Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Identification of potential drug targets in Salmonella Typhimurium using metabolic modelling and experimental validation

almonella enterica serovar Typhimurium is an established model organism for Gram-negative, intracellular pathogens. Owing to the rapid spread of resistance to antibiotics among this group of pathogens, new approaches to identify suitable target proteins are required. Based on the genome sequence of Salmonella Typhimurium and associated databases, a genome-scale metabolic model was constructed. Output was based on an experimental determination of the biomass of Salmonella when growing in glucose minimal medium. Linear programming was used to simulate variations in energy demand, while growing in glucose minimal medium. By grouping reactions with similar flux responses, a sub-network of 34 reactions responding to this variation was identified (the catabolic core). This network was used to identify sets of one and two reactions, that when removed from the genome-scale model interfered with energy and biomass generation. 11 such sets were found to be essential for the production of biomass precursors. Experimental investigation of 7 of these showed that knock-outs of the associated genes resulted in attenuated growth for 4 pairs of reactions, while 3 single reactions were shown to be essential for growth.

Agriculture modifies the seasonal decline of breeding success in a tropical wild bird population

1.Habitat conversion for agriculture is a major driver of biodiversity loss, but our understanding of the demographic processes involved remains poor. We typically investigate the impacts of agriculture in isolation even though populations are likely to experience multiple, concurrent changes in the environment (e.g. land and climate change). Drivers of environmental change may interact to affect demography but the mechanisms have yet to be explored fully in wild populations. 2.Here, we investigate the mechanisms linking agricultural land-use with breeding success using long-term data for the formerly Critically Endangered Mauritius kestrel Falco punctatus; a tropical forest specialist that also occupies agricultural habitats. We specifically focused on the relationship between breeding success, agriculture and the timing of breeding because the latter is sensitive to changes in climatic conditions (spring rainfall), and enables us to explore the interactive effects of different (land and climate) drivers of environmental change. 3.Breeding success, measured as egg survival to fledging, declines seasonally in this population, but we found that the rate of this decline became increasingly rapid as the area of agriculture around a nest site increased. If the relationship between breeding success and agriculture was used in isolation to estimate the demographic impact of agriculture it would significantly under-estimate breeding success in dry (early) springs, and over-estimate breeding success in wet (late) springs. 4.Analysis of prey delivered to nests suggests that the relationship between breeding success and agriculture might be due, in part, to spatial variation in the availability of native, arboreal geckos. 5.Synthesis and applications. Agriculture modifies the seasonal decline in breeding success in this population. As springs are becoming wetter in our study area and since the kestrels breed later in wetter springs, the impact of agriculture on breeding success will become worse over time. Our results suggest that forest restoration designed to reduce the detrimental impacts of agriculture on breeding may also help reduce the detrimental effects of breeding late due to wetter springs. Our results therefore highlight the importance of considering the interactive effects of environmental change when managing wild populations.

Evaluation of milk compositional variables on coagulation properties using partial least squares

The aim of this study was to investigate the effects of numerous milk compositional factors on milk coagulation properties using Partial Least Squares (PLS). Milk from herds of Jersey and Holstein-Friesian cattle was collected across the year and blended (n=55), to maximize variation in composition and coagulation. The milk was analysed for casein, protein, fat, titratable acidity, lactose, Ca2+, urea content, micelles size, fat globule size, somatic cell count and pH. Milk coagulation properties were defined as coagulation time, curd firmness and curd firmness rate measured by a controlled strain rheometer. The models derived from PLS had higher predictive power than previous models demonstrating the value of measuring more milk components. In addition to the well-established relationships with casein and protein levels, CMS and fat globule size were found to have as strong impact on all of the three models. The study also found a positive impact of fat on milk coagulation properties and a strong relationship between lactose and curd firmness, and urea and curd firmness rate, all of which warrant further investigation due to current lack of knowledge of the underlying mechanism. These findings demonstrate the importance of using a wider range of milk compositional variable for the prediction of the milk coagulation properties, and hence as indicators of milk suitability for cheese making.

Effect of blending Jersey and Holstein-Friesian milk on Cheddar cheese processing, composition and quality

The aim of this study was to investigate the effects of numerous milk compositional factors on milk coagulation properties using Partial Least Squares (PLS). Milk from herds of Jersey and Holstein- Friesian cattle was collected across the year and blended (n=55), to maximise variation in composition and coagulation. The milk was analysed for casein, protein, fat, titratable acidity, lactose, Ca2+, urea content, micelles size, fat globule size, somatic cell count and pH. Milk coagulation properties were defined as coagulation time, curd firmness and curd firmness rate measured by a controlled strain rheometer. The models derived from PLS had higher predictive power than previous models demonstrating the value of measuring more milk components. In addition to the well-established relationships with casein and protein levels, CMS and fat globule size were found to have as strong impact on all of the three models. The study also found a positive impact of fat on milk coagulation properties and a strong relationship between lactose and curd firmness, and urea and curd firmness rate, all of which warrant further investigation due to current lack of knowledge of the underlying mechanism. These findings demonstrate the importance of using a wider range of milk compositional variables for the prediction of the milk coagulation properties, and hence as indicators of milk suitability for cheese making.

Liquidity and the drivers of search, due diligence and transaction times for UK commercial real estate investments

Trading commercial real estate involves a process of exchange that is costly and which occurs over an extended and uncertain period of time. This has consequences for the performance and risk of real estate investments. Most research on transaction times has occurred for residential rather than commercial real estate. We study the time taken to transact commercial real estate assets in the UK using a sample of 578 transactions over the period 2004 to 2013. We measure average time to transact from a buyer and seller perspective, distinguishing the search and due diligence phases of the process, and we conduct econometric analysis to explain variation in due diligence times between assets. The median time for purchase of real estate from introduction to completion was 104 days and the median time for sale from marketing to completion was 135 days. There is considerable variation around these times and results suggest that some of this variation is related to market state, type and quality of asset, and type of participants involved in the transaction. Our findings shed light on the drivers of liquidity at an individual asset level and can inform models that quantify the impact of uncertain time on market on real estate investment risk.

Review of current in vivo measurement techniques for quantifying enteric methane emission from ruminants

Ruminant husbandry is a major source of anthropogenic greenhouse gases (GHG). Filling knowledge gaps and providing expert recommendation are important for defining future research priorities, improving methodologies and establishing science-based GHG mitigation solutions to government and non-governmental organisations, advisory/extension networks, and the ruminant livestock sector. The objectives of this review is to summarize published literature to provide a detailed assessment of the methodologies currently in use for measuring enteric methane (CH4) emission from individual animals under specific conditions, and give recommendations regarding their application. The methods described include respiration chambers and enclosures, sulphur hexafluoride tracer (SF6) technique, and techniques based on short-term measurements of gas concentrations in samples of exhaled air. This includes automated head chambers (e.g. the GreenFeed system), the use of carbon dioxide (CO2) as a marker, and (handheld) laser CH4 detection. Each of the techniques are compared and assessed on their capability and limitations, followed by methodology recommendations. It is concluded that there is no ‘one size fits all’ method for measuring CH4 emission by individual animals. Ultimately, the decision as to which method to use should be based on the experimental objectives and resources available. However, the need for high throughput methodology e.g. for screening large numbers of animals for genomic studies, does not justify the use of methods that are inaccurate. All CH4 measurement techniques are subject to experimental variation and random errors. Many sources of variation must be considered when measuring CH4 concentration in exhaled air samples without a quantitative or at least regular collection rate, or use of a marker to indicate (or adjust) for the proportion of exhaled CH4 sampled. Consideration of the number and timing of measurements relative to diurnal patterns of CH4 emission and respiratory exchange are important, as well as consideration of feeding patterns and associated patterns of rumen fermentation rate and other aspects of animal behaviour. Regardless of the method chosen, appropriate calibrations and recovery tests are required for both method establishment and routine operation. Successful and correct use of methods requires careful attention to detail, rigour, and routine self-assessment of the quality of the data they provide.

Influence of environmental stress on distributions of times to first division in Escherichia coli populations, as determined by digital-image analysis of individual cells

The distributions of times to first cell division were determined for populations of Escherichia coli stationary-phase cells inoculated onto agar media. This was accomplished by using automated analysis of digital images of individual cells growing on agar and calculation of the "box area ratio." Using approximately 300 cells per experiment, the mean time to first division and standard deviation for cells grown in liquid medium at 37 degrees C and inoculated on agar and incubated at 20 degrees C were determined as 3.0 h and 0.7 h, respectively. Distributions were observed to tail toward the higher values, but no definitive model distribution was identified. Both preinoculation stress by heating cultures at 50 degrees C and postinoculation stress by growth in the presence of higher concentrations of NaCl increased mean times to first division. Both stresses also resulted in an increase in the spread of the distributions that was proportional to the mean division time, the coefficient of variation being constant at approximately 0.2 in all cases. The "relative division time," which is the time to first division for individual cells expressed in terms of the cell size doubling time, was used as measure of the "work to be done" to prepare for cell division. Relative division times were greater for heat-stressed cells than for those growing under osmotic stress.

The use of image analysis to estimate population growth rate in Daphnia magna

1. Population growth rate (PGR) is central to the theory of population ecology and is crucial for projecting population trends in conservation biology, pest management and wildlife harvesting. Furthermore, PGR is increasingly used to assess the effects of stressors. Image analysis that can automatically count and measure photographed individuals offers a potential methodology for estimating PGR. 2. This study evaluated two ways in which the PGR of Daphnia magna, exposed to different stressors, can be estimated using an image analysis system. The first method estimated PGR as the ratio of counts of individuals obtained at two different times, while the second method estimated PGR as the ratio of population sizes at two different times, where size is measured by the sum of the individuals' surface areas, i.e. total population surface area. This method is attractive if surface area is correlated with reproductive value (RV), as it is for D. magna, because of the theoretical result that PGR is the rate at which the population RV increases. 3. The image analysis system proved reliable and reproducible in counting populations of up to 440 individuals in 5 L of water. Image counts correlated well with manual counts but with a systematic underestimate of about 30%. This does not affect accuracy when estimating PGR as the ratio of two counts. Area estimates of PGR correlated well with count estimates, but were systematically higher, possibly reflecting their greater accuracy in the study situation. 4. Analysis of relevant scenarios suggested the correlation between RV and body size will generally be good for organisms in which fecundity correlates with body size. In these circumstances, area estimation of PGR is theoretically better than count estimation. 5. Synthesis and applications. There are both theoretical and practical advantages to area estimation of population growth rate when individuals' reproductive values are consistently well correlated with their surface areas. Because stressors may affect both the number and quality of individuals, area estimation of population growth rate should improve the accuracy of predicting stress impacts at the population level.

Driving saccade to pursuit using image motion

Within the context of active vision, scant attention has been paid to the execution of motion saccades—rapid re-adjustments of the direction of gaze to attend to moving objects. In this paper we first develop a methodology for, and give real-time demonstrations of, the use of motion detection and segmentation processes to initiate capture saccades towards a moving object. The saccade is driven by both position and velocity of the moving target under the assumption of constant target velocity, using prediction to overcome the delay introduced by visual processing. We next demonstrate the use of a first order approximation to the segmented motion field to compute bounds on the time-to-contact in the presence of looming motion. If the bound falls below a safe limit, a panic saccade is fired, moving the camera away from the approaching object. We then describe the use of image motion to realize smooth pursuit, tracking using velocity information alone, where the camera is moved so as to null a single constant image motion fitted within a central image region. Finally, we glue together capture saccades with smooth pursuit, thus effecting changes in both what is being attended to and how it is being attended to. To couple the different visual activities of waiting, saccading, pursuing and panicking, we use a finite state machine which provides inherent robustness outside of visual processing and provides a means of making repeated exploration. We demonstrate in repeated trials that the transition from saccadic motion to tracking is more likely to succeed using position and velocity control, than when using position alone.

Reactions to peripheral image motion using a head/eye platform

The authors demonstrate four real-time reactive responses to movement in everyday scenes using an active head/eye platform. They first describe the design and realization of a high-bandwidth four-degree-of-freedom head/eye platform and visual feedback loop for the exploration of motion processing within active vision. The vision system divides processing into two scales and two broad functions. At a coarse, quasi-peripheral scale, detection and segmentation of new motion occurs across the whole image, and at fine scale, tracking of already detected motion takes place within a foveal region. Several simple coarse scale motion sensors which run concurrently at 25 Hz with latencies around 100 ms are detailed. The use of these sensors are discussed to drive the following real-time responses: (1) head/eye saccades to moving regions of interest; (2) a panic response to looming motion; (3) an opto-kinetic response to continuous motion across the image and (4) smooth pursuit of a moving target using motion alone.