Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.

Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.

Local examination of skin diffusion using FTIR spectroscopic imaging and multivariate target factor analysis

In the context of trans-dermal drug delivery it is very important to have mechanistic insight into the barrier function of the skin's stratum corneum and the diffusion mechanisms of topically applied drugs. Currently spectroscopic imaging techniques are evolving which enable a spatial examination of various types of samples in a dynamic way. ATR-FTIR imaging opens up the possibility to monitor spatial diffusion profiles across the stratum corneum of a skin sample. Multivariate data analyses methods based on factor analysis are able to provide insight into the large amount of spectroscopically complex and highly overlapping signals generated. Multivariate target factor analysis was used for spectral resolution and local diffusion profiles with time through stratum corneum. A model drug, 4-cyanophenol in polyethylene glycol 600 and water was studied. Results indicate that the average diffusion profiles between spatially different locations show similar profiles despite the heterogeneous nature of the biological sample and the challenging experimental set-up.

A systematic review of the effect of dietary exposure that could be achieved through normal dietary intake on learning and performance of school-aged children of relevance to UK schools

The aim of the present review was to perform a systematic in-depth review of the best evidence from controlled trial studies that have investigated the effects of nutrition, diet and dietary change on learning, education and performance in school-aged children (4-18 years) from the UK and other developed countries. The twenty-nine studies identified for the review examined the effects of breakfast consumption, sugar intake, fish oil and vitamin supplementation and 'good diets'. In summary, the studies included in the present review suggest there is insufficient evidence to identify any effect of nutrition, diet and dietary change on learning, education or performance of school-aged children from the developed world. However, there is emerging evidence for the effects of certain fatty acids which appear to be a function of dose and time. Further research is required in settings of relevance to the UK and must be of high quality, representative of all populations, undertaken for longer durations and use universal validated measures of educational attainment. However, challenges in terms of interpreting the results of such studies within the context of factors such as family and community context, poverty, disease and the rate of individual maturation and neurodevelopment will remain. Whilst the importance of diet in educational attainment remains under investigation, the evidence for promotion of lower-fat, -salt and -sugar diets, high in fruits, vegetables and complex carbohydrates, as well as promotion of physical activity remains unequivocal in terms of health outcomes for all schoolchildren.

Projecting marine fish production and catch potential in Bangladesh in the 21st century under long-term environmental change and management scenarios

The fisheries sector is crucial to the Bangladeshi economy and wellbeing, accounting for 4.4% of national Gross Domestic Product (GDP) and 22.8% of agriculture sector production, and supplying ca.60% of the national animal protein intake. Fish is vital to the 16 million Bangladeshis living near the coast, a number that has doubled since the 1980s. Here we develop and apply tools to project the long term productive capacity of Bangladesh marine fisheries under climate and fisheries management scenarios, based on downscaling a global climate model, using associated river flow and nutrient loading estimates, projecting high resolution changes in physical and biochemical ocean properties, and eventually projecting fish production and catch potential under different fishing mortality targets. We place particular interest on Hilsa shad (Tenualosa ilisha), which accounts for ca.11% of total catches, and Bombay duck (Harpadon nehereus), a low price fish that is the second highest catch in Bangladesh and is highly consumed by low income communities. It is concluded that the impacts of climate change, under greenhouse emissions scenario A1B, are likely to reduce the potential fish production in the Bangladesh Exclusive Economic Zone (EEZ) by less than 10%. However, these impacts are larger for the two target species. Under sustainable management practices we expect Hilsa shad catches to show a minor decline in potential catch by 2030 but a significant (25%) decline by 2060. However, if overexploitation is allowed catches are projected to fall much further, by almost 95% by 2060, compared to the Business as Usual scenario for the start of the 21st century. For Bombay duck, potential catches by 2060 under sustainable scenarios will produce a decline of less than 20% compared to current catches. The results demonstrate that management can mitigate or exacerbate the effects of climate change on ecosystem productivity.

Intercepting beats in predesignated target zones

Moving to a rhythm necessitates precise timing between the movement of the chosen limb and the timing imposed by the beats. However, the temporal information specifying the moment when a beat will sound (the moment onto which one must synchronise one's movement) is not continuously provided by the acoustic array. Because of this informational void, the actors need some form of prospective information that will allow them to act sufficiently ahead of time in order to get their hand in the right place at the right time. In this acoustic interception study, where participants were asked to move between two targets in such a way that they arrived and stopped in the target zone at the same time as a beat sounded, we tested a model derived from tau-coupling theory (Lee DN (1998) Ecol Psychol 10:221-250). This model attempts to explain the form of a potential timing guide that specifies the duration of the inter-beat intervals and also describes how this informational guide can be used in the timing and guidance of movements. The results of our first experiment show that, for inter-beat intervals of less than 3 s, a large proportion of the movement (over 70%) can be explained by the proposed model. However, a second experiment, which augments the time between beats so that it surpasses 3 s, shows a marked decline in the percentage of information/movement coupling. A close analysis of the movement kinematics indicates a lack of control and anticipation in the participants' movements. The implications of these findings, in light of other research studies, are discussed.