Density-dependence and within-host competition in a semelparous parasite of leaf-cutting ants

BACKGROUND: Parasite heterogeneity and within-host competition are thought to be important factors influencing the dynamics of host-parasite relationships. Yet, while there have been many theoretical investigations of how these factors may act, empirical data is more limited. We investigated the effects of parasite density and heterogeneity on parasite virulence and fitness using four strains of the entomopathogenic fungus, Metarhizium anisopliae var. anisopliae, and its leaf-cutting ant host Acromyrmex echinatior as the model system. RESULTS: The relationship between parasite density and infection was sigmoidal, with there being an invasion threshold for an infection to occur (an Allee effect). Although spore production was positively density-dependent, parasite fitness decreased with increasing parasite density, indicating within-host scramble competition. The dynamics differed little between the four strains tested. In mixed infections of three strains the infection-growth dynamics were unaffected by parasite heterogeneity. CONCLUSIONS: The strength of within-host competition makes dispersal the best strategy for the parasite. Parasite heterogeneity may not have effected virulence or the infection dynamics either because the most virulent strain outcompeted the others, or because the interaction involved scramble competition that was impervious to parasite heterogeneity. The dynamics observed may be common for virulent parasites, such as Metarhizium, that produce aggregated transmission stages. Such parasites make useful models for investigating infection dynamics and the impact of parasite competition

Full production cycle performance of gene-edited, sterile Atlantic salmon - growth, smoltification, welfare indicators and fillet composition

Using germ cell-free (GCF), sterile, dnd-knockout salmon for farming could solve the problems associated with precocious maturation and genetic introgression of farmed breeds into wild populations. However, prior to using GCF fish in the salmon farming industry, it is crucial to understand if, or how, the GCF phenotype differs from wild type (WT) counterparts in terms of growth and welfare. To characterize the GCF phenotype throughout a production cycle, we reared GCF and WT salmon in indoor common garden tanks for 3 years, until harvest size. Regarding body size, smoltification markers (mRNA levels of gill Na+/K+-ATPase [NKA] subunits), plasma stress indicators (pH, glucose, sodium, chloride, calcium), relative heart size, prevalence of vertebra deformities and fillet proximate composition, GCF fish could not be distinguished from WTs. Transient differences were detected in plasma concentrations of lactate and osmolality, and only a few genes were differentially expressed in WT and GCF transcriptomes of muscle and pituitary. At harvest, fillets from GCF and WT salmon contained the same amount of omega-3 fatty acids, however the relative content of omega-3 fatty acids was higher in GCF compared to WT males. Towards harvest size, body growth rate, condition factor and relative liver size were significantly higher in WT than in GCF fish, probably relating to initiation of puberty in WTs. Since GCF salmon never become sexually mature, it is possible to postpone the time of harvest to exploit the growth potential uninhibited by sexual maturation. In conclusion, GCF salmon performed to a large extent similarly to their WT counterparts but had the clear advantage of never maturing.publishedVersio

Impact of Common Variation in Bone-Related Genes on Type 2 Diabetes and Related Traits

Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r2 > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post–oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations

Differential effects of dietary protein sources on postprandial low-grade inflammation after a single high fat meal in obese non-diabetic subjects

<p>Abstract</p> <p>Background</p> <p>Obesity is a state of chronic low-grade inflammation. Chronic low-grade inflammation is associated with the pathophysiology of both type-2 diabetes and atherosclerosis. Prevention or reduction of chronic low-grade inflammation may be advantageous in relation to obesity related co-morbidity. In this study we investigated the acute effect of dietary protein sources on postprandial low-grade inflammatory markers after a high-fat meal in obese non-diabetic subjects.</p> <p>Methods</p> <p>We conducted a randomized, acute clinical intervention study in a crossover design. We supplemented a fat rich mixed meal with one of four dietary proteins - cod protein, whey isolate, gluten or casein. 11 obese non-diabetic subjects (age: 40-68, BMI: 30.3-42.0 kg/m2) participated and blood samples were drawn in the 4 h postprandial period. Adiponectin was estimated by ELISA methods and cytokines were analyzed by multiplex assay.</p> <p>Results</p> <p>MCP-1 and CCL5/RANTES displayed significant postprandial dynamics. CCL5/RANTES initially increased after all meals, but overall CCL5/RANTES incremental area under the curve (iAUC) was significantly lower after the whey meal compared with the cod and casein meals (<it>P </it>= 0.0053). MCP-1 was initially suppressed after all protein meals. However, the iAUC was significantly higher after whey meal compared to the cod and gluten meals (<it>P </it>= 0.04).</p> <p>Conclusion</p> <p>We have demonstrated acute differential effects on postprandial low grade inflammation of four dietary proteins in obese non-diabetic subjects. CCL5/RANTES initially increased after all meals but the smallest overall postprandial increase was observed after the whey meal. MCP-1 was initially suppressed after all 4 protein meals and the whey meal caused the smallest overall postprandial suppression.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00863564">NCT00863564</a></p

Illness management and recovery (IMR) in Danish community mental health centres

<p>Abstract</p> <p>Background</p> <p>Schizophrenia and bipolar disorder are severe mental illnesses that can have a significant disabling impact on the lives of people. Psychosocial interventions that stress hope and recovery as a part of a multi-dimensional approach are possibly indicated to support people with severe mental illness in facilitating recovery. Illness Management and Recovery (IMR) is a curriculum-based psychosocial intervention designed as structured program with a recovery-oriented approach. The aim of IMR is to rehabilitate people with severe mental illnesses by helping them acquire knowledge and skills in managing their illness and achieve personal recovery goals. Previous randomised clinical trials indicate that IMR can be implemented with a good effect and a high fidelity though further trials are crucial to demonstrate the potential effectiveness of IMR.</p> <p>Methods/Design</p> <p>The trial design is a randomised, assessor-blinded, multi-centre, clinical trial of the IMR program compared with treatment as usual for 200 participants diagnosed with schizophrenia or bipolar disorder under the care of two community mental health centres in the Capital Region of Denmark. The primary outcome is level of functioning at the end of treatment. The secondary outcomes are disease symptoms; use of alcohol/drugs; individual meaning of recovery; hope; hospital admissions and out-patient psychiatric treatment at the end of treatment and the abovementioned and level of functioning at follow-up 21 months after baseline.</p> <p>Discussion</p> <p>If the results of this trial show IMR to be effective these positive results will strengthen the evidence of IMR as an effective comprehensive psychosocial intervention with a recovery-oriented approach for people with severe mental illness. This will have significant implications for the treatment and recovery of people with severe mental illness.</p> <p>Trial registration</p> <p>Registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01361698">NCT01361698</a>.</p

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

GxE Interaction Influences Trajectories of Hand Grip Strength

Age-related decline in grip strength predicts later life disability, frailty, lower well-being and cognitive change. While grip strength is heritable, genetic influence on change in grip strength has been relatively ignored, with non-shared environmental influence identified as the primary contributor in a single longitudinal study. The extent to which gene-environment interplay, particularly gene-environment interactions, contributes to grip trajectories has yet to be examined. We considered longitudinal grip strength measurements in seven twin studies of aging in the Interplay of Genes and Environment across Multiple Studies consortium. Growth curve parameters were estimated for same-sex pairs, aged 34–99 (N = 10,681). Fisher’s test for mixture distribution of within-monozygotic twin-pair differences (N = 1724) was performed on growth curve parameters. We observed significant gene-environment interaction on grip strength trajectories. Finally, we compared the variability of within-pair differences of growth curve parameters by APOE haplotypes. Though not statistically significant, the results suggested that APOE ɛ2ɛ2/ɛ2ɛ3 haplotypes might buffer environmental influences on grip strength trajectories.peerReviewe