bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis
Authors: McDonald Andrew G. , Mariethoz Julien , Davey Gavin P. , Lisacek Frédérique 
Published: January 2022

ABSTRACTHuman milk oligosaccharides (HMOs) form the third most abundant component of human milk and are known to convey several benefits to the neonate, including protection from viral and bacterial pathogens, training of the immune system, and influencing the gut microbiome. As HMO production during lactation is driven by enzymes that are common to other glycosylation processes, we adapted a model of mucin-type GalNAc-linked glycosylation enzymes to act on free lactose. We identified a subset of 11 enzyme activities that can account for 206 of 226 distinct HMOs isolated from human milk, and constructed a biosynthetic reaction network that identifies 5 new core HMO structures. A comparison of monosaccharide compositions demonstrated that the model was able to discriminate between two possible groups of intermediates between major subnetworks, and to assign possible structures to several previously uncharacterised HMOs. The effect of enzyme knockouts is presented, identifying β-1,4-galactosyltransferase and β-1,3-N-acetylglucosaminyltransferase as key enzyme activities involved in the generation of the observed HMO glycosylation patterns. The model also provides a synthesis chassis for the most common HMOs found in lactating mothers.
A wheat kinase and immune receptor form the host-specificity barrier against the blast fungus
Authors: Arora Sanu , Steed Andrew , Goddard Rachel , Gaurav Kumar , O’Hara Tom , Schoen Adam , Rawat Nidhi , Elkot Ahmed F. , Chinoy Catherine , Nicholson Martha H. , Asuke Soichiro , Steuernagel Burkhard , Yu Guotai , Awal Rajani , Forner-Martínez Macarena , Wingen Luzie , Baggs Erin , Clarke Jonathan , Krasileva Ksenia V. , Tosa Yukio , Jones Jonathan D. G. , Tiwari Vijay K. , Wulff Brande B. H. , Nicholson Paul 
Published: January 2022

AbstractSince emerging in Brazil in 1985, wheat blast has spread throughout South America and recently appeared in Bangladesh and Zambia. We show that two wheat resistance genes, Rwt3 and Rwt4, acting as host-specificity barriers against non-Triticum blast pathotypes encode a nucleotide-binding leucine-rich repeat immune receptor and a tandem kinase, respectively. Molecular isolation of these genes allowed us to develop assays that will ensure the inclusion of these two genes in the wheat cultivars to forestall the recurrence of blast host jumps.
Pyrrole produced byPseudomonas aeruginosainfluences olfactory food choice ofCaenorhabditis elegans
Authors: Prakash Deep , Siddiqui Ritika , Chalasani Sreekanth H. , Singh Varsha 
Published: January 2022

SUMMARYSense of smell can influence dietary choices in animals. So far, most of the research has focused on how animals respond to distinct odors when they are introduced individually. However, it remains unclear how animals evaluate foods that contain a bouquet of olfactory cues with contrasting effects. Here, we utilizeCaenorhabditis elegansas a bacterivore to ask if odors produced by dietary bacteria can regulate worms’ food preferences. We show that the bacteriumPseudomonas aeruginosaproduces a relatively small quantity of a new attractant forC. elegans. We identify the odor as a heterocyclic compound called pyrrole. We find that pyrrole contributes to the sensory decision-making of worms in diet preference assays. Using specific neuronal ablation lines and calcium response assays, we show that AWA odor sensory neurons of worms are necessary for sensing pyrrole. In all, we show that specific odors produced by bacteria can influence food choice behavior of animals.
Biocompatible fluorocarbon liquid underlays for in situ extraction of isoprenoids from microbial cultures
Authors: Overmans Sebastian , Lauersen Kyle J. 
Published: January 2022

AbstractMicrobial production of heterologous metabolites is now a mature technology in many host organisms, opening new avenues for green production processes for specialty chemicals. At lab scale, petroleum-based hydrophobic bio-compatible solvents like dodecane can be used as a second phase on top of microbial cultures to act as a physical sink for heterologous hydrocarbon products like isoprenoids. However, this approach has significant drawbacks at scale due to the difficulty of handling solvents and their potential contamination with unwanted byproducts of their manufacture. We discovered that synthetic perfluorocarbon liquids (FCs), commonly used for heat transfer, can also act as physical sinks for microbially produced isoprenoid compounds. FCs are stable, inert, and are amenable to direct liquid-liquid extraction with alcohols for rapid product isolation. These liquids are more dense than water and form a lower phase to microbial cultures rather than an upper phase as with other solvents. Their ability to form an under-layer or ‘underlay’ also enables the cultivation of microbes directly at the FC-culture medium interface via gravity settling, which could open their application for filamentous or mat-forming organisms. We present comparisons of the isoprenoid extraction potential of three commercial FCs: FC-3283, FC-40, and FC-770 with engineered green microalga cultures producing patchoulol, taxadiene, casbene, or 13R(+) manoyl oxide. We demonstrate that FCs are promising alternatives to traditional solvents and open new avenues in bio-process design for microbial heterologous metabolite milking.
The antimicrobial peptide cathelicidin is critical for the development of Th17 responses in severe inflammatory disease
Authors: Smith Katie J , Minns Danielle , McHugh Brian J , Holloway Rebecca K. , O’Connor Richard , Williams Anna , Melrose Lauren , McPherson Rhoanne , Miron Veronique E. , Davidson Donald J , Findlay Emily Gwyer 
Published: January 2022

AbstractMultiple Sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system.
Tracking human skill learning with a hierarchical Bayesian sequence model
Authors: Éltető Noémi , Nemeth Dezső , Janacsek Karolina , Dayan Peter 
Published: January 2022

AbstractHumans can implicitly learn complex perceptuo-motor skills over the course of large numbers of trials. This likely depends on our becoming better able to take advantage of ever richer and temporally deeper predictive relationships in the environment. Here, we offer a novel characterization of this process, fitting a non-parametric, hierarchical Bayesian sequence model to the reaction times of human participants’ responses over ten sessions, each comprising thousands of trials, in a serial reaction time task involving higher-order dependencies. The model, adapted from the domain of language, forgetfully updates trial-by-trial, and seamlessly combines predictive information from shorter and longer windows onto past events, weighing the windows proportionally to their predictive power. As the model defines a prior over window depths, we were able to determine the extent to which the internal predictions of individual participant depended on how many previous elements.Already in the first session, the model showed that participants had begun to rely on two previous elements (i.e., trigrams), thereby successfully adapting to the most prominent higher-order structure in the task. The extent to which local statistical fluctuations influenced participants’ responses waned over subsequent sessions, as subjects forgot the trigrams less and evidenced skilled performance. By the eighth session, a subset of participants shifted their prior further to consider a context deeper than two previous elements. Finally, participants showed resistance to interference and slow forgetting of the old sequence when it was changed in the final sessions. Model parameters for individual subjects covaried appropriately with independent measures of working memory. In sum, the model offers the first principled account of the adaptive complexity and nuanced dynamics of humans’ internal sequence representations during long-term implicit skill learning.Author summaryA central function of the brain is to predict. One challenge of prediction is that both external events and our own actions can depend on a variably deep temporal context of previous events or actions. For instance, in a short motor routine, like opening a door, our actions only depend on a few previous ones (e.g., push the handle if the key was turned). In longer routines such as coffee making, our actions require a deeper context (e.g., place the moka pot on the hob if coffee is ground, the pot is filled and closed, and the hob is on). We adopted a model from the natural language processing literature that matches humans’ ability to learn variable-length relationships in sequences. This model explained the gradual emergence of more complex sequence knowledge and individual differences in an experiment where humans practiced a perceptual-motor sequence over 10 weekly sessions.
Molecular mechanisms of Plasmodium development in male and female Anopheles mosquitoes
Authors: Haraguchi Asako , Takano Makoto , Hakozaki Jun , Nakayama Kazuhiko , Nakamura Sacré , Yoshikawa Yasunaga , Fukumoto Shinya , Kusakisako Kodai , Ikadai Hiromi 
Published: January 2022

AbstractVector competence influences the ability of Anopheles mosquitoes to transmit Plasmodium parasites. The aim of this study was to determine the competence of male and female Anopheles mosquitoes to support the development of Plasmodium parasites. Male and female A. stephensi (STE2 strain) were infected with in vitro-cultured P. berghei (ANKA strain) ookinetes. We found that the number of oocysts produced was higher in males than in females. RNA-seq analysis of male and female mosquitoes injected with P. berghei ookinetes showed that predominantly genes of unknown function changed in expression levels in response to ookinete infection; however, further studies are required to elucidate their functions. Moreover, male mosquitoes were injected with in vitro-cultured P. falciparum (3D7 strain) gametocytes or zygotes. The development of P. falciparum in males was detected using nested polymerase chain reaction. We found the DNA content was higher on day 15 than on day 0, indicating that P. falciparum developed in the mosquito hemocoel. This study revealed promising new mechanisms underlying the interactions between Plasmodium and mosquitoes.Author SummaryAnopheles mosquitoes transmit Plasmodium parasites that cause malaria disease. Vector competence is the ability of vectors to support pathogen development. The aim of this study was to determine the competence of male and female mosquitoes for Plasmodium parasites. Oocysts were formed in both male and female mosquitoes injected with ookinetes from in vitro-cultured Plasmodium berghei, which causes malaria in mice. The number of oocysts was higher in males, indicating that the competence in males was higher than that in females. RNA-seq analysis showed that the expression of genes of unknown function was highly variable in males and females. The genes defining the competence factors need further study, but the results indicate novel genes may be discovered. Furthermore, the development of Plasmodium falciparum, which causes the most severe malaria in humans, in male mosquitoes injected with in vitro-cultured gametocytes or zygotes was detected. As male mosquitoes do not suck blood, this method may allow us to experiment with Plasmodium more safely.
Three-dimensional actuation of hummingbird wings requires diverse effects from the primary flight muscles
Authors: Agrawal Suyash , Tobalske Bret W. , Anwar Zafar , Luo Haoxiang , Hedrick Tyson L. , Cheng Bo 
Published: January 2022

AbstractHummingbirds have evolved to hover and maneuver with exceptional flight control. This is directly enabled by their musculoskeletal system that successfully exploits the agile motion of flapping wings. Here, we reveal novel principles of hummingbird wing actuation that provide insights into the evolution and robotic emulation of hummingbird flight. We develop a functional model of hummingbird musculoskeletal system, which predicts instantaneous, three-dimensional torque produced by primary (pectoralis and supracoracoideus) and combined secondary muscles. It also reveals primary muscle contractile behavior, including stress, strain, elasticity, and work. Results show that the primary muscles (i.e., the flight “engine”) function as diverse effectors, as they do not simply power the stroke, but also actively deviate and pitch the wing. The secondary muscles produce controlled-tightening effects, by acting against primary muscles in deviation and pitching. The diverse effector capacity of pectoralis is associated with the evolution of a comparatively enormous bicipital crest on humerus.
Geographical and ecological drivers of coexistence dynamics in squamate reptiles
Authors: Alencar Laura R. V. , Quental Tiago B. 
Published: January 2022

AbstractAimSpecies richness varies widely across space. To understand the processes behind these striking patterns, we must know what are the relevant drivers underlying species coexistence. Several factors can potentially shape species coexistence such as the speciation process, the time since divergence between lineages, environmental effects, and intrinsic properties of the organisms. For the first time, we model the coexistence dynamics of lizards and snakes across broad temporal and spatial scales, investigating the role of species interactions, dispersal ability, and geographic area.LocationGlobalTime periodLast 20 million yearsMajor taxa studiedSquamata (lizards and snakes)MethodsWe used 448 closely related species pairs and their age since divergence across 100 dated phylogenies. We categorized each pair as sympatric or allopatric and as occurring on islands or continents. We measured morphological traits to quantify niche divergence and used range and body size as proxies for dispersal ability. We applied a model-comparison framework in lizards and snakes separately to evaluate which factors best explained their coexistence dynamics.ResultsWe found that distinct factors drive the coexistence dynamics in lizards and snakes. In snakes, species pairs that coexist tend to occur on islands and are more different in body size, suggesting that both geographical setting and species interactions might be relevant factors. In contrast, we only found evidence that dispersal ability shaped the coexistence of lizards, where species coexist when they have higher dispersal abilities.Main conclusionsLizards and snakes greatly differ in coexistence dynamics. Higher heterogeneity in coexistence dynamics within lizards and group-specific life-history aspects might help to explain these findings. Our results emphasize that the interaction between where organisms are and who they are, ultimately shapes biodiversity patterns. We also highlight interesting avenues for further studies on species coexistence in deep time.
DiSCs – Domains involving SETDB1 and Cohesin are critical regulators of genome topology and stem cell fate
Authors: Warrier Tushar , El Farran Chadi , Zeng Yingying , Ho Benedict Shao Quan , Xu Don Loi , Bao Qiuye , Zheng Zi Hao , Bi Xuezhi , Tan Kelly Yu Sing , Ng Huck Hui , Ong Derrick Sek Tong , Chu Justin Jang Hann , Sanyal Amartya , Fullwood Melissa Jane , Collins James , Li Hu , Xu Jian , Loh Yuin-Han 
Published: January 2022

AbstractSETDB1 is a key regulator of lineage-specific genes and endogenous retroviral elements (ERVs) through its deposition of repressive H3K9me3 mark. Apart from its H3K9me3 regulatory role, SETDB1 has seldom been studied in terms of its other potential regulatory roles. To investigate this, a genomic survey of SETDB1 binding in mouse embryonic stem cells across multiple libraries was conducted, leading to the unexpected discovery of regions bereft of common repressive histone marks (H3K9me3, H3K27me3). These regions were enriched with the CTCF motif that is often associated with the topological regulator Cohesin. Further profiling of these non-H3K9me3 regions led to the discovery of a cluster of non-repeat loci that were co-bound by SETDB1 and Cohesin. These regions, which we named DiSCs (Domains involving SETDB1 and Cohesin) were seen to be proximal to the gene promoters involved in embryonic stem cell pluripotency and lineage development. Importantly, it was found that SETDB1-Cohesin co-regulate target gene expression and genome topology at these DiSCs. Depletion of SETDB1 led to localized dysregulation of Cohesin binding thereby locally disrupting topological structures. Dysregulated gene expression trends revealed the importance of this cluster in ES cell maintenance as well as at gene ‘islands’ that drive differentiation to other lineages. The ‘unearthing’ of the DiSCs thus unravels a unique topological and transcriptional axis of control regulated chiefly by SETDB1.
Common and lifestyle-specific traits of mycorrhiza-associated metabolite alterations in plant roots reflects strategies of root-mycorrhizal interactions
Authors: Xia Mengxue , Suseela Vidya , McCormack M. Luke , Kennedy Peter G. , Tharayil Nishanth 
Published: January 2022

AbstractConvergent patterns in morphological and genetic traits of mycorrhizas have been well-documented and reflect common selection forces that define mycorrhizas. However, generalizable patterns of mycorrhiza-associated chemical alterations, which are immediately linked to plant and fungal strategies for successful symbiosis, have yet to be emerged. Comparing root metabolomes of phylogenetically-diverse plants inoculated by mycorrhizal fungi across two major lifestyles (arbuscular- vs. ecto-mycorrhizas), our study uncovers metabolite changes unique to each mycorrhizal lifestyle and those common across plant-mycorrhizal combinations irrespective of lifestyles. Arbuscular and ecto- mycorrhizal colonized roots accumulated different sets of carbohydrates, indicating unique carbon partitioning strategies: particularly, arbuscular mycorrhizal roots accumulated cyclic polyols inaccessible for symbionts, suggesting tighter regulation of plants in carbon partitioning. Mycorrhizas also altered specialized metabolism, featuring frequent increases of flavan-3-ols and decreases of flavanols irrespective of mycorrhizal lifestyles, suggesting tactical reconfiguration of specialized metabolites to facilitate/contain symbiosis. Our data show for the first time, to our knowledge, that part of the root metabolite alterations by mycorrhizas were relatively common across plant-mycorrhizal systems, highlighting their potentially critical regulatory and evolutionary role for successful symbiosis. This commonality appears robust to phylogenetic diversity of host plants and thus may be widespread in land plants. Our findings offer future research venues to elucidate the finer roles of these common traits of mycorrhiza-associated metabolite alterations and thus help to eventually develop a comprehensive understanding of this omnipresent plant-fungus partnership.
Sensing Echoes: Temporal Misalignment in Auditory Brainstem Responses as the Earliest Marker of Neurodevelopmental Derailment
Authors: Torres Elizabeth B , Varkey Hannah , Vero Joe , London Eric , Phan Ha , Kittler Phyllis , Gordon Anne , Delgado Rafael E. , Delgado Christine F. , Simpson Elizabeth A. 
Published: January 2022

AbstractNeurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3-4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.Significance StatementAutism is currently detected on average after 4.5 years of age, based on differences in social interactions. Yet basic building blocks that develop to scaffold social interactions are present at birth and quantifiable at clinics. Auditory Brainstem Response tests, routinely given to neonates, infants, and young children, contain information about delays in signal transmission important for sensory integration. Although currently discarded as gross data under traditional statistical approaches, new analytics reveal unambiguous differences in ABR signals’ fluctuations between typically developing neonates and those who received an autism diagnosis. With very little effort and cost, these new analytics could be added to the clinical routine testing of neonates to create a universal screening tool for neurodevelopmental derailment and prodrome of autism.