bluuebunny/crossref_metadata_2025 huggingface dataset:
Healing Adjuncts in Craniofacial Surgery: Review of Dietary Vitamins and Supplements
Authors: Spielman Amanda F. , Epstein Anabel , Jabori Sinan , Mathew Prakash , Thaller Seth
Published: November 2020

Background:

In the United States, the use of herbal supplements on a regular basis ranges from 32% to 97%. Prevalence of supplement use is particularly elevated after facial surgery. It has been reported as high as 50%. Unfortunately, there is a paucity of literature on the dietary use of supplements. They are not regulated by the FDA. Often, they are not reported by patients. This study examines the role of dietary supplements as adjuncts to healing in craniofacial and facial aesthetic surgeries.

Methods:

A comprehensive literature review was conducted using MEDLINE, PubMed, and EMBASE. Databases were screened for papers describing the use of supplements in craniofacial procedures in adult patients using relevant search terms. Data on criteria, outcomes, and patient satisfaction were collected.

Results:

A total of 19 articles were selected from the 806 identified. Fifteen different supplements or combinations of supplements have been studied for use in facial surgeries. Of these 15 supplements, the following demonstrated potential healing benefits: dry ivy leaf extract, Nazalzem ointment (vitamin A and dexpanthenol), combination nasal sprays (phospholipids, fatty acids, vitamin A, and vitamin E), Saireito pills, topical olive oil, yunnan baiyao, melilotus extract, arnica, and combination arnica and ledum. Arnica is the most commonly studied supplement in a variety of facial operations.

Conclusions:

There is ample evidence to support a role for the use of certain dietary supplements to optimize wound healing in craniofacial and facial aesthetic surgery. Controlled diet and use of appropriate supplements may have a synergistic beneficial effect on wound healing following craniofacial surgery. However, there is a need for additional reporting to allow for the creation of stronger guidelines and increased patient screening, reporting, and compliance.
Clinical Application of Carving Template With 3D Reconstruction Technique for Personalized and Precise Treatment of Traumatic Ear Defects
Authors: Song Yupeng , Yang Qinghua , Jiang Haiyue , Dong Weiwei
Published: November 2020

We explored the clinical application of a 3-dimensional (3D) digital reconstruction technique for personalized and precise traumatic ear defect treatment. A 3D scanner was used to obtain 3D images of the unaffected ear. The data were converted into an ear contour model through mirroring using the software, and imported to a rapid prototyping 3D printer to construct an ipsilateral ear model. For treating different types of ear defect patients with individualized treatment programs, the defective ear model was constructed with individualized autogenous costal cartilage carving. We constructed ipsilateral ear defect models in 16 cases and rebuilt the auricular with >10 outer ear substructure units, maintaining a stable cranial angle. At the 6-month follow-up, the reconstructed ear was similar to the unaffected one, and the patient satisfaction was high. Based on a paired t test, the differences in the width of both auricles was statistically significant, with P values of 0.023, respectively. The differences in the P values of the auricle length, circumference and height, at 0.261, 0.333, and 0.197, respectively, were not statistically significant. Compared to the model utilizing the traditional 2D film template of the ear, the 3D reconstruction technology was more intuitive and stereoscopic, and the personalized ear reconstruction was accurate. Thus, 3D digital technology can avail the most suitable personalized treatment for various traumatic ear defects. It can assist in precisely engraving the reconstructed cartilage stent and objectively analyzing the postoperative results. The therapeutic effect was significant.
Taxon incompleteness and discrete time bins affect character change rates in simulated data
Authors: Flores Jorge R.
Published: November 2020

Estimating how fast or slow morphology evolves through time (phenotypic change rate, PR) has become common in macroevolutionary studies and has been important for clarifying key evolutionary events. However, the inclusion of incompletely scored taxa (e.g. fossils) and variable lengths of discrete arbitrary time bins could affect PR estimates and potentially mask real PR patterns. Here, the impact of taxon incompleteness (unscored data) on PR estimates is assessed in simulated data. Three different time bin series were likewise evaluated: bins evenly spanning the tree length (i), a shorter middle bin and longer first and third bins (ii), and a longer middle bin and shorter first and third bins (iii). The results indicate that PR values decrease as taxon incompleteness increases. Statistically significant PR values, and the dispersion among PR values, depended on the time bins. These outcomes imply that taxon incompleteness can undermine our capacity to infer morphology evolutionary dynamics and that these estimates are also influenced by our choice of discrete time bins. More importantly, the present results stress the need for a better approach to deal with taxon incompleteness and arbitrary discrete time bins.
Surface periarterial spaces of the mouse brain are open, not porous
Authors: Min Rivas Fatima , Liu Jia , Martell Benjamin C. , Du Ting , Mestre Humberto , Nedergaard Maiken , Tithof Jeffrey , Thomas John H. , Kelley Douglas H.
Published: November 2020

Fluid-dynamic models of the flow of cerebrospinal fluid in the brain have treated the perivascular spaces either as open (without internal solid obstacles) or as porous. Here, we present experimental evidence that pial (surface) periarterial spaces in mice are essentially open. (1) Paths of particles in the perivascular spaces are smooth, as expected for viscous flow in an open vessel, not diffusive, as expected for flow in a porous medium. (2) Time-averaged velocity profiles in periarterial spaces agree closely with theoretical profiles for viscous flow in realistic models, but not with the nearly uniform profiles expected for porous medium. Because these spaces are open, they have much lower hydraulic resistance than if they were porous. To demonstrate, we compute hydraulic resistance for realistic periarterial spaces, both open and porous, and show that the resistance of the porous spaces are greater, typically by a factor of a hundred or more. The open nature of these periarterial spaces allows significantly greater flow rates and more efficient removal of metabolic waste products.
Will an outbreak exceed available resources for control? Estimating the risk from invading pathogens using practical definitions of a severe epidemic
Authors: Thompson R. N. , Gilligan C. A. , Cunniffe N. J.
Published: November 2020

Forecasting whether or not initial reports of disease will be followed by a severe epidemic is an important component of disease management. Standard epidemic risk estimates involve assuming that infections occur according to a branching process and correspond to the probability that the outbreak persists beyond the initial stochastic phase. However, an alternative assessment is to predict whether or not initial cases will lead to a severe epidemic in which available control resources are exceeded. We show how this risk can be estimated by considering three practically relevant potential definitions of a severe epidemic; namely, an outbreak in which: (i) a large number of hosts are infected simultaneously; (ii) a large total number of infections occur; and (iii) the pathogen remains in the population for a long period. We show that the probability of a severe epidemic under these definitions often coincides with the standard branching process estimate for the major epidemic probability. However, these practically relevant risk assessments can also be different from the major epidemic probability, as well as from each other. This holds in different epidemiological systems, highlighting that careful consideration of how to classify a severe epidemic is vital for accurate epidemic risk quantification.
Learning strategies and long-term memory in Asian short-clawed otters (Aonyx cinereus)
Authors: Saliveros Alexander M. , Blyth Eleanor C. , Easter Carrie , Hume Georgina V. , McAusland Fraser , Hoppitt William , Boogert Neeltje J.
Published: November 2020

Social learning, where information is acquired from others, is taxonomically widespread. There is growing evidence that animals selectively employ ‘social learning strategies', which determine e.g. when to copy others instead of learning asocially and whom to copy. Furthermore, once animals have acquired new information, e.g. regarding profitable resources, it is beneficial for them to commit it to long-term memory (LTM), especially if it allows access to profitable resources in the future. Research into social learning strategies and LTM has covered a wide range of taxa. However, otters (subfamily Lutrinae), popular in zoos due to their social nature and playfulness, remained neglected until a recent study provided evidence of social learning in captive smooth-coated otters (Lutrogale perspicillata), but not in Asian short-clawed otters (Aonyx cinereus). We investigated Asian short-clawed otters' learning strategies and LTM performance in a foraging context. We presented novel extractive foraging tasks twice to captive family groups and used network-based diffusion analysis to provide evidence of a capacity for social learning and LTM in this species. A major cause of wild Asian short-clawed otter declines is prey scarcity. Furthering our understanding of how they learn about and remember novel food sources could inform key conservation strategies.
Testing the carotenoid-based sexual signalling mechanism by altering
CYP2J19
gene expression and colour in a bird species
Authors: Cantarero Alejandro , Andrade Pedro , Carneiro Miguel , Moreno-Borrallo Adrián , Alonso-Alvarez Carlos
Published: November 2020

Ornaments can evolve to reveal individual quality when their production/maintenance costs make them reliable as ‘signals’ or if their expression level is intrinsically linked to condition by some unfalsifiable mechanism (indices). The latter has been mostly associated with traits constrained by body size. In red ketocarotenoid-based colorations, that link could, instead, be established with cell respiration at the inner mitochondrial membrane (IMM). The production mechanism could be independent of resource (yellow carotenoids) availability, thus discarding costs linked to allocation trade-offs. A gene coding for a ketolase enzyme (CYP2J19) responsible for converting dietary yellow carotenoids to red ketocarotenoids has recently been described. We treated male zebra finches with an antioxidant designed to penetrate the IMM (mitoTEMPO) and a thyroid hormone (triiodothyronine) with known hypermetabolic effects. Among hormone controls, MitoTEMPO downregulated
CYP2J19
in the bill (a red ketocarotenoid-based ornament), supporting the mitochondrial involvement in ketolase function. Both treatments interacted when increasing hormone dosage, indicating that mitochondria and thyroid metabolisms could simultaneously regulate coloration. Moreover,
CYP2J19
expression was positively correlated to redness but also to yellow carotenoid levels in the blood. However, treatment effects were not annulated when controlling for blood carotenoid variability, which suggests that costs linked to resource availability could be minor.
Pollen feeding inHeliconiusbutterflies: the singular evolution of an adaptive suite
Authors: Young Fletcher J. , Montgomery Stephen H.
Published: November 2020

Major evolutionary transitions can be triggered by behavioural novelty, and are often associated with ‘adaptive suites’, which involve shifts in multiple co-adapted traits subject to complex interactions.Heliconiusbutterflies represent one such example, actively feeding on pollen, a behaviour unique among butterflies. Pollen feeding permits a prolonged reproductive lifespan, and co-occurs with a constellation of behavioural, neuroanatomical, life history, morphological and physiological traits that are absent in closely related, non-pollen-feeding genera. As a highly tractable system, supported by considerable ecological and genomic data,Heliconiusare an excellent model for investigating how behavioural innovation can trigger a cascade of adaptive shifts in multiple diverse, but interrelated, traits. Here, we synthesize current knowledge of pollen feeding inHeliconius, and explore potential interactions between associated, putatively adaptive, traits. Currently, no physiological, morphological or molecular innovation has been explicitly linked to the origin of pollen feeding, and several hypothesized links between different aspects ofHeliconiusbiology remain poorly tested. However, resolving these uncertainties will contribute to our understanding of how behavioural innovations evolve and subsequently alter the evolutionary trajectories of diverse traits impacting resource acquisition, life history, senescence and cognition.
Work that body: fin and body movements determine herbivore feeding performance within the natural reef environment
Authors: Perevolotsky Tal , Martin Christopher H. , Rivlin Asaph , Holzman Roi
Published: November 2020

Herbivorous fishes form a keystone component of reef ecosystems, yet the functional mechanisms underlying their feeding performance are poorly understood. In water, gravity is counter-balanced by buoyancy, hence fish are recoiled backwards after every bite they take from the substrate. To overcome this recoil and maintain contact with the algae covered substrate, fish need to generate thrust while feeding. However, the locomotory performance of reef herbivores in the context of feeding has hitherto been ignored. We used a three-dimensional high-speed video system to track mouth and body kinematics duringin situfeeding strikes of fishes in the genusZebrasoma, while synchronously recording the forces exerted on the substrate. These herbivores committed stereotypic and coordinated body and fin movements when feeding off the substrate and these movements determined algal biomass removed. Specifically, the speed of rapidly backing away from the substrate was associated with the magnitude of the pull force and the biomass of algae removed from the substrate per feeding bout. Our new framework for measuring biting performancein situdemonstrates that coordinated movements of the body and fins play a crucial role in herbivore foraging performance and may explain major axes of body and fin shape diversification across reef herbivore guilds.
Locomotion and palaeoclimate explain the re-evolution of quadrupedal body form inBrachymeleslizards
Authors: Bergmann Philip J. , Morinaga Gen , Freitas Elyse S. , Irschick Duncan J. , Wagner Günter P. , Siler Cameron D.
Published: November 2020

Evolutionary reversals, including re-evolution of lost structures, are commonly found in phylogenetic studies. However, we lack an understanding of how these reversals happen mechanistically. A snake-like body form has evolved many times in vertebrates, and occasionally a quadrupedal form has re-evolved, including inBrachymeleslizards. We use body form and locomotion data for species ranging from snake-like to quadrupedal to address how a quadrupedal form could re-evolve. We show that large, quadrupedal species are faster at burying and surface locomotion than snake-like species, indicating a lack of expected performance trade-off between these modes of locomotion. Species with limbs use them while burying, suggesting that limbs are useful for burying in wet, packed substrates. Palaeoclimatological data suggest thatBrachymelesoriginally evolved a snake-like form under a drier climate probably with looser soil in which it was easier to dig. The quadrupedal clade evolved as the climate became humid, where limbs and large size facilitated fossorial locomotion in packed soils.
Reintroduced wolves and hunting limit the abundance of a subordinate apex predator in a multi-use landscape
Authors: Elbroch L. Mark , Ferguson Jake M. , Quigley Howard , Craighead Derek , Thompson Daniel J. , Wittmer Heiko U.
Published: November 2020

Top-down effects of apex predators are modulated by human impacts on community composition and species abundances. Consequently, research supporting top-down effects of apex predators occurs almost entirely within protected areas rather than the multi-use landscapes dominating modern ecosystems. Here, we developed an integrated population model to disentangle the concurrent contributions of a reintroduced apex predator, the grey wolf, human hunting and prey abundances on vital rates and abundance of a subordinate apex predator, the puma. Increasing wolf numbers had strong negative effects on puma fecundity, and subadult and adult survival. Puma survival was also influenced by density dependence. Overall, puma dynamics in our multi-use landscape were more strongly influenced by top-down forces exhibited by a reintroduced apex predator, than by human hunting or bottom-up forces (prey abundance) subsidized by humans. Quantitatively, the average annual impact of human hunting on equilibrium puma abundance was equivalent to the effects of 20 wolves. Historically, wolves may have limited pumas across North America and dictated puma scarcity in systems lacking sufficient refugia to mitigate the effects of competition.
Pseudopontixanthobacter vadosimaris gen. nov., sp. nov., isolated from shallow sea near Kueishan Island
Authors: Sun Jia , Guo Jiaying , Lin Ta-Hui , Feng Xuejin , Zhang Rui
Published: November 2020

A Gram-stain-negative and aerobic bacterial strain, designated as JL3514T, was isolated from surface water of the hydrothermal system around Kueishan Island. The isolate formed red colonies and cells were non-flagellated, rod-shaped and contained methanol-soluble pigments. Growth was observed at 10–50 °C (optimum, 30 °C), at pH 5.0–9.0 (optimum, pH 7.0) and in the presence of 0–9 % (w/v) NaCl (optimum, 2 %). Strain JL3514T was positive for catalase and weakly positive for oxidase. Results of 16S rRNA gene sequence analyses showed highest similarities to species in the family

Erythrobacteraceae

, namely

Croceibacterium atlanticum

(96.1 %),

Pelagerythrobacter marensis

(96.0 %),

Tsuneonella rigui

(96.0 %) and

Altericroceibacterium xinjiangense

(96.0 %). Phylogenetic analysis based on core gene sequences revealed that the isolate formed a distinct branch with the related species and it had a lower average amino acid identity value than the suggested threshold for genera boundaries. The major fatty acids (>5 %) were summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c), summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 0, C17 : 1
 ω6c, C14 : 0 2-OH and C12 : 0. The dominant polar lipids comprised diphosphatidylglycerol, sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, glycolipid, two unidentified lipids and one unidentified phospholipid. The main respiratory quinones were ubiquinone-10 (95.7 %) and ubiquinone-9 (4.3 %). The DNA G+C content from the genome was 63.0 mol%. Based on the presented data, we consider strain JL3514T to represent a novel genus of the family

Erythrobacteraceae

, with the name Pseudopontixanthobacter vadosimaris gen. nov., sp. nov. The type strain is JL3514T (=KCTC 62623T=MCCC 1K03561T).
Diversity of the ‘Candidatus Phytoplasma asteris’ and ‘Candidatus Phytoplasma fraxini’ isolates that infect urban trees in Bogotá, Colombia
Authors: Franco-Lara Liliana , García Jennifer Andrea , Bernal Yuly Eilen , Rodríguez Rubén Adolfo
Published: November 2020

Phytoplasmas have been associated with a disease that affects trees of at least 11 species from different botanic families in Bogotá, Colombia. ‘Candidatus Phytoplasma asteris’ and ‘Candidatus Phytoplasma fraxini’ are the major groups of phytoplasma in the area of Bogotá. In this study, the genetic diversity within ‘Ca. P. asteris’ and ‘Ca. P. fraxini’ was studied in five urban tree species: Croton species (Euphorbiaceae), Fraxinus uhdei (Oleaceae), Magnolia grandiflora (Magnoliaceae), Populus nigra (Salicaceae) and Quercus humboldtii (Fagaceae). Analyses of the 16S rRNA gene using nested PCR, RFLP and sequencing showed that phytoplasmas of ‘Ca. P. asteris’ could be assigned to: subgroup 16SrI-B; a new subgroup named 16SrI-AF, with a restriction pattern similar to that of 16SrI-B; and a new subgroup named 16SrI-AG, with a restriction pattern similar to that of 16SrI-K and 16SrI-AH with a restriction pattern similar to that of 16SrI-AC. ‘Ca. P. fraxini’ isolates belonged to a new subgroup named 16SrVII-G, with a restriction pattern similar to that of 16SrVII-A. To complement the identification of the phytoplasma strains, we amplified nonribosomal genes such as leuS and secA. Unexpectedly, it was observed that in 16 trees in which 16S rRNA gene analysis showed the presence of ‘Ca. P. fraxini’ only, the leuS or secA primers amplified sequences exclusively affiliated to ‘Ca. P. asteris. In those plants, sequences belonging to ‘Ca. P. fraxini’ leuS or secA genes were not amplified. The present work contributes to the identification of novel strains of both species in Colombia, and supports previous suggestions that phytoplasmas in South America are highly variable.
Deconstructing the mouse olfactory percept through an olfactory ethological atlas
Authors: Manoel Diogo , Makhlouf Melanie , Arayata Charles J. , Sathappan Abbirami , Da’as Sahar , Abdelrahman Doua , Selvaraj Senthil , Hasnah Reem , Mainland Joel D. , Gerkin Richard C. , Saraiva Luis R.
Published: November 2020

Odor perception in non-humans is poorly understood. Here, we generated the most comprehensive murine olfactory ethological atlas to date, consisting of behavioral responses to a diverse panel of 73 odorants, including 12 at multiple concentrations. These data revealed that the mouse behavior is incredibly diverse, and changes in response to odor identity and intensity. Using only behavioral responses, ~30% of the 73 odorants could be identified with high accuracy (>96%) by a trained classifier. Mouse behavior occupied a low-dimensional space, consistent with analyses of human olfactory perception. While mouse olfactory behavior is difficult to predict from the corresponding human olfactory percept, three fundamental properties are shared: odor valence is the primary axis of olfactory perception; the physicochemical properties of odorants can predict the olfactory percept; and odorant concentration quantitatively and qualitatively impacts olfactory perception. These results provide a template for future comparative studies of olfactory percepts among species.
Identification and phenotype of MAIT cells in cattle and their response to bacterial infections
Authors: Edmans Matthew D. , Connelley Timothy K. , Jayaraman Siddharth , Vrettou Christina , Vordermeier Martin , Mak Jeffrey Y. W. , Liu Ligong , Fairlie David P. , Maze Emmanuel Atangana , Chrun Tiphany , Klenerman Paul , Eckle Sidonia B. G. , Tchilian Elma , Benedictus Lindert
Published: November 2020

Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilise a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such asMycobacterium spp.,Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilising MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localisation, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteriain vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulentMycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.
Short-range template switching in great ape genomes explored using a pair hidden Markov model
Authors: Walker Conor R. , Scally Aylwyn , De Maio Nicola , Goldman Nick
Published: November 2020

Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes’ genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons.
Proteobacteria encode diverse flg22 peptides that elicit varying immune responses inArabidopsis thaliana
Authors: Cheng Janis H.T. , Bredow Melissa , Monaghan Jacqueline , diCenzo George C.
Published: November 2020

Bacterial flagellin protein is a potent microbe-associated molecular pattern. Immune responses are triggered by a 22 amino acid epitope derived from flagellin, known as flg22, upon detection by the pattern recognition receptor FLAGELLIN-SENSING2 (FLS2) in multiple plant species. However, increasing evidence suggests that flg22 epitopes of several bacterial species are not universally immunogenic to plants. We investigated whether flg22 immunogenicity systematically differs between classes of the phylum Proteobacteria, using a dataset of 2,470 flg22 sequences. To predict which species encode highly immunogenic flg22 epitopes, we queried a custom motif (11[ST]xx[DN][DN]xAGxxI21) in the flg22 sequences, followed by sequence conservation analysis and protein structural modelling. These data led us to hypothesize that most flg22 epitopes of the γ- and β-Proteobacteria are highly immunogenic, whereas most flg22 epitopes of the α-, δ-, and ε-Proteobacteria are weakly to moderately immunogenic. To test this hypothesis, we generated synthetic peptides representative of the flg22 epitopes of each proteobacterial class, and we monitored their ability to elicit an immune response inArabidopsis thaliana. Flg22 peptides of the γ- and β-Proteobacteria triggered strong oxidative bursts, whereas peptides from the ε-, δ-, and α-Proteobacteria triggered moderate, weak, or no response, respectively. These data suggest flg22 immunogenicity is not highly conserved across the phylum Proteobacteria. We postulate that sequence divergence of each taxonomic class was present prior to the evolution of FLS2, and that the ligand specificity ofA. thalianaFLS2 was driven by the flg22 epitopes of the γ- and β-proteobacteria, a monophyletic group containing many common phytopathogens.
Navigating the amino acid sequence space between functional proteins using a deep learning framework
Authors: Bitard-Feildel Tristan
Published: November 2020

Motivation

Shedding light on the relationships between protein se-quences and functions is a challenging task with many implications in protein evolution, diseases understanding, and protein design. Protein sequence / function space is however hard to comprehend due to its com-plexity. Generative models help to decipher complex systems thanks to their abilities to learn and recreate data specificity. Applied to protein sequences, they can point out relationships between protein positions and functions capture the sequence patterns associated with functions or navigate through uncharted area of molecular evolution.

Results

In this study, an unsupervised generative approach based on adversarial auto-encoder (AAE) is proposed to generate and explore new sequences with respect to their functions thanks to the prior distribution allowing a continuous exploration of the latent space. AAEs are tested on three protein families known for their multiple functions. Clustering re-sults on the encoded sequences from the latent space computed by AAEs display high level of homogeneity regarding the protein sequence func-tions. The study also reports and analyzes for the first time two sampling strategies based on latent space interpolation and latent space arithmetic to generate intermediate protein sequences sharing sequential and functional properties of original sequences issued from different families and functions. Generated sequences by interpolation between latent space data points demonstrate the ability of the AAE to generalize and to pro-duce meaningful biological sequences from an evolutionary uncharted area of the biological sequence space. Finally, 3D structure models generated by comparative modelling between different combinations of structures of different sub-families and of generated sequences from latent space or sub-family sequences point out to the ability of the latent space arithmetic to successfully transfer functional properties between sub-families. All in all this study confirms the ability of deep learning frameworks to model biological complexity and bring new tools to explore amino acid sequence and functional spaces.

Availability

Code and data used for this study are freely available at https://github.com/T-B-F/aae4seq.

Contact

tristan@bitardfeildel.fr

Supplementary information

Supplementary data are available at online.
Inferring species interactions from ecological survey data: a mechanistic approach to predict quantitative food webs of seed-feeding by carabid beetles
Authors: Pocock Michael J.O. , Schmucki Reto , Bohan David A.
Published: November 2020

Ecological networks are valuable for ecosystem analysis but their use is often limited by a lack of data because many types of ecological interaction, e.g. predation, are short-lived and difficult to observe or detect. There are different methods for inferring the presence of interactions, which we lack methods to predict interaction strengths and so use weighted network analysis.

Here, we develop a trait-based approach suitable for creating quantitative networks, i.e. with varying interaction strengths. We developed the method for seed-feeding carabid ground beetles (Coleoptera: Carabidae) although the principles can be applied to other interactions.

We used existing literature data from experimental seed-feeding trials to predict a per-individual interaction cost index based on carabid and seed size with frequency-dependent prey selection and assuming bottom up control. This was scaled up to the population level to create predicted inferred weighted networks using the abundance of carabids and seeds in samples from arable fields and energetic intake rates of carabids from the literature. From these weighted networks, we also calculated a novel measure of predation pressure.

We applied it to existing ecological survey data from 255 arable fields with carabid data from pitfall traps and plant seeds from seed rain traps. Analysis of these inferred networks led to testable hypotheses about how networks and predation pressure varied amongst fields.

Inferred networks are valuable because (i) they provide null models for the structuring of food webs to test against empirical species interaction data, e.g. DNA analysis of carabid gut regurgitates, and (ii) they allow weighted inferred networks to be constructed whenever we can estimate interactions between species and have ecological census data available. This would permit network analysis even at times and in places when interactions were not directly assessed.
DeepCorn: A Semi-Supervised Deep Learning Method for High-Throughput Image-Based Corn Kernel Counting and Yield Estimation
Authors: Khaki Saeed , Pham Hieu , Han Ye , Kuhl Andy , Kent Wade , Wang Lizhi
Published: November 2020

Abstract

The success of modern farming and plant breeding relies on accurate and efficient collection of data. For a commercial organization that manages large amounts of crops, collecting accurate and consistent data is a bottleneck. Due to limited time and labor, accurately phenotyping crops to record color, head count, height, weight, etc. is severely limited. However, this information, combined with other genetic and environmental factors, is vital for developing new superior crop species that help feed the world’s growing population. Recent advances in machine learning, in particular deep learning, have shown promise in mitigating this bottleneck. In this paper, we propose a novel deep learning method for counting on-ear corn kernels in-field to aid in the gathering of real-time data and, ultimately, to improve decision making to maximize yield. We name this approach DeepCorn, and show that this framework is robust under various conditions and can accurately and efficiently count corn kernels. We also adopt a semi-supervised learning approach to further improve the performance of our proposed method. Our experimental results demonstrate the superiority and effectiveness of our proposed method compared to other state-of-the-art methods.
Reduction of collinear inhibition in observers with central vision loss using anodal transcranial direct current stimulation: A case series
Authors: Raveendran Rajkumar Nallour , Chow Amy , Tsang Katelyn , Chakraborty Arijit , Thompson Benjamin
Published: November 2020

People with central vision loss (CVL) due to macular degeneration are forced to rely on their residual peripheral vision and often develop a preferred retinal locus (PRL), a region of intact peripheral retina that is used for fixation. At the PRL, visual processing is impaired due to crowding (cluttering of visual objects). The problem of crowding still persists when images are magnified to account for the lower resolution of peripheral vision. We assessed whether anodal transcranial direct stimulation (a-tDCS), a neuro-modulation technique that alters cortical inhibition, would reduce collinear inhibition (an early component of crowding) when applied to the visual cortex in patients with CVL. Our results showed that applying a-tDCS to the visual cortex for 20mins reduced crowding in three patients with CVL and that the effect was sustained for up to 30mins. Sham stimulation delivered in a separate session had no effect. These initial observations mandate further research into the use of a-tDCS to enhance cortical processing of residual retinal input in patients with CVL.
Structure, interdomain dynamics and pH-dependent autoactivation of pro-rhodesain, the main lysosomal cysteine protease from African trypanosomes
Authors: Johé Patrick , Jaenicke Elmar , Neuweiler Hannes , Schirmeister Tanja , Kersten Christian , Hellmich Ute A.
Published: November 2020

Rhodesain is the lysosomal cathepsin L-like cysteine protease ofT. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Lysosomal cathepsins are expressed as zymogens with an inactivating pro-domain that is cleaved under acidic conditions. A structure of the uncleaved maturation intermediate from a trypanosomal cathepsin L-like protease is currently not available. We thus established the heterologous expression ofT. brucei rhodesiensepro-rhodesain inE. coliand determined its crystal structure. The trypanosomal pro-domain differs from non-parasitic pro-cathepsins by a unique, extended α-helix that blocks the active site and whose interactions resemble that of the antiprotozoal inhibitor K11777. Interdomain dynamics between pro- and core protease domain as observed by photoinduced electron transfer fluorescence correlation spectroscopy increase at low pH, where pro-rhodesain also undergoes autocleavage. Using the crystal structure, molecular dynamics simulations and mutagenesis, we identify a conserved interdomain salt bridge that prevents premature intramolecular cleavage at higher pH values and may thus present a control switch for the observed pH-sensitivity of pro-enzyme cleavage in (trypanosomal) CathL-like proteases.
The Brain Activation-based Sexual Image Classifier (BASIC): A sensitive and specific fMRI activity pattern for sexual image perception
Authors: van ’t Hof Sophie R. , Van Oudenhove Lukas , Klein Sanja , Reddan Marianne C. , Kragel Philip A. , Stark Rudolf , Wager Tor D.
Published: November 2020

Sexual stimuli processing is a key element in the repertoire of human affective and motivational states. Previous neuroimaging studies of sexual stimulus processing have revealed a complicated mosaic of activated regions, leaving unresolved questions about their sensitivity and specificity to sexual stimuli per se, generalizability across individuals, and potential utility as neuromarkers for sexual stimulus processing. In this study, data on sexual, negative, non-sexual positive, and neutral images from Wehrum et al. (2013) (N = 100) were re-analyzed with multivariate Support Vector Machine models to create the Brain Activation-based Sexual Image Classifier (BASIC) model. This model was tested for sensitivity, specificity, and generalizability in cross-validation (N = 100) and an independent test cohort (N = 18; Kragel et al. 2019). The BASIC model showed highly accurate performance (94-100%) in classifying sexual versus neutral or nonsexual affective images in both datasets. Virtual lesions and test of individual large-scale networks (e.g., ‘visual’ or ‘attention’ networks) show that these individual networks are neither necessary nor sufficient to capture sexual stimulus processing. These findings suggest that brain responses to sexual stimuli constitute a category of mental event that is distinct from general affect and involves multiple brain networks. It is, however, largely conserved across individuals, permitting the development of neuromarkers for sexual processing in individual persons. Future studies could assess performance of BASIC to a broader array of affective/motivational stimuli and link brain responses with physiological and subjective measures of sexual arousal.
Evaluating the reproducibility of single-cell gene regulatory network inference algorithms
Authors: Kang Yoonjee , Thieffry Denis , Cantini Laura
Published: November 2020

Networks are powerful tools to represent and investigate biological systems. The development of algorithms inferring regulatory interactions from functional genomics data has been an active area of research. With the advent of single-cell RNA-seq data (scRNA-seq), numerous methods specifically designed to take advantage of single-cell datasets have been proposed. However, published benchmarks on single-cell network inference are mostly based on simulated data. Once applied to real data, these benchmarks take into account only a small set of genes and only compare the inferred networks with an imposed ground-truth.

Here, we benchmark four single-cell network inference methods based on their reproducibility, i.e. their ability to infer similar networks when applied to two independent datasets for the same biological condition. We tested each of these methods on real data from three biological conditions: human retina, T-cells in colorectal cancer, and human hematopoiesis.

GENIE3 results to be the most reproducible algorithm, independently from the single-cell sequencing platform, the cell type annotation system, the number of cells constituting the dataset, or the thresholding applied to the links of the inferred networks. In order to ensure the reproducibility and ease extensions of this benchmark study, we implemented all the analyses in scNET, a Jupyter notebook available athttps://github.com/ComputationalSystemsBiology/scNET.
Dihydroceramide desaturase promotes the formation of intraluminal vesicles and inhibits autophagy to increase exosome production
Authors: Wu Chen-Yi , Jhang Jhih-Gang , Lin Wan-Syuan , Lin Chih-Wei , Chu Li-An , Chiang Ann-Shyn , Ho Han-Chen , Chan Chih-Chiang , Huang Shu-Yi
Published: November 2020

Exosomes are important for cell-cell communication. Deficiencies in the human dihydroceramide desaturase gene,DEGS1, increase the dihydroceramide-to-ceramide ratio and causes hypomyelinating leukodystrophy. However, the disease mechanism remains unknown. Here, we developed anin vivoassay with spatially controlled expression of exosome markers inDrosophilaeye imaginal discs and showed that the level and activity of the DEGS1 ortholog,ifc, correlated with exosome production. Knocking outifcdecreased the density of the exosome precursor intraluminal vesicles (ILVs) in the multivesicular endosomes and reduced the number of exosomes released. Whileifcoverexpression and autophagy inhibition both enhanced exosome production, combining the two had no additive effect. Moreover, DEGS1 activity was sufficient to drive ILV formationin vitro. Together, DEGS1/Ifc controls the dihydroceramide-to-ceramide ration and enhances exosome secretion by promoting ILV formation and preventing the autophagic degradation of MVEs.

These findings provide a potential cause for the neuropathy associated with DEGS1-deficient mutations.

Graphical Abstract

Highlights

Anin vivosystem was developed for observing exosome production inDrosophila.

Dihydroceramide desaturase (DEGS1/Ifc) promotes exosome production by two means.

Ifc drives membrane invagination to promote the formation of intraluminal vesicles.

Ifc inhibits autophagic degradation of MVEs and increases exosome release.

eTOC Blurb

The level and activity of dihydroceramide desaturase (human DEGS1 and Drosophila Ifc) correlate with exosome production. Wu et al. show that DEGS1 drives the formation of intraluminal vesiclesin vivoandin vitro. Overexpressing Ifc inhibits autophagy and reduces the degradation of multivesicular endosomes, thus increases exosome release.
ECM remodeling and spatial cell cycle coordination determine tissue growth kinetics
Authors: Ainslie Anna P. , Davis John Robert , Williamson John J. , Ferreira Ana , Torres-Sánchez Alejandro , Hoppe Andreas , Mangione Federica , Smith Matthew B. , Martin-Blanco Enrique , Salbreux Guillaume , Tapon Nicolas
Published: November 2020

During development, multicellular organisms undergo stereotypical patterns of tissue growth to yield organs of highly reproducible sizes and shapes. How this process is orchestrated remains unclear. Analysis of the temporal dynamics of tissue growth in theDrosophilaabdomen reveals that cell cycle times are spatially correlated and that growth termination occurs through the rapid emergence of a population of arrested cells rather than a gradual slowing down of cell cycle time. Reduction in apical tension associated with tissue crowding has been proposed as a developmental growth termination mechanism. Surprisingly, we find that growth arrest in the abdomen occurs while apical tension increases, showing that in this tissue a reduction in tension does not underlie the mechanism of growth arrest. However, remodeling of the extracellular matrix is necessary for tissue expansion. Thus, changes in the tissue microenvironment, and a rapid exit from proliferation, control the formation of the adultDrosophilaabdomen.
Docosahexaenoic acid alone and in combination with carboplatin significantly reduces tumor cell growth in preclinical models of ovarian cancer
Authors: Bilyk Olena , Hamedi Bahareh , Dutta Indrani , Newell Marnie , Bukhari Amirali B. , Gamper Armin M. , McVea Rojine C. , Liu Jiahui , Schueler Julia , Siegers Gabrielle M. , Field Catherine J. , Postovit Lynne-Marie
Published: November 2020

Despite recent advances in diagnosis and treatment, ovarian cancer (OC) is the most lethal gynecological malignancy and improving the efficacy of chemotherapy is of great interest. This study increases our understanding of how dietary intervention with docosahexaenoic acid (DHA)-a supplement proven safe for human consumption – enhances the anti-cancer effects of conventional chemotherapy. Our results demonstrated synergistic cell killing by DHA and carboplatin in OC cell lines. Furthermore, DHA supplementation alone and in combination with carboplatin significantly reduced OC growth in a high-grade serous OC patient-derived xenograft mouse model. Carboplatin administered intraperitoneally significantly reduced tumor growth in DHA-fed mice compared to mice on the control diet. Intravenous carboplatin administration in combination with DHA reduced tumor growth similarly to carboplatin or DHA monotherapies. The DHA-induced reduction in tumor growth in this model was associated with increased tumor necrosis and improved survival. As such, our findings provide a strong rationale to move to clinical trials that will determine whether DHA supplementation enhances the efficacy and tolerance of cytotoxic chemotherapy in patients with OC.
Soluble SorCS1 binds the insulin receptor to enhance insulin sensitivity
Authors: Kjolby Mads , Breining Peter , Pedersen Karen Marie , Wellner Niels , Juul Sørensen Karen Marie , Prior Gjesing Anette Marianne , Januliene Dovile , Vittrup Dorthe Maria , Manavalan Arulmani , Rotman Maarten , Thotakura Gangadaar , Hermey Guido , Madsen Peder , Vaegter Christian B. , Thirup Søren , Asplund Olof , Prasad Rashmi B. , Parlevliet Edwin T. , Rensen Patrick C.N. , Madsen Andreas Nygaard , Holst Birgitte , Andersen Olav M. , Möller Arne , Hansen Torben , Nykjaer Anders
Published: November 2020

Type 2 diabetes has reached endemic proportions and is a substantial burden for the affected patients and the society. Along with lifestyle factors, a number of genetic loci predisposing to type 2 diabetes have been identified, includingSORCS1that encodes the transmembrane receptor SorCS1. The ectodomain of SorCS1 (sol-SorCS1) is shed from plasma membranes but the biological function of this fragment is unknown. Here we show that sol-SorCS1 acts as a high-affinity binding partner for the insulin receptor to stabilize the receptor and increase insulin affinity, protein kinase B activation, and glucose uptake in myocytes. Sol-SorCS1 is liberated from adipocytes, and in diabetic patients the plasma concentration positively correlates with body mass index, but inversely with plasma glucose. In mouse models of insulin resistance, exogenous sol-SorCS1 restored insulin sensitivity. We conclude that sol-SorCS1 increases peripheral insulin sensitivity and propose sol-SorCS1 as a novel insulin sensitizing adipokine and potential antidiabetic agent.