Understanding host-microbe interactions in maize kernel and sweetpotato leaf metagenomic profiles.

Functional and quantitative metagenomic profiling remains challenging and limits our understanding of host-microbe interactions. This body of work aims to mediate these challenges by using a novel quantitative reduced representation sequencing strategy (OmeSeq-qRRS), development of a fully automated software for quantitative metagenomic/microbiome profiling (Qmatey: quantitative metagenomic alignment and taxonomic identification using exact-matching) and implementing these tools for understanding plant-microbe-pathogen interactions in maize and sweetpotato. The next generation sequencing-based OmeSeq-qRRS leverages the strengths of shotgun whole genome sequencing and costs lower that the more affordable amplicon sequencing method. The novel FASTQ data compression/indexing and enhanced-multithreading of the MegaBLAST in Qmatey allows for computational speeds several thousand-folds faster than typical runs. Regardless of sample number, the analytical pipeline can be completed within days for genome-wide sequence data and provides broad-spectrum taxonomic profiling (virus to eukaryotes). As a proof of concept, these protocols and novel analytical pipelines were implemented to characterize the viruses within the leaf microbiome of a sweetpotato population that represents the global genetic diversity and the kernel microbiomes of genetically modified (GMO) and nonGMO maize hybrids. The metagenome profiles and high-density SNP data were integrated to identify host genetic factors (disease resistance and intracellular transport candidate genes) that underpin sweetpotato-virus interactions Additionally, microbial community dynamics were observed in the presence of pathogens, leading to the identification of multipartite interactions that modulate disease severity through co-infection and species competition. This study highlights a low-cost, quantitative and strain/species-level metagenomic profiling approach, new tools that complement the assay’s novel features and provide fast computation, and the potential for advancing functional metagenomic studies

Looking into the dragons of cultural ecosystem services

Cultural ecosystem services research is in a somewhat tumultuous state. The cultural ecosystem services (CES) idea is seen simultaneously as a welcoming, expansive addition to conservation policy-making and as a strange, square-peg-in-a-round-hole concept that should be replaced by a more appropriate metaphor or conceptual structure. This confluence of interest and skepticism suggests an opportune moment to take stock of CES, both as a concept and growing scholarly field. Here, we focus on dilemmas that characterize and constitute CES as a field of empirical inquiry and practice. We describe five tensions that characterize the field (and mirror tensions in interdisciplinary work more broadly): universalism and anti-universalism; reductionism and non-reductionism; historical and ahistorical approaches; politicized and depoliticized approaches; and objectivity and situated knowledges. We then suggest five non-mutually-exclusive roles that CES research can (and does) play: The Convener/Illuminator; the Process Police Officer; the Translator; the Revolutionary; and the Policy In-fighter. We provide examples of each tension and role, and posit that clarity and reflexivity may help to make sense of a fertile, if sometimes confusing, interdisciplinary field. Making more sense of, and being more explicit about, the contradictions and contributions of the CES field, can, we suggest, aid decision-makers, CES researchers, and others to better include these values in environmental management

On Visible Homelessness and the Micro-Aesthetics of Public Space

In this article, we investigate the circumstances that have produced the current municipal regulatory approach to homelessness in the City of Melbourne, Victoria, and the ways in which visibly homeless people are policed through a micro-aesthetics of their presence in public space, which involves the monitoring of their bodily demeanour and their physical possessions. Our study contributes to and draws from a range of debates, including studies of the governmental conjunction of poverty and crime, analysis of the co-implication of law and spatiality, research on the criminalisation of homelessness and homeless people, and the burgeoning criminological interest in the significance of the visual field for our understandings of crime and criminality. This article recounts how homelessness, public space and questions of aesthetics have recently coalesced in debates about the regulation of homelessness in the public space of Melbourne’s city centre. It approaches the issues through comparative consideration of genres of municipal management frameworks in other jurisdictions, detailed textual consideration of the Protocol on Homelessness in the City of Melbourne and an empirical study of visible homelessness in the public places of central Melbourne

More Rapid Increase in BMI from Age 5–15 is Associated with Elevated Weight Status at Age 24 among Non-Hispanic White Females

Background: A rapidly increasing BMI trajectory throughout childhood is associated with negative health outcomes in adulthood such as obesity, cardiovascular disease, and diabetes. The purpose of the current study was to assess whether BMI trajectories from age 5–15 predicted changes in weight and BMI from adolescence to adulthood, and dieting-related behaviors in young adulthood. Methods: Non-Hispanic White female participants from Early Dieting in Girls (n=182), a longitudinal cohort study, were followed from age 5 to 15 and completed a follow-up survey at age 24. Participants were classified by age 5–15 BMI trajectory groups: UPC, accelerated weight gain from age 5–9; DDPC, accelerated weight gain from 5 to 9 followed by a decrease; 60PT, weight tracked along 60th percentile; 50PT, weight tracked along 50th percentile. Data at age 24 included self-reported weight, height, dietary restraint, disinhibition, and dieting. Results: Majority of participants (80.8%) completed the follow-up survey; of these participants, 60% in UPC group had obesity at age 24, compared to\u3c10% in the other 3 groups. Participants in the UPC group had greater increases in BMI since age 15, compared to the 50PT group, and trend-level greater weight increases than those in the DDPC and 60PT groups. Dietary restraint, but not disinhibition, differed across the groups. Conclusions: Children with accelerated weight gain continued to have the greatest weight gain from adolescence to adulthood and the highest prevalence of obesity in adulthood

The metabolic syndrome- associated small G protein ARL15 plays a role in adipocyte differentiation and adiponectin secretion.

Common genetic variants at the ARL15 locus are associated with plasma adiponectin, insulin and HDL cholesterol concentrations, obesity, and coronary atherosclerosis. The ARL15 gene encodes a small GTP-binding protein whose function is currently unknown. In this study adipocyte-autonomous roles for ARL15 were investigated using conditional knockdown of Arl15 in murine 3T3-L1 (pre)adipocytes. Arl15 knockdown in differentiated adipocytes impaired adiponectin secretion but not adipsin secretion or insulin action, while in preadipocytes it impaired adipogenesis. In differentiated adipocytes GFP-tagged ARL15 localized predominantly to the Golgi with lower levels detected at the plasma membrane and intracellular vesicles, suggesting involvement in intracellular trafficking. Sequencing of ARL15 in 375 severely insulin resistant patients identified four rare heterozygous variants, including an early nonsense mutation in a proband with femorogluteal lipodystrophy and non classical congenital adrenal hyperplasia, and an essential splice site mutation in a proband with partial lipodystrophy and a history of childhood yolk sac tumour. No nonsense or essential splice site mutations were found in 2,479 controls, while five such variants were found in the ExAC database. These findings provide evidence that ARL15 plays a role in adipocyte differentiation and adiponectin secretion, and raise the possibility that human ARL15 haploinsufficiency predisposes to lipodystrophy

Accumulation of saturated intramyocellular lipid is associated with insulin resistance.

Intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and insulin-sensitive (athletes) states. Biochemical analysis of intramuscular triglyceride composition is confounded by extramyocellular triglycerides in biopsy samples, and hence the specific composition of IMCLs is unknown in these states. 1H magnetic resonance spectroscopy (MRS) can be used to overcome this problem. Thus, we used a recently validated 1H MRS method to compare the compositional saturation index (CH2:CH3) and concentration independent of the composition (CH3) of IMCLs in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic subjects with that of age- and gender-matched athletes (n = 14) and healthy controls (n = 41). The IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic subjects compared with controls but was similar in athletes and controls. IMCL CH2:CH3 was dependent on the IMCL concentration in the controls and, after adjusting the compositional index for quantity (CH2:CH3adj), could distinguish lipodystrophics from athletes. This CH2:CH3adj marker had a stronger relationship with insulin resistance than IMCL concentration alone and was inversely related to VO2max The association of insulin resistance with the accumulation of saturated IMCLs is consistent with a potential pathogenic role for saturated fat and the reported benefits of exercise and diet in insulin-resistant states

Truncation of POC1A associated with short stature and extreme insulin resistance.

We describe a female proband with primordial dwarfism, skeletal dysplasia, facial dysmorphism, extreme dyslipidaemic insulin resistance and fatty liver associated with a novel homozygous frameshift mutation in POC1A, predicted to affect two of the three protein products of the gene. POC1A encodes a protein associated with centrioles throughout the cell cycle and implicated in both mitotic spindle and primary ciliary function. Three homozygous mutations affecting all isoforms of POC1A have recently been implicated in a similar syndrome of primordial dwarfism, although no detailed metabolic phenotypes were described. Primary cells from the proband we describe exhibited increased centrosome amplification and multipolar spindle formation during mitosis, but showed normal DNA content, arguing against mitotic skipping, cleavage failure or cell fusion. Despite evidence of increased DNA damage in cells with supernumerary centrosomes, no aneuploidy was detected. Extensive centrosome clustering both at mitotic spindles and in primary cilia mitigated the consequences of centrosome amplification, and primary ciliary formation was normal. Although further metabolic studies of patients with POC1A mutations are warranted, we suggest that POC1A may be added to ALMS1 and PCNT as examples of centrosomal or pericentriolar proteins whose dysfunction leads to extreme dyslipidaemic insulin resistance. Further investigation of links between these molecular defects and adipose tissue dysfunction is likely to yield insights into mechanisms of adipose tissue maintenance and regeneration that are critical to metabolic health.This work was supported by the Wellcome Trust [grant numbers WT098498, WT098051,WT095515, and WT091310]; the Medical Research Council [MRC_MC_UU_12012/5]; the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Bioscientifica via http://dx.doi.org/10.1530/JME-15-009

Systematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?

BACKGROUND: Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer. METHODS: Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted. RESULTS: Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95). CONCLUSION: Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers

Intralocus Sexual Conflict Diminishes the Benefits of Sexual Selection

Evolution based on the benefits of acquiring “good genes” in sexual selection is only plausible with the reliable transmission of genetic quality from one generation to the next. Accumulating evidence suggests that sexually antagonistic (SA) genes with opposite effects on Darwinian fitness when expressed in the two different sexes may be common in animals and plants. These SA genes should weaken the potential indirect genetic benefits of sexual selection by reducing the fitness of opposite-sex progeny from high-fitness parents. Here we use hemiclonal analysis in the fruit fly, Drosophila melanogaster, to directly measure the inheritance of fitness across generations, over the entire genome. We show that any potential genetic benefits of sexual selection in this system are not merely weakened, but completely reversed over one generation because high-fitness males produce low-fitness daughters and high-fitness mothers produce low-fitness sons. Moreover, male fitness was not inherited by sons, consistent with both theory and recent evidence connecting this form of SA variation with the X chromosome. This inheritance pattern may help to explain how genetic variation for fitness is sustained despite strong sexual selection, and why the ZW sex chromosome system found in birds and butterflies appears to foster the evolution of extreme secondary sexual characters in males

Influence of practice schedules and attention on skill development and retention

Focus of attention during dual-tasks and practice schedules are important components of motor skill performance and learning; often studied in isolation. The current study required participants to complete a simple key-pressing task under a blocked or random practice schedule. To manipulate attention, participants reported their finger position (i.e., skill-focused attention) or the pitch of an auditory tone (i.e., extraneous attention) while performing two variations of a dual-task key-pressing task. Analyses were conducted at baseline, 10 min and 24 h after acquisition. The results revealed that participants in a blocked schedule, extraneous focus condition had significantly faster movement times during retention compared to a blocked schedule, skill focus condition. Furthermore, greatest improvements from baseline to immediate and delayed retention were evident for an extraneous attention compared to the skill-focused attention, regardless of practice schedule. A discussion of the unique benefits an extraneous focus of attention may have on the learning process during dual-task conditions is presented