Trade-offs constrain the success of glyphosate-free farming.

Glyphosate, the most widely used herbicide, is linked with environmental harm and there is a drive to replace it in agricultural systems. We model the impacts of discontinuing glyphosate use and replacing it with cultural control methods. We simulate winter wheat arable systems reliant on glyphosate and typical in northwest Europe. Removing glyphosate was projected to increase weed abundance, herbicide risk to the environment, and arable plant diversity and decrease food production. Weed communities with evolved resistance to non-glyphosate herbicides were not projected to be disproportionately affected by removing glyphosate, despite the lack of alternative herbicidal control options. Crop rotations with more spring cereals or grass leys for weed control increased arable plant diversity. Stale seedbed techniques such as delayed drilling and choosing ploughing instead of minimum tillage had varying effects on weed abundance, food production, and profitability. Ploughing was the most effective alternative to glyphosate for long-term weed control while maintaining production and profit. Our findings emphasize the need for careful consideration of trade-offs arising in scenarios where glyphosate is removed. Integrated Weed Management (IWM) with more use of cultural control methods offers the potential to reduce chemical use but is sensitive to seasonal variability and can incur negative environmental and economic impacts.

Modelling the effect of spatially variable soil properties on the distribution of weeds.

The patch spraying of weeds is an area of precision agriculture that has had limited uptake. This is in part due to the perceived risks associated with not controlling individual weeds. Nevertheless, the inherent patchiness of weeds makes them ideal targets for site-specific management. We propose using a mechanistic model to identify areas of a field vulnerable to invasion by weeds, allowing the creation of treatment maps that are risk averse. We developed a spatially-explicit mechanistic model of the life-cycle of Alopecurus myosuroides, a particularly problematic weed of cereal crops in the UK. In the model, soil conditions which vary across the field, affect the life-cycle of A. myosuroides. The model was validated using data on the within-field distribution of A. myosuroides on commercial farms and its co-location with soil properties. We demonstrate the important role played by soil properties in determining the within-field distribution of A. myosuroides. We also show that scale-dependent correlations between A. myosuroides and soil properties observed in the field are an emergent property of the modelled dynamics of the A. myosuroides life-cycle. Our model could therefore support effective site-specific management of A. myosuroides within fields by predicting areas that are vulnerable to A. myosuroides. The usefulness of this model in its ability to predict patch locations for A. myosuroides highlights the possibility of using similar models for other species where data are available on the response of the species to various soil properties.

Defining the habitat niche of Alopecurus myosuroides at the field scale.

The distribution of Alopecurus myosuroides (black-grass) in fields is patchy. The locations of these patches can be influenced by the environment. This presents an opportunity for precision management through patch spraying. We surveyed five fields on various types of soil using a nested sampling design and recorded both A. myosuroides seedlings in autumn and seed heads in summer. We also measured soil properties at those sampling locations. We found that the patches of seed heads within a field were smaller than the seedling patches, suggesting that techniques for patch spraying based on maps of heads in the previous season could be inherently risky. We also found that the location of A. myosuroides patches within fields can be predicted through their relationship with environmental properties and that these relations are consistent across fields on different soil types. This improved understanding of the relations between soil properties and A. myosuroides seedlings could allow farmers to use pre-existing or suitably supplemented soil maps already in use for the precision application of fertilisers as a starting point in the creation of herbicide application maps.

Designing a sampling scheme to reveal correlations between weeds and soil properties at multiple spatial scales.

Weeds tend to aggregate in patches within fields, and there is evidence that this is partly owing to variation in soil properties. Because the processes driving soil heterogeneity operate at various scales, the strength of the relations between soil properties and weed density would also be expected to be scale-dependent. Quantifying these effects of scale on weed patch dynamics is essential to guide the design of discrete sampling protocols for mapping weed distribution. We developed a general method that uses novel within-field nested sampling and residual maximum-likelihood (reml) estimation to explore scale-dependent relations between weeds and soil properties. We validated the method using a case study of Alopecurus myosuroides in winter wheat. Using reml, we partitioned the variance and covariance into scale-specific components and estimated the correlations between the weed counts and soil properties at each scale. We used variograms to quantify the spatial structure in the data and to map variables by kriging. Our methodology successfully captured the effect of scale on a number of edaphic drivers of weed patchiness. The overall Pearson correlations between A. myosuroides and soil organic matter and clay content were weak and masked the stronger correlations at >50 m. Knowing how the variance was partitioned across the spatial scales, we optimised the sampling design to focus sampling effort at those scales that contributed most to the total variance. The methods have the potential to guide patch spraying of weeds by identifying areas of the field that are vulnerable to weed establishment.

Effects of cigarette smoke on Toll-like receptor (TLR) activation of chronic obstructive pulmonary disease (COPD) macrophages.

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal innate immune response. We have investigated the changes in the innate immune response of COPD alveolar macrophages exposed to both cigarette smoke and Toll-like receptor (TLR) stimulation. COPD and control alveolar macrophages were exposed to cigarette smoke extract (CSE) followed by TLR-2, -4 and -5 ligands [Pam3CSK4, lipopolysaccharide (LPS) and phase I flagellin (FliC), respectively] or non-typeable Haemophilus influenzae (NTHi). CSE exposure suppressed TLR-induced tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and regulated on activation, normal T cell expressed and secreted (RANTES) production in both COPD and control alveolar macrophages, but had no effect on interleukin 8 (CXCL8) production. Similarly, CSE suppressed NTHi-induced TNF-α but not NTHi-induced CXCL8 production in COPD alveolar macrophages. Gene expression analysis showed that CSE suppressed LPS-induced TNF-α transcription but not CXCL8 transcription in COPD alveolar macrophages. The dampening effect of CSE on LPS-induced cytokine production was associated with a reduction in p38, extracellular signal regulated kinase (ERK) and p65 activation. In conclusion, CSE caused a reduced innate immune response in COPD alveolar macrophages, with the exception of persistent CXCL8 production. This could be a mechanism by which alveolar macrophages promote neutrophil chemotaxis under conditions of oxidative stress and bacterial exposure.

Magnetic resonance imaging retinal oximetry: a quantitative physiological biomarker for early diabetic retinopathy?

AIMS: To assess the efficacy of using magnetic resonance imaging measurements of retinal oxygenation response to detect early diabetic retinopathy in patients with Type 2 diabetes. METHODS: Magnetic resonance imaging was conducted during 100% oxygen inhalation in patients with Type 2 diabetes with either no diabetic retinopathy (n = 12) or mild to moderate background diabetic retinopathy (n = 12), as well as in healthy control subjects (n = 12). Meanwhile, changes in retinal oxygenation response were measured. RESULTS: In the healthy control group, levels of retinal oxygenation response increased slowly during 100% oxygen inhalation. In contrast, they increased more quickly and attained homeostasis much earlier in the groups with background diabetic retinopathy (at the 20-min time point) and with no diabetic retinopathy (at the 25-min time point) than in the healthy control group (at the 42-min time point). Furthermore, levels of retinal oxygenation response in the group with background diabetic retinopathy increased more than that of the group with no diabetic retinopathy, which in turn increased more than that of the healthy control group. There are statistically significant differences between the group with background diabetic retinopathy and the healthy control group at 6-, 8-, 10-, 15-, 20- and 25-min time points (P < 0.05). According to the normal range of the healthy control group by setting fundus photography results as 'gold standard' in our research, the sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic area for reporting the early indications of utility of diabetic retinopathy were 83.33%, 58.33%, 50%, 87.5% and 0.774, respectively. CONCLUSIONS: The results indicate that magnetic resonance imaging is a potential screening method and probably a quantitative physiological biomarker to find early diabetic retinopathy in patients with Type 2 diabetes.

Flagellin expression enhances Salmonella accumulation in TLR5-positive macrophages.

Recently, it has been reported that Salmonella secrete flagellin in response to host produced lysophospholipids. However, this monomer of the bacterial flagella activates Toll-like receptor 5 (TLR5) in the innate immune system. The objective of this study was to examine the role of flagellin expression during infection of species-specific macrophages (MPhi) which either expressed or lacked TLR5. Initially, TLR5-activity was confirmed in bovine MPhi using Salmonella typhimurium derived-flagellin. Within these cells, recombinant FliC induced a potent CXCL8 response when compared to the heterogeneous (FliC/FljB) form of purified flagellin. Furthermore, neither form of flagellin induced nitrite secretion which was subsequently detected after exposing bovine MPhi to LPS in the presence of IFN-gamma. Flagellin enhanced the accumulation of Salmonella enteritidis in TLR5-positive bovine and human MPhi which was independent of adhesion in bovine MPhi. In contrast, murine MPhis which lacked TLR5 were equally susceptible to hosting S. enteritidis, with or without flagellin. However, lack of flagellin in S. typhimurium marginally inhibited bacterial accumulation in bovine MPhi, where FljB and FliC compensated for the lack of each other. This study suggests that flagellin may be inducing TLR5-dependent internalisation mechanisms in Mcapital EF, Cyrillic which vary qualitatively between different species and Salmonella serotypes.

Cardiology. Cardiomyoplasty.

Cardiac transplantation is an excellent surgical option that offers positive results for many patients with end stage heart failure (Large 1995). However, the availability of donor hearts does not meet the demand, resulting in the exclusion of patients who, for example, are more than 60 years old and for whom transplantation is contraindicated. Dynamic cardiomyoplasty has been developed to help such a client group.

Cardiology. Minimally invasive cardiac surgery (MICS).

Minimally invasive cardiac surgery (MICS) has been described by some surgeons as a quantum leap forward which could soon replace some forms of traditional surgery. Sally Glennen and Helen Metcalfe describe the procedure and nursing care involved.

Selecting and designing cell lines for improved physiological characteristics.

We have developed several approaches to create cell lines with improved characteristics in cell culture. In some cases it has been possible to isolate natural variants with useful properties. Cholesterol independent variants of the mouse NSO myeloma cell line were isolated by cloning in a selective medium. A glutamine independent variant of a hyridoma was isolated by continuous (chemostat) culture under glutamine limited conditions in the presence of glutamate. Choline independent cells were isolated from a choline limited chemostat. In an alternative approach to modifying cell behaviour, we have used recombinant DNA techniques to introduce the glutamine synthetase (GS) gene to a hybridoma. This resulted in glutamine independence and increased productivity.

Effects of D-3-hydroxybutyrate and acetoacetate on lactate removal in isolated perfused livers from starved and fed rats.

We examined the influence of nutritional state on the role of the hepatic plasma membrane lactate transporter in determining overall hepatic lactate disposal. The effects of infusion of sodium D-3-hydroxybutyrate (DOHB) on lactate uptake were studied in perfused livers from fed or starved rats. In livers from starved rats, DOHB (15 to 20 mmol/L) inhibited lactate removal by approximately 45%. This effect was associated with a decrease in intracellular lactate concentration, with cell pH remaining unchanged. Inhibition was maximal when perfusate lactate was less than 1.6 mmol/L, and was undetectable at concentrations exceeding 2.5 mmol/L. A similar degree of inhibition was observed with infusion of acetoacetate. These observations add to the evidence that the inhibition of lactate removal by DOHB seen in livers from starved animals is mediated through an effect on the hepatocyte lactate transporter. At similar low levels of perfusate lactate, DOHB infusion produced a decrease in output of lactate from livers obtained from fed animals. When such livers were subjected to prolonged preperfusion, lactate removal, rather than output, was observed; in these livers DOHB stimulated lactate removal, an effect directionally opposite to that observed in livers from starved animals. These data confirm that hepatic lactate transport is a limiting factor for lactate utilization in intact livers from starved rats; in contrast, lactate utilization in livers from fed animals is limited at a step subsequent to plasma membrane transport, ie, possibly pyruvate transport into mitochondria.

Hormonal modulation of hepatic plasma membrane lactate transport in cultured rat hepatocytes.

Hormonal modulation of hepatic plasma membrane lactate transport was studied in primary cultures of isolated hepatocytes from fed rats to examine the mechanism for the known enhancement of lactate transport in starvation and diabetes. Total cellular lactate entry was increased by 14% in the presence of dexamethasone; this was accounted for by an approximately 40% increase in the carrier-mediated component of entry with no effect on diffusion. A trend of similar magnitude was evident with glucagon. The effects of dexamethasone and glucagon on lactate transport constitute an additional potential mechanism for enhancement of gluconeogenesis by these hormones.

Enhanced carrier-mediated lactate entry into isolated hepatocytes from starved and diabetic rats.

Hepatic plasma membrane lactate transport was studied in isolated hepatocytes prepared from fed, starved, and streptozotocin diabetic rats. Carrier-mediated lactate entry was determined using the lactate transport inhibitors alpha-cyano-3-hydroxycinnamate and D-3-hydroxybutyrate and was significantly greater in hepatocytes from starved compared to fed rats and in hepatocytes from diabetic fed compared to fed rats. The saturable component of lactate entry which corresponds to carrier-mediated transport was higher in the starved than in the fed state with results from diabetic fed being intermediate between the two. Insulin treatment prevented the increment in carrier-mediated lactate transport observed in hepatocytes from diabetic fed rats. The data indicate that hepatic plasma membrane lactate transport is increased under conditions of starvation and diabetes mellitus. This may partly explain the increased gluconeogenic flux under these conditions.

Carrier-mediated efflux of ketone bodies in isolated rat hepatocytes.

The rate of efflux of ketone bodies has been studied in isolated hepatocytes prepared from starved rats and preloaded with D-3-[14C]hydroxybutyrate. Efflux of ketone bodies was temperature-dependent, saturable and inhibited by alpha-cyano-3-hydroxycinnamate and phloretin. The rate of efflux was also reduced by 6 mmol/l lactate and pyruvate added to the external medium. Under conditions of simulated metabolic acidosis in the hepatocyte suspension medium, ketone body efflux rate was reduced. The experimental data suggest that hepatic plasma membrane ketone body transit is carrier-mediated.