bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrafast end-to-end protein structure prediction enables high-throughput exploration of uncharacterised proteins
Authors: Kandathil Shaun M , Greener Joe G , Lau Andy M , Jones David T 
Published: November 2020

AbstractDeep learning-based prediction of protein structure usually begins by constructing a multiple sequence alignment (MSA) containing homologues of the target protein. The most successful approaches combine large feature sets derived from MSAs, and considerable computational effort is spent deriving these input features. We present a method that greatly reduces the amount of preprocessing required for a target MSA, while producing main chain coordinates as a direct output of a deep neural network. The network makes use of just three recurrent networks and a stack of residual convolutional layers, making the predictor very fast to run, and easy to install and use. Our approach constructs a directly learned representation of the sequences in an MSA, starting from a one-hot encoding of the sequences. When supplemented with an approximate precision matrix, the learned representation can be used to produce structural models of comparable or greater accuracy as compared to our original DMPfold method, while requiring less than a second to produce a typical model. This level of accuracy and speed allows very large-scale 3-D modelling of proteins on minimal hardware, and we demonstrate that by producing models for over 1.3 million uncharacterized regions of proteins extracted from the BFD sequence clusters. After constructing an initial set of approximate models, we select a confident subset of over 30,000 models for further refinement and analysis, revealing putative novel protein folds. We also provide updated models for over 5,000 Pfam families studied in the original DMPfold paper.Significance StatementWe present a deep learning-based predictor of protein tertiary structure that uses only a multiple sequence alignment (MSA) as input. To date, most emphasis has been on the accuracy of such deep learning methods, but here we show that accurate structure prediction is also possible in very short timeframes (a few hundred milliseconds). In our method, the backbone coordinates of the target protein are output directly from the neural network, which makes the predictor extremely fast. As a demonstration, we generated over 1.3 million models of uncharacterised proteins in the BFD, a large sequence database including many metagenomic sequences. Our results showcase the utility of ultrafast and accurate tertiary structure prediction in rapidly exploring the “dark space” of proteins.
A set of common movements within GPCR-G-protein complexes from variability analysis of cryo-EM datasets
Authors: Marino Jacopo , Schertler Gebhard F.X. 
Published: November 2020

AbstractG-protein coupled receptors (GPCRs) are among the most versatile signal transducers in the cell. Once activated, GPCRs sample a large conformational space and couple to G-proteins to initiate distinct signaling pathways. The dynamical behavior of GPCR-G-protein complexes is difficult characterize structurally. Here, we report on the use of variability analysis to characterize the inherent flexibility within the cryo-EM dataset of the rhodopsin-Gi-protein complex (Tsai et al., 2019), on which this article builds on. We compare the outcome of this analysis with recently published results obtained on the cannabinoid-Gi- and secretin-Gs-receptor complexes. Despite differences related to the biochemical compositions of the three samples, a set of consensus movements emerges. We anticipate that systematic variability analysis on GPCR-G-protein complexes may provide useful information not only at the biological level, but also for improving the preparation of more stable samples for cryo-EM single-particle analysis.
A mechanism for hippocampal memory recall based on excitatory-inhibitory fluctuations in neocortex
Authors: Koolschijn Renée S. , Shpektor Anna , Ip I. Betina , Clarke William T. , Dupret David , Emir Uzay E. , Barron Helen C. 
Published: November 2020

ABSTRACTThe brain has a remarkable capacity to acquire and store memories that can later be selectively recalled. These processes are supported by the hippocampus which is thought to index memory recall by reinstating information stored across distributed neocortical circuits. However, the mechanism that supports this interaction remains unclear. Here, in humans, we show that recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex. Moreover, these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data suggest the hippocampus gates memory recall by indexing information stored across neocortical circuits using a disinhibitory mechanism.
LARP6C regulates selective mRNA translation to promote pollen tube guidance inArabidopsis thaliana
Authors: Billey Elodie , Hafidh Said , Cruz-Gallardo Isabel , Litholdo Celso G. , Jean Viviane , Carpentier Marie-Christine , Picart Claire , Kulichova Katarina , Honys David , Conte Maria R. , Deragon Jean-Marc , Bousquet-Antonelli Cécile 
Published: November 2020

ABSTRACTIn angiosperms, non-motile sperm cells are delivered to the ovules for fertilization via a guided growth of the pollen tube. RNA binding proteins are key regulators that control mRNA fate post-transcriptionally and thus essential for normal cell function. But very little is known on the mechanistic bases of mRNA regulations andtrans-acting factors governing male-female signalling. Here we demonstrate that the evolutionarily conserved RNA binding protein LARP6C is necessary for pollen tube guidance and fertilization.larp6closs-of-function mutants exhibit male induced fertility defects as mutant pollen tubes frequently are unable to find ovules for fertilization. In mature pollen, LARP6C localises with a pollen specific poly(A) binding protein to cytoplasmic foci likely containing mRNPs. With RNA immunoprecipitation and sequencing, we demonstrate that LARP6C is associatedin vivowith mRNAs required for pollen tube guidance or polarized cell growth. We further demonstrate usingin vitroandin plantatransient assays that LARP6C binds 5’-UTR box motifs to orchestrate the balance between translation, decay and storage of its mRNA targets. We propose a model where LARP6C maintains its mRNA target in translationally silent state likely to promote localized translation and guided pollen tube growth upon paracrine signalling.
Bacterial respiration during stationary phase induces intracellular damage that leads to dormancy
Authors: Cesar Spencer , Willis Lisa , Huang Kerwyn Casey 
Published: November 2020

AbstractMost bacteria frequently encounter nutrient-depleted conditions, necessitating regulatory mechanisms that alter cellular physiology and allow for survival of starvation. Here, we show that regrowth of Escherichia coli from prolonged stationary phase upon encountering fresh nutrients is heterogeneous, with one subpopulation suddenly regrowing after a delay (dormancy) and another of nongrowing cells that represented an increasing fraction as the culture aged. Moreover, a sizeable fraction of cells rejuvenated immediately, even when the inoculum was from very old cultures. The size of the dormant and nongrowing subpopulations depended on the time cells had endured stationary phase, as opposed to time-dependent changes to the medium. Regrowth of dormant cells was correlated with the dissolution of polar phase-bright foci that likely represent aggregates of damage, and a deep-learning algorithm was able to distinguish cellular fates based on a single stationary-phase image. Growth restarted in dormant cells after the upregulation of chaperones and DNA repair enzymes, and deletion of the chaperone DnaK resulted in compromised stationary-phase cell morphology and higher incidence of non-growing cells. A mathematical model of damage accumulation and division-mediated partitioning was in quantitative agreement with experimental data, including the small population of cells capable of immediate regrowth even in old cultures. Cells that endured stationary-phase without the ability to respire all immediately and homogeneously regrew in fresh nutrients, indicating that respiration in stationary phase is the driver of dormancy. These findings establish the importance of intracellular damage control when nutrients are sparse, and repair when nutrients are plentiful.
Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy
Authors: Lövestam Sofia , Schweighauser Manuel , Murayama Shigeo , Saito Yuko , Tomita Taisuke , Ando Takashi , Hasegawa Kazuko , Yoshida Mari , Tarutani Airi , Hasegawa Masato , Goedert Michel , Scheres Sjors H.W. 
Published: November 2020

AbstractThe propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α-synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α-synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of pathology. Identification of these factors will be essential for understanding the prion-like spreading of α-synuclein proteinopathies.
Establishment ofCulex modestusin Belgium and a glance into the virome of Belgian mosquito species
Authors: Wang Lanjiao , Rosas Ana Lucia Rosales , De Coninck Lander , Shi Chenyan , Bouckaert Johanna , Matthijnssens Jelle , Delang Leen 
Published: November 2020

AbstractCulex modestusmosquitoes are known transmission vectors of West Nile virus and Usutu virus. Their presence has been reported across several European countries, including only one larva confirmed in Belgium in 2018. Mosquitoes were collected in the city of Leuven and surroundings in the summer of 2019 and 2020. Species identification was performed based on morphological features and partial sequences of the mitochondrial cytochrome oxidase subunit 1 (COI) gene. The 107 mosquitoes collected in 2019 belonged to eight mosquito species:Cx. pipiens(24.3%),Cx. modestus(48.6%),Cx. torrentium(0.9%),Culiseta annulata(0.9%),Culiseta morsitans(0.9%),Ae. sticticus(14.0%),Ae. cinereus(9.3%) andAnopheles plumbeus(0.9%), suggesting the presence of an establishedCx. modestuspopulation in Belgium. Collection ofCx. modestusmosquitoes at the same locations in 2020, confirmed the establishment in the region.Haplotype network analysis of the COI sequences forCx. modestusshowed that the Belgian population is rather diverse, suggesting that it may have been established in Belgium for some time. The BelgianCx. modestuspopulation was most closely related to populations from the UK and Germany. Characterization of the virome of the collected mosquitoes resulted in the identification of at least 33 eukaryotic viral species. Nine (near-) complete genomes belonging to 6 viral species were identified, all of which were closely related to known viruses.In conclusion, we here report the presence ofCx. modestusin the surroundings of Leuven, Belgium. As this species is known to be a vector of several arboviruses, the implementation of vector surveillance programs monitoring this species is recommended.ImportanceCulex modestusis a mosquito species that plays a role as a ‘bridge’ vector, being able to transmit pathogens between birds, as well as from birds to mammals, including humans. In Belgium, this mosquito species was considered absent, until the finding of one larva in 2018 and subsequent evidence of a large population in 2019-2020 described here. We collected mosquitoes in the summer of 2019 and 2020 in the city of Leuven and surroundings. The mosquito species was identified by morphological and molecular methods, demonstrating the presence ofCx. modestusin this region. The ability of mosquitoes to transmit pathogens can depend on several factors, one of them being their natural virus composition. Therefore, we identified the mosquito-specific viruses harboured by Belgian mosquitoes. AsCx. modestusis able to transmit viruses such as West Nile virus and Usutu virus, the establishment of this mosquito species may increase the risk of virus transmission in the region. It is thus advisable to implement mosquito surveillance programs monitoring this species.
Dimorphism in Dental Tissues: Sex differences in Archaeological Individuals for Multiple Tooth Types
Authors: Fernée Christianne , Zakrzewski Sonia , Brown Katharine Robson 
Published: November 2020

AbstractObjectivesDimorphism in the dentition has been observed in human populations worldwide. However, research has largely focused on traditional linear crown measurements. As imaging systems, such as micro-computed tomography (micro-CT), become increasingly more accessible, new dental measurements such as dental tissue size and proportions can be obtained. This research investigates the variation of dental tissues and proportions by sex in archaeological samples.Materials and MethodsUpper and lower first incisor to second premolar tooth rows were obtained from 30 individuals (n=300), from 3 archaeological samples. The teeth were micro-CT scanned and surface area and volumetric measurements were obtained from the surface meshes extracted. Dental wear was also recorded and differences between sexes determined.ResultsEnamel and crown measurements were found to be larger in females. Conversely, dentine and root measurements were larger in males.DiscussionThe findings support the potential use of dental tissues to estimate sex of individuals from archaeological samples, whilst also indicating that individuals aged using current dental ageing methods may be under- or over-aged due to sex differences in enamel thickness.
Identification of Gli1 as a progenitor cell marker for meniscus development and injury repair
Authors: Wei Yulong , Sun Hao , Gui Tao , Yao Lutian , Zhong Leilei , Yu Wei , Heo Su-Jin , Han Lin , Liu X. Sherry , Zhang Yejia , Koyama Eiki , Long Fanxin , Zgonis Miltiadis , Mauck Robert L , Ahn Jaimo , Qin Ling 
Published: November 2020

AbstractMeniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using Gli1-CreER tdTomato mice, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1+ cells. Normally, the tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh activator right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.
Visual motion processing recruits regions selective for auditory motion in early deaf individuals
Authors: Benetti Stefania , Zonca Joshua , Ferrari Ambra , Rezk Mohamed , Rabini Giuseppe , Collignon Olivier 
Published: November 2020

AbstractIn early deaf individuals, the auditory deprived temporal brain regions become engaged in visual processing. In our study we tested further the hypothesis that intrinsic functional specialization guides the expression of cross-modal responses in the deprived auditory cortex. We used functional MRI to characterize the brain response to horizontal, radial and stochastic visual motion in early deaf and hearing individuals matched for the use of oral or sign language. Visual motion showed enhanced response in the ‘deaf’ mid-lateral planum temporale, a region selective to auditory motion as demonstrated by a separate auditory motion localizer in hearing people. Moreover, multivariate pattern analysis revealed that this reorganized temporal region showed enhanced decoding of motion categories in the deaf group, while visual motion-selective region hMT+/V5 showed reduced decoding when compared to hearing people. Dynamic Causal Modelling revealed that the ‘deaf’ motion-selective temporal region shows a specific increase of its functional interactions with hMT+/V5 and is now part of a large-scale visual motion selective network. In addition, we observed preferential responses to radial, compared to horizontal, visual motion in the ‘deaf’ right superior temporal cortex region that also show preferential response to approaching/receding sounds in the hearing brain. Overall, our results suggest that the early experience of auditory deprivation interacts with intrinsic constraints and triggers a large-scale reallocation of computational load between auditory and visual brain regions that typically support the multisensory processing of motion information.HighlightsAuditory motion-sensitive regions respond to visual motion in the deafReorganized auditory cortex can discriminate between visual motion trajectoriesPart of the deaf auditory cortex shows preference for in-depth visual motionDeafness might lead to computational reallocation between auditory/visual regions.
Deep neural network and field experiments reveal how transparent wing windows reduce detectability in moths
Authors: Arias Mónica , Tedore Cynthia , Elias Marianne , Leroy Lucie , Madec Clément , Matos Louane , Renoult Julien P. , Gomez Doris 
Published: November 2020

AbstractLepidoptera – a group of insects in which wing transparency has arisen multiple times - exhibit much variation in the size and position of transparent wing zones. However, little is known as to how this variability affects detectability. Here, we test how the size and position of transparent elements affect predation of artificial moths by wild birds in the field. We also test whether deep neural networks (DNNs) might be a reasonable proxy for live predators, as this would enable one to rapidly test a larger range of hypotheses than is possible with live animals. We compare our field results with results from six different DNN architectures (AlexNet, VGG-16, VGG-19, ResNet-18, SqueezeNet, and GoogLeNet). Our field experiment demonstrated the effectiveness of transparent elements touching wing borders at reducing detectability, but showed no effect of transparent element size. DNN simulations only partly matched field results, as larger transparent elements were also harder for DNNs to detect. The lack of consistency between wild predators’ and DNNs’ responses raises questions about what both experiments were effectively testing, what is perceived by each predator type, and whether DNNs can be considered to be effective models for testing hypotheses about animal perception and cognition.
Cooperation with non-kin: Context-dependent acceptance of alien queens by polygynous ant workers
Authors: De Gasperin Ornela , Blacher Pierre , Chapuisat Michel 
Published: November 2020

AbstractRelatedness underlies the evolution of reproductive altruism, yet eusocial insect colonies occasionally accept unrelated reproductive queens. To better understand this seemingly paradox, we investigated whether acceptance of unrelated queens by workers is an incidental phenomenon resulting from failure to recognize non-nestmate queens, or whether it is an adaptive behavior favored in specific contexts where cooperation is preferable to rejection. Our study system is the socially polymorphic Alpine silver ant,Formica selysi. Within populations some colonies have a single queen (monogynous), and others have multiple, sometimes unrelated, breeding queens (polygynous). Social organization is determined by a supergene with two haplotypes. In a first experiment we investigated whether workers from polygynous colonies were inherently more prone to accepting unrelated queens than workers from the alternate, monogynous social form. We found that workers rejected all alien queens, independently of their social origin and of the number of queens heading their colony. We then investigated whether queen acceptance was favored in specific conditions. We found that workers from polygynous colonies accepted alien queens when these queens were accompanied by workers. These results show that workers flexibly adjust their acceptance of alien queens according to the situation. We discuss how conditional acceptance of unrelated queens may be adaptive by providing benefits through increased colony size and/or genetic diversity, and by avoiding the rejection costs resulting from fighting.
Phytochrome contributes to blue-light-mediated stem elongation and associated shade-avoidance response in mature Arabidopsis plants
Authors: Kong Yun , Zheng Youbin 
Published: November 2020

AbstractOur recent studies on ornamental plants and microgreens indicate that blue-light-mediated stem elongation is related to phytochrome activity, which was based on the calculated phytochrome photoequilibrium. To examine whether phytochromes really contribute to the blue light’s effect, plant phenotypic responses were investigated in wild type Arabidopsis (Col-0), and its quintuple phytochrome (phyA phyB phyC phyD phyE) mutant plants under the following light treatments: (1) R, a pure red light from 660-nm LED; (2) B, a pure blue light from 455-nm LED; (3) BR, a impure blue light from LED combination of 94% B and 6% R; and (4) BRF, another impure blue light from LED combination of BR and 6 µmol m−2 s−1 of FR (735 nm). For all the light treatments, a photosynthetic photon flux density of ≈100 μmol m−2 s−1 were provided by 24-h lighting daily inside a walk-in growth chamber, which had an air temperature of ≈ 23 °C. The calculated phytochrome photoequilibrium was 0.89, 0.50, 0.69, and 0.60 for R, B, BR, and BRF, respectively, indicating a higher phytochrome activity under R and BR than B and BRF. After 18 days of light treatment, B or BRF increased main stem length in wild-type plants compared with R, but BR had an inhibition effect similar to R. Also, B and BRF relative to R or BR induced earlier flowering and reduced leaf size in wild type plants, showing typical shade-avoidance responses. In phytochrome-deficient mutant plants, the above shade-avoidance responses were inhibited under B or BRF, and induced under BR. However, as an exception, hypocotyl length, a growth trait during the de-etiolation stage, was reduced under B, BR and BRF vs. R regardless of phytochrome absence. It suggests that for mature Arabidopsis plants, phytochrome plays an active role in blue-light-mediated stem elongation and associated shade-avoidance response.