This leads to significant uncertainty in forecasts from convection‐permitting numerical weather prediction (NWP) models. This contribution presents a comprehensive method to retrieve turbulence using Doppler weather radar to investigate turbulence in observed clouds. This method involves isolating the turbulent component of the Doppler velocity spectrum width, expressing turbulence intensity as an eddy dissipation rate, ϵ. By applying this method throughout large datasets of observations collected over the southern United Kingdom using the (0.28° beam‐width) Chilbolton Advanced Meteorological Radar (CAMRa), statistics of convective cloud turbulence are presented. Two contrasting case days are examined: a shallow “shower” case, and a “deep convection” case, exhibiting stronger and deeper updraughts. In our observations, ϵ generally ranges from 10−3 to 10−1 m2/s3, with the largest values found within, around and above convective updraughts. Vertical profiles of ϵ suggest that turbulence is much stronger in deep convection; 95th percentile values increase with height from 0.03 to 0.1 m2/s3, compared to approximately constant values of 0.02–0.03 m2/s3 throughout the depth of shower cloud. In updraught regions on both days, the 95th percentile of ϵ has significant (p < 10−3) positive correlations with the updraught velocity, and the horizontal shear in the updraught velocity, with weaker positive correlations with updraught dimensions. The ϵ‐retrieval method presented considers a very broad range of conditions, providing a reliable framework for turbulence retrieval using high‐resolution Doppler weather radar. In applying this method across many observations, the derived turbulence statistics will form the basis for evaluating the parametrization of turbulence in NWP models

Predicting Transcription Factor Specificity with All-Atom Models

The binding of a transcription factor (TF) to a DNA operator site can initiate or repress the expression of a gene. Computational prediction of sites recognized by a TF has traditionally relied upon knowledge of several cognate sites, rather than an ab initio approach. Here, we examine the possibility of using structure-based energy calculations that require no knowledge of bound sites but rather start with the structure of a protein-DNA complex. We study the PurR E. coli TF, and explore to which extent atomistic models of protein-DNA complexes can be used to distinguish between cognate and non-cognate DNA sites. Particular emphasis is placed on systematic evaluation of this approach by comparing its performance with bioinformatic methods, by testing it against random decoys and sites of homologous TFs. We also examine a set of experimental mutations in both DNA and the protein. Using our explicit estimates of energy, we show that the specificity for PurR is dominated by direct protein-DNA interactions, and weakly influenced by bending of DNA.Comment: 26 pages, 3 figure

Temporal changes in distributions and the species atlas: how can British and Irish plant data shoulder the inferential burden?

Species distribution atlases often rely on volunteer effort to achieve their desired coverage, an activity now typically discussed, at least in academia, under the general theme of “citizen science”. Such data, however, are rarely without complex biases, particularly with respect to the estimation of trends in species’ distributions over many decades. The data of the Botanical Society of Britain and Ireland (BSBI) are no exception to this, and both careful thought in data aggregation (spatial, temporal, and taxonomic) and appropriate modelling procedures are required to overcome these challenges. We discuss these issues, with a primary focus on the statistical models that have been put forward to adjust for such biases. Such models include the Telfer method, various “reporting rate” approaches based on generalised linear models, the frequency scaling using local occupancy (“Frescalo”) model, occupancy models, and spatial smoothing methods. In each case the strengths and limitations in relation to estimating trends from distribution data with important time-varying biases are assessed. Various properties of BSBI data, in particular the increasing numbers of records at fine spatial and temporal scales over the past century, coupled with a general lack of re-visits to sites at such finer scales and the time-varying biases previously mentioned, imply that methods that can be sensibly applied at coarser levels are likely to be most appropriate for estimating accurate long-term trends in distributions. We conclude that Frescalo, which can be seen as a type of occupancy model where an adjustment for overlooked species is made in relation to spatial rather than temporal replication, whilst simultaneously adjusting for variable regional effort, is currently the most sophisticated tool for achieving this. Although recording community-accepted adjustments to data collection practices may allow for a greater application of occupancy modelling or other approaches in the future, methods that seek accurate trends over the long-term are necessarily limited either to scales at which various properties of the data in hand are most likely to be unbiased, or at which the biases are well enough understood to be modelled accurately

Hierarchies of trade in Yiwu and Dushanbe: the case of an Uzbek merchant family from Tajikistan

This article focuses on the trading trajectory of an Uzbek family of merchants from Tajikistan. This family runs businesses in both Tajikistan’s capital, Dushanbe, and China’s famous international trading city: Yiwu. The analysis is centred on the accounts placed by Tajikistan’s Uzbek merchants about their historically sustained experience, often across several generations, in trading activities. These merchants’ claims of belonging to a ‘historical’ trading community rather than being ‘newcomers’ to long-distance commerce are articulated in relation to notions of ‘hierarchies of trade’ as they evolve in a twofold relational model linking Yiwu’s Changchun neighbourhood and Dushanbe. I suggest that the forms of conviviality enacted in Yiwu’s Changchun neighbourhood need to be understood in terms of the historical, multinational and transregional contacts that have occurred within the spaces of the former Soviet Union, as well as along the China-Russia and China-Central Asian borders. Equally, the hierarchies of trade of Uzbek merchants from Tajikistan in Yiwu’s Changchun neighbourhood cut-across markers of identity that juxtapose the roles of Tajik and Uzbek communities in Tajikistan’s contemporary politics and economics

DTMp : a comenius 2.1 project to produce a differentiated teaching module for primary school trainee teachers

This work was supported by the EU through Comenius 2.1 granr no. 118096 for the DTMp Project.As European classrooms become more heterogeneous, the movement towards inclusive education becomes more urgent as well as more challenging. This paper describes the process of developing and running a proposal for a Comenius 2.1 project aimed at developing training materials for the preparation of pre-service teachers in responding to diversity in primary classrooms. The project, started in October 2004, has collected the concerns and experiences of responding to diversity of 35 teachers (5 each from 7 different countries) through semi-structured interviews, and produced the first draft of a multilingual handbook for trainees. The handbook in hard copy and web-based format, will be piloted in 2005-06 in the seven participating countries, namely Malta (coordinator), Czech Republic, Germany, Lithuania, Netherlands, Sweden and the UK. This paper will focus on the process of trans-European sharing of research and development of the training course.peer-reviewe

Responding to student diversity : tutor's manual

The handbook was conceived during a meeting in Malta in 2003 among an international group of teacher educators spanning from Sweden to Malta and Greece and to the U.S. The concept was then worked out as a Comenius 2.1 Project DTMp (Differentiated Teaching Module – primary) over three years from 2004 to 2007 (see Box 1, p. viii, and www.dtmp.org). The DTMp Project team consisted of an even wider and more diverse group coming from seven EU countries, namely Malta (Coordinator), Czech Republic, Germany, Lithuania, Netherlands, Sweden, and United Kingdom. The background of each partner varied as well: one from an inclusive education concern, one from differentiated teaching, two from issues of disability and one from issues of disaffected students, one from socio-emotional development concerns, and one each from the pedagogy of language and mathematics. We also listened to teachers from the seven countries who were trying to reach out to the diversity of their children in the classroom, and you will find the text peppered with the experiences they related to us. We felt that this diversity enriched our teamwork and our products.peer-reviewe