bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of motile cilia in the development and physiology of the nervous system
Authors: Ringers Christa , Olstad Emilie W. , Jurisch-Yaksi Nathalie 
Published: December 2019

Motile cilia are miniature, whip-like organelles whose beating generates a directional fluid flow. The flow generated by ciliated epithelia is a subject of great interest, as defective ciliary motility results in severe human diseases called motile ciliopathies. Despite the abundance of motile cilia in diverse organs including the nervous system, their role in organ development and homeostasis remains poorly understood. Recently, much progress has been made regarding the identity of motile ciliated cells and the role of motile-cilia-mediated flow in the development and physiology of the nervous system. In this review, we will discuss these recent advances from sensory organs, specifically the nose and the ear, to the spinal cord and brain ventricles.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Simulations of particle tracking in the oligociliated mouse node and implications for left–right symmetry-breaking mechanics
Authors: Gallagher M. T. , Montenegro-Johnson T. D. , Smith D. J. 
Published: December 2019

The concept of internal anatomical asymmetry is familiar–usually in humans the heart is on the left and the liver is on the right; however, how does the developing embryo know to produce this consistent laterality? Symmetry-breaking initiates with left–right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However, the question of what converts this flow into left–right asymmetric development remains unanswered. A leading hypothesis is that flow transports morphogen-containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observe in wild-type and mutant experiments, we extend the open-source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two and 112 beating cilia. Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wild-type mouse embryos: uniformly random release, localized cilium stress-induced release and localized release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localized release model resulting in significant transport in the oligociliated embryo.
This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Cilia in the developing zebrafish ear
Authors: Whitfield Tanya T. 
Published: December 2019

The inner ear, which mediates the senses of hearing and balance, derives from a simple ectodermal vesicle in the vertebrate embryo. In the zebrafish, the otic placode and vesicle express a whole suite of genes required for ciliogenesis and ciliary motility. Every cell of the otic epithelium is ciliated at early stages; at least three different ciliary subtypes can be distinguished on the basis of length, motility, genetic requirements and function. In the early otic vesicle, most cilia are short and immotile. Long, immotile kinocilia on the first sensory hair cells tether the otoliths, biomineralized aggregates of calcium carbonate and protein. Small numbers of motile cilia at the poles of the otic vesicle contribute to the accuracy of otolith tethering, but neither the presence of cilia nor ciliary motility is absolutely required for this process. Instead, otolith tethering is dependent on the presence of hair cells and the function of the glycoprotein Otogelin. Otic cilia or ciliary proteins also mediate sensitivity to ototoxins and coordinate responses to extracellular signals. Other studies are beginning to unravel the role of ciliary proteins in cellular compartments other than the kinocilium, where they are important for the integrity and survival of the sensory hair cell.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
The unity and diversity of the ciliary central apparatus
Authors: Zhao Lei , Hou Yuqing , McNeill Nathan A. , Witman George B. 
Published: December 2019

Nearly all motile cilia and flagella (terms here used interchangeably) have a ‘9+2’ axoneme containing nine outer doublet microtubules and two central microtubules. The central pair of microtubules plus associated projections, termed the central apparatus (CA), is involved in the control of flagellar motility and is essential for the normal movement of ‘9+2’ cilia. Research using the green algaChlamydomonas reinhardtii, an important model system for studying cilia, has provided most of our knowledge of the protein composition of the CA, and recent work using this organism has expanded the number of known and candidate CA proteins nearly threefold. Here we take advantage of this enhanced proteome to examine the genomes of a wide range of eukaryotic organisms, representing all of the major phylogenetic groups, to identify predicted orthologues of theC. reinhardtiiCA proteins and explore how widely the proteins are conserved and whether there are patterns to this conservation. We also discuss in detail two contrasting groups of CA proteins—the ASH-domain proteins, which are broadly conserved, and the PAS proteins, which are restricted primarily to the volvocalean algae.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Reorganization of complex ciliary flows around regeneratingStentor coeruleus
Authors: Wan Kirsty Y. , Hürlimann Sylvia K. , Fenix Aidan M. , McGillivary Rebecca M. , Makushok Tatyana , Burns Evan , Sheung Janet Y. , Marshall Wallace F. 
Published: December 2019

The phenomenon of ciliary coordination has garnered increasing attention in recent decades and multiple theories have been proposed to explain its occurrence in different biological systems. While hydrodynamic interactions are thought to dictate the large-scale coordinated activity of epithelial cilia for fluid transport, it is rather basal coupling that accounts for synchronous swimming gaits in model microeukaryotes such asChlamydomonas.Unicellular ciliates present a fascinating yet understudied context in which coordination is found to persist in ciliary arrays positioned across millimetre scales on the same cell. Here, we focus on the ciliateStentor coeruleus, chosen for its large size, complex ciliary organization, and capacity for cellular regeneration. These large protists exhibit ciliary differentiation between cortical rows of short body cilia used for swimming, and an anterior ring of longer, fused cilia called the membranellar band (MB). The oral cilia in the MB beat metachronously to produce strong feeding currents. Remarkably, upon injury, the MB can be shed and regenerated de novo. Here, we follow and track this developmental sequence in its entirety to elucidate the emergence of coordinated ciliary beating: from band formation, elongation, curling and final migration towards the cell anterior. We reveal a complex interplay between hydrodynamics and ciliary restructuring inStentor, and highlight for the first time the importance of a ring-like topology for achieving long-range metachronism in ciliated structures.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Diversity of cilia-based mechanosensory systems and their functions in marine animal behaviour
Authors: Bezares-Calderón Luis Alberto , Berger Jürgen , Jékely Gáspár 
Published: December 2019

Sensory cells that detect mechanical forces usually have one or more specialized cilia. These mechanosensory cells underlie hearing, proprioception or gravity sensation. To date, it is unclear how cilia contribute to detecting mechanical forces and what is the relationship between mechanosensory ciliated cells in different animal groups and sensory systems. Here, we review examples of ciliated sensory cells with a focus on marine invertebrate animals. We discuss how various ciliated cells mediate mechanosensory responses during feeding, tactic responses or predator–prey interactions. We also highlight some of these systems as interesting and accessible models for future in-depth behavioural, functional and molecular studies. We envisage that embracing a broader diversity of organisms could lead to a more complete view of cilia-based mechanosensation.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Synchrony and symmetry-breaking in active flagellar coordination
Authors: Wan Kirsty Y. 
Published: December 2019

Living creatures exhibit a remarkable diversity of locomotion mechanisms, evolving structures specialized for interacting with their environment. In the vast majority of cases, locomotor behaviours such as flying, crawling and running are orchestrated by nervous systems. Surprisingly, microorganisms can enact analogous movement gaits for swimming using multiple, fast-moving cellular protrusions called cilia and flagella. Here, I demonstrate intermittency, reversible rhythmogenesis and gait mechanosensitivity in algal flagella, to reveal the active nature of locomotor patterning. In addition to maintaining free-swimming gaits, I show that the algal flagellar apparatus functions as a central pattern generator that encodes the beating of each flagellum in a network in adistinguishablemanner. The latter provides a novel symmetry-breaking mechanism for cell reorientation. These findings imply that the capacity to generate and coordinate complex locomotor patterns does not require neural circuitry but rather the minimal ingredients are present in simple unicellular organisms.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Chemosensing versus mechanosensing in nodal and Kupffer's vesicle cilia and in other left–right organizer organs
Authors: Cartwright Julyan H. E. , Piro Oreste , Tuval Idan 
Published: December 2019

How is sensing carried out by cilia in the mouse node, zebrafish Kupffer's vesicle and similar left–right (LR) organizer organs in other species? Two possibilities have been put forward. In the former, cilia would detect some chemical species in the fluid; in the latter, they would detect fluid flow. In either case, the hypothesis is that an imbalance would be detected between this signalling coming from cilia on the left and right sides of the organizer, which would initiate a cascade of signals leading ultimately to the breaking of LR symmetry in the developing body plan of the organism. We review the evidence for both hypotheses.
This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations
Authors: Ali Hebah , Puccio Ignazio , Akarca Ayse U , Bob Roshanak , Pomplun Sabine , Wong Wai Keong , Gupta Rajeev , Sekhar Mallika , Lambert Jonathan , Al-Masri Hytham , Stein Harald , Marafioti Teresa 
Published: December 2019

SummaryThe discovery of mutated Calreticulin (CALR) in myeloproliferative neoplasms (MPN) has provided proof of clonality, diagnostic importance, and influence on prognosis of this pathology. The identification of this MPN-associated driver mutation -currently based on molecular assays- is represented as a major diagnostic criterion for essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF) in the updated World Health Organization (WHO) 2008 classification. In the present study, we validated by immunohistochemistry the diagnostic usefulness of the monoclonal CAL2 antibody. Cases of acute myeloid leukaemia (AML) and myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) have been also investigated to assess the specificity of CAL2 antibody. For this purpose, the result of the CAL2 immunostaining was compared with the result of molecular assays. Additionally, we investigated by double staining whether expression of mutated CALR can also be demonstrated on cells of the erythroid and myeloid lineage. We confirmed the usefulness of the CAL2 monoclonal antibody in successfully detecting mutant CALR in bone marrow biopsies. We showed that the immune-reactivity of CAL2 was absolutely restricted to the presence of CALR mutations, which were seen only in ET and MDS/MPN biopsies, but not in AML biopsies (14/14). There was 100% concordance in biopsy specimens with the concomitant molecular results. We applied double staining technique and confirmed that a subpopulation of granulopoietic and erythropoietic cells express mutated CALR as demonstrated with the CAL2 antibody in cases of MPNs. This supports the suggestion that the CALR mutations occur in a multipotent progenitor capable of generating both myeloid and erythroid progeny with preferential expansion of megakaryocytic cell lineage as a result of CALR mutation in an immature hematopoietic stem cell.
Emergence of mcr-9.1 in ESBL-producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome and Mobilome
Authors: Sekyere John Osei , Maningi Nontuthuko E. , Modipane Lesedi , Mbelle Nontombi Marylucy 
Published: December 2019

AbstractBackgroundExtended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with little therapeutic options.MethodsEleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analysed to determine their resistome, mobilome, and evolutionary relationship to global strains. The global phylogenomics of mcr-9.1-bearing genomes were further analysed.Results & conclusionTen isolates were ESBL positive. The isolates were multidrug-resistant and phylogenetically related to global clones, but distant from local strains. Multiple resistance genes, including blaCTX-M-15blaTEM-1 and mcr-9.1 were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH and ColRNAI. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A-F), with those of this study belonging to clade B. Enterobacter sp. and Salmonella sp. are the main hosts of mcr-9.1 globally, albeit diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices.
Diabetes mellitus, glycemic traits, and cerebrovascular disease: a Mendelian randomization study
Authors: Georgakis Marios K. , Harshfield Eric L , Malik Rainer , Franceschini Nora , Langenberg Claudia , Wareham Nicholas J. , Markus Hugh S. , Dichgans Martin 
Published: December 2019

ABSTRACTRationaleType 2 diabetes mellitus (T2D) is an established risk factor for cerebrovascular disease but the mechanisms underlying this association remain elusive. Disentangling the causal effects of T2D, hyperglycemia, and pre-diabetic phenotypes (insulin resistance, β-cell dysfunction) on major etiological stroke subtypes (ischemic stroke, intracerebral hemorrhage, ischemic stroke subtypes) could inform the development of preventive strategies.ObjectiveWe employed Mendelian randomization (MR) to explore the effects of genetic predisposition to T2D, hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.Methods and ResultsWe selected instruments for genetic predisposition to T2D, HbA1c levels, fasting glucose levels, insulin resistance, and β-cell dysfunction (proxied by pro-insulin levels) based on published genome-wide association studies (up to 898,130 individuals). Applying two-sample MR, we examined associations with ischemic stroke, intracerebral hemorrhage, and ischemic stroke subtypes (large artery, cardioembolic, small vessel stroke; up to 60,341 cases and 454,450 controls). We further explored associations with the related phenotypes of carotid atherosclerosis, imaging markers of cerebral white matter integrity, and brain atrophy. Genetic predisposition to T2D and elevated HbA1c levels in the pre-diabetic range were associated with higher risk of any ischemic stroke, large artery stroke, carotid plaque and small vessel stroke. Independently of HbA1c levels, we further found genetic predisposition to insulin resistance to be associated with large artery and small vessel stroke, whereas predisposition to β-cell dysfunction was associated with small vessel stroke. Predisposition to β-cell dysfunction was further associated with intracerebral hemorrhage, lower grey matter volume, and total brain volume.ConclusionsThis study supports causal effects of T2D and hyperglycemia on large artery and small vessel stroke. We show differential effects of genetically determined insulin resistance and β-cell dysfunction on large artery and small vessel stroke that might have implications for anti-diabetic treatments targeting these mechanisms.
Efficient data management infrastructure for the integration of imaging and omics data in life science research
Authors: Cuellar Luis Kuhn , Friedrich Andreas , Gabernet Gisela , de la Garza Luis , Fillinger Sven , Seyboldt Adrian , Oven-Krockhaus Sven zur , Wanke Friederike , Richter Sandra , Thaiss Wolfgang M. , Horger Marius , Malek Nisar , Harter Klaus , Bitzer Michael , Nahnsen Sven 
Published: December 2019

AbstractAs technical developments in omics and biomedical imaging drive the increase in quality, modality, and throughput of data generation in life sciences, the need for information systems capable of integrative, long-term storage and management of these heterogeneous digital assets is also increasing. Here, we propose an approach based on principles of Service Oriented Architecture design, to allow the integrated management and analysis of multi-omics and biomedical imaging data. The proposed architecture introduces an interoperable image management system, the OMERO server, into the backend of qPortal, a FAIR-compliant web-based platform for omics data management. The implementation of an integrated metadata model, the development of software components to enable the communication with the OMERO server, and an extension to the data management operations of established software, allows for FAIR management of heterogeneous omics and biomedical imaging data within an integrated system, which facilitates metadata queries from web-based scientific applications. The applicability of the proposed architecture is demonstrated in two prototypical use cases, a plant biology study using confocal scanning microscopy, and a clinical study on hepatocellular carcinoma, with data from a variety of medical imaging and omics modalities. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, as the joint analysis of omics and imaging data becomes not only desirable but necessary to derive novel insights into biological processes. In particular for powerful machine learning applications where the availability of large datasets with high quality phenotypic annotations is a requirement.
Dual role of auxin in regulating plant defense and bacterial virulence gene expression duringPseudomonas syringae PtoDC3000 pathogenesis
Authors: Djami-Tchatchou Arnaud T. , Harrison Gregory A. , Harper Chris P. , Wang Renhou , Prigge Michael J. , Estelle Mark , Kunkel Barbara N. 
Published: December 2019

ABSTRACTModification of host hormone biology is a common strategy used by plant pathogens to promote disease. For example, the bacterial pathogenPseudomonas syringaestrainPtoDC3000 produces the plant hormone auxin (Indole-3-acetic acid, or IAA) to promotePtoDC3000 growth in plant tissue. Previous studies suggest that auxin may promotePtoDC3000 pathogenesis through multiple mechanisms, including both suppression of salicylic acid (SA)-mediated host defenses and via an unknown mechanism that appears to be independent of SA. To test if host auxin signaling is important during pathogenesis, we took advantage ofArabidopsis thalianalines impaired in either auxin signaling or perception. We found that disruption of auxin signaling in plants expressing an inducible dominantaxr2-1mutation resulted in decreased bacterial growth, demonstrating that host auxin signaling is required for normal susceptibility toPtoDC3000, and this phenotype was dependent on SA-mediated defenses. However, despite exhibiting decreased auxin perception,tir1 afb1 afb4 afb5quadruple mutant plants lacking four of the six known auxin co-receptors supported increased levels of bacterial growth. This mutant also exhibited elevated IAA levels, suggesting that the increased IAA in these plants may promotePtoDC3000 growth independent of host auxin signaling, perhaps through a direct effect on the pathogen. In support of this, we found that IAA directly impacted the pathogen, by modulating expression of bacterial virulence genes, both in liquid culture and in planta. Thus, in addition to suppressing host defenses, IAA acts as a microbial signaling molecule that regulates bacterial virulence gene expression.
Vulnerability and life-history traits correlate with the load of deleterious mutations in fish
Authors: Rolland Jonathan , Romiguier Jonathan 
Published: December 2019

AbstractUnderstanding why some species accumulate more deleterious substitutions than others is an important question relevant in evolutionary biology and conservation sciences. Previous studies conducted in terrestrial taxa suggest that life history traits correlate with the efficiency of purifying selection and accumulation of deleterious mutations. Using a large genome dataset of 76 species of fishes, we show that the rate of deleterious mutation accumulation (measured via dN/dS,i.e.non-synonymous over synonymous substitution rate) is associated to the vulnerability, the life-history strategies, and the latitude of species. Our results, focusing on a large clade of aquatic species, generalizes previous patterns found so far in few clades of terrestrial vertebrates. These results also suggest that vulnerable species accumulate more deleterious substitutions than non-threatened ones, which give insights in how life-history traits, populations sizes and genetic risk of extinction can be tightly interconnected.