Practices to enhance peer program implementation integrity to safeguard peer leaders and learners

The powerful influence of peers on fellow students’ learning engagement and their ability to foster self-efficacy is well recognised. A positive learner mindset can be fostered through establishment of guided meaningful relationships formed between peers. Recognising the value of peer connections in shaping the student learning experience, peer programs have been widely adopted by universities as a mechanism to facilitate these connections. While potentially beneficial, a lack of knowledge and inexperience by program implementers can lead to program outcomes being compromised. To mitigate this risk, QUT has established university wide systems and benchmarks for enacting peer programs. These measures aim to promote program implementation integrity by supporting and developing the knowledge and capabilities of peer leaders and program coordinators. This paper describes a range of measures that have been instigated to optimise the quality of programs and ensure outcomes are mutually constructive and beneficial for all stakeholders.

Relation between variants in the neurotrophin receptor gene, NTRK3, and white matter integrity in healthy young adults

The NTRK3 gene (also known as TRKC) encodes a high affinity receptor for the neurotrophin 3'-nucleotidase (NT3), which is implicated in oligodendrocyte and myelin development. We previously found that white matter integrity in young adults is related to common variants in genes encoding neurotrophins and their receptors. This underscores the importance of neurotrophins for white matter development. NTRK3 variants are putative risk factors for schizophrenia, bipolar disorder, and obsessive-compulsive disorder hoarding, suggesting that some NTRK3 variants may affect the brain.To test this, we scanned 392 healthy adult twins and their siblings (mean age, 23.6. ±. 2.2. years; range: 20-29. years) with 105-gradient 4-Tesla diffusion tensor imaging (DTI). We identified 18 single nucleotide polymorphisms (SNPs) in the NTRK3 gene that have been associated with neuropsychiatric disorders. We used a multi-SNP model, adjusting for family relatedness, age, and sex, to relate these variants to voxelwise fractional anisotropy (FA) - a DTI measure of white matter integrity.FA was optimally predicted (based on the highest false discovery rate critical p), by five SNPs (rs1017412, rs2114252, rs16941261, rs3784406, and rs7176429; overall FDR critical p=. 0.028). Gene effects were widespread and included the corpus callosum genu and inferior longitudinal fasciculus - regions implicated in several neuropsychiatric disorders and previously associated with other neurotrophin-related genetic variants in an overlapping sample of subjects. NTRK3 genetic variants, and neurotrophins more generally, may influence white matter integrity in brain regions implicated in neuropsychiatric disorders.

Obesity gene NEGR1 associated with white matter integrity in healthy young adults

Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes - NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF- AS, ATXN2L, ATP2A1, KCTD15, and TNN13K - are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30. years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity.

Reducing structural variation to determine the genetics of white matter integrity across hemispheres - a dti study of 100 twins

Studies of cerebral asymmetry can open doors to understanding the functional specialization of each brain hemisphere, and how this is altered in disease. Here we examined hemispheric asymmetries in fiber architecture using diffusion tensor imaging (DTI) in 100 subjects, using high-dimensional fluid warping to disentangle shape differences from measures sensitive to myelination. Confounding effects of purely structural asymmetries were reduced by using co-registered structural images to fluidly warp 3D maps of fiber characteristics (fractional and geodesic anisotropy) to a structurally symmetric minimal deformation template (MDT). We performed a quantitative genetic analysis on 100 subjects to determine whether the sources of the remaining signal asymmetries were primarily genetic or environmental. A twin design was used to identify the heritable features of fiber asymmetry in various regions of interest, to further assist in the discovery of genes influencing brain micro-architecture and brain lateralization. Genetic influences and left/right asymmetries were detected in the fiber architecture of the frontal lobes, with minor differences depending on the choice of registration template.

Predicting white matter integrity from multiple common genetic variants

Several common genetic variants have recently been discovered that appear to influence white matter microstructure, as measured by diffusion tensor imaging (DTI). Each genetic variant explains only a small proportion of the variance in brain microstructure, so we set out to explore their combined effect on the white matter integrity of the corpus callosum. We measured six common candidate single-nucleotide polymorphisms (SNPs) in the COMT, NTRK1, BDNF, ErbB4, CLU, and HFE genes, and investigated their individual and aggregate effects on white matter structure in 395 healthy adult twins and siblings (age: 20-30 years). All subjects were scanned with 4-tesla 94-direction high angular resolution diffusion imaging. When combined using mixed-effects linear regression, a joint model based on five of the candidate SNPs (COMT, NTRK1, ErbB4, CLU, and HFE) explained ∼ 6% of the variance in the average fractional anisotropy (FA) of the corpus callosum. This predictive model had detectable effects on FA at 82% of the corpus callosum voxels, including the genu, body, and splenium. Predicting the brain's fiber microstructure from genotypes may ultimately help in early risk assessment, and eventually, in personalized treatment for neuropsychiatric disorders in which brain integrity and connectivity are affected.

Tensor-based analysis of genetic influences on brain integrity using DTI in 100 twins

Information from the full diffusion tensor (DT) was used to compute voxel-wise genetic contributions to brain fiber microstructure. First, we designed a new multivariate intraclass correlation formula in the log-Euclidean framework. We then analyzed used the full multivariate structure of the tensor in a multivariate version of a voxel-wise maximum-likelihood structural equation model (SEM) that computes the variance contributions in the DTs from genetic (A), common environmental (C) and unique environmental (E) factors. Our algorithm was tested on DT images from 25 identical and 25 fraternal twin pairs. After linear and fluid registration to a mean template, we computed the intraclass correlation and Falconer's heritability statistic for several scalar DT-derived measures and for the full multivariate tensors. Covariance matrices were found from the DTs, and inputted into SEM. Analyzing the full DT enhanced the detection of A and C effects. This approach should empower imaging genetics studies that use DTI.

White matter integrity measured by fractional anisotropy correlates poorly with actual individual fiber anisotropy

Fractional anisotropy (FA), a very widely used measure of fiber integrity based on diffusion tensor imaging (DTI), is a problematic concept as it is influenced by several quantities including the number of dominant fiber directions within each voxel, each fiber's anisotropy, and partial volume effects from neighboring gray matter. High-angular resolution diffusion imaging (HARDI) can resolve more complex diffusion geometries than standard DTI, including fibers crossing or mixing. The tensor distribution function (TDF) can be used to reconstruct multiple underlying fibers per voxel, representing the diffusion profile as a probabilistic mixture of tensors. Here we found that DTIderived mean diffusivity (MD) correlates well with actual individual fiber MD, but DTI-derived FA correlates poorly with actual individual fiber anisotropy, and may be suboptimal when used to detect disease processes that affect myelination. Analysis of the TDFs revealed that almost 40% of voxels in the white matter had more than one dominant fiber present. To more accurately assess fiber integrity in these cases, we here propose the differential diffusivity (DD), which measures the average anisotropy based on all dominant directions in each voxel.

A mitochondrial genome phylogeny of owlet moths (Lepidoptera: Noctuoidea), and examination of the utility of mitochondrial genomes for lepidopteran phylogenetics

A phylogenetic hypothesis for the lepidopteran superfamily Noctuoidea was inferred based on the complete mitochondrial (mt) genomes of 12 species (six newly sequenced). The monophyly of each noctuoid family in the latest classification was well supported. Novel and robust relationships were recovered at the family level, in contrast to previous analyses using nuclear genes. Erebidae was recovered as sister to (Nolidae+(Euteliidae+Noctuidae)), while Notodontidae was sister to all these taxa (the putatively basalmost lineage Oenosandridae was not included). In order to improve phylogenetic resolution using mt genomes, various analytical approaches were tested: Bayesian inference (BI) vs. maximum likelihood (ML), excluding vs. including RNA genes (rRNA or tRNA), and Gblocks treatment. The evolutionary signal within mt genomes had low sensitivity to analytical changes. Inference methods had the most significant influence. Inclusion of tRNAs positively increased the congruence of topologies, while inclusion of rRNAs resulted in a range of phylogenetic relationships varying depending on other analytical factors. The two Gblocks parameter settings had opposite effects on nodal support between the two inference methods. The relaxed parameter (GBRA) resulted in higher support values in BI analyses, while the strict parameter (GBDH) resulted in higher support values in ML analyses.

The first mitochondrial genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997 (Diptera: Sciomyzoidea: Sepsidae), with mitochondrial genome phylogeny of cyclorrhapha

Sepsid flies (Diptera: Sepsidae) are important model insects for sexual selection research. In order to develop mitochondrial (mt) genome data for this significant group, we sequenced the first complete mt genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997. The circular 15,878 bp mt genome is typical of Diptera, containing all 37 genes usually present in bilaterian animals. We discovered inaccurate annotations of fly mt genomes previously deposited on GenBank and thus re-annotated all published mt genomes of Cyclorrhapha. These re-annotations were based on comparative analysis of homologous genes, and provide a statistical analysis of start and stop codon positions. We further detected two 18 bp of conserved intergenic sequences from tRNAGlu-tRNAPhe and ND1-tRNASer(UCN) across Cyclorrhapha, which are the mtTERM binding site motifs. Additionally, we compared automated annotation software MITOS with hand annotation method. Phylogenetic trees based on the mt genome data from Cyclorrhapha were inferred by Maximum-likelihood and Bayesian methods, strongly supported a close relationship between Sepsidae and the Tephritoidea.

The evolutionary history of termites as inferred from 66 mitochondrial genomes

Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.

Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins

Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.

Priority threat management of non-native plants to maintain ecosystem integrity across heterogeneous landscapes

Invasive non-native plants have negatively impacted on biodiversity and ecosystem functions world-wide. Because of the large number of species, their wide distributions and varying degrees of impact, we need a more effective method for prioritizing control strategies for cost-effective investment across heterogeneous landscapes. Here, we develop a prioritization framework that synthesizes scientific data, elicits knowledge from experts and stakeholders to identify control strategies, and appraises the cost-effectiveness of strategies. Our objective was to identify the most cost-effective strategies for reducing the total area dominated by high-impact non-native plants in the Lake Eyre Basin (LEB). We use a case study of the ˜120 million ha Lake Eyre Basin that comprises some of the most distinctive Australian landscapes, including Uluru-Kata Tjuta National Park. More than 240 non-native plant species are recorded in the Lake Eyre Basin, with many predicted to spread, but there are insufficient resources to control all species. Lake Eyre Basin experts identified 12 strategies to control, contain or eradicate non-native species over the next 50 years. The total cost of the proposed Lake Eyre Basin strategies was estimated at AU$1·7 billion, an average of AU$34 million annually. Implementation of these strategies is estimated to reduce non-native plant dominance by 17 million ha – there would be a 32% reduction in the likely area dominated by non-native plants within 50 years if these strategies were implemented. The three most cost-effective strategies were controlling Parkinsonia aculeata, Ziziphus mauritiana and Prosopis spp. These three strategies combined were estimated to cost only 0·01% of total cost of all the strategies, but would provide 20% of the total benefits. Over 50 years, cost-effective spending of AU$2·3 million could eradicate all non-native plant species from the only threatened ecological community within the Lake Eyre Basin, the Great Artesian Basin discharge springs. Synthesis and applications. Our framework, based on a case study of the ˜120 million ha Lake Eyre Basin in Australia, provides a rationale for financially efficient investment in non-native plant management and reveals combinations of strategies that are optimal for different budgets. It also highlights knowledge gaps and incidental findings that could improve effective management of non-native plants, for example addressing the reliability of species distribution data and prevalence of information sharing across states and regions.

Mitochondrial DNA sequence analysis from multiple gene fragments reveals genetic heterogeneity of Crassostrea ariakensis in East Asia

The native Asian oyster, Crassostrea ariakensis is one of the most common and important Crassostrea species that occur naturally along the coast of East Asia. Molecular species diagnosis is a prerequisite for population genetic analysis of wild oyster populations because oyster species cannot be discriminated reliably using external morphological characters alone due to character ambiguity. To date there have been few phylogeographic studies of natural edible oyster populations in East Asia, in particular this is true of the common species in Korea C. ariakensis. We therefore assessed the levels and patterns of molecular genetic variation in East Asian wild populations of C. ariakensis from Korea, Japan, and China using DNA sequence analysis of five concatenated mtDNA regions namely; 16S rRNA, cytochrome oxidase I, cytochrome oxidase II, cytochrome oxidase III, and cytochrome b. Two divergent C. ariakensis clades were identified between southern China and remaining sites from the northern region. In addition, hierarchical AMOVA and pairwise UST analyses showed that genetic diversity was discontinuous among wild populations of C. ariakensis in East Asia. Biogeographical and historical sea level changes are discussed as potential factors that may have influenced the genetic heterogeneity of wild C. ariakensis stocks across this region.

Super DNAging - New insights into DNA integrity, genome stability and telomeres in the oldest old

Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to “averagely” aged humans. These inverse observations in nonagenarians (90–99 years), centenarians (100–109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in “super old” humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in “successful agers”. There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching “super old” age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere shortening.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.