bluuebunny/crossref_metadata_2025 huggingface dataset:
History modulates early sensory processing of salient distractors
Authors: Adam Kirsten C.S. , Serences John T.
Published: October 2020

To find important objects, we must focus on our goals, ignore distractions, and take our changing environment into account. This is formalized in models of visual search whereby goal-driven, stimulus-driven and history-driven factors are integrated into a priority map that guides attention. Stimulus history robustly influences where attention is allocated even when the physical stimulus is the same: when a salient distractor is repeated over time, it captures attention less effectively. A key open question is how we come to ignore salient distractors when they are repeated. Goal-driven accounts propose that we use an active, expectation-driven mechanism to attenuate the distractor signal (e.g., predictive coding), whereas stimulus-driven accounts propose that the distractor signal is attenuated due to passive changes to neural activity and inter-item competition (e.g., adaptation). To test these competing accounts, we measured item-specific fMRI responses in human visual cortex during a visual search task where trial history was manipulated (colors unpredictably switched or were repeated). Consistent with a stimulus-driven account of history-based distractor suppression, we found that repeated singleton distractors were suppressed starting in V1, and distractor suppression did not increase in later visual areas. In contrast, we observed signatures of goal-driven target enhancement that were absent in V1, increased across visual areas, and were not modulated by stimulus history. Our data suggest that stimulus history does not alter goal-driven expectations, but rather modulates canonically stimulus-driven sensory responses to contribute to a temporally-integrated representation of priority.

Significance Statement

Visual search refers to our ability to find what we are looking for in a cluttered visual world (e.g., finding your keys). To perform visual search, we must integrate information about our goals (e.g., ‘find the red key-chain’), the environment (e.g., salient items capture your attention), and changes to the environment (i.e., stimulus history). Although stimulus history impacts behavior, the neural mechanisms that mediate history-driven effects remain debated. Here, we leveraged fMRI and multivariate analysis techniques to measure history-driven changes to the neural representation of items during visual search. We found that stimulus history influenced the representation of a salient ‘pop-out’ distractor starting in V1, suggesting that stimulus history operates via modulations in early sensory processing rather than goal-driven expectations.
Genomic features underlying the evolutionary transitions ofApibacterto honey bee gut symbionts
Authors: Zhang Wenjun , Zhang Xue , Su Qinzhi , Tang Min , Zheng Hao , Zhou Xin
Published: October 2020

The symbiotic bacteria associated with honey bee gut have likely transformed from a free-living or parasitic lifestyle, through a close evolutionary association with the insect host. However, little is known about the genomic mechanism underlying bacterial transition to exclusive adaptation to the bee gut. Here we compared the genomes of bee gut symbiontsApibacterwith their close relatives living in different lifestyles. We found that despite of general reduction in theApibactergenome, genes involved in amino acid synthesis and monosaccharide detoxification were retained, which were likely beneficial to the host. Interestingly, the microaerobicApibacterspecies have specifically acquired genes encoding for the nitrate respiration (NAR). The NAR system is also conserved in the cohabiting bee microbeSnodgrassella, although with a differed structure. This convergence implies a crucial role of respiratory nitrate reduction for microaerophilic microbiomes to colonize bee gut epithelium. Genes involved in lipid, histidine degradation are substantially lost inApibacter, indicating a transition of the energy source utilization. Particularly, genes involved in the phenylacetate degradation to generate host toxic compounds, as well as other virulence factors were lost, suggesting the loss of pathogenicity. Antibiotic resistance genes were only sporadically distributed amongApibacterspecies, but condensed in their pathogenic relatives, which may be related to the remotely living feature and less exposure to antibiotics of their bee hosts. Collectively, this study advances our understanding of genomic transition underlying specialization in bee gut symbionts.

Importance

Investigations aiming to uncover the genetic determinants underlying the transition to a gut symbiotic lifestyle were scarce. The vertical transmitted honey bee gut symbionts of genusApibacterprovided an rare opportunity to tackle this, as evolving from family Flavobacteriaceae, they had phylogenetic close relatives living various lifestyles. Here, we documented thatApibacterhave both preserved and horizontally acquired host beneficial genes including monosaccharides detoxification that may have seeded a mutualistic relationship with the host. In contrast, multiple virulence factors and antibiotic resistance genes have been lost. Importantly, an highly efficient and genomic well organized respiratory nitrate reduction pathway is conserved across allApibacterspp., as well as in majority ofSnodgrassella, which colonize the same habitat asApibacter, suggesting an crucial role it played in living inside the gut. These findings highlight genomic changes paving ways to the transition to a honey bee gut symbiotic lifestyle.
Tracing and testing the COVID-19 contact chain: cost-benefit tradeoffs
Authors: Kim Jungyeol , Chen Xingran , Bidokhti Shirin Saeedi , Sarkar Saswati
Published: October 2020

Traditional contact tracing for COVID-19 tests the direct contacts of those who test positive even if the contacts do not show any symptom. But, why should the testing stop at direct contacts, and not test secondary, tertiary contacts or even contacts further down? The question arises because by the time an infected individual is tested the infection starting from him may have infected a chain of individuals. One deterrent in testing long chains of individuals right away may be that it substantially increases the testing load, or does it? We investigate the costs and benefits of testing the contact chain of an individual who tests positive. For this investigation, we utilize multiple human contact networks, spanning two real-world data sets of spatio-temporal records of human presence over certain periods of time, as also networks of a classical synthetic variety. Over the diverse set of contact patterns, we discover that testing the contact chain can both substantially reduce over time both the cumulative infection count and the testing load. We consider elements of human behavior that enhance the spread of the disease and lower the efficacy of testing strategies, and show that testing the contact chain enhances the resilience to adverse impacts of these elements. We also discover a phenomenon of diminishing return beyond a threshold value on the depth of the chain to be tested in one go, the threshold then provides the most desirable tradeoff between benefit in terms of reducing the cumulative infection count, enhancing resilience to adverse impacts of human behavior, and cost in terms of increasing the testing load.
Circulating levels of calcitonin gene-related peptide (CGRP) are lower in COVID-19 patients
Authors: Ochoa-Callejero Laura , García-Sanmartín Josune , Villoslada-Blanco Pablo , Íñiguez María , Pérez-Matute Patricia , Brody Rachel , Oteo José A. , Martínez Alfredo
Published: October 2020

Background

To better understand the biology of COVID-19, we have explored the behavior of calcitonin gene-related peptide (CGRP), an angiogenic, vasodilating, and immune modulating peptide, in SARS-CoV-2 positive patients.

Methods

Levels of CGRP in the serum of 57 COVID-19 patients (24 asymptomatic, 23 hospitalized in the general ward, and 10 admitted to the intensive care unit) and healthy donors (n=24) were measured by ELISA. In addition, to better understand the physiological consequences of the observed variations, we investigated by immunofluorescence the distribution of RAMP1, one of the components of the CGRP receptor, in autopsy lung specimens.

Results

CGRP levels greatly decreased in COVID-19 patients (p<0.001) when compared to controls, and there were no significant differences due to disease severity, sex, age, or comorbidities. We found that COVID-19 patients treated with proton pump inhibitors had lower levels of CGRP than other patients not taking this treatment (p=0.001). RAMP1 immunoreactivity was found in smooth muscle cells of large blood vessels and the bronchial tree, and in the airways epithelium. In COVID-19 samples, RAMP1 was also found in proliferating type II pneumocytes, a common finding in these patients.

Conclusions

The lower levels of CGRP should negatively impact the respiratory physiology of COVID-19 patients due to vasoconstriction, improper angiogenesis, less epithelial repair, and faulty immune response. Therefore, restoring CGRP levels in these patients may represent a novel therapeutic approach for COVID-19.
Biomathematical models for genetic diversity analyses in complete genomes of SARS-CoV-2
Authors: Ramos Robson da Silva , Felix Pierre Teodósio , Ramos Venâncio Dallynne Bárbara , Nascimento Filho Cícero Batista do , Paulino Antônio João
Published: October 2020

In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2, publicly available on the National Center for Biotechnology Information (NCBI) platform and from six countries in South America (Brazil, Chile, Peru, Colombia, Uruguay and Venezuela with 16, 11, 1, 1, 1, 7 haplotypes, respectively), all with an extension of 29,906 bp and Phred values ≥ 40. These haplotypes were previously used for phylogenetic analyses, following the alignment protocols of the MEGA X software; where all gaps and unconserved sites were extracted for the construction of phylogenetic trees. The specific methodologies for Paired FSTestimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, were obtained using 20,000 random permutation.
Vulnerability to rumors during the COVID-19 pandemic: Results of a national survey
Authors: En Long Victoria Jane , Koh Wei Shien , Saw Young Ern , Liu Jean CJ
Published: October 2020

Amidst the COVID-19 pandemic, many rumors have emerged. Given prior research linking rumor exposure to mental well-being, we conducted a nation-wide survey to document the base rate of rumor exposure and factors associated with rumor vulnerability. Between March to July 2020, 1237 participants were surveyed on 5 widely-disseminated COVID-19 rumors (that drinking water frequently could be preventive, that eating garlic could be preventive, that the outbreak arose because of bat soup consumption, that the virus was created in an American lab, and that the virus was created in a Chinese lab). For each rumor, participants reported whether they had heard, shared or believed each rumor. Although most participants had been exposed to COVID-19 rumors, few shared or believed these. Sharing behaviors sometimes occurred in the absence of belief; however, education emerged as a protective factor for both sharing and belief. Together, our results suggest that campaigns targeting skills associated with higher education (e.g. epistemology) may prove more effective than counter-rumor messages.

Highlights

Prior studies linked exposure to COVID-19 rumors with poor mental health.

In a community sample, most participants reported having heard rumors.

Few participants shared or believed rumors.

Sharing sometimes occurred in the absence of belief.

More educated individuals believed and shared fewer rumors.
Cardiovascular risk factors are independently associated with COVID-19 mortality: a prospective cohort study
Authors: Collard Didier , Nurmohamed Nick S. , Kaiser Yannick , Reeskamp Laurens F. , Dormans Tom , Moeniralam Hazra , Simsek Suat , Douma Renée A. , Eerens Annet , Reidinga Auke C. , Elbers Paul , Beudel Martijn , Vogt Liffert , Stroes Erik S.G. , van den Born Bert-Jan H.
Published: October 2020

Objectives

Recent reports suggest a high prevalence of hypertension and diabetes in COVID-19 patients, but the role of cardiovascular disease (CVD) risk factors in the clinical course of COVID-19 is unknown. We evaluated the time-to-event relationship between hypertension, dyslipidemia, diabetes, and COVID-19 outcomes.

Design

We analyzed data from the prospective Dutch COVID-PREDICT cohort, an ongoing prospective study of patients admitted for COVID-19 infection.

Setting

Patients from 8 participating hospitals, including two university hospitals from the COVID-PREDICT cohort were included.

Participants

Admitted, adult patients with a positive COVID-19 polymerase chain reaction (PCR) or high suspicion based on CT-imaging of the thorax. Patients were followed for major outcomes during hospitalization. CVD risk factors were established via home medication lists and divided in antihypertensives, lipid lowering therapy, and antidiabetics.

Primary and secondary outcomes measures

The primary outcome was mortality during the first 21 days following admission, secondary outcomes consisted of ICU-admission and ICU-mortality. Kaplan-Meier and Cox-regression analyses were used to determine the association with CVD risk factors.

Results

We included 1604 patients with a mean age of 66±15 of whom 60.5% were men. Antihypertensives, lipid lowering therapy, and antidiabetics were used by 45%, 34.7%, and 22.1% of patients. After adjustment for age and sex, the presence of ≥2 risk factors was associated with increased mortality risk (HR 1.52, 95%CI 1.15-2.02), but not with ICU-admission. Moreover, the use of ≥2 antidiabetics and ≥2 antihypertensives was associated with mortality independent of age and sex with HRs of respectively 2.09 (95%CI 1.55-2.80) and 1.46 (95%CI 1.11-1.91).

Conclusions

The accumulation of hypertension, dyslipidemia and diabetes leads to a stepwise increased risk for short-term mortality in hospitalized COVID-19 patients independent of age and sex. Further studies investigating how these risk factors disproportionately affect COVID-19 patients are warranted.

Strengths and limitations of this study

While previous data reported a high prevalence of CVD risk factors in COVID-19 patients, this study investigated whether diabetes, dyslipidemia and hypertension predict adverse outcomes.

This study is limited by the use of medication as surrogate for cardiovascular risk factors

The causality of the investigated risk factors remains to be addressed in future studies.
Differential inhibition of GABA release from mouse hippocampal interneuron subtypes by the volatile anesthetic isoflurane
Authors: Speigel Iris A. , Hemmings Hugh C.
Published: October 2020

General anesthesia is critical to modern medicine and animal research, but the cellular and molecular actions of general anesthetics on the central nervous system remain poorly understood. Volatile anesthetics such as isoflurane disrupt synaptic transmission and inhibit synaptic vesicle release in a neurotransmitter-selective manner. For example, GABA release from interneurons is less sensitive to isoflurane inhibition than are glutamate or dopamine release. Hippocampal and cortical interneuron subpopulations have diverse neurophysiological and synaptic properties, and their individual subtype-specific responses to isoflurane are unknown. We used live-cell optical imaging of exocytosis using fluorescent biosensors expressed in transgenic mouse hippocampal neuron cultures to delineate interneuron subtype-specific effects of isoflurane on synaptic vesicle exocytosis. We found that a clinically relevant concentration of isoflurane (0.5 mM) differentially modulated action potential-mediated exocytosis from GABAergic interneurons: parvalbumin-expressing interneurons were inhibited to 83.1±11.7% of control, whereas somatostatin-expressing and interneurons glutamatergic neurons were inhibited to 58.6±13.3% and 64.5±8.5% of control, respectively. The role of presynaptic voltage-gated sodium channel (Nav) subtype expression in determining isoflurane sensitivity was probed by overexpression or knockdown of specific Navsubtypes, which have distinct sensitivities to isoflurane and are differentially expressed between glutamatergic and GABAergic neurons. We found that the sensitivity of exocytosis to isoflurane was determined by the relative expression of Nav1.1 (associated with lower sensitivity) and Nav1.6 (associated with higher sensitivity). Thus the selective effects of isoflurane on synaptic vesicle exocytosis from hippocampal interneuron subtypes is determined by synaptic diversity in the relative expression of Nav1.1 and Nav1.6.

Significance statement

The volatile anesthetic isoflurane inhibits hippocampal GABAergic interneuron synaptic vesicle exocytosis with differences in potency between interneuron subtypes. This neuron subtype-specific pharmacology derives in part from synaptic diversity in the expression of presynaptic voltage-gated sodium channels that have different sensitivities to anesthetic modulation of channel function. GABAergic interneurons are generally more resistant to the presynaptic effects of isoflurane owing to predominant Nav1.1 expression, whereas glutamatergic neurons are more sensitive owing to predominant Nav1.6 expression, which supports heterogenous pharmacologic effects on specific neural circuits.
Purification, characterization and influence on membrane properties of the plant-specific sphingolipids GIPC
Authors: Cassim Adiilah Mamode , Navon Yotam , Gao Yu , Decossas Marion , Fouillen Laetitia , Grélard Axelle , Nagano Minoru , Lambert Olivier , Bahammou Delphine , Van Delft Pierre , Maneta-Peyret Lilly , Simon-Plas Françoise , Heux Laurent , Fragneto Giovanna , Mortimer Jenny C. , Deleu Magali , Lins Laurence , Mongrand Sébastien
Published: October 2020

The plant plasma membrane (PM) is an essential barrier between the cell and the external environment. The PM is crucial for signal perception and transmission. It consists of an asymmetrical lipid bilayer made up of three different lipid classes: sphingolipids, sterols and phospholipids. The most abundant sphingolipids in the plant PM are the Glycosyl Inositol Phosphoryl Ceramides (GIPCs), representing up to 40% of total sphingolipids, assumed to be almost exclusively in the outer leaflet of the PM. In this study, we investigated the structure of GIPCs and their role in membrane organization. Since GIPCs are not commercially available, we developed a protocol to extract and isolate GIPC-enriched fractions from eudicots (cauliflower and tobacco) and monocots (leek and rice). Lipidomic analysis confirmed the presence of different long chain bases and fatty acids. The glycan head groups of the different GIPC series from monocots and dicots were analysed by GC-MS showing different sugar moieties. Multiple biophysics tools namely Langmuir monolayer, ζ-Potential, light scattering, neutron reflectivity, solid state2H-NMR and molecular modelling were used to investigate the physical properties of the GIPCs, as well as their interaction with free and conjugated phytosterols. We showed that GIPCs increase the thickness and electronegativity of model membranes, interact differentially with the phytosterols species and regulate the gel-to-fluid phase transition during temperature variations.
Intrusive Experiences In Post-Traumatic Stress Disorder: Treatment Response Induces Changes In The Effective Connectivity of The Anterior Insula
Authors: Leroy Arnaud , Very Etienne , Birmes Philippe , Szaffarczyk Sébastien , Lopes Renaud , Outteryck Olivier , Faure Cécile , Duhem Stéphane , Grandgenèvre Pierre , Warembourg Frédérique , Vaiva Guillaume , Jardri Renaud
Published: October 2020

Background

One of the core features of posttraumatic stress disorder (PTSD) is reexperiencing the trauma. The anterior insula (AI) was proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in reexperiencing trauma, as well as its putative modulation by effective therapy, still need to be specified.

Methods

Thirty PTSD patients were enrolled and exposed to traumatic memory reactivation therapy. Resting-state fMRI scans were acquired before and after treatment. To explore AI directed influences over the rest of the brain, we referred to a mixed-model using pre/post Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of reexperiencing trauma, we investigated how intrusive severity affected: (i) causality maps and (ii) the spatial stability of other intrinsic brain networks.

Results

We observed dynamic changes in AI effective connectivity in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found positively correlated with flashback severity, while reexperiencing was linked with a strongerdefault mode network(DMN) and more unstablecentral executive network(CEN) connectivity.

Conclusion

We showed that directed changes in AI signaling to the DMN and CEN at rest may underlie the degree of intrusive symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.
Axon Diameter Measurements using Diffusion MRI are Infeasible
Authors: Paquette Michael , Eichner Cornelius , Knösche Thomas R. , Anwander Alfred
Published: October 2020

The feasibility of non-invasive axonal diameter quantification with diffusion MRI is a strongly debated topic due to the neuroscientific potential of such information and its relevance for the axonal signal transmission speed. It has been shown that under ideal conditions, the minimal diameter producing detectable signal decay is bigger than most human axons in the brain, even using the strongest currently available MRI systems. We show that resolving the simplest situations including multiple diameters is unfeasible even with diameters much bigger than the diameter limit. Additionally, the recently proposed effective diameter resulting from fitting a single value over a distribution is almost exclusively influenced by the biggest axons. We show how impractical this metric is for comparing different distributions. Overall, axon diameters currently cannot be quantified by diffusion MRI in any relevant way.
Acute treatment with TrkB agonist LM22A-4 confers neuroprotection and preserves myelin integrity in a mouse model of pediatric traumatic brain injury
Authors: Fletcher Jessica L. , Dill Larissa K. , Wood Rhiannon J. , Wang Sharon , Robertson Kate , Murray Simon S. , Zamani Akram , Semple Bridgette D.
Published: October 2020

Young children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on the pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would minimize tissue damage and support functional recovery. We focused on myelinated tracts— the corpus callosum and external capsules—based on recent evidence that TrkB activation potentiates oligodendrocyte remyelination. Male mice at postnatal day 21 received an experimental TBI or sham surgery. Acutely post-injury, extensive cell death, a robust glial response and disruption of compact myelin were evident in the injured brain. TBI or sham mice then received intranasal saline vehicle or LM22A-4 for 14 days. Behavior testing was performed from 4 weeks post-injury, and brains were collected at 5 weeks for histology. TBI mice showed hyperactivity, reduced anxiety-like behavior, and social memory impairments. LM22A-4 ameliorated the abnormal anxiolytic phenotype but had no effect on social memory deficits. Use of spectral confocal reflectance microscopy detected persistent myelin fragmentation in the external capsule of TBI mice at 5 weeks post-injury, which was accompanied by regionally distinct deficits in oligodendrocyte progenitor cells and postmitotic oligodendrocytes, as well as chronic reactive gliosis and atrophy of the corpus callosum and injured external capsule. LM22A-4 treatment ameliorated myelin deficits in the perilesional external capsule, as well as tissue volume loss and the extent of reactive gliosis. However, there was no effect of this TrkB agonist on oligodendroglial populations detected at 5 weeks post-injury. Collectively, our results demonstrate that targeting TrkB immediately after TBI during early life confers neuroprotection and preserves myelin integrity, and this was associated with some improved neurobehavioral outcomes as the pediatric injured brain matures.
The cardiac TRPA1 channel drives calcium-mediated mechano-arrhythmogenesis
Authors: Cameron Breanne A. , Stoyek Matthew R. , Bak Jessi J. , Connolly Michael S. , DeLong Emma A. , Greiner Joachim , Peyronnet Rémi , Kohl Peter , Quinn T Alexander
Published: October 2020

SUMMARY PARAGRAPH

Maintenance of cardiac function involves a regulatory loop in which electrical excitation causes the heart to contract through excitation-contraction coupling (ECC),1and the mechanical state of the heart directly affects its electrical activity through mechano-electric coupling (MEC).2However, in pathological states such as acute ischaemia that alter early or late electro-mechanical coordination (i.e., disturbances in ECC or repolarisation-relaxation coupling, RRC), MEC may contribute to the initiation and / or sustenance of arrhythmias (mechano-arrhythmogenesis).3The molecular identity of specific factor(s) underlying mechano-arrhythmogenesis in acute ischaemia, however, remain undefined.4By rapid stretch of rabbit single left ventricular cardiomyocytes, we show that upon ATP-sensitive potassium channel-induced alterations of RRC, overall vulnerability to mechano-arrhythmogenesis is increased, with mechano-sensitive5–11transient receptor potential kinase ankyrin 1 (TRPA1) channels12acting as the molecular driver through a Ca2+-mediated mechanism. Specifically, TRPA1 activation drives stretch-induced excitation and creates a substrate for self-sustained arrhythmias, which are maintained by increased cytosolic free Ca2+concentration ([Ca2+]i) and spontaneous [Ca2+]ioscillations. This TRPA1-dependent mechano-arrhythmogenesis involves microtubules, and can be prevented by block of TRPA1 or buffering of [Ca2+]i. Thus, in cardiac pathologies with disturbed RRC dynamics and / or augmented TRPA1 activity, TRPA1 may represent an anti-arrhythmic target with untapped therapeutic potential.13–17
Cross species multi-omics reveals cell wall sequestration and elevated global transcription as mechanisms of boron tolerance in plants
Authors: Wang Guannan , DiTusa Sandra Feuer , Oh Dong-Ha , Herrmann Achim D. , Mendoza-Cozatl David G. , O’Neill Malcolm A. , Smith Aaron P. , Dassanayake Maheshi
Published: October 2020

Boron toxicity is a worldwide problem for crop production, yet we have only a limited understanding of the genetic responses and adaptive mechanisms to this environmental stress in plants. Here we identified responses to excess boron in boron stress-sensitiveArabidopsis thalianaand its boron stress-tolerant extremophyte relativeSchrenkiella parvulausing comparative genomics, transcriptomics, metabolomics, and ionomics. S. parvulamaintains a lower level of total boron and free boric acid in its roots and shoots and sustains growth for longer durations thanA. thalianawhen grown with excess boron.S. parvulalikely excludes boron more efficiently thanA. thaliana, which we propose is partly driven by BOR5, a boron transporter that we functionally characterized in the current study. Both species allocate significant transcriptomic and metabolomic resources to enable their cell walls to serve as a partial sink for excess boron, particularly discernable inA. thalianashoots. We provide evidence that theS. parvulatranscriptome is pre-adapted to boron toxicity, exhibiting substantial overlap with the boron-stressed transcriptome ofA. thaliana. Our transcriptomic and metabolomics data also suggest that RNA metabolism is a primary target of boron toxicity. Cytoplasmic boric acid likely forms complexes with ribose and ribose-containing compounds critical to RNA and other primary metabolic functions. A model depicting some of the cellular responses that enable a plant to grow in the presence of normally toxic levels of boron is presented.
Parallelized calculation of permutation tests
Authors: Ekvall Markus , Höhle Michael , Käll Lukas
Published: October 2020

Motivation

Permutation tests offer a straight forward framework to assess the significance of differences in sample statistics. A significant advantage of permutation tests are the relatively few assumptions about the distribution of the test statistic are needed, as they rely on the assumption of exchangeability of the group labels. They have great value, as they allow a sensitivity analysis to determine the extent to which the assumed broad sample distribution of the test statistic applies. However, in this situation, permutation tests are rarely applied because the running time of naive implementations is too slow and grows exponentially with the sample size. Nevertheless, continued development in the 1980s introduced dynamic programming algorithms that compute exact permutation tests in polynomial time. Albeit this significant running time reduction, the exact test has not yet become one of the predominant statistical tests for medium sample size. Here, we propose a computational parallelization of one such dynamic programming-based permutation test, the Green algorithm, which makes the permutation test more attractive.

Results

Parallelization of the Green algorithm was found possible by nontrivial rearrangement of the structure of the algorithm. A speed-up – by orders of magnitude – is achievable by executing the parallelized algorithm on a GPU. We demonstrate that the execution time essentially becomes a non-issue for sample sizes, even as high as hundreds of samples. This improvement makes our method an attractive alternative to, e.g., the widely used asymptotic Mann-Whitney U-test.

Availability

In Python 3 code from the GitHub repositoryhttps://github.com/statisticalbiotechnology/parallelPermutationTestunder an Apache 2.0 license.

Contact

lukask@kth.se

Supplementary information

Supplementary data are available atBioinformaticsonline.
Aberrant ventral dentate gyrus structure and function in individuals susceptible to post-traumatic stress disorder
Authors: Dirven Bart C.J. , van der Geugten Dewi , van Bodegom Miranda , Madder Leonie , van Agen Laura , Homberg Judith R. , Kozicz Tamas , Henckens Marloes J.A.G.
Published: October 2020

Post-traumatic stress disorder (PTSD) is a psychiatric disorder vulnerable individuals can develop following a traumatic event, whereas others are resilient. Enhanced insight into the mechanistic underpinnings contributing to these inter-individual differences in PTSD susceptibility is key to improved treatment and prevention. Aberrant function of the hippocampal dentate gyrus (DG) may contribute to its psychopathology, with the dorsal DG potentially encoding trauma memory generalization and the ventral DG anxiety. Using a mouse model, we investigated the association between deviant DG structure and function and susceptibility to develop PTSD-like symptoms following trauma. Mice were exposed to a traumatic event (unpredictable, inescapable foot shocks) and tested for PTSD symptomatology following recovery. In three independent experiments, DG neuronal morphology, synaptic protein gene expression and neuronal activity during trauma encoding and recall were assessed. Behaviorally, PTSD-like animals displayed some increased anxiety-like behavior already prior to trauma, increased novelty-induced freezing, but no clear differences in remote trauma memory recall. Comparison of the ventral DG of PTSD-like vs resilient mice revealed lower spine density, reduced expression of the postsynaptic protein homer 1b/c gene, a larger population of neurons active during trauma encoding and a greater presence of somatostatin neurons to be associated with PTSD susceptibility. In contrast, the dorsal DG of PTSD-like animals did not differ in terms of spine density or gene expression, but displayed more active neurons during trauma encoding and a lower amount of somatostatin neurons. These data propose a critical role for -mainly the ventral-DG in establishing symptomatology addressed in this PTSD model.
Physical modelling of multivalent interactions in the nuclear pore complex
Authors: Davis Luke K. , Šarić Anđela , Hoogenboom Bart W. , Zilman Anton
Published: October 2020

In the nuclear pore complex (NPC), intrinsically disordered proteins (FG Nups) along with their interactions with more globular proteins called nuclear transport receptors (NTRs) are vital to the selectivity of transport into and out of the cell nucleus. While such interactions can be modelled at different levels of coarse graining,in-vitroexperimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, where the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and non-cohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity at a level of minimal complexity, and compare them to experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs plays a minor role for their equilibrium binding properties, but is of significance when it comes to (un)binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.
Reward Value Is More Important Than Physical Saliency During Bumblebee Visual Search For Multiple Rewarding Targets
Authors: Nityananda Vivek , Chittka Lars
Published: October 2020

Several animals, including bees, use visual search to distinguish targets of interest and ignore distractors. While bee flower choice is well studied, we know relatively little about how they choose between multiple rewarding flowers in complex floral environments. Two important factors that could influence bee visual search for multiple flowers are the physical saliency (colour contrast against the background) of flowers and the reward value associated with them. We here investigated how these two different factors contribute to bee visual search. We trained bees to independently recognize two rewarding colours that in different experiments differed in either physical saliency, reward value or both. We then measured their choices and attention to these colours in the presence of distractors in a test without reinforcement. We found that bees preferred more salient or higher rewarding flowers and ignored distractors. When the high-reward flowers were less salient than the low-reward flowers, bees were nonetheless equally likely to choose high-reward flowers. Bees were more also more likely to attend to these high-reward flowers, with higher inspection times around them and faster search times when choosing them. When flowers differed in reward, we also found an effect of the training order with low-reward targets being more likely to be chosen if they had been encountered during the more immediate training session prior to the test. Our results parallel recent findings from humans demonstrating that reward value can attract attention even when targets are less salient and irrelevant to the current task.
Spatial relations trigger visual binding of people
Authors: Adibpour Parvaneh , Hochmann Jean-Rémy , Papeo Liuba
Published: October 2020

To navigate the social world, humans must represent social entities, and the relationships between those entities, starting with spatial relationships. Recent research suggests that two bodies are processed with particularly high efficiency in visual perception, when they are in a spatial positioning that cues interaction, i.e. close and face-to-face. Socially relevant spatial relations such as facingness may facilitate visual perception by triggering grouping of bodies into a new integrated percept, which would make the stimuli more visible and easier to process. We used electroencephalography and a frequency-tagging paradigm to measure a neural correlate of grouping (or visual binding), while female and male participants saw images of two bodies face-to-face or back-to-back. The two bodies in a dyad flickered at frequency F1 and F2, respectively, and appeared together at a third frequency Fd (dyad frequency). This stimulation should elicit a periodic neural response for each body at F1 and F2, and a third response at Fd, which would be larger for face-to-face (vs.back-to-back) bodies, if those stimuli yield additional integrative processing. Results showed that responses at F1 and F2 were higher for upright than for inverted bodies, demonstrating that our paradigm could capture neural activity associated with viewing bodies. Crucially, the response to dyads at Fd was larger for face-to-face (vs.back-to-back) dyads, suggesting integration mediated by grouping. We propose that spatial relations that recur in social interaction (i.e., facingness) promote binding of multiple bodies into a new representation. This mechanism can explain how the visual system contributes to integrating and transforming the representation of disconnected body-shapes into structured representations of social events.
Flash properties of Gaussia Luciferase are the result of covalent inhibition after a limited number of cycles
Authors: Dijkema Fenne Marjolein , Nordentoft Matilde Knapkøien , Didriksen Anders Krøll , Corneliussen Anders Sværke , Willemoës Martin , Winther Jakob R.
Published: October 2020

Luciferases are widely used as reporters for gene expression and for sensitive detection systems. While luciferases from firefly andRenillahave long been used for analysis of intracellular expression, the luciferase (GLuc) from the marine copepodGaussia princeps, has gained popularity, primarily because it is secreted and displays a very high light intensity. Firefly luciferase is characterized by kinetic behavior which is consistent with conventional steady-state Michaelis-Menten kinetics (termed “glow” kinetics). GLuc, conversely, displays what has been termed “flash” kinetics which signify a burst in light emission followed by a rapid decay. As the mechanistic background for this behavior is poorly characterized, we decided to decipher the mechanism in more detail. We show that decay in light signal is not due to depletion of substrate, but rather is caused by the irreversible inactivation of the enzyme. Inactivation takes place after between 10 and 200 reaction cycles, depending on substrate concentration. We found that the rate of inactivation is described by the sum of two exponentials with associated rate constants. The dominant of these of these increases linearly with substrate concentration while the minor is substrate-concentration independent. In terms of rate of initial luminescence reaction, this increases with the substrate concentration to the power of 1.53 and shows no signs of saturation up to 10 μM coelenterazine. Finally, we found that the inactivated form of the enzyme has a larger apparent size in both size exclusion chromatography and SDS-PAGE analysis and shows a fluorescence peak at 410 nm when excited at 333 nm. These findings indicate that the “flash” kinetics inGaussialuciferase are caused by an irreversible covalent binding to a derivative of the substrate during the reaction.
The underlying mechanisms of improved balance after one and ten sessions of balance training in older adults
Authors: Alizadehsaravi Leila , Koster Ruud A.J. , Muijres Wouter , Maas Huub , Bruijn Sjoerd M. , van Dieën Jaap H.
Published: October 2020

Training improves balance control in older adults, but the time course and neural mechanisms underlying these improvements are unclear. We studied balance robustness and performance, H-reflex gains, paired reflex depression, and co-contraction duration in ankle muscles after one and ten training sessions in 22 older adults (+65yrs). Mediolateral balance robustness, time to balance loss in unipedal standing on a platform with decreasing rotational stiffness, improved (33%) after one session, with no further improvement after ten sessions. Balance performance, absolute mediolateral center of mass velocity, improved (18.75%) after one session in perturbed unipedal standing and (18.18%) after ten sessions in unperturbed unipedal standing. Co-contraction duration of soleus/tibialis anterior increased (16%) after ten sessions. H-reflex gain and paired reflex depression excitability did not change. H-reflex gains were lower, and soleus/tibialis anterior co-contraction duration was higher in participants with more robust balance after ten sessions, and co-contraction duration was higher in participants with better balance performance at several time-points. Changes in robustness and performance were uncorrelated with changes in co-contraction duration, H-reflex gain, or paired reflex depression. In older adults, balance robustness improved over a single session, while performance improved gradually over multiple sessions. Changes in co-contraction and excitability of ankle muscles were not exclusive causes of improved balance.

Highlights

Balance robustness and balance performance in perturbed unipedal standing was improved after one balance training session, with no further improvement after ten sessions.

Balance performance in unperturbed unipedal standing was improved after ten sessions

H-reflex and paired reflex depression did not change after training in unipedal or bipedal standing.

Co-contraction duration of antagonistic ankle muscles increased after ten sessions in perturbed and unperturbed unipedal standing.

Changes in co-contraction duration and excitability of ankle muscles were not exclusive causes of improved balance.
Testcrosses are an efficient strategy for identifyingcisregulatory variation: Bayesian analysis of allele specific expression (BASE)
Authors: Miller Brecca , Morse Alison , Borgert Jacqueline E. , Liu Zihao , Sinclair Kelsey , Gamble Gavin , Zou Fei , Newman Jeremy , León-Novelo Luis , Marroni Fabio , McIntyre Lauren M.
Published: October 2020

Allelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicatescisacting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? Tests of allelic effect are performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least (n2-n)/2wherenis the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between non-tester alleles, allowingnalleles to be compared withncrosses. Using a mouse dataset where both testcrosses and direct comparisons have been performed, we show that ∼75% of the predicted differences between non-tester alleles are validated in a background of ∼10% differences in AI. The testing for AI involves several complex bioinformatics steps. BASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BASE has been packaged in Galaxy, made available in Nextflow and sbatch. (https://github.com/McIntyre-Lab/BASE_2020). In the mouse data, the direct test identifies moreciseffects than the testcross.Cis-by-transinteractions withtrans-acting factors on the X contributing to observedciseffects in autosomal genes in the direct cross remains a possible explanation for the discrepancy.
Widespread agrochemicals differentially affect zooplankton biomass and community structure
Authors: Hébert Marie-Pier , Fugère Vincent , Beisner Beatrix E. , da Costa Naíla Barbosa , Barrett Rowan D. H. , Bell Graham , Shapiro B. Jesse , Yargeau Viviane , Gonzalez Andrew , Fussmann Gregor F.
Published: October 2020

Anthropogenic environmental change is causing habitat deterioration at unprecedented rates in freshwater ecosystems. Despite increasing more rapidly than other agents of global change, synthetic chemical pollution –including agrochemicals such as pesticides– has received relatively little attention in freshwater biotic assessments. Determining the effects of multiple agrochemicals on complex community and ecosystem properties remains a major challenge, requiring a cross-field integration of ecology and ecotoxicology. Using a large-scale array of experimental ponds, we investigated the response of zooplankton community properties (biomass, composition, diversity metrics) to the individual and joint presence of three widespread agrochemicals: the herbicide glyphosate, the neonicotinoid insecticide imidacloprid, and fertilisers. We tracked temporal variation in community biomass and structure (i.e., composition, diversity metrics) along single and combined pesticide gradients (each spanning eight levels), under low (mesotrophic) and high (eutrophic) nutrient-enriched conditions, and quantified (i) agrochemical interactions, (ii) response threshold concentrations, and (iii) community resistance and recovery. We found that major zooplankton groups differed in their sensitivity to pesticides: ≥3 µg/L imidacloprid impaired copepods, rotifers collapsed at glyphosate levels ≥0.3 mg/L, whereas some cladocerans were highly tolerant to pesticide contamination. Glyphosate was the most influential driver of community properties, with biomass and community structure responding rapidly but recovering unequally over time. Zooplankton biomass showed little resistance when first exposed to glyphosate, but rapidly recovered and even increased with glyphosate concentration; in contrast, richness declined in more contaminated ponds but failed to recover. Our results show that the biomass of tolerant taxa compensated for the loss of sensitive species, conferring greater resistance upon subsequent exposure; a rare example of pollution-induced community tolerance in freshwater metazoans. Overall, zooplankton biomass appears to be more resilient to agrochemical pollution than community structure, yet all community properties measured in this study were affected at glyphosate levels below common water quality guidelines in North America.