Transgenic maize engineered to express insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has become widely adopted in U.S. agriculture. In 2009, Bt maize was planted on more than ...22.2 million hectares, constituting 63% of the U.S. crop. Using statistical analysis of per capita growth rate estimates, we found that areawide suppression of the primary pest Ostrinia nubilalis (European corn borer) is associated with Bt maize use. Cumulative benefits over 14 years are an estimated $3.2 billion for maize growers in Illinois, Minnesota, and Wisconsin, with more than $2.4 billion of this total accruing to non-Bt maize growers. Comparable estimates for Iowa and Nebraska are $3.6 billion in total, with $1.9 billion for non-Bt maize growers. These results affirm theoretical predictions of pest population suppression and highlight economic incentives for growers to maintain non-Bt maize refugia for sustainable insect resistance management.
Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose ...transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source, regulating glucose transport capacity during moderate-intensity exercise.
Background & Aims An association between inflammatory activity and colorectal neoplasia (CRN) has been documented in patients with ulcerative colitis (UC). However, previous studies did not address ...the duration of inflammation or the effects of therapy on risk for CRN. We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN. Methods We collected data from 141 patients with UC without CRN (controls) and 59 matched patients with UC who developed CRN (cases), comparing disease extent and duration and patients' ages. We used a new 6-point histologic inflammatory activity (HIA) scale to score biopsy fragments (n = 4449). Information on medications, smoking status, primary sclerosing cholangitis, and family history of CRN were collected from the University of Chicago Inflammatory Bowel Disease Endoscopy Database. Relationships between HIA, clinical features, and CRN were assessed by conditional logistic regression. Results Cases and controls were similar in numbers of procedures and biopsies, exposure to steroids or mesalamine, smoking status, and family history of CRN. They differed in proportion of men vs women, exposure to immune modulators, and primary sclerosing cholangitis prevalence. In univariate analysis, HIA was positively associated with CRN (odds ratio OR, 2.56 per unit increase; P = .001), whereas immune modulators (including azathioprine, 6-mercaptopurine, and methotrexate) reduced the risk for CRN (OR, 0.35; P < .01). HIA was also associated with CRN in multivariate analysis (OR, 3.68; P = .001). Conclusions In a case–control study, we associated increased inflammation with CRN in patients with UC. Use of immune modulators reduced the risk for CRN, indicating that these drugs have chemoprotective effects. On the basis of these data, we propose new stratified surveillance and treatment strategies to prevent and detect CRN in patients with UC.
A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might ...also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL) of children with autism (n = 82) and controls (n = 64). Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
Reactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate if increased ...NADPH oxidase (NOX)2-dependent activity during exercise is required for long-term high-intensity interval training (HIIT) in skeletal muscle using a mouse model lacking functional NOX2 complex due to absent p47phox (Ncf1) subunit expression (ncf1* mutation).
HIIT was investigated after an acute bout of exercise and after a chronic intervention (3x/week for 6 weeks) in wild-type (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using an electroporated genetically-encoded biosensor. Immunoblotting and single-fiber microscopy was performed to measure classical exercise-training responsive endpoints in skeletal muscle.
A single bout of HIIT increased NOX2 activity measured as p47-roGFP oxidation immediately after exercise but not 1 h or 4 h after exercise. After a 6-week HIIT regimen, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase 2, catalase, hexokinase II, pyruvate dehydrogenase and protein markers of mitochondrial oxidative phosphorylation complexes. Strikingly, HIIT-training increased mitochondrial network area and decreased fragmentation in WT mice only.
This study suggests that HIIT exercise increases NOX2 activity in skeletal muscle and shows that NOX2 activity is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.
This review summarises existing evidence on the impact of organic food on human health. It compares organic vs. conventional food production with respect to parameters important to human health and ...discusses the potential impact of organic management practices with an emphasis on EU conditions. Organic food consumption may reduce the risk of allergic disease and of overweight and obesity, but the evidence is not conclusive due to likely residual confounding, as consumers of organic food tend to have healthier lifestyles overall. However, animal experiments suggest that identically composed feed from organic or conventional production impacts in different ways on growth and development. In organic agriculture, the use of pesticides is restricted, while residues in conventional fruits and vegetables constitute the main source of human pesticide exposures. Epidemiological studies have reported adverse effects of certain pesticides on children's cognitive development at current levels of exposure, but these data have so far not been applied in formal risk assessments of individual pesticides. Differences in the composition between organic and conventional crops are limited, such as a modestly higher content of phenolic compounds in organic fruit and vegetables, and likely also a lower content of cadmium in organic cereal crops. Organic dairy products, and perhaps also meats, have a higher content of omega-3 fatty acids compared to conventional products. However, these differences are likely of marginal nutritional significance. Of greater concern is the prevalent use of antibiotics in conventional animal production as a key driver of antibiotic resistance in society; antibiotic use is less intensive in organic production. Overall, this review emphasises several documented and likely human health benefits associated with organic food production, and application of such production methods is likely to be beneficial within conventional agriculture, e.g., in integrated pest management.
Regular exercise elicits advantageous metabolic adaptations in skeletal muscle, such as improved insulin sensitivity. However, the underpinning molecular mechanisms and the effect of diet on muscle ...exercise training benefits are unclear. We therefore characterized the skeletal muscle proteome following exercise training (ET) in mice fed chow or high-fat diet (HFD). ET increased exercise performance, lowered body-weight, decreased fat mass and improved muscle insulin action in chow- and HFD-fed mice. At the molecular level, ET regulated 170 muscle proteins in chow-fed mice, but only 29 proteins in HFD-fed mice. HFD per se altered 56 proteins, most of which were regulated in a similar direction by ET. To identify proteins that might have particular health-related bearing on skeletal muscle metabolism, we filtered for differentially regulated proteins in response to ET and HFD. This yielded 15 proteins, including the major urinary protein 1 (MUP1), which was the protein most decreased after HFD, but increased with ET. The ET-induced Mup1 expression was absent in mouse muscle lacking functional AMPK. MUP1 also potentiated insulin-stimulated GLUT4 translocation in cultured muscle cells. Collectively, we provide a resource of ET-regulated proteins in insulin-sensitive and insulin-resistant skeletal muscle. The identification of MUP1 as a diet-, ET- and AMPK-regulated skeletal muscle protein that improves insulin sensitivity in muscle cells demonstrates the usefulness of these data.
Key points
The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo.
High‐fat diet (HFD) exacerbates muscle insulin resistance in Rac1 ...muscle knockout (mKO) mice.
Muscle Rac1 KO protects against HFD‐induced insulin resistance in fat tissue indicating tissue cross‐talk.
A fatty diet markedly reduces insulin clearance in mice.
Insulin resistance and perturbations in glucose metabolism underpin common lifestyle diseases such as type 2 diabetes and obesity. Insulin resistance in muscle is characterized by compromised activity of the GTPase, Ras‐related C3 Botulinum toxin substrate 1 (Rac1), yet the role of Rac1 in insulin‐stimulated glucose uptake in vivo and diet‐induced insulin resistance is unknown. Inducible muscle‐specific Rac1 knockout (Rac1 mKO) and wild type (WT) littermate mice were either fed a chow or a 60% high‐fat diet (HFD). Insulin‐stimulated 2‐deoxy‐glucose uptake, intracellular signalling, protein expression, substrate utilization, and glucose and insulin tolerance were assessed. In chow‐fed mice, in vivo insulin‐stimulated glucose uptake was reduced in triceps, soleus and gastrocnemius muscles from Rac1 mKO mice. HFD‐induced whole body insulin resistance was exacerbated by the lack of muscle Rac1 and glucose uptake was reduced in all muscles, except for soleus. Muscle Akt (also known as protein kinase B) signalling was unaffected by diet or genotype. In adipose tissue, Rac1 mKO mice were protected from HFD‐induced insulin resistance (with respect to both glucose uptake and phosphorylated‐Akt), rendering their whole body glucose tolerance comparable to WT mice on HFD. Our findings show that lack of Rac1 exacerbates HFD‐induced insulin resistance in skeletal muscle. Whole body glucose tolerance, however, was largely unaffected in Rac1 mKO mice, likely due to improved insulin‐stimulated glucose uptake in adipose tissue. We conclude that lack of Rac1 in the context of obesity is detrimental to insulin‐stimulated muscle glucose uptake in muscle independently of Akt signalling.
Key points
The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo.
High‐fat diet (HFD) exacerbates muscle insulin resistance in Rac1 muscle knockout (mKO) mice.
Muscle Rac1 KO protects against HFD‐induced insulin resistance in fat tissue indicating tissue cross‐talk.
A fatty diet markedly reduces insulin clearance in mice.
Metabolic dysfunction and insulin resistance are emerging as hallmarks of cancer and cachexia, and impair cancer prognosis. Yet, the molecular mechanisms underlying impaired metabolic regulation are ...not fully understood. To elucidate the mechanisms behind cancer‐induced insulin resistance in muscle, we isolated extensor digitorum longus (EDL) and soleus muscles from Lewis Lung Carcinoma tumor‐bearing mice. Three weeks after tumor inoculation, muscles were isolated and stimulated with or without a submaximal dose of insulin (1.5 nM). Glucose transport was measured using 2‐3HDeoxy‐Glucose and intramyocellular signaling was investigated using immunoblotting. In soleus muscles from tumor‐bearing mice, insulin‐stimulated glucose transport was abrogated concomitantly with abolished insulin‐induced TBC1D4 and GSK3 phosphorylation. In EDL, glucose transport and TBC1D4 phosphorylation were not impaired in muscles from tumor‐bearing mice, while AMPK signaling was elevated. Anabolic insulin signaling via phosphorylation of the mTORC1 targets, p70S6K thr389, and ribosomal‐S6 ser235, were decreased by cancer in soleus muscle while increased or unaffected in EDL. In contrast, the mTOR substrate, pULK1 ser757, was reduced in both soleus and EDL by cancer. Hence, cancer causes considerable changes in skeletal muscle insulin signaling that is dependent on muscle‐type, which could contribute to metabolic dysregulation in cancer. Thus, the skeletal muscle could be a target for managing metabolic dysfunction in cancer.
Although N fertilizers are not acidic, their inputs to soil are acid forming. As a result of the long-term use of N fertilizers, soils in the Great Plains are becoming more acidic and this acidity ...may become a yield-limiting factor. In 1970, long-term plots were initiated to compare sources (anhydrous NH3, NH4NO3, urea, and S-coated urea), application rates (34, 68, 136, and 272 kg N ha−1), and an untreated check (0 N) on wheat (Triticum aestivum L.) grain yield, soil pH, exchangeable base cations, and Al saturation. For the soil properties evaluated, significant differences among the different N sources did not exist after 30 annual applications of N fertilizer. The long-term N fertilization significantly reduced soil pH in the surface soil layer (0–15 cm), especially at the higher application levels. Soil pH decreased with time and was significantly related to the amount of total N applied for each N source. Nitrogen fertilization with each N source significantly increased exchangeable Al and Al saturation (Alsat) but decreased exchangeable base cations (Ca2+ and Mg2+). Both exchangeable Al and Alsat increased with increasing N rate and were inversely related to soil pH. Despite decreased soil pH levels to <5.0 as early as 1980 in the experiment, significant reductions of wheat yield did not occur until 1995. Reductions in yield occurring between 1995 and 2002 coincided with the greatest change in soil pH occurring during the same time period.
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