bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomics provides a robust framework for the relationships of the major clades of cladobranch sea slugs (Mollusca, Gastropoda, Heterobranchia), but fails to resolve the position of the enigmatic genusEmbletonia
Authors: Karmeinski Dario , Meusemann Karen , Goodheart Jessica A. , Schroedl Michael , Martynov Alexander , Korshunova Tatiana , Wägele Heike , Donath Alexander
Published: September 2020

Background

Cladobranch sea slugs represent roughly half of the biodiversity of soft-bodied, marine gastropod molluscs (Nudibranchia) on the planet. Despite their global distribution from shallow waters to the deep sea, from tropical into polar seas, and their important role in marine ecosystems and for humans (as bioindicators and providers of medical drug leads), the evolutionary history of cladobranch sea slugs is not yet fully understood. Here, we amplify the current knowledge on the phylogenetic relationships by extending the cladobranch and outgroup taxon sampling using transcriptome data.

Results

We generated new transcriptome data for 19 species of cladobranch sea slugs and two additional outgroup taxa. We complemented our taxon sampling with previously published transcriptome data, resulting in a final supermatrix covering 56 species from all but one accepted cladobranch superfamilies. Transcriptome assembly using six different assemblers, selection of those assemblies providing the largest amount of potentially phylogenetically informative sites, and quality-driven compilation of data sets resulted in three different supermatrices: one with a full coverage of genes per species (446 single-copy protein-coding genes) and two with a less stringent coverage (667 genes with 98.9% partition coverage and 1,767 genes with 86% partition coverage, respectively). We used these supermatrices to infer statistically robust maximum-likelihood trees. All analyses, irrespective of the data set, indicate maximum statistical support for all major splits and phylogenetic relationships on family level. The only discordance between the inferred trees is the position ofEmbletonia pulchra. Extensive testing using Four-cluster Likelihood Mapping, Approximately Unbiased tests, and Quartet Scores revealed that its position is not due to any informative phylogenetic signal, but caused by confounding signal.

Conclusions

Our data matrices and the inferred trees inferred can serve as a solid foundation for future work on the taxonomy and evolutionary history of Cladobranchia. The correct placement ofE. pulchra, however, proves challenging, even with large data sets. Moreover, quartet mapping shows that confounding signal present in the data is sufficient to explain the inferred position ofE. pulchra, again leaving its phylogenetic position as an enigma.
Mining the potential ofVRS1-5gene to raise barley grain yield
Authors: Shen Liping , Liu Yangyang , Sun Zhiwen , Wang Ziying , Zhang Lili , Cai Yu , Jiao Yuannian , Wu He , Shen Kuocheng , Yang Ping , Guo Zifeng
Published: September 2020

VRS1-5genes determine spike row types during the early stages of spike development in barley (Hordeum vulgare), yet their functions for the determination of grain yield during the late stages of spike development are largely unknown. To assess the role ofVRS1-5genes in determining grain yield components, we sequencedVRS1-5genes from 894 worldwide barley accessions and measured 19 spike morphology traits in four environments. Single nucleotide polymorphism SNP markers and gene marker-based haplotypes forVRS1-5displayed close associations with spike morphology traits. We further developed a spatiote-temporal transcriptome atlas (255 samples) at 17 stages and five positions along the spike, that linked spike morphology to spikelet development and expression patterns ofVRS1-5genes. Phenotypic measurements demonstrated that mutations inVRS1-5suppress the initiation of spikelet primordia and, trigger spikelet abortion by increasing cytokinin content and improving sensitivity of spikelet primordia to cytokinin. Our integrated results illustrate how breeding can globally alter spike morphology through diversity at theVRS1-5genes, which show great potential in increasing barley grain yield.
Membrane binding controls ordered self-assembly of animal septins
Authors: Szuba Agata , Bano Fouzia , Iv François , Mavrakis Manos , Richter Ralf P. , Bertin Aurelie , Koenderink Gijsje H.
Published: September 2020

Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here we show by cell-free reconstitution that membrane binding requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septins form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12 to 18 nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4 nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.
Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain
Authors: Perisé-Barrios Ana Judith , Tomeo-Martín Beatriz Davinia , Gómez-Ochoa Pablo , Delgado-Bonet Pablo , Plaza Pedro , Palau-Concejo Paula , González Jorge , Ortiz-Diez Gustavo , Meléndez-Lazo Antonio , Gentil Michaela , García-Castro Javier , Barbero-Fernández Alicia
Published: September 2020

COVID-19 is a zoonotic disease originated by SARS-CoV-2. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Therefore it is necessary to describe the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19. The potential for companion animals contributing to the continued human-to-human disease, infectivity, and community spread is an urgent issue to be considered.

Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound study, and computed tomography. Nasopharyngeal and rectal swab were analyzed to detect canine pathogens, including SARS-CoV-2. Twenty healthy dogs living in SARS-CoV-2 positive households were included. Immunoglobulin detection by different immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial pattern, with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. Forty dogs were negative for SARS-CoV-2 butMycoplasmaspp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2.

Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Moreover, dogs living in COVID-19 positive households could have been more exposed to be infected during outbreaks.
Rapid, dose-dependent and efficient inactivation of surface dried SARS-CoV-2 by 254 nm UV-C irradiation
Authors: Ruetalo Natalia , Businger Ramona , Schindler Michael
Published: September 2020

Background

The SARS-CoV-2 pandemic urges for cheap, reliable, and rapid technologies for disinfection and decontamination. One frequently proposed method is UV-C irradiation. However, UV-C doses necessary to achieve inactivation of high-titer SARS-CoV-2 are poorly defined.

Methods

Using a box and two handheld systems designed to decontaminate objects and surfaces we evaluated the efficacy of 254 nm UV-C treatment to inactivate surface dried SARS-CoV-2.

Results

Drying for two hours did not have a major impact on the infectivity of SARS-CoV-2, indicating that exhaled virus in droplets or aerosols stays infectious on surfaces at least for a certain amount of time. Short exposure of high titer surface dried virus (3-5*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total inactivation of SARS-CoV-2. Dose-dependency experiments revealed that 3.5 mJ/cm2were still effective to achieve a > 6-log reduction in viral titers whereas 1.75 mJ/cm2lowered infectivity only by one order of magnitude.

Conclusions

Our results demonstrate that SARS-CoV-2 is rapidly inactivated by relatively low doses of UV-C irradiation. Furthermore, the data reveal that the relationship between UV-C dose and log-viral titer reduction of surface residing SARS-CoV-2 is non-linear. In the context of UV-C-based technologies used to disinfect surfaces, our findings emphasize the necessity to assure sufficient and complete exposure of all relevant areas by integrated UV-C doses of at least 3.5 mJ/cm2at 254 nm. Altogether, UV-C treatment is an effective non-chemical possibility to decontaminate surfaces from high-titer infectious SARS-CoV-2.
Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets
Authors: Hui Yan , Tamez-Hidalgo Paulina , Cieplak Tomasz , Satessa Gizaw Dabessa , Kot Witold , Søren Søren Kjærulff , Nielsen Mette Olaf , Nielsen Dennis Sandris , Krych Lukasz
Published: September 2020

The direct use of medical zinc oxide (ZnO) in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders. This study assessed whether rapeseed meal added two brown macroalagae species (Saccharina latissimaandAscophylum nodosum) and fermented using lactic acid bacteria (FRS) could improve piglet performance and gut health. The weaned piglets were fed one of three different feeding regimens (n = 230 each): basal diet, 2.5% and 5% FRS from day 28 of life to day 85. The piglets fed with 2.5% FRS presented superior phenotype with alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier as well as numerically improvements of final body weight. Colon microbiota composition was determined using amplicon sequencing of the V3 and V1 – V8 region of the 16S rRNA gene using Illumina Nextseq and Oxford Nanopore MinION sequencing, respectively. The two amplicon sequencing strategies showed high consistence between the detected bacteria. Both sequencing technologies showed that the FRS fed piglets had a distinctly different microbial composition relative to the basal diet. Compared with piglets fed the basal diet,Prevotella stercoreawas verified by both technologies to be more abundant in the FRS piglets, and positively correlated with colon mucosa thickness and negatively correlated with blood levels of leucocytes and IgG. In conclusion, FRS supplementation improved gut health of weaner piglets, and altered their gut microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not cause further improvements.
The protected physiological status of intracellularSalmonella entericapersisters reduces host cell-imposed stress
Authors: Schulte Marc , Olschewski Katharina , Hensel Michael
Published: September 2020

Today, we are faced with increasingly occurring bacterial infections that are hard to treat and often tend to relapse. These recurrent infections can occur possibly due to antibiotic-tolerant persister cells. Antibiotic persistent bacteria represent a small part of a bacterial population that enters a non-replicating (NR) state arising from phenotypic switching. Intracellularly, after uptake by phagocytic cells,Salmonella entericaserovar Typhimurium (STM) forms persister cells that are able to subvert immune defenses of the host. However, the clear physiological state and perceptual properties are still poorly understood and many questions remain unanswered. Here we describe further development of fluorescent protein-based reporter plasmids that were used to detect intracellular NR persister cells and monitor the expression of stress response genes via extensive flow cytometric analyses. Moreover, we performed extensive measurements of the metabolic properties of NR STM at the early course of infection. Our studies demonstrate that NR STM persister cells perceive their environment and are capable respond to stress factors. Since persisters showed a lower stress response compared to replicating (R) STM, which was not a consequence of a lower metabolic capacity, the persistent status of STM serves as protective niche. Furthermore, up to 95% of NR STM were metabolically active at the beginning of infection additionally showing no difference in the metabolic capacity compared to R STM. The accessory capability of NR STM persisters to sense and to react to stress with constant metabolic activity may supports the pathogen to create a more permissive environment for recurrent infections.
Humans Discriminate Individual Large-Billed Crows by their Calls
Authors: Schalz Sabrina , Dickins Thomas E.
Published: September 2020

Previous research has shown that humans can discriminate two individual rhesus monkeys (Macaca mulatta), as well as two individual zebra finches (Taeniopygia guttata) by their vocalizations. The discrimination of individual zebra finches largely relies on differences in pitch contour, although this is not the only relevant cue. The purpose of the present experiment was to examine whether humans can also discriminate two individual large-billed crows (Corvus macrorhynchos) by their calls. Discrimination was tested with a forced-choice Same-Different Paradigm. Results show a high discrimination accuracy without prior training, although the scores obtained here were lower than those in the zebra finch discrimination task. There was no significant learning trend across trials. Future studies should investigate which acoustic cues participants use for the discrimination of individual crows and expand these findings with more non-human animal vocalizations.
Mis-splicing ofMdm2leads to Increased P53-Activity and Craniofacial Defects in a MFDMEftud2Mutant Mouse Model
Authors: Beauchamp Marie-Claude , Djedid Anissa , Bareke Eric , Merkuri Fjodor , Aber Rachel , Tam Annie S. , Lines Matthew A. , Boycott Kym M. , Stirling Peter C. , Fish Jennifer L. , Majewski Jacek , Jerome-Majewska Loydie A.
Published: September 2020

EFTUD2, a GTPase and core component of the splicesome, is mutated in patients with mandibulofacial dysostosis with microcephaly (MFDM). We generated a mutant mouse line with conditional mutation inEftud2and usedWnt1-Cre2to delete it in neural crest cells. Homozygous deletion ofEftud2leads to neural crest cell death and malformations in the brain and craniofacial region of embryos. RNAseq analysis of embryonic mutant heads revealed a significant increase in exon skipping, in retained introns and enriched levels ofMdm2transcripts lacking exon 3. Mutants also had increased nuclear P53, higher expression of P53-target genes, and increased cell death. Their craniofacial development was significantly improved when treated with Pifithrin-α, an inihibitor of P53. We propose that craniofacial defects caused by mutations ofEFTUD2are a result of mis-splicing ofMdm2and P53-associated cell death. Hence, drugs that reduce P53 activity may help prevent craniofacial defects associated with spliceosomopathies.
The fitness landscapes of translation
Authors: Josupeit Mario , Krug Joachim
Published: September 2020

Motivated by recent experiments on an antibiotic resistance gene, we investigate genetic interactions between synonymous mutations in the framework of exclusion models of translation. We show that the range of possible interactions is markedly different depending on whether translation efficiency is assumed to be proportional to ribosome current or ribosome speed. In the first case every mutational effect has a definite sign that is independent of genetic background, whereas in the second case the effect-sign can vary depending on the presence of other mutations. The latter result is demonstrated using configurations of multiple translational bottlenecks induced by slow codons.
Actuation Enhances Patterning in Human Neural Tube Organoids
Authors: Fattah Abdel Rahman Abdel , Daza Brian , Rustandi Gregorius , Berrocal-Rubio Miguel Angel , Gorissen Benjamin , Poovathingal Suresh , Davie Kristofer , Cao Xuanye , Rosenzweig Derek Hadar , Lei Yunping , Finnell Richard , Verfaillie Catherine , Sampaolesi Maurilio , Dedecker Peter , Van Oosterwyck Hans , Aerts Stein , Ranga Adrian
Published: September 2020

Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.
Aptamer based spatiotemporally controlled growth factor patterning for tunable local microvascular network formation in engineered tissues
Authors: Rana Deepti , Kandar Ajoy , Salehi-Nik Nasim , Inci Ilyas , Koopman Bart , Rouwkema Jeroen
Published: September 2020

Spatiotemporally controlled growth factor availability is of crucial importance for achieving hierarchically organized vascular network formation within engineering tissues. Even though current growth factor delivery systems can provide sustained release and growth factor delivery on demand, they generally do not facilitate temporal control over the release rates and thus adaptation in accordance with the needs of growing engineered tissue. Additionally, with conventional growth factor loading methods, growth factors are often subjected to organic solvents or harsh conditions, leading to lower bioactivity and denaturation of the proteins. To overcome these limitations, this manuscript reports on the development of VEGF specific 5’ acrydite modified aptamer functionalized GelMA hydrogels. The covalently incorporated aptamers can selectively bind to proteins with high affinity and specificity, and can thus sequester the target protein from the surrounding environment. The manuscript shows that this not only provides temporal control over the growth factor release via complementary sequence hybridization, but also enables local control of microvascular network formation in 3D.
Protonation states in SARS-CoV-2 main protease mapped by neutron crystallography
Authors: Kneller Daniel W. , Phillips Gwyndalyn , Weiss Kevin L. , Pant Swati , Zhang Qiu , O’Neill Hugh M. , Coates Leighton , Kovalevsky Andrey
Published: September 2020

The main protease (3CL Mpro) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication, possessing an unusual catalytic dyad composed of His41 and Cys145. A long-standing question in the field has been what the protonation states of the ionizable residues in the substrate-binding active site cavity are. Here, we present the room-temperature neutron structure of 3CL Mprofrom SARS-CoV-2, which allows direct determination of hydrogen atom positions and, hence, protonation states. The catalytic site natively adopts a zwitterionic reactive state where His41 is doubly protonated and positively charged, and Cys145 is in the negatively charged thiolate state. The neutron structure also identified the protonation states of other amino acid residues, mapping electrical charges and intricate hydrogen bonding networks in the SARS-CoV-2 3CL Mproactive site cavity and dimer interface. This structure highlights the ability of neutron protein crystallography for experimentally determining protonation states at near-physiological temperature – the critical information for structure-assisted and computational drug design.
The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins
Authors: Geller Alexander Martin , Pollin Inbal , Zlotkin David , Danov Aleks , Nachmias Nimrod , Andreopoulos William B , Shemesh Keren , Levy Asaf
Published: September 2020

Bacteria employ toxin delivery systems to exclude bacterial competitors and to infect host cells. Characterization of these systems and the toxins they secrete is important for understanding microbial interactions and virulence in different ecosystems. The extracellular Contractile Injection System (eCIS) is a toxin delivery particle that evolved from a bacteriophage tail. Four known eCIS systems have been shown to mediate interactions between bacteria and their invertebrate hosts, but the broad ecological function of these systems remains unknown. Here, we identify eCIS loci in 1,249 prokaryotic genomes and reveal a striking enrichment of these loci in environmental microbes and absence from mammalian pathogens. We uncovered 13 toxin genes that associate with eCIS from diverse microbes and show that they can inhibit growth of bacteria, yeast or both. We also found immunity genes that protect bacteria from self-intoxication, supporting an antibacterial role for eCIS. Furthermore, we identified multiple new eCIS core genes including a conserved eCIS transcriptional regulator. Finally, we present our data through eCIStem; an extensive eCIS repository. Our findings define eCIS as a widespread environmental prokaryotic toxin delivery system that likely mediates antagonistic interactions with eukaryotes and prokaryotes. Future understanding of eCIS functions can be leveraged for the development of new biological control systems, antimicrobials, and cell-free protein delivery tools.
De novoDNA methylation controls neuronal maturation during adult hippocampal neurogenesis
Authors: Zocher Sara , Overall Rupert W , Berdugo-Vega Gabriel , Rund Nicole , Karasinsky Anne , Adusumilli Vijay S , Steinhauer Christina , Scheibenstock Sina , Händler Kristian , Schultze Joachim L , Calegari Federico , Kempermann Gerd
Published: September 2020

Dynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for adult neural stem cell differentiation and related brain function has, however, remained unknown. Here, we show that neurogenesis-associatedde novoDNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of bothde novoDNA methyltransferasesDnmt3aandDnmt3bin adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new-born neurons, resulting in reduced hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.
Coherent theta activity in the medial and orbital frontal cortices encodes reward value
Authors: Amarante Linda M. , Laubach Mark
Published: September 2020

This study examined how the medial frontal (MFC) and orbital frontal (OFC) cortices process reward information. We simultaneously recorded local field potentials in the two areas as rats consumed liquid sucrose rewards. Both areas exhibited a 4-8 Hz “theta” rhythm that was phase locked to the lick cycle. The rhythm tracked shifts in sucrose concentrations and fluid volumes, demonstrating that it is sensitive to differences in reward magnitude. The coupling between the rhythm and licking was stronger in MFC than OFC and varied with response vigor and absolute reward value in the MFC. Spectral analysis revealed zero-lag coherence between the cortical areas, and found evidence for a directionality of the rhythm, with MFC leading OFC. Our findings suggest that consummatory behavior generates simultaneous theta range activity in the MFC and OFC that encodes the value of consumed fluids, with the MFC having a top-down role in the control of consumption.
Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication
Authors: Carter Christoph C. , Olivier Jean Paul , Kaushansky Alexis , Mast Fred D. , Aitchison John D.
Published: September 2020

The mechanistic target of rapamycin (mTOR) functions in at least two distinct complexes: mTORC1, which regulates cellular anabolic-catabolic homeostasis, and mTORC2, which is an important regulator of cell survival and cytoskeletal maintenance. mTORC1 has been implicated in the pathogenesis of flaviviruses including dengue, where it contributes to the establishment of a pro-viral autophagic state. In contrast, the role of mTORC2 in viral pathogenesis is unknown. In this study, we explore the consequences of a physical protein-protein interaction between dengue non-structural protein 5 (NS5) and host cell mTOR proteins during infection. Using shRNA to differentially target mTORC1 and mTORC2 complexes, we show that mTORC2 is required for optimal dengue replication. Furthermore, we show that mTORC2 is activated during viral replication, and that mTORC2 counteracts virus-induced apoptosis, promoting the survival of infected cells. This work reveals a novel mechanism by which the dengue flavivirus can promote cell survival to maximize viral replication.
The His-tag as a decoy modulating preferred orientation in cryoEM
Authors: Bromberg Raquel , Guo Yirui , Plymire Daniel , Emde Tabitha , Puzio Maciej , Borek Dominika , Otwinowski Zbyszek
Published: September 2020

The His-tag is a widely used affinity tag that facilitates purification by means of affinity chromatography of recombinant proteins for functional and structural studies. We show here that His-tag presence affects how coproheme decarboxylase interacts with the water-air interface during grid preparation for cryoEM. Depending on His-tag presence or absence, we observe significant changes in patterns of preferred orientation. The analysis of particle orientations suggests that His-tag presence can mask the hydrophobic patches on a protein’s surface that mediate the interactions with the water-air interface, while the hydrophobic linker between a His-tag and the coding sequence of the protein may enhance other interactions with water-air interface. Our observations suggest that tagging, including rational design of the linkers between an affinity tag and a protein of interest, offer a promising approach to modulating interactions with the water-air interface.

Synopsis

A His-tag affects the interactions of particles with the water-air interface in cryo-electron microscopy (cryoEM) single particle reconstruction (SPR), and thus may be used to modulate these interactions, including inducing changes in patterns of preferred orientation.
Cone Opponent Functional Domains in Primary Visual Cortex Combine Signals for Color Appearance Mechanisms
Authors: Li Peichao , Garg Anupam K. , Zhang Li A. , Rashid Mohammad S. , Callaway Edward M.
Published: September 2020

Studies of color perception have led to mechanistic models of how cone-opponent signals from retinal ganglion cells are integrated to generate color appearance. But it is unknown how this hypothesized integration occurs in the brain. Here we show that cone-opponent signals transmitted from retina to primary visual cortex (V1) are integrated through highly organized circuits within V1 to implement the color opponent interactions required for color appearance. Combining intrinsic signal optical imaging (ISI) and 2-photon calcium imaging (2PCI) at single cell resolution, we demonstrate cone-opponent functional domains (COFDs) that combine L/M cone-opponent and S/L+M cone-opponent signals following the rules predicted from psychophysical studies of color perception. These give rise to an orderly organization of hue preferences of the neurons within the COFDs and the generation of hue “pinwheels”. Thus, spatially organized neural circuits mediate an orderly transition from cone-opponency to color appearance that begins in V1.
The interplay between asymmetric and symmetric DNA loop extrusion
Authors: Banigan Edward J. , Mirny Leonid A.
Published: September 2020

Compaction of chromosomes is essential for reliable transmission of genetic information. Experiments suggest that this ∼ 1000-fold compaction is driven by condensin complexes that extrude chromatin loops,i.e., progressively collect chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates thatsymmetrictwo-sided loop extrusion can achieve such compaction, but recent single-molecule studies observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, andasymmetrictwo-sided extrusion.

We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling of two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.
Gene expression changes of seven stonefly species in responses to a latitudinal-environmental gradient
Authors: Gamboa Maribet , Gotoh Yusuke , Doloiras-Laraño Arnelyn D. , Watanabe Kozo
Published: September 2020

Latitudinal variation has been known to create strong selection pressure for genomic variation that enables the adaptation and survival of organisms. By altering gene expression patterns, organisms can modify their adaptive potential to heterogeneous environmental conditions along a latitudinal gradient; however, there is a gap in our understanding of how physiological consequences in wild species are affected and how changing environmental conditions act on multiple species. Here, we investigated how seven stream stonefly species sampled from four geographical regions in Japan differ in their responses to latitudinal variations by measuring gene expression (RNA-sequencing) differences within species and gene co-expression among species. We found that a large number of genes (622) were differentially expressed along the latitudinal gradient. The high species-specific gene expression diversity found at higher latitude regions was probably associated with low temperatures and high water discharge, which suggests the adaptive potential of stonefly specie. In contrast, similar gene expression patterns among species was observed at lower latitudes, which suggests that strong environmental stress occurs in warmer regions. Weighted gene co-expression network analysis (WGCNA) identified 22 genes with similar expression patterns among species along the latitudinal gradient. Among the four geographical regions, high differential expression patterns in the co-expressed genes from two regions were found, suggesting that the local environment strongly affects gene expression patterns among species in these regions. Respiration, metabolism, and developmental co-expressed genes exhibited a latitudinal cline, showing clear evidence of divergent adaptive responses to latitude. Our findings demonstrate that stonefly species are differentially adapted to local environmental conditions, and imply that adaptation in gene expression could be shared by multiple species under environmental stress conditions. This study highlights the importance of considering multiple species when evaluating the consequences of environmental changes on aquatic insect communities, and possible mechanisms to cope with environmental changes.
Reduction of visual stimulus artifacts using a spherical tank for small, aquatic animals
Authors: Wang Kun , Arrenberg Burkhard , Hinz Julian , Arrenberg Aristides B
Published: September 2020

Delivering appropriate stimuli remains a challenge in vision research, particularly for aquatic animals such as zebrafish. Due to the shape of the water tank and the associated optical paths of light rays, the stimulus can be subject to unwanted refraction or reflection artifacts, which may spoil the experiment and result in wrong conclusions. Here, we employ computer graphics simulations and calcium imaging in the zebrafish optic tectum to show, how a spherical glass container optically outperforms many previously used water containers, including Petri dish lids. We demonstrate that aquatic vision experiments suffering from total internal reflection artifacts at the water surface or at the flat container bottom may result in the erroneous detection of visual neurons with bipartite receptive fields and in the apparent absence of neurons selective for vertical motion. Our results and demonstrations will help aquatic vision neuroscientists on optimizing their stimulation setups.
Short-term Neuropsychiatric Outcomes and Quality of Life in COVID-19 Survivors
Authors: Méndez Raúl , Balanzá-Martínez Vicent , Luperdi Sussy C. , Estrada Itziar , Latorre Ana , González-Jiménez Paula , Feced Laura , Bouzas Leyre , Yépez Katheryn , Ferrando Ana , Hervás David , Zaldívar Enrique , Reyes Soledad , Berk Michael , Menéndez Rosario
Published: September 2020

Background

The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms, and QoL in COVID-19 survivors shortly after hospital discharge.

Methods

This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed-up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity, and QoL (mental and physical components) was administered by telephone.

Findings

Of the 229 screened patients, 179 were included in the final analysis. Among survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%), and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety were 29.6%, depression (26.8%), and post-traumatic stress disorder (25.1%) respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients, respectively. Delirium and stress-related symptoms increased approximately 4-fold the odds of developing neurocognitive impairment. Female gender and neurocognitive impairment diagnosis were related with an increase of 2.5 and 4.56- fold odds respectively of psychiatric morbidity.

Interpretation

Hospitalized COVID-19 survivors showed a high prevalence of neurocognitive impairment, psychiatric morbidity, and poor QoL in the short-term. It is uncertain if these impacts persist over the long-term.
Challenges and opportunities of the COVID-19 pandemic for perinatal mental health care: a mixed methods study of mental health care staff
Authors: Wilson CA , Dalton-Locke C , Johnson S , Simpson A , Oram S , Howard LM
Published: September 2020

Purpose

the aim of this study was to explore staff perceptions of the impact of the COVID-19 pandemic on mental health service delivery and outcomes for women who were pregnant or in the first year after birth (‘perinatal’ women).

Methods

secondary analysis of an online mixed-methods survey open to all mental health care staff in the UK involving 363 staff working with women in the perinatal period.

Results

staff perceived the mental health of perinatal women to be particularly vulnerable to the impact of stressors associated with the pandemic such as social isolation (rated by 79.3% as relevant or extremely relevant; 288/363) and domestic violence and abuse (53.3%; 192/360). As a result of changes to mental health and other health and social care services, staff reported feeling less able to assess women, particularly their relationship with their baby (43.3%; 90/208), and to mobilise safeguarding procedures (29.4%; 62/211). While 42% of staff reported that some women engaged poorly with virtual appointments, they also found flexible remote consulting to be beneficial for some women and helped time management due to reductions in travel time.

Conclusions

delivery of perinatal care needs to be tailored to the needs of women; virtual appointments are perceived not to be appropriate for assessments but may be helpful for some women in subsequent interactions. Safeguarding and other risk assessment procedures must remain robust in spite of modifications made to service delivery during pandemics.
Delaying or Delivering: Identification of novel NAM-1 alleles which delay senescence to extend grain fill duration of wheat
Authors: Chapman Elizabeth A. , Orford Simon , Lage Jacob , Griffiths Simon
Published: September 2020

Senescence is a complex quantitative trait under genetic and environmental control, involving the remobilisation of resources from vegetative tissue into grain. Delayed senescence, or ‘staygreen’ traits, are associated with conferring stress tolerance, with extended photosynthetic activity hypothesised to sustain grain filling. The genetics of senescence regulation are largely unknown, with senescence variation often correlated with phenological traits. Here, we confirm staygreen phenotypes of twoTriticum aestivumcv. Paragon EMS mutants previously identified during a forward genetic screen and selected for their agronomic performance, similar phenology and differential senescence phenotypes. Through grain filling experiments, we confirm a positive relationship between onset of senescence and grain fill duration, reporting an associated ∼14 % increase in final dry grain weight for one mutant,P< 0.05. Recombinant Inbred Line (RIL) populations segregating for senescence were developed for trait mapping purposes, and phenotyped over multiple years under field conditions. Staygreen traits were mapped using exome-capture enabled bulk segregant analysis (BSA), whereupon senescence was quantified, and metrics compared to qualify senescence traits and aid RIL selection. Using BSA we mapped our two staygreen traits to two independent, dominant, loci of 4.8 and 16.7 Mb in size encompassing 56 and 142 genes. Combining single marker association analysis with variant effect prediction, we identified SNPs encoding self-validating mutations located inNAM-1homoeologues and propose these as gene candidates.

Applying an exome-capture enabled Bulk Segregant Analysis, we identified novelNAM-1alleles underpinning two staygreen traits associated with enhancing grain fill duration and grain weight
Dual symbiosis in the deep-sea hydrothermal vent snailGigantopelta aegisrevealed by its hologenome
Authors: Lan Yi , Sun Jin , Chen Chong , Sun Yanan , Zhou Yadong , Yang Yi , Zhang Weipeng , Li Runsheng , Zhou Kun , Wong Wai Chuen , Kwan Yick Hang , Cheng Aifang , Bougouffa Salim , Van Dover Cindy Lee , Qiu Jian-Wen , Qian Pei-Yuan
Published: September 2020

Animals endemic to deep-sea hydrothermal vents often form obligatory relationships with bacterial symbionts, maintained by intricate host-symbiont interactions. Endosymbiosis with more than one symbiont is uncommon, and most genomic studies focusing on such ‘dual symbiosis’ systems have not investigated the host and the symbionts to a similar depth simultaneously. Here, we report a novel dual symbiosis among the peltospirid snailGigantopelta aegisand its two Gammaproteobacteria endosymbionts – one being a sulphur oxidiser and the other a methane oxidiser. We assembled high-quality genomes for all three parties of this holobiont, with a chromosome-level assembly for the snail host (1.15 Gb, N50 = 82 Mb, 15 pseudo-chromosomes). In-depth analyses of these genomes reveal an intimate mutualistic relationship with complementarity in nutrition and metabolic codependency, resulting in a system highly versatile in transportation and utilisation of chemical energy. Moreover,G. aegishas an enhanced immune capability that likely facilitates the possession of more than one type of symbiont. Comparisons withChrysomallon squamiferum, another chemosymbiotic snail in the same family but only with one sulphur-oxidising endosymbiont, show that the two snails’ sulphur-oxidising endosymbionts are phylogenetically distant, agreeing with previous results that the two snails have evolved endosymbiosis independently and convergently. Notably, the same capabilities of biosynthesis of specific nutrition lacking in the host genome are shared by the two sulphur-oxidising endosymbionts of the two snail genera, which may be a key criterion in the selection of symbionts by the hosts.
Curcumin promotes progression of AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway
Authors: Dai Jian , Li Ying , Kametani Fuyuki , Cui Xiaoran , Igarashi Yuichi , Huo Jia , Miyahara Hiroki , Mori Masayuki , Higuchi Keiichi
Published: September 2020

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. Liver weights and plasma ApoA-II and high-density lipoprotein concentrations were significantly elevated in curcumin-supplemented groups. RNA-sequence analysis revealed that curcumin intake affected hepatic lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) pathway, especially PPARα activation, resulting in increasedApoa2mRNA expression. The increase in liver weights was due to activation of PPARα and peroxisome proliferation. Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner.
Attention affects overall gain but not selective contrast at meter frequencies in the neural processing of rhythm
Authors: Lenc Tomas , Keller Peter E. , Varlet Manuel , Nozaradan Sylvie
Published: September 2020

When listening to music, humans spontaneously perceive and synchronize movement to periodic pulses of meter. A growing body of evidence suggests that this widespread ability is related to neural processes that selectively enhance meter periodicities. However, to what extent these neural processes are affected by the attentional state of the listener remains largely unknown. Here, we recorded EEG while participants listened to auditory rhythms and detected small changes in tempo or pitch of the stimulus, or performed a visual task. The overall neural response to the auditory input decreased when participants attended the visual modality, indicating generally lower sensitivity to acoustic information. However, the selective contrast at meter periodicities did not differ across the three tasks. Moreover, this selective contrast could be trivially accounted for by biologically-plausible models of subcortical auditory processing, but only when meter periodicities were already prominent in the acoustic input. However, when meter periodicities were not prominent in the auditory input, the EEG responses could not be explained by low-level processing. This was also confirmed by early auditory responses that originate predominantly in early auditory areas and were recorded in the same EEG. The contrast at meter periodicities in these early responses was consistently smaller than in the EEG responses originating mainly from higher-level processing stages. Together, these results demonstrate that selective contrast at meter periodicities involves higher-level neural processes that may be engaged automatically, irrespective of behavioral context. This robust shaping of the neural representation of rhythm might thus contribute to spontaneous and effortless synchronization to musical meter in humans across cultures.
A second PI(4,5)P2binding site determines PI(4,5)P2sensitivity of the tubby domain
Authors: Thallmair Veronika , Schultz Lea , Marrink Siewert J. , Oliver Dominik , Thallmair Sebastian
Published: September 2020

Phosphosinositides (PIs) are lipid signaling molecules that operate by recruiting proteins to cellular membranes via PI recognition domains. Such domains are also used widely as fluorescence-coupled biosensors for cellular PIs. For PI(4,5)P2, the dominant PI of the plasma membrane (PM), only two recognition domains have been characterized in detail and used as sensors. One of them, the tubby domain, which is conserved in the tubby-like protein (TULP) family, is essential for targeting proteins into cilia in a process involving reversible membrane association. However, the PI(4,5)P2binding properties of tubby domains have remained enigmatic.

Here we used coarse-grained molecular dynamics (MD) simulations to explore PI(4,5)P2binding by the prototypic tubby domain (tubbyCT). While the MD simulations showed a comparatively low PI(4,5)P2affinity of the previously described canonical binding site, they unexpectedly revealed an adjacent second binding site, consisting of a conserved cationic cluster at the protein-membrane interface. Population of this second site dramatically increased membrane association of tubbyCT. Although less specific than the canonical binding pocket, this second site preferred binding of PI(4,5)P2over PI(4)P and phosphatidyl serine. Mutations in this site impaired PI(4,5)P2-dependent PM localization in living cells and PI(4,5)P2interactionin silico.

Thus, the second binding site essentially contributes to the effective affinity and hence PM association of the tubby domain. The two-ligand binding mode may serve to sharpen the membrane association-dissociation cycle of TULPs that underlies delivery of ciliary cargo.