Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Data-Limited Population-Status Evaluation of Two Coastal Fishes in Southern Angola Using Recreational Catch Length-Frequency Data

Excessive truncation of a population’s size structure is often identified as an important deleterious effect of exploitation, yet the effect on population persistence of size-structure truncation caused by exploitation is often not quantified due to data limitations. In this study, we estimate changes in eggs per recruit (EPR) using annual length-frequency samples over a 9 year period to assess persistence of the two most important recreational fishes in southern Angola: west coast dusky kob (Argyrosomus coronus) and leerfish (Lichia amia). Using a length- and age-structured model, we improve on an existing method to fit this type of model to length-frequency data and estimate EPR. The objectives of the methodological changes are to add flexibility and robustness to the approach for assessing population status in data-limited situations. Results indicate that dusky kob presents very low levels of EPR (5%-10% of the per recruit reproductive capacity in the absence of fishing) in 2013, whereas large inter-annual variability in leerfish estimates suggest caution must be applied when drawing conclusions about its exploitation status. Using simulated length frequency data with known parameter values, we demonstrate that recruitment decline due to overexploitation leads to overestimation of EPR values. Considering the low levels of EPR estimated for the study species, recruitment limitation is not impossible and true EPR values may be even lower than our estimates. It is, therefore, likely that management action, such as the creation of Marine Protected Areas, is needed to reconstitute the west coast dusky kob population.     

Evaluation of two communication tools,slideshow and theater,to improve participants’ understanding of a clinical trial in the informed consent procedure on Pemba Island,Tanzania

BackgroundClinical trial participants are required to sign an informed consent form (ICF). However, information is lacking on the most effective methods to convey trial relevant information prior to inviting participants to sign the ICF, being particularly pertinent in low-income countries. A previous study on Pemba Island, Tanzania, found that a verbal information session (IS) was significantly better than providing an ICF alone. However, knowledge gaps remained. Building on these findings, we investigated the effect of adding a slideshow or a theater to the IS in the informed consent procedure of an anthelminthic clinical trial.Methodology/principal findingsA total of 604 caregivers were randomized into the control group that only received an ICF (n = 150) or an ICF plus one of three intervention strategies: (i) verbal IS (n = 135), (ii) verbal IS with a slideshow (n = 174) or (iii) verbal IS followed by a theater (n = 145). All modes of information covered the same key messages. Participants’ understanding was assessed using a semi-structured questionnaire. The mean score of caregivers in the control group (ICF only) was 4.41 (standard deviation = 1.47). Caregivers attending the IS alone were more knowledgeable than those in the control group (estimated difference in mean scores: 2.40, 95% confidence interval (CI) 1.95 to 2.86, p < 0.01). However, there was no evidence of an improvement compared to the IS only when participants attended a slideshow (0.09, 95% CI -0.53 to 0.35, p = 0.68) or a theater (0.28, 95% CI -0.27 to 0.82, p = 0.32). Three out of 10 key messages remained largely misunderstood, regardless of the mode of information group.Conclusions/significanceOur study confirmed that, in this setting, an ICF alone was not sufficient to convey clinical trial-related information. An IS was beneficial, however, additional theater and slideshows did not further improve understanding. Future research should explore methods to improve communication between study teams and participants for different key messages, study types and settings.     

Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

The total burden of rare,non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability.     

Impacts of a native parasitic plant on an introduced and a native host species: implications for the control of an invasive weed

Background and Aims: While invasive species may escape from natural enemies in thenew range, the establishment of novel biotic interactions withspecies native to the invaded range can determine their success.Biological control of plant populations can be achieved by manipulationof a species' enemies in the invaded range. Interactions weretherefore investigated between a native parasitic plant andan invasive legume in Mediterranean-type woodlands of SouthAustralia. Methods: The effects of the native stem parasite, Cassytha pubescens,on the introduced host, Cytisus scoparius, and a co-occurringnative host, Leptospermum myrsinoides, were compared. The hypothesisthat the parasitic plant would have a greater impact on theintroduced host than the native host was tested. In a fieldstudy, photosynthesis, growth and survival of hosts and parasitewere examined. Key Results: As predicted, Cassytha had greater impacts on the introducedhost than the native host. Dead Cytisus were associated withdense Cassytha infections but mortality of Leptospermum wasnot correlated with parasite infection. Cassytha infection reducedthe photosynthetic rates of both hosts. Infected Cytisus showedslower recovery of photosystem II efficiency, lower transpirationrates and reduced photosynthetic biomass in comparison withuninfected plants. Parasite photosynthetic rates and growthrates were higher when growing on the introduced host Cytisus,than on Leptospermum. Conclusions: Infection by a native parasitic plant had strong negative effectson the physiology and above-ground biomass allocation of anintroduced species and was correlated with increased plant mortality.The greater impact of the parasite on the introduced host maybe due to either the greater resources that this host providesor increased resistance to infection by the native host. Thisdisparity of effects between introduced host and native hostindicates the potential for Cassytha to be exploited as a controltool.