bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selecting the best meta-analytic estimator for evidence-based practice: a simulation study
Authors: Doi Suhail A.R. , Furuya-Kanamori Luis 
Published: November 2019

ABSTRACT
Studies included in meta-analysis can produce results that depart from the true population parameter of interest due to systematic and/or random errors. Synthesis of these results in meta-analysis aims to generate an estimate closer to the true population parameter by minimizing these errors across studies. The inverse variance heterogeneity (IVhet), quality effects and random effects models of meta-analysis all attempt to do this, but there remains controversy around the estimator that best achieves this goal of reducing error. In an attempt to answer this question, a simulation study was conducted to compare estimator performance. Five thousand iterations at 10 different levels of heterogeneity were run, with each iteration generating one meta-analysis. The results demonstrate that the IVhet and quality effects estimators, though biased, have the lowest mean squared error. These estimators also achieved a coverage probability at or above the nominal level (95%), whereas the coverage probability under the random effects estimator significantly declined (<80%) as heterogeneity increased despite a similar confidence interval width. Based on our findings, we would recommend the use of the IVhet and quality effects models and a discontinuation of traditional random effects models currently in use for meta-analysis.
Artificial selection finds new hypotheses for the mechanism of Wolbachia-mediated dengue blocking in mosquitoes
Authors: Ford S.A. , Albert I. , Allen S. L. , Chenoweth S. , Jones M. , Koh C. , Sebastian A. , Sigle L.T. , McGraw E.A. 
Published: November 2019

AbstractWolbachia is an intracellular bacterium that blocks virus replication in insects and has been introduced into the mosquito, Aedes aegypti for the biocontrol of arboviruses including dengue, Zika and chikungunya. Despite ongoing research, the mechanism of Wolbachia-mediated virus blocking remains unclear. We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia-mediated dengue blocking. From our results, we hypothesise that Wolbachia may block virus replication by increasing the regeneration rate of mosquito cells via the Notch signalling pathway. We also propose that Wolbachia modulates the host’s transcriptional pausing pathway either to prime the host’s anti-viral response or to directly inhibit viral replication.
Evolutionary Stalling and a Limit on the Power of Natural Selection to Improve a Cellular Module
Authors: Venkataram Sandeep , Monasky Ross , Sikaroodi Shohreh H , Kryazhimskiy Sergey , Kaçar Betül 
Published: November 2019

AbstractCells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here, we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.
Tuning of feedforward control enables stable muscle force-length dynamics after loss of autogenic proprioceptive feedback
Authors: Gordon JC , Holt NC , Biewener AA , Daley MA 
Published: November 2019

AbstractAnimals must integrate feedforward, feedback and intrinsic mechanical control mechanisms to maintain stable locomotion. Recent studies of guinea fowl (Numida meleagris) revealed that the distal leg muscles rapidly modulate force and work output to minimize perturbations in uneven terrain. Here we probe the role of reflexes in the rapid perturbation response of muscle by studying the effects of proprioceptive loss. We induced bilateral loss of autogenic proprioception in the lateral gastrocnemius muscle (LG) using self-reinnervation. We compared ankle kinematics andin vivomuscle dynamics in birds with reinnervated LG and intact LG. Reinnervated and intact muscles exhibit similar force-length dynamics, with rapid changes in work to stabilize running obstacle terrain. Reinnervated LG exhibits 23ms earlier steady-state activation, consistent with feedforward tuning of activation phase to compensate for lost proprioception. Modulation of force duration is impaired in rLG, confirming the role of reflex feedback in regulating force duration in intact muscle.
Dimensional neuroimaging: (Internet) Gaming Disorder symptoms according to the WHO and APA frameworks associate with lower striatal volume
Authors: Zhou Xinqi , Wu Renjing , Liu Congcong , Kou Juan , Chen Yuanshu , Pontes Halley M. , Yao Dezhong , Kendrick Keith M. , Becker Benjamin , Montag Christian 
Published: November 2019

AbstractGrowing concerns about the addictive nature of internet and computer games led to the endorsement of Internet Gaming Disorder (IGD) as an emerging disorder by the American Psychological Association (APA) in 2013 and the recognition of Gaming Disorder (GD) as a new diagnosis by the World Health Organization (WHO) in 2019. While the definition of clear diagnostic criteria for IGD is beneficial for clinicians and those in need of treatment, it may also stigmatize normal behavior. Furthermore, the neurobiological mechanisms underlying IGD symptoms, and whether they resemble those of other addictive disorders remains highly debated. To this end the present study employed a dimensional imaging approach to determine associations between IGD symptom-load according to the APA and WHO diagnostic frameworks and brain structure in a comparably large sample of healthy subjects. It was found that higher symptom-load on psychometric tests assessing the APA and WHO diagnostic frameworks convergently associated with lower volumes of the striatum. The present results suggest for the first time a neurobiological foundation of the proposed diagnostic criteria for IGD according to both diagnostic classification systems, further indicating that the transition from non-disordered to disordered gaming is accompanied by progressive neuroplastic changes in the striatum, thus resembling progressive changes in other addictive disorders.
Mid-Infrared Spectroscopic Analysis of Raw Milk to Predict the Blood Plasma Non-Esterified Fatty Acid Concentration in Dairy Cows
Authors: Aernouts Ben , Adriaens Ines , Diaz-Olivares José , Saeys Wouter , Mäntysaari Päivi , Kokkonen Tuomo , Mehtiö Terhi , Kajava Sari , Lidauer Paula , Lidauer Martin H. , Pastell Matti 
Published: November 2019

ABSTRACTIn high yielding dairy cattle, severe postpartum negative energy status is often associated with metabolic and infectious disorders that negatively affect production, fertility and welfare. Mobilization of adipose tissue associated with a negative energy status is reflected through an increased level of non-esterified fatty acids (NEFA) in the blood plasma. Earlier, identification of a negative energy status through the detection of increased blood plasma NEFA concentration required laborious and stressful blood sampling. More recently there have been attempts to predict blood NEFA concentration from milk samples. This study aimed to develop and validate a model to predict the blood plasma NEFA concentration using milk mid-infrared (MIR) spectra that are routinely measured in the context of milk recording. To this end, blood plasma and milk samples were collected in weeks 2, 3 and 20 post-partum for 192 lactations in 3 different herds. The blood plasma samples were taken in the morning, while representative milk samples were collected during the morning and evening milk session on the same day. To predict the blood plasma NEFA concentration from the milk MIR spectra, partial least squares regression models were trained on part of the observations from the first herd. The models were then thoroughly validated on all other observations of the first herd and on the observations of the two independent herds to explore their robustness and wide applicability. The final model can accurately predict blood plasma NEFA concentrations below 0.6 mmol/L with a root mean square error of prediction (RMSE) of less than 0.143 mmol/L. However, for blood plasma with more than 1.2 mmol/L NEFA, the model clearly underestimates the true level. Additionally, it was found that morning blood plasma NEFA levels were predicted with a significantly higher accuracy (p = 0.009) using MIR spectra of evening milk samples compared to morning samples, with RMSEP values of respectively 0.182 and 0.197 mmol/L and R2 values of 0.613 and 0.502. These results suggest a time delay between variations in blood plasma NEFA and related milk biomarkers. Based on the MIR spectra of evening milk samples, cows at risk for a negative energy status, indicated with detrimental morning blood plasma NEFA levels (> 0.6 mmol/L), could be identified with a sensitivity and specificity of respectively 0.831 and 0.800. As this model can be applied to millions of historical and future milk MIR spectra, it opens opportunities for regular metabolic screening and improved resilience phenotyping.
Cell therapy as a new approach on hepatic fibrosis of murine model ofSchistosoma mansoniinfection
Authors: Muslimah N. ALsulami 
Published: November 2019

AbstractSchistosomiasis is an acute and chronic disease caused by blood flukes (trematode worms) of the genusSchistosoma. Schistosomiasis is disease that are prevalent in or unique to tropical and subtropical regions. Previous studies have shown that the role of bone marrow mesenchymal stem cells (BMSCs) therapy in improvement of hepatic fibrosis. Therefore, the current study was designed to assess the therapeutic role of BMSCs in murine schistosomiasis mansoni. BMSCs derived male mice were intraperitoneal injected into female mice that receivedS. mansonicercariae through subcutaneous route. Mice were divided into four groups: negative control group (noninfected non treated); positive control group (infected non treated); BMSCs treated group; and untreated group. Liver histopathology and immunohistochemically were evaluated. BMSC intraperitoneal injection resulted in a significant reduction in liver collagen, granuloma size, and significant increase in OV-6 expression in the Schistosomiasis treated mice group. There was overall improvement of the pathological changes of the liver. The findings support that BMSCs has a regenerative potential in the histopathology and function of the liver tissue by decreasing liver fibrosis.
14-3-3ζ mediates an alternative, non-thermogenic mechanism to reduce heat loss and improve cold tolerance
Authors: Diallo Kadidia , Dussault Sylvie , Noll Christophe , Lopez Angel F. , Rivard Alain , Carpentier André C. , Lim Gareth E. 
Published: November 2019

SummaryFollowing prolonged cold exposure, adaptive thermogenic pathways are activated to maintain homeothermy, and elevations in body temperature are generally associated with UCP1-dependent and -independent increases in energy expenditure. One of the earliest, identified functions of the molecular scaffold, 14-3-3ζ, was its role in the synthesis of norepinephrine, a key endogenous factor that stimulates thermogenesis. This suggests that 14-3-3ζ may have critical roles in cold-induced thermogenesis. Herein, we report that transgenic over-expression of TAP-14-3-3ζ in mice significantly improved tolerance to prolonged cold. When compared to wildtype controls, TAP mice displayed significantly elevated body temperatures and paradoxical decreases in energy expenditure. No changes in β-adrenergic sensitivity or oxidative metabolism were observed; instead, 14-3-3ζ over-expression significantly decreased thermal conductance via increased peripheral vasoconstriction. These findings suggest 14-3-3ζ mediates alternative, non-thermogenic mechanisms to mitigate heat loss for homeothermy. Our results point to an unexpected role of 14-3-3ζ in the regulation of body temperature.Graphical abstract
When is a control not a control? Reactive microglia occur throughout the control contralateral visual pathway in experimental glaucoma
Authors: Tribble James R , Kokkali Eirini , Otmani Amin , Plastino Flavia , Lardner Emma , Vohra Rupali , Kolko Miriam , André Helder , Morgan James E , Williams Pete A 
Published: November 2019

AbstractPurposeAnimal models show retinal ganglion cell injuries that replicate features of glaucoma and the contralateral eye is commonly used as an internal control. There is significant cross-over of retinal ganglion cell axons from the ipsilateral to the contralateral side at the level of the optic chiasm which may confound findings when damage is restricted to one eye. The effect of unilateral glaucoma on neuroinflammatory damage to the contralateral visual pathway has largely been unexplored.MethodsOcular hypertensive glaucoma was induced unilaterally or bilaterally in the rat and retinal ganglion cell neurodegenerative events were assessed. Neuroinflammation was quantified in the retina, optic nerve head, optic nerve, lateral geniculate nucleus, and superior colliculus by high resolution imaging, and in the retina by flow cytometry and protein arrays.ResultsFollowing ocular hypertensive stress, peripheral monocytes enter the retina, and microglia become reactive. This effect is more marked in animals with bilateral ocular hypertensive glaucoma. In rats where glaucoma was induced unilaterally there was significant microglia activation in the contralateral (control) eye. Microglial activation extended into the optic nerve and terminal visual thalami, where it was similar across hemispheres irrespective of whether ocular hypertension was unilateral or bilateral.ConclusionsThese data suggest that caution is warranted when using the contralateral eye as control in unilateral models of glaucoma.Translational RelevanceUse of a contralateral eye as a control may confound discovery of human relevant mechanism and treatments in animal models. We also identify neuroinflammatory protein responses that warrant further investigation as potential disease modifiable targets.
Persistent deleterious effects of an unstable deleteriousWolbachiainfection
Authors: Ross Perran A. , Axford Jason K. , Callahan Ashley G. , Richardson Kelly M. , Hoffmann Ary A. 
Published: November 2019

AbstractWolbachiaare being used to reduce dengue transmission byAedes aegyptimosquitoes around the world. To date releases have mostly involvedWolbachiastrains with limited fitness effects but strains with larger fitness costs could be used to suppress mosquito populations. However, such infections are expected to evolve towards decreased deleterious effects. Here we investigate potential evolutionary changes in thewMelPop infection transferred fromDrosophila melanogastertoAedes aegyptimore than ten years (~120 generations) ago. We show that most deleterious effects of this infection have persisted despite strong selection to ameliorate them. ThewMelPop infection is difficult to maintain in laboratory colonies, likely due to the persistent deleterious effects coupled with occasional maternal transmission leakage. Furthermore, female mosquitoes can be scored incorrectly as infected due to transmission ofWolbachiathrough mating. Infection loss in colonies was not associated with evolutionary changes in the nuclear background. These findings suggest thatWolbachiatransinfections with deleterious effects may have stable phenotypes which could ensure their long-term effectiveness if released in natural populations to reduce population size.Author summaryMosquitoes infected withWolbachiabacteria are being deployed into the field where they can suppress mosquito populations and reduce dengue transmission. These programs rely on the use ofWolbachiastrains that have desirable phenotypes, which can include deleterious fitness effects, reproductive manipulation and virus blocking. However, theory predicts thatWolbachiawill evolve to become less costly to their hosts, reducing the effectiveness of these programs. We investigate the potential for evolutionary changes by performing a comprehensive phenotypic analysis of a deleteriousWolbachiastrain,wMelPop, that was introduced toAedes aegyptimosquitoes fromDrosophilaover ten years ago. In contrast to theoretical expectations and research fromDrosophila, our results suggest thatWolbachiastrains with deleterious effects may have stable phenotypes, ensuring their long-term effectiveness if released into natural populations.
CORE GREML: Estimating covariance between random effects in linear mixed models for genomic analyses of complex traits
Authors: Zhou Xuan , Im Hae Kyung , Lee S. Hong 
Published: November 2019

AbstractLinear mixed models (LMMs) using genome-based restricted maximum likelihood (GREML) are a key variance partitioning tool, where effects of multiple sources, such as different functional genomic regions, on phenotypes are treated as random. Classic LMMs assume independence between random effects, which can cause biased estimation of variance components. Here, we relax this independence assumption by introducing a generalised GREML, called CORE GREML, that can explicitly estimate the covariance between random effects. Using extensive simulations, we show that CORE GREML outperforms the conventional GREML, providing unbiased estimates of variance and covariance components. Using data from the UK biobank, we demonstrate that CORE GREML is useful for genomic partitioning analyses and for genome-transcriptome partitioning of phenotypic variance. For example, we found that the transcriptome, imputed using genotype data, explained a significant proportion of phenotypic variance for height (0.15, se = 5.4e-3, p-value = 1.5e-283), and that these transcriptomic effects on phenotypes correlated with effects of the genome (r = 0.35, se = 4.6e-2, p-value = 1.2e-14). We conclude that the covariance between random effects is a key parameter that needs to be estimated, especially when partitioning phenotypic variance by omic layer.
Kinship does not predict the structure of a shark social network
Authors: Mourier Johann , Planes Serge 
Published: November 2019

ABSTRACTGenetic relatedness in animal societies is often a factor that drives the structure of social groups. In the marine world, most studies which have investigated this question have focused on marine mammals such as whales and dolphins. For sharks, recent studies have demonstrated preferential associations among individuals from which social communities emerge. Assortment patterns have been found according to phenotypic or behavioural traits but the role of genetic relatedness in shaping the social structure of adult shark populations has, to the best our knowledge, never been investigated. Here, we used a social network analysis crossed with DNA microsatellite genotyping to investigate the role of the genetic relatedness in the social structure of a blacktip reef shark (Carcharhinus melanopterus) population. Based on data from 156 groups of sharks, we used generalized affiliation indices to isolate social preferences from non-social associations, controlling for the contribution of sex, size, gregariousness, spatial and temporal overlap on social associations, to test for the influence of genetic relatedness on social structure. A double permutation procedure was employed to confirm our results and account for issues arising from potentially elevated type I and type II error rates. Kinship was not a predictor of associations and affiliations among sharks at the dyad or community levels as individuals tended to associate independently of the genetic relatedness among them. The lack of parental care in this species may contribute to the breakdown of family links in the population early in life, thereby preventing the formation of kin-based social networks.
The necrotrophic fungusMacrophomina phaseolinainduces oxidative stress-associated genes and related biochemical responses in charcoal rot susceptible sorghum genotypes
Authors: Bandara Ananda Y. , Weerasooriya Dilooshi K. , Liu Sanzhen , Little Christopher R. 
Published: November 2019

ABSTRACTMacrophomina phaseolina(MP) is a necrotrophic fungus that causes charcoal rot disease in sorghum [Sorghum bicolor(L.) Moench]. The host resistance and susceptibility mechanisms for this disease are poorly understood. Here, the transcriptional and biochemical aspects of the oxidative stress and antioxidant system of charcoal rot resistant and susceptible sorghum genotypes in response to MP inoculation were investigated. RNA sequencing revealed 96 differentially expressed genes between resistant (SC599) and susceptible (Tx7000) genotypes that are related to the host oxidative stress and antioxidant system. Follow-up functional experiments demonstrated MP’s ability to significantly increase reactive oxygen (ROS) and nitrogen species (RNS) content in the susceptible genotypes. This was confirmed by increased malondialdehyde content, an indicator of ROS/RNS-mediated lipid peroxidation. The presence of nitric oxide (NO) in stalk tissues of susceptible genotypes was confirmed using a NO-specific fluorescent probe (DAF-FM DA) and visualized by confocal microscopy. Inoculation significantly increased peroxidase activity in susceptible genotypes while catalase activity was significantly higher in MP-inoculated resistant genotypes. MP inoculation significantly reduced superoxide dismutase activity in all genotypes. These findings suggested MP’s ability to promote a host-derived oxidative stress response in susceptible sorghum genotypes, which contributes to induced cell death-associated disease susceptibility to this necrotrophic phytopathogen.