bluuebunny/crossref_metadata_2025 huggingface dataset:
Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
Authors: Tekriwal Anand , Lintz Mario J. , Thompson John A. , Felsen Gidon
Published: June 2020

Parkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson’s disease (PD) have not been accounted for by this simple “rate model” framework, including the observation in PD patients that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference in impairment due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian (hemi-PD) mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemi-PD mice exhibited a bias ipsilateral to the side of dopaminergic cell loss that was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in parkinsonian SNr activity during movement preparation could account for the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements, consistent with some aspects of the rate model. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified than stimulus-guided movements.
High resolution genome-wide occupancy inCandida spp. using ChEC-seq
Authors: Tebbji Faiza , Khemiri Inès , Sellam Adnane
Published: June 2020

To persist in their hostile and dynamic human host environments, fungal pathogens has to sense and adapt by modulating their gene expression to fulfil their cellular needs. Understanding transcriptional regulation on a global scale would uncover cellular processes linked to persistence and virulence mechanisms that could be targeted for antifungal therapeutics. Infections associated with the yeastCandida albicans, a highly prevalent fungal pathogen, and the multi-resistant related speciesC. aurisare becoming a serious public health threat. To define the set of a gene regulated by a transcriptional regulator inC. albicans, Chromatin Immuno-Precipitation (ChIP) based techniques including ChIP-chip or ChIP-seq has been widely used. Here, we describe a new set of PCR-based MNase-tagging plasmids forC. albicansand otherCandida spp. to determine genome-wide location of any transcriptional regulator of interest using Chromatin endogenous cleavage (ChEC) coupled to high-throughput sequencing (ChEC-seq). The ChEC procedure does not require protein-DNA crosslinking or sonication avoiding thus artefacts related to epitope masking or the hyper-ChIPable euchromatic phenomenon. In a proof-of-concept application of ChEC-seq, we provided a high-resolution binding map of the SWI/SNF chromatin remodeling complex, a master regulator of fungal fitness inC. albicansin addition to the transcription factor NsiI that is an ortholog of the DNA-binding protein Reb1 for which genome-wide occupancy were previously established inSaccharomyces cerevisiae. The ChEC-seq procedure described here will allow a high-resolution genomic location definition which will enable a better understanding of transcriptional regulatory circuits that govern fungal fitness and drug resistance in these medically important fungi.

Importance

Systemic fungal infections caused byCandida albicansand the ‘superbug’C. aurisare becoming a serious public health threat. The ability of these yeasts to cause disease is linked to their faculty to modulate the expression of genes that mediate their escape from the immune surveillance and their persistence in the different unfavourable niches within the host. Comprehensive knowledge on gene expression control of fungal fitness is consequently an interesting framework for the identification of essential infection processes that could be hindered by chemicals as potential therapeutics. Here, we expanded the use of ChEC-seq, a technique that was initially developed in the yeast modelSaccharomyces cerevisiaeto identify genes that are modulated by a transcriptional regulator, to the pathogenic yeastsC. albicansandC. auris. This robust technique will allow a better characterization of key gene expression regulators and their contribution to virulence and antifungal resistance in these pathogenic yeasts.
Photoperiodic induction without light-mediated circadian entrainment in a high arctic resident bird
Authors: Appenroth Daniel , Melum Vebjørn J. , West Alexander C. , Dardente Hugues , Hazlerigg David G. , Wagner Gabriela C.
Published: June 2020

Organisms use changes in photoperiod to anticipate and exploit favourable conditions in a seasonal environment. While species living at temperate latitudes receive day length information as a year-round input, species living in the Arctic may spend as much as two-thirds of the year without experiencing dawn or dusk. This suggests that specialised mechanisms may be required to maintain seasonal synchrony in polar regions.

Svalbard ptarmigan (Lagopus muta hyperborea) are resident at 74-81° north latitude. They spend winter in constant darkness (DD) and summer in constant light (LL); extreme photoperiodic conditions under which they do not display overt circadian rhythms.

Here we explored how arctic adaptation in circadian biology affects photoperiodic time measurement in captive Svalbard ptarmigan. For this purpose, DD-adapted birds, showing no circadian behaviour, either remained in prolonged DD, were transferred into a simulated natural photoperiod (SNP) or were transferred directly into LL. Birds transferred from DD to LL exhibited a strong photoperiodic response in terms of activation of the hypothalamic thyrotropin-mediated photoperiodic response pathway. This was assayed through expression of theEya3, Tshβ and deiodinase genes, as well as gonadal development. While transfer to SNP established synchronous diurnal activity patterns, activity in birds transferred from DD to LL showed no evidence of circadian rhythmicity.

These data show that the Svalbard ptarmigan does not require circadian entrainment to develop a photoperiodic response involving conserved molecular elements found in temperate species. Further studies are required to define how exactly arctic adaptation modifies seasonal timer mechanisms.

Summary statement

Svalbard ptarmigan show photoperiodic responses when transferred from constant darkness to constant light without circadian entrainment.
Developmental pathways regulate cytokine-driven effector and feedback responses in the intestinal epithelium
Authors: Lindholm Håvard T. , Parmar Naveen , Drurey Claire , Ostrop Jenny , Díez-Sanchez Alberto , Maizels Rick M. , Oudhoff Menno J.
Published: June 2020

The intestinal tract is a common site for infection, and it relies on an appropriate immune response to defend against pathogens. The intestinal epithelium has an important role in effector responses, which is coordinated by immune-type specific cytokines. It is incompletely understood how cytokines drive epithelial responses. Here, using organoid-cytokine co-cultures, we provide a comprehensive analysis of how key cytokines affect the intestinal epithelium, and relate this toin vivoinfection models. We use imaging, based on a convolutional neural network, and transcriptomic analysis to reveal that cytokines use developmental pathways to define intestinal epithelial effector responses. For example, we find IL-22 and IL-13 dichotomously induce goblet cells, in which only IL-13 driven goblet cells are associated with NOTCH signaling. We further show that IL-13 induces BMP signalling to act as a negative feedback loop in IL-13 induced tuft cell hyperplasia, an important aspect of type 2 immunity. Together, we show that targeting developmental pathways may be a useful tool to tailor epithelial effector responses that are necessary for immunity to infection.
Genome-wide epigenomic stress response in the European sea bass (Dicentrarchus labrax, L.)
Authors: Krick M.V. , Desmarais E. , Samaras A. , Gueret E. , Dimitroglou A. , Pavlidis M. , Tsigenopoulos C.S. , Guinand B.
Published: June 2020

Background

While the stress response inspired genome-wide epigenetic studies in vertebrate models, it remains mostly ignored in fish. We modified the epiGBS (epiGenotyping By sequencing) technique to explore changes in genome-wide cytosine methylation to a repeated acute stress challenge in the nucleated red blood cells (RBCs) of the European sea bass (Dicentrarchus labrax). This species is widely studied in both the natural and farmed environments, including issues regarding health and welfare.

Results

We retrieved 501,108,033 sequencing reads after trimming, with a mean mapping efficiency of 73.0% (unique best hits). Fifty-seven differentially methylated cytosines (DMCs) close to 51 distinct stress-related genes distributed on 17 of 24 linkage groups (LGs) were detected between RBCs of pre- and post-stress individuals. Literature surveys indicated that thirty-eight of these genes were previously reported as differentially expressed in the brain of zebrafish, most of them involved in stress coping differences. DMC-related genes associated to the Brain Derived Neurotrophic Factor, a protein that favors stress adaptation and fear memory, are especially relevant.

Conclusion

We provide an improved epiGBS protocol with increased multiplexing and sequencing capacities that offer new opportunities to improve data acquisition and to investigate important biological processes at a genome-wide level, such as the stress response. Minimally invasive RBCs deserve more attention to investigate the epigenetic response to stress without sacrificing fish.
Colletotrichumspp. from soybean cause disease on lupin but can also induce plant growth-promoting effects
Authors: Wirtz Louisa , Massola Júnior Nelson Sidnei , Rebellato Linhares de Castro Renata , Ruge-Wehling Brigitte , Schaffrath Ulrich , Loehrer Marco
Published: June 2020

Protein crop plants such as soybean and lupin attract increasing attention because of their potential use as forage, green manure or for the production of oil and protein for human consumption. While soybean production only recently gained more importance in Germany and within the whole EU in frame of protein strategies, lupin production already is well established in Germany. The cultivation of lupins is impeded by the hemibiotrophic ascomyceteColletotrichum lupini, the causing agent of anthracnose disease. Worldwide, soybean is also a host for a variety ofColletotrichumspecies, but so far this seems not to be the case in Germany. Cross-virulence between lupin and soybean infecting isolates is a potential threat, especially taking into consideration the overlap of possible soybean and lupine growing areas in Germany. To address this question, we systematically investigated the interaction of differentColletotrichumspecies isolated from soybean in Brazil on actual German soybean and lupin plant cultivars. Conversely, we tested the interaction of a German field isolate ofC. lupiniwith soybean. Under controlled conditions,Colletotrichumspecies from soybean and lupin were able to cross-infect the other host plant with varying degrees of virulence, thus underpinning the potential risk of increased anthracnose diseases in the future. Interestingly, we observed a pronounced plant growth-promoting effect for some host-pathogen combinations which might open the route to the use of beneficial biological agents in lupine and soybean production.
Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins
Authors: Díez José-María , Romero Carolina , Vergara-Alert Júlia , Belló-Perez Melissa , Rodon Jordi , Honrubia José Manuel , Segalés Joaquim , Sola Isabel , Enjuanes Luis , Gajardo Rodrigo
Published: June 2020

Background

There is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy.

Methods

The neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10dilution which reduced the viral titer by 50%).

Results

All IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV.

Conclusion

In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.
Object and object-memory representations across the proximodistal axis of CA1
Authors: Vandrey Brianna , Ainge James A.
Published: June 2020

Episodic memory requires information about objects to be integrated into a spatial framework. Place cells in the hippocampus encode spatial representations of objects that could be generated through signalling from the entorhinal cortex. Projections from lateral and medial entorhinal cortex to the hippocampus terminate in distal and proximal CA1, respectively. We recorded place cells in distal and proximal CA1 as rats explored an environment that contained objects. Place cells in distal CA1 demonstrated higher measures of spatial tuning and expressed place fields closer to objects. Further, remapping to object displacement was modulated by place field proximity to objects in distal, but not proximal CA1. Finally, representations of previous object locations were more precise in distal CA1. Our data suggest that lateral entorhinal cortex inputs to the hippocampus support spatial representations that are more precise and responsive to objects in cue-rich environments. This is consistent with functional segregation in the entorhinal-hippocampal circuits underlying object-place memory.
Analysis of receptor-ligand pairings and distribution of myeloid subpopulations across the animal kingdom reveals neutrophil evolution was facilitated by colony-stimulating factors
Authors: Pinheiro Damilola , Mahwin Marie-Anne , Prendecki Maria , Woollard Kevin J
Published: June 2020

Neutrophils or heterophils constitute the largest population of phagocytic granulocytes in the blood of mammals and birds. The development and function of neutrophils and monocytes is primarily governed by the granulocyte colony-stimulating factor receptor family (CSF3R/CSF3) and macrophage colony-stimulating factor receptor family (CSF1R/IL34/CSF1) respectively. Using various techniques this study considered how the emergence of receptor:ligand pairings shaped the distribution of blood myeloid cell populations. Comparative gene analysis supported the ancestral pairings of CSF1R/IL34 and CSF3R/CSF3, and the emergence of CSF1 later in tetrapod lineages after the advent of Jawed/Jawless fish. Further analysis suggested that the emergence of CSF3 lead to reorganisation of granulocyte distribution between amphibian and early reptiles. However, the advent of endothermy likely contributed to the dominance of the neutrophil/heterophil in modern-day mammals and birds. In summary, we show that the emergence of CSF3R/CSF3 was a key factor in the subsequent evolution of the modern-day mammalian neutrophil.

Impact statement

Colony-stimulating factors (CSFs) are important for myeloid phagocyte development. The emergence of CSF3/CSF3R in tetrapod lineages has uniquely contributed to physical, functional and structural adaptions observed in mammalian neutrophils.
The SPIRE1 actin nucleator coordinates actin/myosin functions in the regulation of mitochondrial motility
Authors: Straub Felix , Welz Tobias , Alberico Hannah , Brandão Rafael Oliveira , Huber Anna , Samol-Wolf Annette , Brakebusch Cord , Woods Dori , Kollmar Martin , Martin-Gonzalez Javier , Kerkhoff Eugen
Published: June 2020

Subcellular localisation of mitochondria provides a spatial and temporal organisation for cellular energy demands. Long-range mitochondrial transport is mediated by microtubule tracks and associated dynein and kinesin motor proteins. The actin cytoskeleton has a more versatile role and provides transport, tethering, and anchoring functions. SPIRE actin nucleators organise actin filament networks at vesicle membranes, which serve as tracks for myosin 5 motor protein-driven transport processes. Following alternative splicing, SPIRE1 is targeted to mitochondria. In analogy to vesicular SPIRE functions, we have analysed whether SPIRE1 regulates mitochondrial motility. By tracking mitochondria of living fibroblast cells fromSPIRE1mutant mice and splice-variant specific mitochondrial SPIRE1 knockout mice, we determined that the loss of SPIRE1 function increased mitochondrial motility. TheSPIRE1mutant phenotype was reversed by transient overexpression of mitochondrial SPIRE1, which almost completely inhibited motility. Conserved myosin 5 and formin interaction motifs contributed to this inhibition. Consistently, mitochondrial SPIRE1 targeted myosin 5 motors and formin actin filament generators to mitochondria. Our results indicate that SPIRE1 organises an actin/myosin network at mitochondria, which opposes mitochondrial motility.

Summary statement

The mitochondrial SPIRE1 protein targets myosin 5 motor proteins and formin actin-filament nucleators/elongators towards mitochondria and negatively regulates mitochondrial motility.
Structure of the yeast Nup84-Nup133 complex details flexibility and reveals universal conservation of the membrane anchoring ALPS motif
Authors: Nordeen Sarah A. , Turman Daniel L. , Schwartz Thomas U.
Published: June 2020

The hallmark of the eukaryotic cell is the complex endomembrane system that compartmentalizes cellular functions. Transport into and out of the nucleus, occurs through the Nuclear Pore Complex (NPC). The heptameric Nup84 or Y complex is an essential scaffolding component of the NPC. Here we report two nanobody-bound structures: the full-length Nup84-Nup133 C-terminal domain complex and the Nup133 N-terminal domain, both fromS. cerevisiae. Together with previously published structures, this work enables the structural description of the entire 575 kDa Y complex, from one species. The structure of Nup84-Nup1 33CTDdetails the high flexibility of this dimeric unit of the Y complex. Further, the Nup133NTDcontains a structurally conserved amphipathic lipid packing sensor (ALPS) motif, confirmed by liposome interaction studies. The new structures reveal important details about the function of the Y complex that affect our understanding of NPC structure and assembly.
High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States
Authors: McNamara Ryan P. , Caro-Vegas Carolina , Landis Justin T. , Moorad Razia , Pluta Linda J. , Eason Anthony B. , Thompson Cecilia , Bailey Aubrey , Villamor Femi Cleola S. , Lange Philip T. , Wong Jason P. , Seltzer Tischan , Seltzer Jedediah , Zhou Yijun , Vahrson Wolfgang , Juarez Angelica , Meyo James O. , Calabre Tiphaine , Broussard Grant , Rivera-Soto Ricardo , Chappell Danielle L. , Baric Ralph S. , Damania Blossom , Miller Melissa B. , Dittmer Dirk P.
Published: June 2020

SARS-CoV-2 is constantly evolving. Prior studies have focused on high case-density locations, such as the Northern and Western metropolitan areas in the U.S. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant. The presence of D614G was associated with a higher genome copy number and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3’ untranslated region. The data are consistent with community spread within the local population and the larger continental U.S. No strain had mutations in the target sites used in common diagnostic assays. The data instill confidence in the sensitivity of current tests and validate “testing by sequencing” as a new option to uncover cases, particularly those not conforming to the standard clinical presentation of COVID-19. This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S.
Are isokinetic leg torques and kick velocity reliable predictors for competitive success in taekwondo athletes?
Authors: Moreira Pedro Vieira Sarmet , Falco Coral , Menegaldo Luciano Luporini , Goethel Márcio Fagundes , de Paula Leandro Vinhas , Gonçalves Mauro
Published: June 2020

The aim of the study was to analyzed the relationship between isokinetic knee and hip peak torques and Roundhouse-kick velocities and expertise level (Elite vs. Subelite) of Taekwondo athletes. Seven elite and seven sub-elite athletes were tested for kick kinematic, power of impact and for isokinetic peak torque (PT) at slow (60°/s) and high (240°/s) concentric mode. PTs were compared between groups and correlated with the data of kick performance. It was found inter-group differences in hip flexors and extensors PT at the isokinetic fast speed. The hip flexion PT at 60°/s and 240°/s were negatively correlated with the kick time (R = −0.46, and R = −0.62, respectively). Hip flexion torque at 60°/s was also positively correlated (R = 0.52) with the peak of linear velocity of the foot (LVF) and the power of impact (R = 0.51). Peak torque of hip extension at 60°/s and hip abduction at 240°/s were correlated with the LVF (R= 0.56 and R = 0.46). Discriminant analysis presented an accuracy of 85.7% in predicting expertise level based on fast torques of hip flexion and extension and on the knee extension velocity during the kick. This study demonstrated that hip muscles strength is probably the dominant muscular factor for determining kick performance. Knee angular velocity combined with hip torques are the best discriminators for the competitive level in taekwondo athletes.
Prevalence and Virulence Gene Profiles ofEscherichia coliO157 from Cattle Slaughtered in Buea, Cameroon
Authors: Akomoneh Elvis Achondou , Esemu Seraphine Nkie , Kfusi Achah Jerome , Ndip Roland N. , Ndip Lucy M.
Published: June 2020

Background

Escherichia coliO157 is an emerging foodborne pathogen of great public health concern. It has been associated with bloody diarrhoea, haemorrhagic colitis and haemolytic uremic syndrome in humans. Most human infections have been traced to cattle and the consumption of contaminated cattle products. In order to understand the risk associated with the consumption of cattle products, this study sought to investigate the prevalence and identify virulence genes inE. coliO157 from cattle in Cameroon.

Method

A total of 512 rectal samples were obtained and analysed using conventional bacteriological methods (enrichment on modified Tryptone Soy Broth and selective plating on Cefixime-Tellurite Sorbitol Mac-Conkey Agar) for the isolation ofE. coliO157. PresumptiveE. coliO157 isolates were confirmed serologically using E. COLIPRO™O157 latex agglutination test and molecularly using PCR targeting therfbgene in the isolates. Characterisation of the confirmedE. coliO157 strains was done by amplification ofstx1,stx2,eaeAandhlyAvirulence genes using both singleplex and multiplex PCR.

Results

E. coliO157 was detected in 56 (10.9%) of the 512 samples examined. The presence of the virulence genesstx2, eaeAandhylAwas demonstrated in 96.4% (54/56) of the isolates andstx1in 40 (71.4%) of the 54. The isolates exhibited three genetic profiles (I-III) with I (stx1, stx2, eaeAandhlyA) being the most prevalent (40/56; 71.4%) while two isolates had none of the virulence genes tested.

Conclusion

A proportion of cattle slaughtered in abattoirs in Buea are infected with pathogenicE. coliO157 and could be a potential source of human infections. We recommend proper animal food processing measures and proper hygiene be prescribed and implemented to reduce the risk of beef contamination.
Mechanotendography: description and evaluation of a new method for investigating the physiological mechanical oscillations of tendons using a piezo-based measurement system
Authors: Schaefer Laura V , Bittmann Frank N
Published: June 2020

The mechanotendography (MTG) analyzes mechanical oscillations of tendons during muscular actions. It can be assessed as equivalent to mechanomyography just applied for tendons. Since this method is unknown, the aim of this investigation was to evaluate the technical reliability of a piezo-based measurement system used for MTG.

The reliability measurements were performed using audio files played by a subwoofer. The thereby generated mechanical pressure waves were recorded by a piezoelectric sensor based measurement system. The piezo sensor was fixed onto the subwoofer’s coverage. An audio of 40 Hz-sine oscillations and, to stay close to human applications, four different formerly in vivo recorded MTG-signals from Achilles and triceps brachii tendon were converted into audio files and were used as test signals. Five trials with each audio were performed. One audio was used for repetition trials on another day. The correlation of the recorded signals were estimated by the Spearman correlation coefficient (MCC), the intraclass-correlation-coefficient (ICC(3,1)), Cronbach’s alpha (CA) and by mean distances (MD) between the signals. They were compared between repetition and random matched signals.

The repetition trials show high correlations (MCC: 0.86 ± 0.13, ICC: 0.89 ± 0.12, CA: 0.98 ± 0.03), low MD (0.03 ± 0.03V) and differ significantly from the random matched signals (MCC: 0.15 ± 0.10, ICC: 0.17 ± 0.09, CA: 0.37 ± 0.16, MD: 0.19 ± 0.01V) (p= 0.001 – 0.043).

This speaks for an excellent reliability of the piezo-based measurement system in a technical setting. Since research showed that the skin above superficial tendons oscillates adequately, we estimate this tool as valid for the application in musculoskeletal systems. It might provide further insight into the functional behavior of tendons during muscular activity.
Genoprotective effects of Chaga mushroom (Inonotus obliquus) polysaccharides in UVB-exposed embryonic zebrafish (Danio rerio) through coordinated expression of DNA repair genes
Authors: Eid Jehane Ibrahim , Mohanty Swabhiman , Das Biswadeep
Published: June 2020

Background

Chaga mushroom(Inonotus obliquus)is one of the most promising antioxidants with incredible health-promoting effects. Chaga polysaccharides (IOP) have been reported to enhance immune response and alleviate oxidative stress during development. However, the effects of IOP on the genotoxicity in model organisms are yet to be clarified.

Methods

Zebrafish embryos (12 hours post fertilization, hpf) were exposed to transient UVB (12 J/m2/s, 310 nm) for 10 secs using a UV hybridisation chamber, followed by IOP treatment (2.5 mg/mL) at 24 hpf for up to 7 days post fertilization (dpf). The genotoxic effects were assessed using acridine orange staining, alkaline comet assay, and qRT-PCR for screening DNA repair genes.

Results

We found significant reduction in DNA damage and amelioration of the deformed structures in the IOP-treated zebrafish exposed to UVB (p < 0.05) at 5 dpf and thereafter. In addition, the relative mRNA expressions ofXRCC-5, XRCC-6, RAD51, P53,andGADD45were significantly upregulated in the IOP-treated UVB-exposed zebrafish. Pathway analysis demonstrated coordinated regulation of DNA repair genes, suggesting collective response during UVB exposure.

Conclusions

Overall, IOP treatment ameliorated the genotoxic effects in UVB-exposed zebrafish embryos, which eventually assisted in normal development. The study suggested the efficacy of Chaga mushroom polysaccharides in mitigating UV-induced DNA damage.
Words in context: tracking context-processing during language comprehension using computational language models and MEG
Authors: Lopopolo Alessandro , Schoffelen Jan Mathijs , van den Bosch Antal , Willems Roel M.
Published: June 2020

The meaning of a word depends on its lexical semantics and on the context in which it is embedded. At the basis of this lays the distinction between lexical retrieval and integration, two basic operations supporting language comprehension. In this paper, we investigate how lexical retrieval and integration are implemented in the brain by comparing MEG activity to word representations generated by computational language models. We test both non-contextualized embeddings, representing words independently from their context, and contextualized embeddings, which instead integrate contextual information in their representations. Using representational similarity analysis over cortical regions and over time, we observed that brain activity in the left anterior temporal pole and inferior frontal regions shows higher similarity with contextualized word embeddings compared to non-contextualized embeddings, between 300 and 500 ms after word presentation. On the other hand, non-contextualized word embeddings show higher similarity with brain activity in the left lateral and anterior temporal lobe at earlier latencies – areas and latencies related to lexical retrieval. Our results highlight how lexical retrieval and context integration can be tracked in the brain using word embeddings obtained with computational models. These results also suggest that the distinction between lexical retrieval and integration might be framed in terms of context-independent and contextualized representations.
The Pleistocene-Holocene aquatic molluscs as indicators of the past ecosystem changes in Transbaikalia (Eastern Siberia, Russia)
Authors: Klishko Olga K. , Kovychev Evgeniy V. , Vinarski Maxim V. , Bogan Arthur E. , Jurgenson Georgiy. A.
Published: June 2020

Data on historical change of the Transbaikalian malacofauna in the Neopleistocene and Holocene is presented. Fossil shells from archeological excavations of the ancient settlements dating from the Neolithic period to Medieval and also from a drill hole of the Neopleistocene alluvial deposits were collected. In total nine species of bivalve molluscs from the families Margaritiferidae, Unionidae, Limnocardiidae, Glycymerididae, including one marine species, and two gastropod species from families Viviparidae and Planorbidae were identified. The time of the existence of each fossil species was determined by radiocarbon dating. It was found that the species ranged in age from more 50,000 and 2,080–1,210 years ago. Five species inhabited the Transbaikal region and are locally extirpated in the present. Their disjunctive ranges in the past included southern Europe and Western and Eastern Siberia to Transbaikalia and in the east to Far East and Primorye of Russia. The time of existence and extirpation of the thermophilic species of generaAdacna, Planorbis, LanceolariaandAmuropaludinacorresponds to cycles of the warming and cooling in Pleistocene and Holocene according to regional climate chronological scales. It was possible to separate these species as indicators of paleoclimate. Change of the species composition of the malacofauna of region connected with natural cycles of climatochrons in the Pleistocene and Holocene is the appearance of the climatogenic succession. In the course of this succession the disappearance of the stenothermal species occurred on a regional level and decreasing their global ranges.
DReSS: A difference measurement based on reachability between state spaces of Boolean networks
Authors: Yin Ziqiao , Guo Binghui , Ma Shuangge Steven , Sun Yifan , Mi Zhilong , Zheng Zhiming
Published: June 2020

Researches on dynamical features of biological systems are mostly based on fixed network structure. However, both biological factors and data factors can cause structural perturbations to biological regulatory networks. There are researches focus on the influence of such structural perturbations to the systems’ dynamical features. Reachability is one of the most important dynamical features, which describe whether a state can automatically evolve into another state. However, there is still no method can quantitively describe the reachability differences of two state spaces caused by structural perturbations. DReSS, Difference based on Reachability between State Spaces, is proposed in this research to solve this problem. First, basic properties of DReSS such as non-negativity, symmetry and subadditivity are proved based on the definition. And two more indexes, diagDReSS and iDReSS are proposed based on the definition of DReSS. Second, typical examples likeDReSS= 0or1 are shown to explain the meaning of DReSS family, and the differences between DReSS and traditional graph distance are shown based on the calculation steps of DReSS. Finally, differences of DReSS distribution between real biological regulatory network and random networks are compared. Multiple interaction positions in real biological regulatory network show significant different DReSS value with those in random networks while none of them show significant different diagDReSS value, which illustrates that the structural perturbations tend to affect reachability inside and between attractor basins rather than to affect attractor set itself.

Author summary

Boolean network is a kind of networks which is widely used to model biological regulatory systems. There are structural perturbations in biological systems based on both biological factors and data-related factors. We propose a measurement called DReSS to describe the difference between state spaces of Boolean networks, which can be used to evaluate the influence of specific structural perturbations of a network to its state space quantitively. We can use DReSS to detect the sensitive interactions in a regulatory network, where structural perturbations can influence its state space significantly. We proved properties of DReSS including non-negativity, symmetry and subadditivity, and gave examples to explain the meaning of some special DReSS values. Finally, we present an example of using DReSS to detect sensitive vertexes in yeast cell cycle regulatory network. DReSS can provide a new perspective on how different interactions affect the state space of a specific regulatory network differently.
A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1
Authors: Meserve Joy H. , Nelson Jessica C. , Marsden Kurt C. , Hsu Jerry , Echeverry Fabio A. , Jain Roshan A. , Wolman Marc A. , Pereda Alberto E. , Granato Michael
Published: June 2020

The acoustic startle response is an evolutionary conserved avoidance behavior. Disruptions in startle behavior, in particular startle magnitude, are a hallmark of several human neurological disorders. While the neural circuitry underlying startle behavior has been studied extensively, the repertoire of genes and genetic pathways that regulate this locomotor behavior has not been explored using an unbiased genetic approach. To identify such genes, we took advantage of the stereotypic startle behavior in zebrafish larvae and performed a forward genetic screen coupled with whole genome analysis. This identified mutants in eight genes critical for startle behavior, including two genes encoding proteins associated with human neurological disorders, Dolichol kinase (Dolk), a broadly expressed regulator of the glycoprotein biosynthesis pathway, and the potassium Shaker-like channel subunit Kv1.1. We demonstrate that Kv1.1 acts independently of supraspinal inputs to regulate locomotion, suggesting its site of action is within spinal circuitry. Moreover, we show that Kv1.1 protein is mis-localized indolkmutants, suggesting they act in a common genetic pathway to regulate movement magnitude. Combined, our results identify a diverse set of eight genes all associated with human disorders that regulate zebrafish startle behavior and reveal a previously unappreciated role for Dolk and Kv1.1 in regulating movement magnitude via a common genetic pathway.

Author summary

Underlying all animal behaviors are neural circuits, which are controlled by numerous molecular pathways that direct neuron development and activity. To identify and study these molecular pathways that control behavior, we use a simple vertebrate behavior, the acoustic startle response, in the larval zebrafish. In response to an intense noise, larval zebrafish will quickly turn and swim away to escape. From a genetic screen, we have identified a number of mutants that behave in abnormal ways in response to an acoustic stimulus. We cloned these mutants and identified eight genes that regulate startle behavior. All eight genes are associated with human disorders, and here we focus on two genes,dolkandkcna1a, encoding Dolk, a key regulator of protein glycosylation, and the potassium channel Kv1.1, respectively. We demonstrate that loss ofdolkorkcna1acauses larval zebrafish to perform exaggerated swim movements and that Dolk is required for Kv1.1 protein localization to axons of neurons throughout the nervous system, providing strong evidence thatdolkandkcna1aact in a common molecular pathway. Combined, our studies provide new insights into the genetic regulation of startle behavior.
Structures of FHOD1-Nesprin1/2 complexes reveal alternate binding modes for the FH3 domain of formins
Authors: Lim Sing Mei , Cruz Victor E. , Antoku Susumu , Gundersen Gregg G. , Schwartz Thomas U.
Published: June 2020

The nuclear position in eukaryotic cells is controlled by a nucleo-cytoskeletal network, with important roles in cell differentiation, division and movement. Forces are transmitted through conserved linker of nucleoskeleton and cytoskeleton (LINC) complexes that traverse the nuclear envelope and engage on either side of the membrane with diverse binding partners. Nesprin-2 giant (Nes2G), a LINC element in the outer nuclear membrane, connects to the actin network directly as well as through FHOD1, a formin whose major activity is bundling actin. Much of the molecular details of this process remain poorly understood. Here, we report the crystal structure of Nes2G bound to FHOD1. We show that the G-binding domain of FHOD1 is rather a spectrin repeat binding enhancer for the neighboring FH3 domain, possibly establishing a common binding mode among this subclass of formins. The FHOD1-Nes2G complex structure suggests that spectrin repeat binding by FHOD1 is likely not regulated by the DAD helix of FHOD1. Finally, we establish that Nes1G also has one FHOD1 binding spectrin repeat, indicating that these abundant, giant Nesprins have overlapping functions in actin-bundle recruitment for nuclear movement.
Gradient analysis of landscape variation in Norway
Authors: Simensen Trond , Halvorsen Rune , Erikstad Lars
Published: June 2020

A multitude of landscape characterisation and mapping methods exist, but few methods take into account that landscapes properties vary in a gradual, continuous manner along multiple directions of variation. In this study, we used gradient analytic methods, rooted in ecological continuum theory, to analyse landscape variation throughout Norway. The aim is to explain differences in landscape properties in the simplest possible way, by identifying ‘complex landscape gradients’ (CLGs), i.e. composite gradients of co-occurring landscape elements and properties.

We collected data by stratified sampling of 100 test areas (20×20 km), in which we delineated a total of 3966 observation units (landscape polygons 4–30 km²) based on geomorphological criteria. For each observation unit, 85 landscape variables were recorded. We identified patterns of variation in landscape element composition by parallel use of two multivariate statistical methods, detrended correspondence analysis (DCA) and global nonmetric multidimensional scaling (GNMDS).

The analyses revealed that the most important properties explaining differences in total landscape elements composition was location of the landscape relative to the coastline and coarse-scale landform variation. Most landscape elements had distinct optima within specific segments along broad-scale complex-gradients in landscape properties. A tentative landscape-type hierarchy was built by an iterative procedure by which the amount of compositional turnover in landscape-element composition between adjacent types was standardised. Six ‘major landscape types’ were identified based on geomorphological criteria. Within each major type, we identified a unique set of 2–5 important CLGs, representing geo-ecological, bio-ecological, and land use-related landscape variation. Minor landscape types were obtained by combining segments along two or more CLGs.

The study shows that geological diversity, biological diversity and human land-use are tightly intertwined at the landscape level of ecological complexity, and that predominantly abiotic processes control and constrain both biotic processes and human land use.
Plant Genotype Influences Physicochemical Properties of Substrate as well as Bacterial and Fungal Assemblages in the Rhizosphere of Balsam Poplar
Authors: Rheault Karelle , Lachance Denis , Morency Marie-Josée , Thiffault Évelyne , Guittonny Marie , Isabel Nathalie , Martineau Christine , Séguin Armand
Published: June 2020

Abandoned unrestored mines are an important environmental issue since they typically remain unvegetated for decades, exposing vast amounts of mine waste to erosion. Several factors limit the revegetation of these sites, including extreme abiotic conditions and unfavorable biotic conditions. However, some pioneer tree species having high level of genetic diversity, such as balsam poplar (Populus balsamifera), are able to naturally colonize these sites and initiate plant succession. This suggests that some tree genotypes are likely more suited for acclimation to the conditions of mine wastes. In this study, two contrasting mine waste storage facilities (waste rock versus tailings) from the Abitibi region of Quebec (Canada), on which poplars have grown naturally, were selected. First, we assessedin situthe impact of vegetation presence on each type of mine wastes. The presence of balsam poplars improved soil health locally by improving physicochemical properties (e.g. higher nutrient content and pH) of the mine wastes and causing an important shift in their bacterial and fungal community compositions, going from lithotrophic communities that dominate mine waste environments to heterotrophic communities involved in nutrient cycling. Next, in a greenhouse experiment, ten genotypes ofP. balsamiferacollected on both mine sites and from a natural forest nearby were grown in these mine wastes. Tree growth was monitored during two growing seasons, after which the effect of genotype-by-environment interactions was assessed by measuring the physicochemical properties of the substrates and the changes in microbial communities, using a metabarcoding approach. Although substrate type was identified as the main driver of rhizosphere microbiome diversity and community structure, a significant effect of tree genotype was also detected, particularly for bacterial communities. Plant genotype also influenced aboveground tree growth and the physicochemical properties of the substrates. These results highlight the influence of balsam poplar genotype on the soil environment and the potential importance of tree genotype selection in the context of mine waste revegetation.
A simple canonical circuitry for non-stationary normalization by inhibition to explain and predict change detection in monkey area MT
Authors: Ernst Udo , Chen Xiao , Bohnenkamp Lisa , Galashan Fingal Orlando , Wegener Detlef
Published: June 2020

Sudden changes in visual scenes often indicate important events for behavior. For their quick and reliable detection, the brain must be capable to process these changes as independent as possible from its current activation state. In motion-selective area MT, neurons respond to instantaneous speed changes with pronounced transients, often far exceeding the expected response as derived from their speed tuning profile. We here show that this complex, non-linear behavior emerges from the combined temporal dynamics of excitation and divisive inhibition, and provide a comprehensive formal analysis. A central prediction derived from this investigation is that attention increases the steepness of the transient response irrespective of the activation state prior to a stimulus change, and irrespective of the sign of the change. Extracellular recordings of attention-dependent representation of both speed increments and decrements confirmed this prediction and suggest that improved change detection derives from basic computations in a canonical cortical circuitry.
PCNA Antagonizes Cohesin-dependent Roles in Genomic Stability
Authors: Zuilkoski Caitlin M. , Skibbens Robert V.
Published: June 2020

PCNA sliding clamp binds factors through which histone deposition, chromatin remodeling, and DNA repair are coupled to DNA replication. PCNA also directly binds Eco1/Ctf7 acetyltransferase, which in turn activates cohesins and establishes cohesion between nascent sister chromatids. While increased recruitment thus explains the mechanism through which elevated levels of chromatin-bound PCNA rescueeco1mutant cell growth, the mechanism through which PCNA instead worsens cohesin mutant cell growth remains unknown. Possibilities include that elevated levels of long-lived chromatin-bound PCNA reduce either cohesin deposition onto DNA or cohesin acetylation. Instead, our results reveal that PCNA increases the levels of both chromatin-bound cohesin and cohesin acetylation. Beyond sister chromatid cohesion, PCNA also plays a critical role genomic stability such that high levels of chromatin-bound PCNA destabilize the DNA replication fork. At a relatively modest increase of chromatin-bound PCNA, however, fork stability and progression appear normal in wildtype cells. Our results reveal that even this moderate increase of PCNA sensitizes cohesin mutant cells to DNA damaging agents and in a process that involves the DNA damage response kinase Mec1(ATR), but not Tel1(ATM). These and other findings document that PCNA mis-regulation results in genome instabilities that normally are resolved by cohesin and suggest that elevating levels of chromatin-bound PCNA may target cohesinopathic cells linked to cancer.