bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences of attentional networks function in athletes from open-skill sports: an functional near-infrared spectroscopy study
Authors: Yu Miao , Liu Yi Bing , Yang Guang
Published: September 2019

Objective

The purpose of this study was to investigate the attentional networks function characteristics of interceptive and strategic sports athletes from open-skill sports.

Methods

We used a revised lateralized attention network task to measure attentional networks efficiency and activation related to flanker conflict effects, alerting effects, and orienting effects changes on the right frontoparietal network using functional near-infrared spectroscopy in 20 strategic sports athletes, 20 interceptive sports athletes, and 22 college students.

Results

The interceptive sports athletes had the fastest overall reaction time. Strategic sports athletes had the highest accuracy and smallest flanker conflict effect on accuracy. Compared with non-athletes, strategic sports athletes had a higher alerting effect, validity effect, and disengaging effect on reaction time; the disengaging effect was particularly higher than that in the interceptive sports athletes. This was accompanied by higher activity in the right frontoparietal network.

Conclusions

The open-skill athletes demonstrate significantly more efficient attentional function compared to non-athletes. Athletes from interceptive sports demonstrated increased speed when solving conflict, while those from strategic sports demonstrated higher accuracy. In addition, top-down control appears to play an important role in strategic sports athletes making a cautious decision. This can be attributed to the right frontoparietal network.
Differential effects of inferior olive lesion on vestibulo-ocular and optokinetic motor learning
Authors: Pham Ngoc Chien , Kim Yong Gyu , Kim Sang Jeong , Kim Chang-Hee
Published: September 2019

The combined operation of optokinetic reflex (OKR) and vestibular-ocular reflex (VOR) is essential for image stability during self-motion. Retinal slip signals, which provide neural substrate for OKR and VOR plasticity, are delivered to the inferior olive. Although it has been assumed that the neural circuitry and mechanisms underlying OKR and VOR plasticity are shared, differential role of the inferior olive in the plasticity of OKR and VOR has not been clearly established. To investigate the differential effect of inferior olive lesion on OKR and VOR plasticity, we examined the change of OKR and VOR gains after gain-up and gain-down VOR training. The results demonstrated that inferior olive-lesion differentially affected cerebellum-dependent motor learning. In control mice, OKR gain increased after both gain-up and gain-down VOR training, and VOR gain increased after gain-up VOR training and decreased after gain-down VOR training. In inferior olive-lesioned mice, OKR gain decreased after both gain-up and gain-down VOR training, and while VOR gain did not significantly change after gain-up VOR training, VOR gain decreased after gain-down VOR training. We suggest that multiple mechanisms of plasticity are differentially involved in VOR and OKR adaptation, and gain-up and gain-down VOR learning rely on different plasticity mechanisms.
Phenotypic integration and modularity drives skull shape divergence in the Arctic fox (
Vulpes lagopus
) from the Commander Islands
Authors: Martín-Serra Alberto , Nanova Olga , Varón-González Ceferino , Ortega Germán , Figueirido Borja
Published: September 2019

Phenotypic integration and modularity influence morphological disparity and evolvability. However, studies addressing how morphological integration and modularity change for long periods of genetic isolation are scarce. Here, we investigate patterns of phenotypic integration and modularity in the skull of phenotypically and genetically distinct populations of the Artic fox (
Vulpes lagopus
) from the Commander Islands of the Aleutian belt (i.e. Bering and Mednyi) that were isolated
ca
10 000 years by ice-free waters of the Bering sea. We use three-dimensional geometric morphometrics to quantify the strength of modularity and integration from inter-individual variation (static) and from fluctuating asymmetry (random developmental variation) in both island populations compared to the mainland population (i.e. Chukotka) and we investigated how changes in morphological integration and modularity affect disparity and the directionality of trait divergence. Our results indicate a decrease in morphological integration concomitant to an increase in disparity at a developmental level, from mainland to the smallest and farthest population of Mednyi. However, phenotypic integration is higher in both island populations accompanied by a reduction in disparity compared to the population of mainland at a static level. This higher integration may have favoured morphological adaptive changes towards specific feeding behaviours related to the extreme environmental settings of islands. Our study demonstrates how shifts in phenotypic integration and modularity can facilitate phenotypic evolvability at the intraspecific level that may lead to lineage divergence at macroevolutioanry scales.
A keeper of many crypts: a behaviour-manipulating parasite attacks a taxonomically diverse array of oak gall wasp species
Authors: Ward Anna K. G. , Khodor Omar S. , Egan Scott P. , Weinersmith Kelly L. , Forbes Andrew A.
Published: September 2019

Parasites of animals and plants can encounter trade-offs between their specificity to any single host and their fitness on alternative hosts. For parasites that manipulate their host's behaviour, the added complexity of that manipulation may further limit the parasite's host range. However, this is rarely tested. The recently described crypt-keeper wasp,
Euderus set
, changes the behaviour of the gall wasp
Bassettia pallida
such that
B. pallida
chews a significantly smaller exit hole in the side of its larval chamber and ‘plugs’ that hole with its head before dying.
Euderus set
benefits from this head plug, as it facilitates the escape of the parasitoid from the crypt after it completes development. Here, we find direct and indirect evidence that
E. set
attacks and manipulates the behaviour of at least six additional gall wasp species, and that these hosts are taxonomically diverse. Interestingly, each of
E. set
's hosts has converged upon similarities in their extended phenotypes: the galls they induce on oaks share characters that may make them vulnerable to attack by
E. set
. The specialization required to behaviourally manipulate hosts may be less important in determining the range of hosts in this parasitoid system than other dimensions of the host–parasitoid interaction, like the host's physical defences.
Functional divergence of bitter taste receptors in a nectar-feeding bird
Authors: Wang Yi , Jiao Hengwu , Jiang Peihua , Zhao Huabin
Published: September 2019

Nectar may contain many secondary metabolites that are commonly toxic and bitter-tasting. It has been hypothesized that such bitter-tasting secondary metabolites might keep the nectar exclusive to only a few pollinators. To test this hypothesis, we examined functional changes of bitter taste receptor genes (
Tas2r
s) in a species of nectar-feeding bird (Anna's hummingbird) by comparing these genes with those from two closely related insect-feeding species (chimney swift and chuck-will's widow). We previously identified a larger number of
Tas2r
s in the hummingbird than in its close insectivorous relatives. In the present study, we demonstrate higher sensitivity and new functions in the hummingbird
Tas2r
gene copies generated by a lineage-specific duplication, which has been shaped by positive selection. These results suggest that the bitter taste may lead to increased sensitivities and specialized abilities of the hummingbird to detect bitter-tasting nectar. Moreover, this study potentially supports the hypothesis that bitter-tasting nectar may have been specialized for some pollinators, thus enforcing plant–pollinator mutualism.
Persistent homology analysis of brain transcriptome data in autism
Authors: Shnier Daniel , Voineagu Mircea A. , Voineagu Irina
Published: September 2019

Persistent homology methods have found applications in the analysis of multiple types of biological data, particularly imaging data or data with a spatial and/or temporal component. However, few studies have assessed the use of persistent homology for the analysis of gene expression data. Here we apply persistent homology methods to investigate the global properties of gene expression in post-mortem brain tissue (cerebral cortex) of individuals with autism spectrum disorders (ASD) and matched controls. We observe a significant difference in the geometry of inter-sample relationships between autism and healthy controls as measured by the sum of the death times of zero-dimensional components and the Euler characteristic. This observation is replicated across two distinct datasets, and we interpret it as evidence for an increased heterogeneity of gene expression in autism. We also assessed the topology of gene-level point clouds and did not observe significant differences between ASD and control transcriptomes, suggesting that the overall transcriptome organization is similar in ASD and healthy cerebral cortex. Overall, our study provides a novel framework for persistent homology analyses of gene expression data for genetically complex disorders.
Gene drives in plants: opportunities and challenges for weed control and engineered resilience
Authors: Barrett Luke G. , Legros Mathieu , Kumaran Nagalingam , Glassop Donna , Raghu S. , Gardiner Donald M.
Published: September 2019

Plant species, populations and communities are under threat from climate change, invasive pathogens, weeds and habitat fragmentation. Despite considerable research effort invested in genome engineering for crop improvement, the development of genetic tools for the management of wild plant populations has rarely been given detailed consideration. Gene drive systems that allow direct genetic management of plant populations via the spread of fitness-altering genetic modifications could be of great utility. However, despite the rapid development of synthetic tools and their enormous promise, little explicit consideration has been given to their application in plants and, to date, they remain untested. This article considers the potential utility of gene drives for the management of wild plant populations, and examines the factors that might influence the design, spread and efficacy of synthetic drives. To gain insight into optimal ways to design and deploy synthetic drive systems, we investigate the diversity of mechanisms underlying natural gene drives and their dynamics within plant populations and species. We also review potential approaches for engineering gene drives and discuss their potential application to plant genomes. We highlight the importance of considering the impact of plant life-history and genetic architecture on the dynamics of drive, investigate the potential for different types of resistance evolution, and touch on the ethical, regulatory and social challenges ahead.
Allometry of mitochondrial efficiency is set by metabolic intensity
Authors: Mélanie Boël , Caroline Romestaing , Yann Voituron , Damien Roussel
Published: September 2019

Metabolic activity sets the rates of individual resource uptake from the environment and resource allocations. For this reason, the relationship with body size has been heavily documented from ecosystems to cells. Until now, most of the studies used the fluxes of oxygen as a proxy of energy output without knowledge of the efficiency of biological systems to convert oxygen into ATP. The aim of this study was to examine the allometry of coupling efficiency (ATP/O) of skeletal muscle mitochondria isolated from 12 mammal species ranging from 6 g to 550 kg. Mitochondrial efficiencies were measured at different steady states of phosphorylation. The efficiencies increased sharply at higher metabolic rates. We have shown that body mass dependence of mitochondrial efficiency depends on metabolic intensity in skeletal muscles of mammals. Mitochondrial efficiency positively depends on body mass when mitochondria are close to the basal metabolic rate; however, the efficiency is independent of body mass at the maximum metabolic rate. As a result, it follows that large mammals exhibit a faster dynamic increase in ATP/O than small species when mitochondria shift from basal to maximal activities. Finally, the invariant value of maximal coupling efficiency across mammal species could partly explain why scaling exponent values are very close to 1 at maximal metabolic rates.
Rotavirus G9P[4], G9P[6] and G1P[6] strains isolated from children with acute gastroenteritis in Pune, western India, 2013–2015: evidence for recombination in genes encoding VP3, VP4 and NSP1
Authors: Tatte Vaishali S. , Maran Deepthy , Walimbe Atul M. , Gopalkrishna Varanasi
Published: September 2019

Species A rotaviruses (RVAs) are genetically diverse pathogens. These are the most evolutionarily adaptable organisms, with a multitude of mechanisms for evolutionary change. To date, full-genome classification has been proved to be an excellent tool for studying the evolution of unusual rotavirus strains. As limited data are available from Pune (Maharashtra), western India, the current study was undertaken with the aim of understanding the genetic diversity in three (G1P[6], G9P[4] and G9P[4])﻿ unusual RVA strains circulating in Pune, India during 2013–2015. Full-genome analysis of these strains classified them as G1-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1, G9-P[4]-I2-R2-C2-[M1-M2_R]-[A1-A2_R]-N2-T2-E6-H2 and G9-[P4-P6_R]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Sequencing and phylogenetic analysis of the structural and non-structural genes of these unusual RVA strains showed nucleotide/amino acid identities of 82.3–98.5 %/77.3–99.8 % and 86.6–97.6 %/89.6–97.8 % between the strains of the study. Evidence of recombination events was found within the genes encoding VP3, VP4 and NSP1, which showed a combination of genetic information for genogroup 1 [M1/P[6]/A1] and genogroup 2 [M2/P[4]/A2] strains. This study will facilitate future investigations into the molecular pathogenesis of such RVAs as the exchange of whole or partial genetic material between rotaviruses through recombination contributes directly to their diversification, adaptation and evolution.
Investigating the added value of biomarkers compared with self-reported smoking in predicting future e-cigarette use: Evidence from a longitudinal UK cohort study
Authors: Khouja Jasmine N. , Munafò Marcus R. , Relton Caroline L. , Taylor Amy E. , Gage Suzanne H. , Richmond Rebecca C.
Published: September 2019

Introduction

Biomarkers can be used to assess smoking behaviour more accurately and objectively than self-report. This study assessed the association between cotinine (a biomarker of smoke exposure) and later e-cigarette use among a population who were unexposed to e-cigarettes in youth.

Methods

Young people in the Avon Longitudinal Study of Parents and Children took part in the study. We observed associations between cotinine at 15 years (measured between 2006 and 2008 before the wide availability of e-cigarettes) and self-reported ever use of e-cigarettes at 22 (measured between 2014 and 2015 when e-cigarettes were widely available) using logistic regression. A range of potential confounders were adjusted for (age, sex, body mass index, alcohol use and passive smoke exposure). Additionally, we adjusted for the young people’s self-reported smoking status/history to explore potential misreporting and measurement error.

Results

In a sample of N=1,194 young people, cotinine levels consistent with active smoking at 15 years were associated with increased odds of e-cigarette ever use at 22 years (Odds Ratio [OR]=7.24, 95% CI 3.29 to 15.93) even when self-reported active smoking status at age 16 (OR=3.14, 95% CI 1.32 to 7.48) and latent classes of smoking behaviour from 14 to 16 (OR=2.70, 95% CI 0.98 to 7.44) were included in the model.

Conclusions

Cotinine levels consistent with smoking in adolescence were strongly associated with increased odds of later e-cigarette use, even after adjusting for reported smoking behaviour at age 16 and smoking transitions from 14 to 16.
A Genome-Wide Association Study of the Frailty Index Highlights Synaptic Pathways in Aging
Authors: Atkins Janice L , Jylhävä Juulia , Pedersen Nancy L , Magnusson Patrik K , Lu Yi , Wang Yunzhang , Hägg Sara , Melzer David , Williams Dylan M , Pilling Luke C
Published: September 2019

Frailty is a common geriatric syndrome, strongly associated with disability, mortality and hospitalisation. The mechanisms underlying frailty are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 19 and 45%. Understanding the genetic determinants and biological mechanisms underpinning frailty may help to delay or even prevent frailty. We performed a genome-wide association study (GWAS) of a frailty index (FI) in European descent participants from UK Biobank (n=164,610, aged 60-70 years). FI calculation was based on 49 self-reported items on symptoms, disabilities and diagnosed diseases. We identified 26 independent genetic signals at 24 loci associated with the FI (p<5*10−8). Many of these loci have previously been associated with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, three appear to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 14% (0.14, SE 0.006). A genetic risk score for the FI, derived solely from the UK Biobank data, was significantly associated with FI in the Swedish TwinGene study (n=10,616, beta: 0.11, 95% CI: 0.02-0.20, p=0.015). In pathway analysis, genes associated with synapse function were significantly enriched (p<3*10−6). We also used Mendelian randomization to identify modifiable traits and exposures that may affect the risk of frailty, with a higher educational attainment genetic risk score being associated with a lower risk of frailty. Risk of frailty is influenced by many genetic factors, including well-known disease risk factors and mental health, with particular emphasis on synapse maintenance pathways.
Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not cognitive control: converging fMRI evidence from Go-Nogo and Flanker tasks
Authors: Lesage E. , Sutherland M.T. , Ross T.J. , Salmeron B.J. , Stein E.A.
Published: September 2019

ABSTRACT

Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here, we examine the effects of nicotine dependence (trait; smokers versus non-smoking controls), and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of cognitive control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence and pharmacological manipulation. However, effects were driven entirely by conditions that required less cognitive control. When demand for cognitive control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task, or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus, findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.
Range Extension of Cryptonanus agricolai (Didelphimorphia, Didelphidae) and First Record in the Atlantic Forest Core
Authors: Guerra Edú Baptista , Costa Leonora Pires
Published: September 2019

According to the Wallacean shortfall, knowledge about the geographic distribution of most species is still incomplete. Cryptonanus agricolai (Moojen, 1943) is a didelphid marsupial considered Data Deficient by IUCN, since species records are few and sparse. Although little information is available for the species, it is commonly associated with xeric habitats from Caatinga and open formations of the Cerrado in east-central Brazil. Here we report the first records of C. agricolai in the Atlantic Forest core, a new ecoregion of occurrence for the species, based on a recent collected voucher - identified through morphological and molecular analysis - from a Mussununga formation in Reserva Biológica do Córrego do Veado, southeastern Brazil. This record extends the occurrence of the species to more than 1 700 000 km2 and lower its altitudinal range limit to 108 m.

Ampliação da distribuição de Cryptonanus agricolai (Didelphimorphia, Didelphidae) e primeiro registro no centro da Mata Atlântica. De acordo com a Lacuna Wallaceana, o conhecimento sobre a distribuição geográfica da maioria das espécies está incompleto. Cryptonanus agricolai (Moojen, 1943) é um marsupial didelfídeo classificado pela IUCN na categoria Dados Insuficientes, uma vez que os registros existentes são poucos e esparsos. Embora haja pouca informação disponível para tal espécie, ela é comumente associada a habitats xéricos da Caatinga e formações abertas do Cerrado no centro-leste do Brasil. Aqui relatamos os primeiros registros de C. agricolai na Mata Atlântica, notadamente uma nova ecorregião de ocorrência para a espécie, com base em um espécime recentemente coletado – e identificado através de análises morfológicas e moleculares - em formação de Mussununga na Reserva Biológica do Córrego do Veado, sudeste do Brasil. Nossos achados ampliam a ocorrência da espécie para mais de 1 700 000 km2 e estabelece novo limite inferior de altitude para 108 m. Palavras-chave. Corredor Central da Mata Atlântica. Lacuna Wallaceana. Marsupial. Mussununga.
Faces under continuous flash suppression capture attention faster than objects, but without a face evoked steady-state visual potential: Is curvilinearity responsible for the behavioral effect?
Authors: Engell Andrew D. , Quillian Henry
Published: September 2019

Face perception is a vital part of human social interactions. The social value of faces makes their efficient detection evolutionarily advantageous. It has been suggested that this might occur nonconsciously, but experimental results are equivocal thus far. Here, we probe nonconscious face perception using a novel combination of binocular rivalry with continuous flash suppression, and steady-state visually evoked potentials. In the first two experiments, participants viewed either non-face objects, neutral faces (Study 1), or fearful faces (Study 2). Consistent with the hypothesis that faces are processed nonconsciously, we found that faces broke through suppression faster than objects. We did not, however, observe a concomitant face-selective SSVEP. Study 3 was run to reconcile this paradox. We hypothesized that the faster breakthrough time was due to a mid-level visual feature, curvilinearity, rather than high-level category membership, which would explain the behavioral difference without neural evidence of face-selective processing. We tested this hypothesis by presenting participants with four different groups of stimuli outside of conscious awareness: rectilinear objects (e.g., chessboard), curvilinear objects (e.g., dartboard), faces, and objects that were not dominantly curvilinear or rectilinear. We found that faces and curvilinear objects broke through suppression faster than objects and rectilinear objects. Moreover, there was no difference between faces and curvilinear objects. These results support our hypothesis that the observed behavioral advantage for faces is due to their curvilinearity, rather than category membership.

Highlights

Faces presented outside of awareness do not evoke a steady-state visually evoked potential.

This is true for both neutral and fearful faces.

However, faces do breakthrough interocular suppression faster than objects.

Curvilinear objects breakthrough interocular suppression faster than rectilinear objects.

The breakthrough time advantage for faces over objects is due to their curvilinearity.
Consumption of a Western-style diet modulates the response of the murine gut microbiome to ciprofloxacin
Authors: Cabral Damien J. , Wurster Jenna I. , Korry Benjamin J. , Penumutchu Swathi , Belenky Peter
Published: September 2019

Dietary composition and antibiotic use are known to have major impacts on the structure and function of the gut microbiome, often resulting in dysbiosis. Despite this, little research has been done to explore the role of host diet as a determinant of antibiotic-induced microbiome disruption.

Here, we utilize a multi-omic approach to characterize the impact of Western-style diet consumption on ciprofloxacin-induced changes to gut microbiome community structure and transcriptional activity. We found that mice consuming a Western-style diet experienced a greater expansion ofFirmicutesfollowing ciprofloxacin treatment than those eating a control diet. At the transcriptional level, we found that ciprofloxacin induced a reduction in the abundance of TCA cycle transcripts on both diets, suggesting that carbon metabolism plays a key role in the response of the gut microbiome to this antibiotic. Despite this shared response, we observed extensive differences in the response of the microbiota to ciprofloxacin on each diet. In particular, at the whole-community level we detected an increase in starch degradation, glycolysis, and pyruvate fermentation following antibiotic treatment in mice on the Western diet, which we did not observe in mice on the control diet. Similarly, we observed diet-specific changes in the transcriptional activity of two important commensal bacteria,Akkermansia muciniphilaandBacteroides thetaiotaomicron, involving diverse cellular processes such as nutrient acquisition, stress responses, and capsular polysaccharide (CPS) biosynthesis. These findings demonstrate that host diet plays a key role in determining the extent of disruption of microbiome composition and function induced by antibiotic treatment.

Importance

While both diet and antibiotics are individually known to have profound impacts on gut microbiome composition, little work has been done to examine the effect of these two factors combined. A number of negative health outcomes, including diabetes and obesity, are associated with diets high in simple sugars in fats but low in host-indigestible fiber, and some of these outcomes may be mediated by the gut microbiome. Likewise, treatment with broad-spectrum antibiotics and the resulting dysbiosis is associated with many of the same detrimental side effects. Previous work has shown that nutrient availability, as influenced by host diet, plays an important role in determining the extent of antibiotic-induced disruption to the gut microbiome. Due to the growing incidence of disorders related to antibiotic-induced dysbiosis, it is essential to determine how the prevalence of high fat and sugar “Western”-style diets impacts the response of the microbiome to antibiotics.
Towards a fine-scale population health monitoring system
Authors: Belbin Gillian M , Wenric Stephane , Cullina Sinead , Glicksberg Benjamin S , Moscati Arden , Wojcik Genevieve L , Shemirani Ruhollah , Beckmann Noam D , Cohain Ariella , Sorokin Elena P , Park Danny S , Ambite Jose-Luis , Ellis Steve , Auton Adam ,   CBIPM Genomics Team,   CBIPM Genomics Team,   Regeneron Genetics Center, Bottinger Erwin P. , Cho Judy H , Loos Ruth JF , Abul-husn Noura S , Zaitlen Noah A , Gignoux Christopher R , Kenny Eimear E
Published: September 2019

Understanding population health disparities is an essential component of equitable precision health efforts. Epidemiology research often relies on definitions of race and ethnicity, but these population labels may not adequately capture disease burdens specific to sub-populations. Here we propose a framework for repurposing data from Electronic Health Records (EHRs) in concert with genomic data to explore enrichment of disease within sub-populations. Using data from a diverse biobank in New York City, we genetically identified 17 sub-populations, and noted the presence of genetic founder effects in 7. By then linking community membership to the EHR, we were able to identify over 600 health outcomes that were statistically enriched within a specific population, with many representing known associations, and many others being novel. This work reinforces the utility of linking genomic data to EHRs, and provides a framework towards fine-scale monitoring of population health.
ProfilingAPOL1Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics
Authors: Liu Esther , Radmanesh Behram , Chung Byungha H. , Donnan Michael D. , Yi Dan , Dadi Amal , Smith Kelly D. , Himmelfarb Jonathan , Li Mingyao , Freedman Benjamin S. , Lin Jennie
Published: September 2019

Background

DNA variants inAPOL1associate with kidney disease, but the pathophysiological mechanisms remain incompletely understood. Model organisms lack theAPOL1gene, limiting the degree to which disease states can be recapitulated. Here we present single-cell RNA sequencing (scRNA-seq) of genome-edited human kidney organoids as a platform for profiling effects ofAPOL1risk variants in diverse nephron cell types.

Methods

We performed footprint-free CRISPR-Cas9 genome editing of human induced pluripotent stem cells (iPSCs) to knock inAPOL1high-risk G1 variants at the native genomic locus. iPSCs were differentiated into kidney organoids, treated with vehicle, IFN-γ, or the combination of IFN-γ and tunicamycin, and analyzed with scRNA-seq to profile cell-specific changes in differential gene expression patterns, compared to isogenic G0 controls.

Results

Both G0 and G1 iPSCs differentiated into kidney organoids containing nephron-like structures with glomerular epithelial cells, proximal tubules, distal tubules, and endothelial cells. Organoids expressed detectableAPOL1only after exposure to IFN-γ. scRNA-seq revealed cell type-specific differences in G1 organoid response toAPOL1induction. Additional stress of tunicamycin exposure led to increased glomerular epithelial cell dedifferentiation in G1 organoids.

Conclusions

Single-cell transcriptomic profiling of human genome-edited kidney organoids expressingAPOL1risk variants provides a novel platform for studying the pathophysiology of APOL1-mediated kidney disease.

SIGNIFICANCE STATEMENT

Gaps persist in our mechanistic understanding of APOL1-mediated kidney disease. The authors apply genome-edited human kidney organoids, combined with single-cell transcriptomics, to profileAPOL1risk variants at the native genomic locus in different cell types. This approach captures interferon-mediated induction ofAPOL1gene expression and reveals cellular dedifferentiation after a secondary insult of endoplasmic reticulum stress. This system provides a human cellular platform to interrogate complex mechanisms and human-specific regulators underlying APOL1-mediated kidney disease.
KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction
Authors: Diaz Rebeca , Kronenberg Nils M. , Martinelli Angela , Liehm Philipp , Riches Andrew C. , Gather Malte C. , Paracchini Silvia
Published: September 2019

Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood.

We developed the first cellular knockout model for KIAA0319 via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We found that KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that KIAA0319 depletion reduces the number of podosomes formed by the cells.

Our results suggest an involvement of KIAA0319 in cilia biology and force regulation and show for the first time that podosomes exert highly dynamic, piconewton vertical forces in epithelial cells.
Salivary molecular spectroscopy: a rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment
Authors: Caixeta D.C. , Aguiar E. M. G. , Cardoso-Sousa L. , Coelho L.M.D , Oliveira S.W. , Espindola F.S. , Raniero L , Crosara K.T.B. , Baker M.J. , Siqueira W.L. , Sabino-Silva R.
Published: September 2019

Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and diabetic 6U-treated of insulin (D6U) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D6U rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D6U rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm−1and 836 cm−1, respectively. Moreover, 1452 cm−1and 836 cm−1spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R2of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology.
Actin shells control buckling and wrinkling of biomembranes
Authors: Kusters Remy , Simon Camille , Dos Santos Rogério Lopes , Caorsi Valentina , Wu Sangsong , Joanny Jean-Francois , Sens Pierre , Sykes Cecile
Published: September 2019

Global changes of cell shape under mechanical or osmotic external stresses are mostly controlled by the mechanics of the cortical actin cytoskeleton underlying the cell membrane. Some aspects of this process can be recapitulated in vitro on reconstituted actin-and-membrane systems. In this paper, we investigate how the mechanical properties of a branched actin network shell, polymerized at the surface of a liposome, control membrane shape when the volume is reduced. We observe a variety of membrane shapes depending on the actin thickness. Thin shells undergo buckling, characterized by a cup-shape deformation of the membrane that coincides with the one of the actin network. Thick shells produce membrane wrinkles, but do not deform their outer layer. For intermediate micrometerthick shells, wrinkling of the membrane is observed, and the actin layer is slightly deformed. Confronting our experimental results with a theoretical description, we determine the transition between buckling and wrinkling depending on the thickness of the actin shell and the size of the liposome. We thus unveil the generic mechanism by which biomembranes are able to accommodate their shape against mechanical compression, through thickness adaptation of their cortical cytoskeleton.
Azadirachta indica (A. Juss.) reduces circulating Dirofilaria immitis microfilariae in vivo
Authors: Mukherjee Niladri , Joardar Nikhilesh , Mukherjee Suprabhat , Sinha Babu Santi P.
Published: September 2019

The present study enumerates the effectiveness of ethanolic leaf extract of A. indica against circulating microfilariae (mf) of D. immitis in vivo of Canis familiaris. An ethanolic extract was prepared from the leaves of A. indica (EEA) and treated on dogs infected with the filarial nematode Dirofilaria immitis, the causative agent of canine cardiopulmonary dirofilariasis. Before treatment, all the infected dogs were vigilantly supervised for any natural fluctuation of mf count. Two doses; 25 and 50 mg/kg body weight/twice a day; both for 15 days were selected for in vivo tests along with a control group which received an empty capsule during the study period. The highest reduction of circulating mf was counted on day 60, showing mf reduction of 77.9% and 86.7% respectively for the two doses. Thereafter mf density increased with a minor change and maintained reduction of 49.5% and 64.1% on day 180 respectively. Additionally, no appreciable side effects in the treated dogs were recorded as evident from serum toxicity parameter analyses. In conclusion, the ethanolic formulation of A. indica leaves possesses considerable effectiveness against D. immitis in vivo with no toxic modification in the host after exposure. Thus, EEA appears to be a good alternative remedy against heartworm infection in infected dogs.
Escherichia ruysiae sp. nov., isolated from an international traveller
Authors: van der Putten Boas C.L. , Matamoros S. , Mende D.R. ,   COMBAT consortium, Schultsz C.
Published: September 2019

The Escherichia genus comprises four species and at least five lineages currently not assigned to any species, termed ‘Escherichia cryptic clades’. We isolated an Escherichia strain from an international traveller and resolved the complete DNA sequence of the chromosome and an IncI multi-drug resistance plasmid using Illumina and Nanopore whole-genome sequencing (WGS). Strain OPT1704T can be differentiated from existing Escherichia spp. using biochemical (VITEK2) and genomic tests (average nucleotide identity [ANI] and digital DNA:DNA hybridisation [dDDH]). Phylogenetic analysis based on alignment of 16S rRNA sequences and 682 concatenated core genes showed similar results. Our analysis further revealed that strain OPT1704T falls within Escherichia cryptic clade IV, and is closely related to cryptic clade III. Combining our analyses with publicly available WGS data of cryptic clades III and IV from Enterobase confirmed the close relationship between clades III and IV (>96% interclade ANI), warranting assignment of both clades to the same novel species. We propose E. ruysiae sp. nov. as a novel species, encompassing Escherichia cryptic clades III and IV (type strain OPT1704T = NCCB 100732T = NCTC 14359T).

Author notes

The Genbank accession number for the 16S rRNA gene sequence of strain OPT1704T is LR745848. The Genbank accession number for the complete genome sequence of strain OPT1704T is CABVLQ000000000.
PHD3 controls energy homeostasis and exercise capacity
Authors: Yoon Haejin , Spinelli Jessica B. , Zaganjor Elma , Wong Samantha J. , German Natalie J. , Randall Elizabeth C. , Dean Afsah , Clermont Allen , Paulo Joao A. , Garcia Daniel , Li Hao , Agar Nathalie Y. R. , Goodyear Laurie J. , Shaw Reuben J. , Gygi Steven P. , Auwerx Johan , Haigis Marcia C.
Published: September 2019

This manuscript was submitted in error therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
A new biologically active molecular scaffold: crystal structure of 7-(3-hydroxyphenyl)-4-methyl-2H-[1,2,4]triazolo[3,2-c][1,2,4]triazole and selective antiproliferative activity of three isomeric triazolo–triazoles
Authors: Fusco Sandra , Capasso Domenica , Centore Roberto , Di Gaetano Sonia , Parisi Emmanuele
Published: September 2019

A study of three isomeric compounds containing a phenolic moiety attached to the nitrogen-rich triazolo–triazole bicycle is presented. In the three isomers, the phenolic OH group is in the ortho, meta and para positions. The crystal structure analysis of the meta isomer (C10H9N5O) shows that the 2H-tautomer is present in the crystal and that the molecule adopts a substantially planar geometry. However, the conformation found in the crystal is different compared to the monoprotonated cation of the same compound previously investigated in several salts. The packing of the meta isomer is driven by the formation of strong hydrogen bonds and shows the formation of infinite planar ribbons, parallel to a, formed around 21 crystallographic axes. The three isomers were tested against some cancer cell lines and also against normal cell lines. The ortho isomer shows a weak antiproliferative activity, the meta isomer shows significant antiproliferative activity against some cancer lines and no activity against healthy cell lines, and the para isomer is active against all the tested cell lines.
Gaining, maintaining and repairing organisational legitimacy
Authors: Kuruppu Sanjaya C. , Milne Markus J. , Tilt Carol A.
Published: September 2019

Purpose

The purpose of this paper is to examine how legitimacy is gained, maintained or repaired through direct action with salient stakeholders and/or through external reporting, by using a number of empirical case vignettes within a single case study organisation.

Design/methodology/approach

The study investigates a foreign affiliate of a large multinational organisation involved in an environmentally sensitive industry. Data collection included semi-structured interviews with 26 participants, organisational reports and participation in the organisation’s annual environmental management seminar and a stakeholder engagement meeting.

Findings

Four vignettes featuring environmental issues illustrate the complexity of organisational responses. Issue visibility, stakeholder salience and stakeholder interconnectedness influence a company’s action to manage legitimacy. In the short-term, environmental issues which affected salient stakeholders resulted in swift and direct action to protect pragmatic legitimacy, but external reporting did not feature in legitimacy management efforts. Highly visible issues to the public, regulators and the media, however, resulted in direct action together with external reporting to manage wider stakeholder perceptions. External reporting was used superficially, along with a broad suite of communication strategies, to gain legitimacy in the long-term decision about the company’s future in New Zealand.

Research limitations/implications

This paper outlines how episodic encounters to manage strategic legitimacy with salient stakeholders in the short-term are theoretically distinct, but nonetheless linked to continual efforts to maintain institutional legitimacy. Case vignettes highlight how pragmatic legitimacy via dispositional legitimacy can be managed with direct action in the short-term to influence a limited range of salient stakeholders. The way external reporting features in legitimacy management is limited, although this has predominantly been the focus of prior research. Only where an environmental incident damages legitimacy to a larger number of stakeholders is external reporting also used to buttress community support.

Originality/value

The concept of legitimacy is comprehensively applied, linking the strategic and institutional arms of legitimacy and illustrating how episodic actions are taken to manage legitimacy in the short-term with continual efforts to manage legitimacy in the long-term. Stakeholder salience and networks are brought in as novel theoretical extensions to provide a deeper understanding of the interrelationships between these key concepts with a unique case study.
Health behaviors and goal setting among Karen youth
Authors: Danner Christine , Freeman Katie , Friedrichsen Samantha , Brandenburg Dana
Published: September 2019

Purpose

The purpose of this paper is to describe and compare the health behaviors of Karen youth with that of the other subpopulation seen at a Minnesota clinic.

Design/methodology/approach

Demographic information and data on health status, recommended health behaviors and goal-setting patterns were collected via a review of the medical records of patients seen at a family medicine residency clinic in St Paul, Minnesota during a one-year period (July 2015–June 2016). Data were summarized using descriptive statistics. Data on Karen patients were compared with data on other populations.

Findings

The study included 765 youths aged 3–17 years. The Karen youth in the study engaged in recommended health behaviors more frequently than their peers on almost every measure. There were statistically significant differences in the amount of sleep, intake of fruits and vegetables, screen time, number of active days per week and consumption of sugar-sweetened drinks between the Karen and their peers overall. Karen youth also reported consuming fewer sweets and fried or processed food than their peers, and they had lower BMI percentiles than other youth.

Research limitations/implications

The study relied on participant self-report, which is subject to potential inaccuracies in recall and reporting.

Originality/value

To the authors’ knowledge, this is the first study detailing health behaviors of Karen youth in the USA. The findings suggest a window of opportunity to support and empower Karen families to maintain healthy habits in order to prevent the development of chronic disease in this community.
Factors of subjective household economic well-being in transition countries
Authors: Salnikova Daria
Published: September 2019

Purpose

The purpose of this paper is to analyze the relationship between social capital and subjective ranking of household economic well-being in transition countries. The current study tests whether the performance of formal institutions moderates this link.

Design/methodology/approach

The analyses are based on the data from the second wave of the Life in Transition Survey. The measures “generosity of welfare policy (social safety nets)” and “ability of formal institutions to control inflation” were provided by the Bertelsmann Transformation Index Project. The study uses four measures of social capital: trust in family, trust in friends and acquaintances, trust in most people and the number of support sources. To test the hypotheses, the study employs mixed-effects regression models.

Findings

The study indicates a significant positive effect of social capital on subjective household well-being. Formal institutions do not have a significant effect on subjective ranking of household well-being. The evidence on institutions as moderators rejects the substitution effect between formal institutions and social capital. Higher generosity of welfare policy institutions and higher ability of formal institutions to control inflation strengthen the positive effect of particular trust (trust in family and trust in friends and acquaintances) on subjective ranking on the ladder of social standing (subjective ranking of household well-being), which is in line with the “crowding in” theory.

Originality/value

The paper adds on the limited research on transition countries. The paper contributes to the discussion on “crowding in” and “crowding out” effects of formal institutions on social capital.