bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-consistent triple decomposition of the turbulent flow over a backward-facing step under finite amplitude harmonic forcing
Authors: Yim E. , Meliga P. , Gallaire F.
Published: May 2019

We investigate the saturation of harmonically forced disturbances in the turbulent flow over a backward-facing step subjected to a finite amplitude forcing. The analysis relies on a triple decomposition of the unsteady flow into mean, coherent and incoherent components. The coherent–incoherent interaction is lumped into a Reynolds averaged Navier–Stokes (RANS) eddy viscosity model, and the mean–coherent interaction is analysed via a semi-linear resolvent analysis building on the laminar approach by Mantič-Lugo & Gallaire (2016
J. Fluid Mech.
793
, 777–797. (
doi:10.1017/jfm.2016.109
)). This provides a self-consistent modelling of the interaction between all three components, in the sense that the coherent perturbation structures selected by the resolvent analysis are those whose Reynolds stresses force the mean flow in such a way that the mean flow generates exactly the aforementioned perturbations, while also accounting for the effect of the incoherent scale. The model does not require any input from numerical or experimental data, and accurately predicts the saturation of the forced coherent disturbances, as established from comparison to time-averages of unsteady RANS simulation data.
Swelling effects on localized adhesion of an elastic ribbon
Authors: Curatolo M. , Nardinocchi P. , Teresi L. , Holmes D. P.
Published: May 2019

We investigate the adhesion mechanism between an elastic strip of vinylpolysiloxane bent in a racquet-like shape, and a thick elastomeric substrate with the aim to understand how local swelling modifies adhesion. Using a modified loop–tack adhesion test, we place a droplet of silicone oil in between the two materials, vary the dwell time and measure the force required to separate the two interfaces. The experiments are then compared with an analytical model that describes how the critical peel force is modified as the interfacial surface energy changes over time. Our study reveals that in certain circumstances swelling can enhance adhesion. More specifically, strong adhesion is obtained when most of the droplet is absorbed by the solid. By contrast, when the droplet remains at the interface a small adhesive force is measured.
Mutation-rate plasticity and the germline of unicellular organisms
Authors: Aanen Duur K. , Debets Alfons J. M.
Published: May 2019

The mutation rate is a fundamental factor in evolutionary genetics. Recently, mutation rates were found to be strongly reduced at high density in a wide range of unicellular organisms, prokaryotic and eukaryotic. Independently, cell division was found to become more asymmetrical at increasing density in diverse organisms; some ‘mother’ cells continue dividing, while their ‘offspring’ cells do not divide further. Here, we investigate how this increased asymmetry in cell division at high density can be reconciled with reduced mutation-rate estimates. We calculated the expected number of mutant cells due to replication errors under various modes of segregation of template-DNA strands and copy-DNA strands, both under symmetrical (exponential) and asymmetrical (linear) growth. We show that the observed reduction in the mutation rate at high density can be explained if mother cells preferentially retain the template-DNA strands, since new mutations are then confined to non-dividing daughter cells, thus reducing the spread of mutant cells. Any other inheritance mode results in anincreasein the number of mutant cells at higher density. The proposed hypothesis that patterns of DNA-strand segregation are density-dependent fundamentally challenges our current understanding of mutation-rate estimates and extends the distinction between germline and soma to unicellular organisms.
Range-wide spatial mapping reveals convergent character displacement of bird song
Authors: Kirschel Alexander N. G. , Seddon Nathalie , Tobias Joseph A.
Published: May 2019

A long-held view in evolutionary biology is that character displacement generates divergent phenotypes in closely related coexisting species to avoid the costs of hybridization or ecological competition, whereas an alternative possibility is that signals of dominance or aggression may instead converge to facilitate coexistence among ecological competitors. Although this counterintuitive process—termed convergent agonistic character displacement—is supported by recent theoretical and empirical studies, the extent to which it drives spatial patterns of trait evolution at continental scales remains unclear. By modelling the variation in song structure of two ecologically similar species ofHypocnemisantbird across western Amazonia, we show that their territorial signals converge such that trait similarity peaks in the sympatric zone, where intense interspecific territoriality between these taxa has previously been demonstrated. We also use remote sensing data to show that signal convergence is not explained by environmental gradients and is thus unlikely to evolve by sensory drive (i.e. acoustic adaptation to the sound transmission properties of habitats). Our results suggest that agonistic character displacement driven by interspecific competition can generate spatial patterns opposite to those predicted by classic character displacement theory, and highlight the potential role of social selection in shaping geographical variation in signal phenotypes of ecological competitors.
Dissecting human North African gene-flow into its western coastal surroundings
Authors: Arauna Lara R. , Hellenthal Garrett , Comas David
Published: May 2019

North African history and populations have exerted a pivotal influence on surrounding geographical regions, although scant genetic studies have addressed this issue. Our aim is to understand human historical migrations in the coastal surroundings of North Africa. We built a refined genome-wide dataset of North African populations to unearth the fine-scale genetic structure of the region, using haplotype information. The results suggest that the gene-flow from North Africa into the European Mediterranean coast (Tuscany and the Iberian Peninsula) arrived mainly from the Mediterranean coast of North Africa. In Tuscany, this North African admixture date estimate suggests the movement of peoples during the fall of the Roman Empire around the fourth century. In the Iberian Peninsula, the North African component probably reflects the impact of the Arab expansion since the seventh century and the subsequent expansion of the Christian Kingdoms. By contrast, the North African component in the Canary Islands has a source genetically related to present-day people from the Atlantic North African coast. We also find sub-Saharan gene-flow from the Senegambia region in the Canary Islands. Specifically, we detect a complex signal of admixture involving Atlantic, Senegambian and European sources intermixing around the fifteenth century, soon after the Castilian conquest. Our results highlight the differential genetic influence of North Africa into the surrounding coast and show that specific historical events have not only had a socio-cultural impact but additionally modified the gene pool of the populations.
Identification of two new trichome-specific promoters of Nicotiana tabacum
Authors: Pottier Mathieu , Laterre Raphaëlle , Van Wessem Astrid , Ramirez Aldana M. , Herman Xavier , Boutry Marc , Hachez Charles
Published: May 2019

Main conclusion pRbcS-T1 and pMALD1, two new trichome-specific promoters of Nicotiana tabacum, were identified and their strength and specificity were compared to those of previously described promoters in this species.

Nicotiana tabacum has emerged as a suitable host for metabolic engineering of terpenoids and derivatives in tall glandular trichomes, which actively synthesize and secrete specialized metabolites. However, implementation of an entire biosynthetic pathway in glandular trichomes requires the identification of trichome-specific promoters to appropriately drive the expression of the transgenes needed to set up the desired pathway. In this context, RT-qPCR analysis was carried out on wild-type N. tabacum plants to compare the expression pattern and gene expression level of NtRbcS-T1 and NtMALD1, two newly identified genes expressed in glandular trichomes, with those of NtCYP71D16, NtCBTS2α, NtCPS2, and NtLTP1, which were reported in the literature to be specifically expressed in glandular trichomes. We show that NtRbcS-T1 and NtMALD1 are specifically expressed in glandular trichomes like NtCYP71D16, NtCBTS2α, and NtCPS2, while NtLTP1 is also expressed in other leaf tissues as well as in the stem. Transcriptional fusions of each of the six promoters to the GUS-VENUS reporter gene were introduced in N. tabacum by Agrobacterium-mediated transformation. Almost all transgenic lines displayed GUS activity in tall glandular trichomes, indicating that the appropriate cis regulatory elements were included in the selected promoter regions. However, unlike for the other promoters, no trichome-specific line was obtained for pNtLTP1:GUS-VENUS, thus in agreement with the RT-qPCR data. These data thus provide two new transcription promoters that could be used in metabolic engineering of glandular trichomes.
High-speed volumetric fluorescein angiography (vFA) by oblique scanning laser ophthalmoscopy in mouse retina
Authors: Song Weiye , Zhou Libo , Yi Ji
Published: May 2019

Oblique scanning laser ophthalmoscopy (oSLO) is a recently developed technique to provide three-dimensional volumetric fluorescence imaging in retina over a large field of view, without the need for depth sectioning. Here in the paper, we present high-speed volumetric fluorescein angiography (vFA) in mouse retina in vivo by oSLO. By simply using a low-cost industrial CMOS camera, we improved the imaging speed by ~10 times comparing to our previous results, achieving vFA at 2 volumes per second. Enabled by high-speed vFA, we visualized hemodynamics at single capillary level in 3D and provided methods to quantify capillary hematocrit, absolute capillary blood flow speed, and detection of capillary flow stagnancy and stalling. The quantitative metrics for capillary hemodynamics at 3D retinal capillary network can offer valuable insight in vision science and retinal pathologies.
Prevalence of pulmonary tuberculosis among patients presenting with cough of any duration in Addis Ababa, Ethiopia
Authors: Negesse Aynye , Belay Mulugeta , Medhin Girmay , Ayalew Sosina , Mihret Adane , Legesse Mengistu
Published: May 2019

Background

The current practice in Ethiopia to diagnose tuberculosis is screening patients with cough for at least two weeks. A health facility based study was conducted to estimate the prevalence of smear and culture positive pulmonary TB among patients presenting with cough ≥2 weeks and <2 weeks in Addis Ababa, Ethiopia.

Methods

A cross-sectional study design was used to recruit patients with cough of any duration from four selected health centers in Addis Ababa, between August and December 2016. Sputum samples were collected from patients reporting productive cough of any duration and screened for Pulmonary Tuberculosis (PTB) using smear microscopy and culture methods. Mycobacterium tuberculosis isolates obtained from culture positive samples were characterized using RD9 deletion typing.

Results

Majority (39.7%) of the 725 study participants was in the age range of 20-30 years, and 5.0% were smear positive using smear microscopy. The prevalence of smear positive PTB among patients presented with cough duration of ≥2 weeks was significantly higher compared to those patients presented with cough duration of <2 weeks (10.9% versus 0.7%; χ2=38.98; p=0.001). Using culture method, a total of 86 (11.9%) participants were positive for mycobacteria, and the prevalence (14.6%) of PTB among patients presented with cough duration of ≥2 weeks was not significantly higher compared to prevalence (9.9%) in those patients presented with cough duration of <2 weeks (χ2=3.63; p=0.057). Molecular characterization of 86 culture positive mycobacterial isolates showed that 41 were infected with Mtb; 19(46.3%) from those who had cough duration of <2 weeks and 22(53.7%) from those who had cough duration of ≥2 weeks.

Conclusion

Screening of PTB using smear microscopy alone and cough duration of at least two weeks would negatively affect early diagnosis and treatment initiation in a considerable number of PTB patients who reports cough duration of <2 weeks with the potential of contributing to the spread of TB. Therefore, screening of patients with cough of any duration using both smear microscopy and culture methods is likely to contribute to the success of any effort towards the control of TB.
Toggling Geobacter sulfurreducens metabolic state reveals hidden behaviour and expanded applicability to sustainable energy applications
Authors: Zarabadi Mir Pouyan , Charette Steve J. , Greener Jesse
Published: May 2019

Electroactive biofilms are under intense scrutiny due to their potential to enable new sustainable technologies for energy production and bioremediation. However, severely reduced metabolic activity at low concentrations is a barrier to their implementation. A microfluidic approach was used for real-time respiration experiments on a Geobacter sulfurreducens biofilm to overcome these constraints. Precise changes to solution conditions enabled rapid and reversible switching between biofilm metabolic states, leading to the following discoveries. (i) Flow reactors can maintain biofilm activity at concentrations as low as 15 µM; (ii) a “pseudo-active” metabolic state separates active and inactive states; and (iii) acetate conversion can be as high as 90 percent for active biofilms at the pseudo-activity threshold.
The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores
Authors: Wu Zhenyong , Dharan Nadiv , McDargh Zachary A. , Thiyagarajan Sathish , O’Shaughnessy Ben , Karatekin Erdem
Published: May 2019

All membrane fusion reactions proceed through an initial fusion pore, including calcium-triggered release of neurotransmitters and hormones. Expansion of this small pore to release cargo is energetically costly and regulated by cells, but the mechanisms are poorly understood. Here we show that the neuronal/exocytic calcium sensor Synaptotagmin-1 (Syt1) promotes expansion of fusion pores induced by SNARE proteins. Pore dilation relied on calcium-induced insertion of the tandem C2 domain hydrophobic loops of Syt1 into the membrane, previously shown to reorient the C2 domain. Mathematical modelling suggests that C2B reorientation rotates a bound SNARE complex so that it exerts force on the membranes in a mechanical lever action that increases the height of the fusion pore, provoking pore dilation to offset the bending energy penalty. We conclude that Syt1 exerts novel non-local calcium-dependent mechanical forces on fusion pores that dilate pores and assist neurotransmitter and hormone release.

SIGNIFICANCE STATEMENT

During neurotransmitter release, calcium-induced membrane insertion of the C2B domain of Synaptotagmin re-orients the bound SNARE complex which dilates the fusion pore in a mechanical lever action.
The Catalytic Core of DEMETER Guides Active DNA Demethylation in Arabidopsis
Authors: Zhang Changqing , Hung Yu-Hung , Zhang Xiang-Qian , Zhang Dapeng , Frost Jennifer M. , Liu Fang , Xiao Wenyan , Iyer Lakshminarayan M. , Aravind L. , Huh Jin Hoe , Fischer Robert L. , Hsieh Tzung-Fu
Published: May 2019

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization, and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, and how it is recruited to these differing chromatin landscapes is unknown. The C-terminal DME catalytic core consists of three conserved regions required for catalysis in vitro. We show that the catalytic core of DME guides active demethylation at endogenous targets, rescuing the developmental and genomic hypermethylation phenotypes of DME mutants. However, without the N-terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. We used comparative analysis to reveal that the conserved DME N-terminal domains are only present in the flowering plants, whereas the domain architecture of DME-like proteins in non-vascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in all plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N-terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.
Tractostorm: Rater reproducibility assessment in tractography dissection of the pyramidal tract
Authors: Rheault Francois , De Benedictis Alessandro , Daducci Alessandro , Maffei Chiara , Tax Chantal M.W , Romascano David , Caverzasi Eduardo , Morency Felix C. , Corrivetti Francesco , Pestilli Franco , Girard Gabriel , Theaud Guillaume , Zemmoura Ilyess , Hau Janice , Glavin Kelly , Jordan Kesshi M. , Pomiecko Kristofer , Chamberland Maxime , Barakovic Muhamed , Goyette Nil , Poulin Philippe , Chenot Quentin , Panesar Sandip S. , Sarubbo Silvio , Petit Laurent , Descoteaux Maxime
Published: May 2019

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection”. Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. The contribution of this study is to provide the first large-scale, international, multi-center variability assessment of the “virtual dissection” of the pyramidal tract (PyT). Eleven (11) experts and thirteen (13) non-experts in neuroanatomy and “virtual dissection” were asked to perform 30 PyT segmentation and their results were compared using various voxel-wise and streamline-wise measures. Overall the voxel representation is always more reproducible than streamlines (≈70% and ≈35% overlap respectively) and distances between segmentations are also lower for voxel-wise than streamline-wise measures (¾3mm and ¾ûmm respectively). This needs to be seriously considered before using tract-based measures (e.g. bundle volume versus streamline count) for an analysis. We show and argue that future bundle segmentation protocols need to be designed to be more robust to human subjectivity. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction techniques in this era of open and collaborative science.
Developmental exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) selectively decreases brain dopamine levels in northern leopard frogs
Authors: Foguth Rachel M. , Flynn R. Wesley , de Perre Chloe , Iacchetta Michael , Lee Linda S. , Sepúlveda Maria S. , Cannon Jason R.
Published: May 2019

Per- and polyfluoroalkyl substances (PFAS) are synthetic compounds that are a major public health concern due to widespread use, long environmental and biological half-lives, detection in most human plasma samples, and links to multiple adverse health outcomes. The literature suggests that some PFAS may be neurotoxic. However, there are major gaps in the literature with respect to how environmentally-relevant doses during development may influence the nervous system. To address this gap, we utilized a sentinel species, Northern leopard frogs (Lithobates pipiens) to determine the effects of developmental exposure to environmentally relevant perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on major neurotransmitter systems. Frog larvae at Gosner stage 25 were exposed to 10, 100, or 1000 ppb PFOS or PFOA for 30 days before neurochemical analysis. High performance liquid chromatography (HPLC) with electrochemical detection or fluorescent detection assays was used to measure neurotransmitter levels, which were normalized to protein levels in each sample. Dopamine (DA) decreased significantly in the brains of frogs treated with PFOA (1000 ppb) and PFOS (100 and 1000 ppb). Significant increases in DA turnover also resulted from PFOA and PFOS treatment. Neither PFOS, nor PFOA produced detectable alterations in serotonin (nor its metabolite), norepinephrine, gamma-amino butyric acid (GABA), glutamate, or acetylcholine. PFAS body burdens showed that PFOS accumulated relative to dose, while PFOA did not. These data suggest that DArgic neurotransmission is selectively affected in developmentally exposed amphibians and that PFAS should be evaluated for a potential role in diseases that target the DA system.
Comparison of vibrotactile and joint-torque feedback in a myoelectric upper-limb prosthesis
Authors: Thomas Neha , Ung Garrett , McGarvey Colette , Brown Jeremy D.
Published: May 2019

Background

Despite the technological advancements in myoelectric prostheses, body-powered prostheses remain a popular choice for amputees, in part due to the natural sensory advantage they provide. Research on haptic feedback in myoelectric prostheses has delivered mixed results. Furthermore, there is limited research comparing various haptic feedback modalities in myoelectric prostheses. In this paper, we present a comparison of the feedback intrinsically present in body-powered prostheses (joint-torque feedback) to a commonly proposed feedback modality for myoelectric prostheses (vibrotactile feedback). In so doing, we seek to understand whether the advantages of kinesthetic feedback present in body-powered prostheses translate to myoelectric prostheses, and whether there are differences between kinesthetic and cutaneous feedback in prosthetic applications.

Methods

We developed an experimental testbed that features a cable-driven, voluntary-closing 1-DoF prosthesis, a capstan-driven elbow exoskeleton, and a vibrotactile actuation unit. The system can present grip force to users as either a flexion moment about the elbow or vibration on the wrist. To provide an equal comparison of joint-torque and vibrotactile feedback, a stimulus intensity matching scheme was utilized. Non-amputee participants (n=12) were asked to discriminate objects of varying stiffness with the prosthesis in three conditions: no haptic feedback, vibrotactile feedback, and joint-torque feedback.

Results

Results indicate that haptic feedback increased discrimination accuracy over no haptic feedback, but the difference between joint-torque feedback and vibrotactile feedback was not significant. In addition, our results highlight nuanced differences in performance depending on the objects’ stiffness, and suggest that participants likely pay less attention to incidental cues with the addition of haptic feedback.

Conclusion

Even when haptic feedback is not modality matched to the task, such as in the case of vibrotactile feedback, performance with a myoelectric prosthesis can improve significantly. This implies it is possible to achieve the same benefits with vibrotactile feedback, which is cheaper and easier to implement than other forms of feedback.
Direct monitoring of cAMP at the cardiac ryanodine receptor using a novel targeted fluorescence biosensor mouse
Authors: Berisha Filip , Götz Konrad R. , Wegener Jörg W. , Jungen Christiane , Pape Ulrike , Kraft Axel E. , Warnke Svenja , Lindner Diana , Westermann Dirk , Blankenberg Stefan , Meyer Christian , Hasenfuß Gerd , Lehnart Stephan E. , Nikolaev Viacheslav O.
Published: May 2019

Rationale

Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which, upon β-adrenergic receptor (β-AR) stimulation, acts in microdomains to regulate cardiac excitation-contraction coupling by activating the cAMP-dependent protein kinase (PKA) phosphorylation of calcium handling proteins. One crucial microdomain is in vicinity of the cardiac ryanodine receptor type 2 (RyR2) which is associated with arrhythmogenic diastolic calcium leak from the sarcoplasmic reticulum (SR) often occurring upon RyR2 hyperphosphorylation by PKA and calcium/calmodulin-dependent kinase.

Objective

We sought to establish a real time approach capable of directly visualizing cAMP and its pathological changes in the vicinity of RyR2 by generating a proper targeted biosensor and transgenic mouse model to express it in adult cardiomyocytes.

Methods and Results

We generated transgenic mice expressing a novel targeted fluorescent biosensor for RyR2-associated cAMP in adult mouse cardiomyocytes. In healthy cardiomyocytes, β1-AR but not β2-AR stimulation strongly increased local RyR2-associated cAMP levels. However, in cardiac hypertrophy induced by aortic banding, there was a marked subcellular redistribution of phosphodiesterases (PDEs) 2, 3 and 4, which included a dramatic loss of the local pool of PDE4. This was also accompanied by measurable β2-AR-induced cAMP signals, increased SR calcium leak and arrhythmia susceptibility.

Conclusions

Our new targeted biosensor expressed in transgenic mice can visualize cAMP levels in the vicinity of cardiac RyR2 in healthy and diseased cardiomyocytes. In the future, this novel biosensor can be used to better understand alterations of RyR2-associated cAMP in cardiovascular diseases and local actions of new therapies.
The effect of phosphatidylserine on the membrane insertion of the cancer-targeting ATRAM peptide is defined by the non-inserting end
Authors: Nguyen V. P. , Dixson A. C. , Barrera F. N.
Published: May 2019

The acidity-triggered rational membrane (ATRAM) peptide was designed to target acidic diseases such as cancer. An acidic extracellular medium, such as that found in aggressive tumors, drives the protonation of the glutamic acids in ATRAM, leading to the membrane translocation of its C-terminus and the formation of a transmembrane helix. Compared to healthy cells, cancerous cells often increase exposure of the negatively charged phosphatidylserine (PS) on the outer leaflet of the plasma membrane. Here we use a reconstituted vesicle system to explore how phosphatidylserine influences the interaction of ATRAM with membranes. To explore this, we used two new variants of ATRAM, termed K2-ATRAM and Y-ATRAM, with small modifications at the non-inserting N-terminus. We observed that the effect of PS on the membrane insertion pK and lipid partitioning hinged on the sequence of the non-inserting end. Our data additionally indicate that the effect of PS on the insertion pK does not merely depend on electrostatics, but it is multifactorial. Here we show how small sequence changes can impact the interaction of a peptide with membranes of mixed lipid composition. These data illustrate how model studies using neutral bilayers, which do not mimic the negative charge found in the plasma membrane of cancer cells, may fail to capture important aspects of the interaction of anticancer peptides with tumor cells. This information can guide the design of therapeutic peptides that target the acidic environments of different diseased tissues.

Statement of Significance

Current targeted therapies for cancer have limited success due to drug resistance. Resistance often arises after mutation of the receptor being targeted. A more general target is needed to prevent drug resistance. Most aggressive solid tumors have an extracellular medium. We propose that extracellular acidity is promising for improved targeted therapies. The acidity-triggered rational membrane (ATRAM) inserts in membranes only under acidic conditions. However, it is now known how the lipid changes that occur in the plasma membrane of cancer cells impact the membrane insertion of ATRAM. Here we perform biophysical experiments that show that PS, a lipid exposed in the cancer cell, can impact the membrane insertion of ATRAM. We also uncovered a region of the peptide important for insertion.
Genome-scale comparative analysis for host resistance against sea lice between Atlantic salmon and rainbow trout
Authors: Cáceres Pablo , Barría Agustín , Christensen Kris A. , Bassini Liane N. , Correa Katharina , Lhorente Jean P. , Yáñez José M.
Published: May 2019

Sea lice (Caligus rogercresseyi) are ectoparasites that cause major production losses in the salmon aquaculture industry worldwide. Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) are two of the most susceptible salmonid species to sea lice infestation. The goal of this study was to identify common candidate genes involved in resistance against sea lice. For this, 2,626 Atlantic salmon and 2,643 rainbow trout from breeding populations were challenged with sea lice and genotyped with a 50k and 57k SNP panel. We ran two independent genome-wide association studies for sea lice resistance on each species and identified 7 and 13 windows explaining 3% and 2.7% respectively the genetic variance. Heritabilities were observed with values of 0.19 for salmon and 0.08 for trout. We identified genes associated with immune responses, cytoskeletal factors and cell migration. We found 15 orthogroups which allowed us to identifydust8anddust10as candidate genes in orthogroup 13. This suggests that similar mechanisms can regulate resistance in different species; however, they most likely do not share the same standing variation within the genomic regions and genes that regulate resistance. Our results provide further knowledge and may help establish better control for sea lice in fish populations.
Reconstructing Phylogenetic Relationships Based on Repeat Sequence Similarities
Authors: Vitales Daniel , Garcia Sònia , Dodsworth Steven
Published: May 2019

A recent phylogenetic method based on genome-wide abundance of different repeat types proved to be useful in reconstructing the evolutionary history of several plant and animal groups. Here, we demonstrate that an alternative information source from the repeatome can also be employed to infer phylogenetic relationships among taxa. Specifically, this novel approach makes use of the repeat sequence similarity matrices obtained from the comparative clustering analyses of RepeatExplorer 2, which are subsequently transformed to between-taxa distance matrices. These pairwise matrices are used to construct neighbour-joining trees for each of the top most-abundant clusters and they are finally summarized in a consensus network. This methodology was tested on three groups of angiosperms and one group of insects, resulting in congruent evolutionary hypotheses compared to more standard systematic analyses based on commonly used DNA markers. We propose that the combined application of these phylogenetic approaches based on repeat abundances and repeat sequence similarities could be helpful to understand mechanisms governing genome and repeatome evolution.
Introgressed Manihot glaziovii Alleles in Modern Cassava Germplasm Benefit Important Traits and Are Under Balancing Selection
Authors: Wolfe Marnin D. , Bauchet Guillaume J. , Chan Ariel W. , Lozano Roberto , Ramu Punna , Egesi Chiedozie , Kawuki Robert , Kulakow Peter , Rabbi Ismail , Jannink Jean-Luc
Published: May 2019

1.

Introgression of alleles from wild relatives has often been adaptive, usually for disease resistance, in plant breeding. However, the significance of historical hybridization events in modern breeding is often not clear. Cassava (Manihot esculenta) is among the most important staple foods in the world, sustaining hundreds of millions of people in the tropics, especially in sub-Saharan Africa. Widespread genotyping makes cassava a model for clonally-propagated root and tuber crops in the developing world and provides an opportunity to study the modern benefits and consequences of historical introgression. We detected large introgressed M. glaziovii genome-segments in a collection of 2742 modern cassava landraces and elite germplasm, the legacy of 1930’s era breeding to combat epidemics disease. African landraces and improved varieties were on average 3.8% (max 13.6%) introgressed. Introgressions accounted for significant (mean 20%, max 56%) portion of the heritability of tested traits M. glaziovii alleles on the distal 10Mb of chr. 1 increased dry matter and root number. On chr. 4, introgressed alleles in a 20Mb region improved harvest index and brown streak disease tolerance. Three cycles of selection initially doubled the introgression frequency on chr. 1. Later stage variety trials selectively excluded homozygotes which indicates a heterozygous advantage. We show that maintaining large recombination-suppressed introgressions in the heterozygous state allows the accumulation of deleterious mutations. We conclude that targeted recombination of introgression segments would therefore increase the efficiency of cassava breeding by allowing simultaneous fixation of beneficial alleles and purging of genetic load.

Significance Statement

Crosses to wild relatives have often been adaptive for crop breeding, but their modern importance is usually poorly understood. Cassava (Manihot esculenta) is an important staple crop, feeding hundreds of millions in the developing world, and is a model for vegetatively-propagated non-inbred crops. In the 1930’s, crossing to M. glaziovii averted mosaic disease epidemic in Africa. We reveal that large genome segments, the legacy of those crosses, benefit a number of traits including yield in modern cassava and are consistently favored during selection. Elite cultivars are almost exclusively heterozygous for wild alleles; homozygotes are rejected during early stage trials, suggesting inbreeding depression. More recombination around beneficial wild alleles will allow purging of genetic load and increase genetic gain in cassava.
A role for phagocytosis in inducing cell death during thymocyte negative selection
Authors: Kurd Nadia S. , Lutes Lydia K. , Yoon Jaewon , Dzhagalov Ivan L. , Hoover Ashley , Robey Ellen A.
Published: May 2019

Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, we demonstrate that phagocytosis promotes negative selection, and that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a two-step model for negative selection in which thymocytes initiate the death process following strong TCR signaling, but ultimately depend upon phagocytosis for their timely death. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate.
F-actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes
Authors: van Bommel Bas , Konietzny Anja , Kobler Oliver , Bär Julia , Mikhaylova Marina
Published: May 2019

Organelle positioning within neurites is required for proper neuronal function. In dendrites with their complex cytoskeletal organization, transport of organelles is guided by local specializations of the microtubule and actin cytoskeleton, and by coordinated activity of different motor proteins. Here, we focus on the actin cytoskeleton in the dendritic shaft and describe dense structures consisting of longitudinal and branched actin filaments. These actin patches are devoid of microtubules and are frequently located at the base of spines, or form an actin mesh around excitatory shaft synapses. Using lysosomes as an example, we demonstrate that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations. We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin-driven cargo. In addition, we identify myosin Va as an active tether which mediates long-term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.
Are place cells just memory cells? Memory compression leads to spatial tuning and history dependence
Authors: Benna Marcus K. , Fusi Stefano
Published: May 2019

The observation of place cells has suggested that the hippocampus plays a special role in encoding spatial information. However, place cell responses are modulated by several non-spatial variables, and reported to be rather unstable. Here we propose a memory model of the hippocampus that provides a novel interpretation of place cells consistent with these observations. We hypothesize that the hippocampus is a memory device that takes advantage of the correlations between sensory experiences to generate compressed representations of the episodes that are stored in memory. A simple neural network model that can efficiently compress information naturally produces place cells that are similar to those observed in experiments. It predicts that the activity of these cells is variable and that the fluctuations of the place fields encode information about the recent history of sensory experiences. Place cells may simply be a consequence of a memory compression process implemented in the hippocampus.

Significance Statement

Numerous studies on humans revealed the importance of the hippocampus in memory formation. The rodent literature instead focused on the spatial representations that are observed in navigation experiments. Here we propose a simple model of the hippocampus that reconciles the main findings of the human and rodent studies. The model assumes that the hippocampus is a memory system that generates compressed representations of sensory experiences using previously acquired knowledge about the statistics of the world. These experiences can then be memorized more efficiently. The sensory experiences during the exploration of an environment, when compressed by the hippocampus, lead naturally to spatial representations similar to those observed in rodent studies and to the emergence of place cells.
Cell-to-cell Mathematical modeling of arrhythmia phenomena in excitable media
Authors: Garza Gabriel López
Published: May 2019

In this document are modeled arrhythmias with cellular automaton and ordinary differential equations systems. With an aperiodic, self-similar distribution of two-dimensional arrangement of cells, it is possible to simulate such phenomena as fibrillation, fluttering and a sequence of fibrillation-fluttering. The topology of the cytoarchitecture of a network of cells may determine the initiation and development of arrhythmias.
Still moving: The double-drift illusion survives smooth pursuit
Authors: Cavanagh Patrick , Tse Peter U.
Published: May 2019

If a gabor pattern drifts in one direction while its internal texture drifts in the orthogonal direction, observers see a remarkable shift in its perceived direction when it is viewed in the periphery. The reported direction of the double-drift stimulus (also known as the infinite regress and curveball illusions) is some combination of the actual external motion of the gabor envelope and the internal motion of its texture (Tse & Hsieh, 2006). Here we find that if the observers track a fixation point that moves in tandem with the gabor, the illusion is undiminished. The pursuit of the moving fixation spot keeps the gabor roughly fixed at one location on the retina, cancelling its external motion, leaving only the internal motion. The gabor is seen to move in the world at roughly its actual speed as the motion of the eye is discounted at some point to recover velocities in world coordinates (e.g. Wallach, 1959). Our finding indicates that the combination of internal and external motion that produces the double drift illusion must happen after the eye movement signals have been factored into stimulus motions. We also test the double drift effect at various path lengths, durations, and speeds, with both mid-grey and black backgrounds, all with a static fixation. These results confirm that a simple vector combination of the two speeds alone accounts for virtually all the direction shifts on the grey background. On the black background, the illusion is eliminated. These results place constraints on where perceived spatial coordinates arise in the visual processing hierarchy to locations at or beyond where compensation for pursuit eye movements arise, specifically V3A, V6, MSTd, and VIP (e.g., Nau et al, 2018).
Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation
Authors: Behring Jessica B , van der Post Sjoerd , Mooradian Arshag D , Egan Matthew J , Zimmerman Maxwell I , Clements Jenna L. , Bowman Gregory R , Held Jason M
Published: May 2019

Stimulation of receptor tyrosine kinases (RTK) such as EGF locally increase reactive oxygen species (ROS) levels at the plasma membrane that oxidize cysteines in proteins to enhance downstream signaling. Spatial confinement of ROS is an important regulatory mechanism to redox signaling, but it remains unknown why stimulation of different receptor tyrosine kinases (RTKs) at the plasma membrane target distinct sets of downstream proteins. To uncover additional mechanisms specifying which cysteines are redox regulated by EGF stimulation, we performed time-resolved quantification of the oxidation of 4,200 cysteine sites subsequent to EGF stimulation in A431 cells. EGF induces three distinct spatiotemporal patterns of cysteine oxidation in functionally organized protein networks, consistent with the spatial confinement model. Unexpectedly, protein crystal structure analysis and molecular dynamic simulation indicate widespread redox regulation of cryptic cysteines that are only solvent exposed upon changes in protein conformation. Phosphorylation and increased flux of nucleotide substrates serve as two distinct modes by which EGF specifies which cryptic cysteines become solvent exposed and redox regulated. Since proteins structurally regulated by different RTKs or cellular perturbations are largely unique, solvent exposure and redox regulation of cryptic cysteines is an important mechanism contextually delineating redox signaling networks.

Significance Statement

Cellular redox processes are interconnected, but are not in equilibrium. Thus, understanding the redox biology of cells requires a systems-level, rather than reductionist, approach. Factors specifying which cysteines are redox regulated by a stimulus remain poorly characterized but are critical to understanding the fundamental properties of redox signaling networks. Here, we show that EGF stimulation induces oxidation of specific cysteines in 3 distinct spatiotemporal patterns. Redox regulated proteins include many proteins in the EGF pathway as well as many cysteines with known functional importance. Many redox regulated cysteines are cryptic and solvent exposed by changes in protein structure that were induced by EGF treatment. The novel finding that cryptic cysteines are redox regulated has important implications for how redox signaling networks are specified and regulated to minimize crosstalk. In addition, this time-resolved dataset of the redox kinetics of 4,200 cysteine sites is an important resource for others and is an important technological achievement towards systems-level understanding of cellular redox biology.
In vivoInteractions between Myosin XI, Vesicles, and Filamentous Actin Are Fast and Transient
Authors: Bibeau Jeffrey P. , Furt Fabienne , Mousavi S. Iman , Kingsley James L. , Levine Max F. , Tüzel Erkan , Vidali Luis
Published: May 2019

The apical actin cytoskeleton and active membrane trafficking machinery are essential in driving polarized cell growth. To better understand the interactions between myosin XI, vesicles, and actin filamentin vivo, we performed Fluorescence Recovery After Photobleaching (FRAP) and showed that the dynamics of myosin XIa at the tip are actin-dependent and that approximately half of myosin XI is bound to vesicles in the cell. To obtain single particle information, we used Variable Angle Epifluorescence Microscopy (VAEM) inPhyscomitrella patensprotoplasts to demonstrate that myosin XIa and VAMP72-labeled vesicles localize in time and space for periods lasting only a few seconds. Using tracking data with Hidden Markov Modeling (HMM), we showed that myosin XIa and VAMP72-labeled vesicles exhibit short runs of actin-dependent directed transport. We also found that the interaction of myosin XI with vesicles is short lived. Together, this bound fraction, fast off-rate, and short run lengths are expected to be critical for the dynamic oscillations observed at the cell apex, and may be vital for the regulation and recycling of the exocytosis machinery; while simultaneously promoting the vesicle focusing and secretion at the tip, necessary for cell wall expansion.
Matryoshka RNA virus 1: a novel RNA virus associated with Plasmodium parasites in human malaria
Authors: Charon Justine , Grigg Matthew J. , Eden John-Sebastian , Piera Kim A. , William Timothy , Rose Karrie , Davenport Miles P. , Anstey Nicholas M. , Holmes Edward C.
Published: May 2019

Parasites of the genus Plasmodium cause human malaria. Yet nothing is known about the viruses that infect these divergent eukaryotes. We investigated the Plasmodium virome by performing a meta-transcriptomic analysis of blood samples from malaria patients infected with P. vivax, P. falciparum or P. knowlesi. This revealed a novel bi-segmented narna-like RNA virus restricted to P. vivax and named Matryoshka RNA virus 1 (MaRNAV-1) to reflect its “Russian doll” nature: a virus, infecting a parasite, infecting an animal. MaRNAV-1 was abundant in geographically diverse P. vivax from humans and mosquitoes. Notably, a related virus (MaRNAV-2) was identified in Australian birds infected with a Leucocytozoon - eukaryotic parasites that group with Plasmodium in the Apicomplexa subclass hematozoa. This is the first report of a Plasmodium virus. As well as broadening our understanding of the eukaryotic virosphere, the restriction to P. vivax may help understand P. vivax-specific biology in humans and mosquitoes.