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High osmolarity, bound water, and hydrostatic pressure contribute to notochord mechanics and its morphogenesis into the nucleus pulposus (NP) compartment of the intervertebral disc. Indeed, the osmoadaptive transcription factor, nuclear factor of activated T-cells 5 (NFAT5 aka TonEBP), is robustly expressed by resident cells of the notochord and NP. Nevertheless, the molecular mechanisms that drive notochord osmoregulation and the functions of NFAT5 in disc embryogenesis remain largely unexplored. In this study, we show that deletion of NFAT5 in mice results in delayed vertebral column development and a reduced NP aspect ratio in the caudal spine. This phenotype is associated with lower levels of the T-box transcription factor, Brachyury, delayed expression of notochord phenotypic markers, and decreased collagen II deposition in the perinotochordal sheath and condensing mesenchyme. In addition, NFAT5 mutants showed a stage-dependent dysregulation of sonic hedgehog (Shh) signaling with non-classical expression of Gli1. Generation of mice with notochord-specific deletion of IFT88 (ShhcreER T2 ;Ift88 f/f ) supported this mode of Gli1 regulation. Using isolated primary NP cells and bioinformatics approaches, we further show that Ptch1 and Smo expression is controlled by NFAT5 in a cell autonomous manner. Altogether, our results demonstrate that NFAT5 contributes to notochord and disc embryogenesis through its regulation of hallmark notochord phenotypic markers, extracellular matrix, and Shh signaling. • Loss of NFAT5 delays the development of the vertebral column. • NFAT5 is required for notochord cells to acquire their molecular signature. • NFAT5 regulates collagen deposition during intervertebral disc embryogenesis. • NFAT5 controls Shh signaling in an NP cell-autonomous manner. [ABSTRACT FROM AUTHOR]

Dyslexia is a common neurodevelopmental disorder caused by a significant genetic component. The KIAA0319 gene is one of the most robust dyslexia susceptibility factors but its function remains poorly understood. Initial RNA‐interference studies in rats suggested a role in neuronal migration whereas subsequent work with double knock‐out mouse models for both Kiaa0319 and its paralogue Kiaa0319‐like reported effects in the auditory system but not in neuronal migration. To further understand the role of KIAA0319 during neurodevelopment, we carried out an expression study of its zebrafish orthologue at different embryonic stages. We used different approaches including RNAscope in situ hybridization combined with light‐sheet microscopy. The results show particularly high expression during the first few hours of development. Later, expression becomes localized in well‐defined structures. In addition to high expression in the brain, we report for the first time expression in the eyes and the notochord. Surprisingly, kiaa0319‐like, which generally shows a similar expression pattern to kiaa0319, was not expressed in the notochord suggesting a distinct role for kiaa0319 in this structure. This observation was supported by the identification of notochord enhancers enriched upstream of the KIAA0319 transcription start site, in both zebrafish and humans. This study supports a developmental role for KIAA0319 in the brain as well as in other developing structures, particularly in the notochord which, is key for establishing body patterning in vertebrates. [ABSTRACT FROM AUTHOR]

The ability to make transgenic Hydra lines has allowed for quantitative in vivo studies of Hydra regeneration and physiology. These studies commonly include excision, grafting and transplantation experiments along with high-resolution imaging of live animals, which can be challenging due to the animal's response to touch and light stimuli. While various anesthetics have been used in Hydra studies, they tend to be toxic over the course of a few hours or their long-term effects on animal health are unknown. Here, we show that the monoterpenoid alcohol linalool is a useful anesthetic for Hydra. Linalool is easy to use, non-toxic, fast acting, and reversible. It has no detectable long-term effects on cell viability or cell proliferation. We demonstrate that the same animal can be immobilized in linalool multiple times at intervals of several hours for repeated imaging over 2–3 days. This uniquely allows for in vivo imaging of dynamic processes such as head regeneration. We directly compare linalool to currently used anesthetics and show its superior performance. Linalool will be a useful tool for tissue manipulation and imaging in Hydra research in both research and teaching contexts. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to improve shearer positioning accuracy. Shearer positioning using an inertial navigation system (INS) is a highly useful technology; however, positioning accuracy is seriously hindered by INS attitude error, particularly heading drift. Design/methodology/approach: A shearer positioning model with double-INS based on extended Kalman filter was proposed. The constant distance between two INSs (INS 1 and INS 2) was selected as the observation vector. Allan variance was used to identify the noise type of the vertical-axis gyroscope, and the stochastic process of heading drift for two INSs was obtained and divided into incongruous drift and concurrent drift. Findings: Simulation was then carried out to determine the optimal arrangement of the two INSs. For incongruous drift, the optimal arrangement satisfied the condition that the line connecting INS 1 and INS 2 was perpendicular to the shearer lateral axis (in the shearer coordinate frame) and parallel to the east-north plane (in the east-north-up coordinate frame). Under optimal arrangement, the positioning accuracy increased against the distance between INS 1 and INS 2. For concurrent drift, the double-INS positioning model had no effect. Under the circumstances, the number of INSs should be increased so that the uncertainty of INS drift was reflected as much as possible. Originality/value: A new double-INS positioning model was proposed with the constant distance between the two INSs. The optimal arrangement for double-INS was obtained. [ABSTRACT FROM AUTHOR]

Degeneration of the human intervertebral disc (IVD) is assumed to underlie severe clinical symptoms, in particular chronic back pain. Since adhesion/growth‐regulatory galectins are linked to arthritis/osteoarthritis pathogenesis by activating a pro‐degradative/‐inflammatory gene expression signature, we hypothesized a similar functional involvement of galectins in IVD degeneration. Immunohistochemical evidence for the presence of galectins‐1 and ‐3 in IVD is provided comparatively for specimens of spondylochondrosis, spondylolisthesis, and spinal deformity. Immunopositivity was detected in sections of fixed IVD specimens in each cellular compartment with age‐, disease‐, and galectin‐type‐related differences. Of note, presence of both galectins correlated with IVD degeneration, whereas correlation with age was seen only for galectin‐3. In addition, staining profiles for these two galectins showed different distribution patterns in serial sections, an indication for non‐redundant functionalities. In vitro, both galectins bound to IVD cells in a glycan‐dependent manner. However, exclusively galectin‐1 binding triggered a significant induction of functional disease markers (i.e., IL6, CXCL8, and MMP1/3/13) with involvement of the nuclear factor‐kB pathway. This study thus gives direction to further network analyses and functional studies on galectins in IVD degeneration. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2204–2216, 2019 [ABSTRACT FROM AUTHOR]

Many research applications of neuroimaging use magnetic resonance imaging (MRI). As such, recommendations for image analysis and standardized imaging pipelines exist. Clinical imaging, however, relies heavily on X-ray computed tomography (CT) scans for diagnosis and prognosis. Currently, there is only one image processing pipeline for head CT, which focuses mainly on head CT data with lesions. We present tools and a complete pipeline for processing CT data, focusing on open-source solutions, that focus on head CT but are applicable to most CT analyses. We describe going from raw DICOM data to a spatially normalized brain within CT presenting a full example with code. Overall, we recommend anonymizing data with Clinical Trials Processor, converting DICOM data to NIfTI using dcm2niix, using BET for brain extraction, and registration using a publicly-available CT template for analysis. [ABSTRACT FROM AUTHOR]

Research on creative industries (CI) has acknowledged the collective dimension of creation without addressing the crucial role of process and organization in handling such a collective endeavour. Indeed, this research stream has developed independently from the one on new product development (NPD), which focuses on the development process. Inspired by the NPD literature and anchored in the literature on CI, this article aims to enhance our understanding of the creation processes in CI in order to show how the challenges are overcome. Based on a large body of case studies carried out in 12 sub‐sectors of CI, we show that the projects developed in these industries follow a process that combines and iterates four elementary activities: inspiration, framing, prototyping and validation. These activities take place alternatively in a conceptual or a material world and combine collective and individual contributions. A critical player who gives the momentum and makes the crucial decisions heads this process. [ABSTRACT FROM AUTHOR]

The most common technology of removing the sugar beet haulm in the world is a continuous cut of the entire mass of the green haulm with further additional removal of the upper parts of the sugar beet heads, which is carried out without extracting the roots from the ground. This is the scheme according to which most top harvesting machines, manufactured in the world, now operate. However, we have found in our studies that, due to additional cutting off the upper parts of the root crop heads, up to 10% of the sugar-bearing mass is lost. Besides, there is an urgent need for immediate processing of the sugar beet root crops, as losses of the sugar juice occur, and bacteria enter inside of the root crop through the cut-off part, causing rotting. Therefore, a more favourable operation for harvesting root crop tops is not cutting off their heads but cleaning them from the residues of the foliage. In addition, the operation of cleaning the sugar beet roots from the residues of the foliage is subject to rather high requirements due to the absence of the green and dry residues on the heads of the roots, as well as the losses and damage of the root crops themselves. The purpose of this investigation is to develop a theory of the force interaction of the flexible cleaning blade with the sugar beet head in the process of its cleaning when the blade is mounted on the vertical driving shaft. The methods used of the investigation are those of modelling, higher mathematics and theoretical mechanics, as well as programming and numerical calculations on the computer. As a result of the research, an equivalent scheme was developed and a mathematical model was constructed describing the force interaction of the flexible cleaning blade with the surface of the sugar beet root. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis that has not significantly improved in the past several decades. A prognostic‐related signature was needed. Methods: The Cancer Genome Atlas and GSE41613 databases were downloaded as a training and validation set, respectively. We identified 12 genes that demonstrated progression and prognostic value, and then, a gene signature was constructed. Results: This classification could reflect distinct characteristics, phenotypically and molecularly, among HNSCC tumors. It could stratify patients with significantly different survival rates (median survival: 2083 days vs 927 days; P = 3.85E‐08) in the training cohort and validation cohort (P = 0.007) and was significantly involved in immune/inflammatory response and tumor progression processes. Conclusions: This bioinformatics‐based signature suggested the presence of two distinct populations of patients with HNSCC with distinguishable phenotypic characteristics and clinical outcomes and might provide insight for new types of immune therapy. [ABSTRACT FROM AUTHOR]

Wireless mobile network likely will be a set of self-directed systems. In which they are not only based on the unfixed infrastructure-less wireless network. This paper gives a major scope for routing ad-hoc network using fuzzy hierarchical ant colony optimization routing by maintaining the sustainability of the cluster head inside a cluster is very difficult in the adhoc network. The selected cluster head among the nodes is based on the quality of service parameter of the nodes. The weight assigned to the cluster head will determine how long the cluster head will hold. The fuzzy hierarchical ant colony optimization routing is used to select the optimized cluster head by way of in a cluster and the optimal cluster head will increase the routing. Ant colony optimization, Fuzzy Rules for Cluster Head Selection Process and Cluster's Gateway are the three processes involved in the proposed FHACO protocol. The parameters taken for our proposed algorithm are the buffer size, energy consumption, routing overhead, packet delivery ratio and end to end delay throughput of wireless system. The system is implemented in network simulator-2 and it is assessed to gather weighted clustering technique. The experimental analysis shows that fuzzy hierarchical ant colony optimization produces a better result in maintaining the persistence of the cluster head. [ABSTRACT FROM AUTHOR]

Highlights • Trepanning head and hybrid process approach enable thick part drilling (up to 2 mm). • High power fs lasers are required for high AR holes drilling with negligible HAZ. • Step by step analysis leads to time processing reduction: 30 s, AR = 10, zero taper. Abstract Use of high average power, high repetition rate, ultra-short pulse lasers jointly with trepanning head (enabling both beam rotation and inclination) has been shown to be an effective tool to obtain holes with high machining quality, zero or even negative taper, aspect ratio as high as > 10 and high throughput. Nevertheless, in standard operating conditions (focal length 50 mm – 100 mm, spot size of 20–30 μm, and pulse energy comprised between some tens and hundred μJ), this technological approach shows its limitations when material thickness is higher than nearly 1 mm. Here a novel approach is proposed consisting of a top-down, hybrid (sequence of trepanning, drilling and trepanning) drilling process. By systematic variation of process parameters (beam inclination angle, focus re- positioning, etc.) this approach has been optimized to drill zero tapering holes in stainless steel 316 L having a thickness varying from 0.9 mm to 2 mm. An analysis of the impact induced by each process step on the hole evolution (both geometry and ablated volume) has been carried out and in particular the role it plays on the hole shape evolution the dust generated by the material ablation before to be evacuated, has been highlighted. Importantly, a zero-tapering hole with aspect ratio of 10 was obtained in a 2 mm thick sample with a processing time of 32 s. Finally, an analysis of the thermal effects on the internal part of the holes was carried out by SEM micrograph and here reported. [ABSTRACT FROM AUTHOR]

The notochord is an essential part of human development that regresses with age. Masses derived from notochordal tissue may be encountered during imaging of the neuroaxis. Fortunately, the majority of these are benign and can usually be differentiated by radiological and clinical findings. In this manuscript, we discuss the clinical and radiologic presentation of the four notochordal derived masses and present a brief overview of their management. • Notochordal derived masses are frequently encountered during imaging of the neuroaxis, but clinical and radiological data can help differentiate the benign lesions from the chordoma. • The presence of a soft tissue mass or osteolysis should raise concern for a chordoma and biopsy is necessary. • The benign notochordal cell tumor can MRI characteristics that may mimic a metastasis, but the other imaging features may help point toward the BNCT. • Chordomas most frequently metastasize to lung, bone and liver in descending order. [ABSTRACT FROM AUTHOR]

For diesel engine misfire fault diagnosis under strong noise, a new method based on variational mode decomposition (VMD) and cross wavelet transform (XWT) is proposed. Firstly, the vibration signal of cylinder head is processed by stages according to the working cycle of diesel engine, and then the vibration signal of each working cycle is re-sampled according to the same angle. Then the vibration signal of cylinder head is decomposed by VMD to denoise adaptively and reconstruct the signal. Next, XWT is used to analyze the time-frequency correlation of any two continuous working cycle signals, and the non-periodic components and random noise in the vibration signals are further eliminated to extract the combustion characteristics of diesel engines. Finally, the misfire fault of diesel engine is diagnosed by calculating the energy proportion of each cylinder in time-frequency space. The effectiveness of the proposed method is verified by simulation and experiment. [ABSTRACT FROM AUTHOR]

• Inhibition of notochord resorption upon thyroid hormone receptor β but not α knockout. • Notochord specific high level expression of thyroid hormone receptor β. • Tissue specific upregulation of matrix metalloproteinase (MMP) genes in the tail. • A role of matrix metalloproteinase MMP9-TH and MMP13 in notochord resorption. Tail resorption during anuran metamorphosis is perhaps the most dramatic tissue transformation that occurs during vertebrate development. Earlier studies in highly related anuran species Xenopus laevis and Xenopus tropicalis have shown that thyroid hormone (T3) receptor (TR) plays a necessary and sufficient role to mediate the causative effect of T3 on metamorphosis. Of the two known TR genes in vertebrates, TRα is highly expressed during both premetamorphosis and metamorphosis while TRβ expression is low in premetamorphic tadpoles but highly upregulated as a direct target gene of T3 during metamorphosis, suggesting potentially different functions during metamorphosis. Indeed, gene knockout studies have shown that knocking out TRα and TRβ has different effects on tadpole development. In particularly, homozygous TRβ knockout tadpoles become tailed frogs well after sibling wild type ones complete metamorphosis. Most noticeably, in TRβ-knockout tadpoles, an apparently normal notochord is present when the notochord in wild-type and TRα-knockout tadpoles disappears. Here, we have investigated how tail notochord resorption is regulated by TR. We show that TRβ is selectively very highly expressed in the notochord compared to TRα. We have also discovered differential regulation of several matrix metalloproteinases (MMPs), which are known to be upregulated by T3 and implicated to play a role in tissue resorption by degrading the extracellular matrix (ECM). In particular, MMP9-TH and MMP13 are extremely highly expressed in the notochord compared to the rest of the tail. In situ hybridization analyses show that these MMPs are expressed in the outer sheath cells and/or the connective tissue sheath surrounding the notochord. Our findings suggest that high levels of TRβ expression in the notochord specifically upregulate these MMPs, which in turn degrades the ECM, leading to the collapse of the notochord and its subsequent resorption during metamorphosis. [ABSTRACT FROM AUTHOR]

Cloud detection algorithms have emerged to automate image data analysis because of its prime influential factor in remote sensing image quality. Cloud detection algorithm still needs domain-expert intervention and large number of training examples to ensure good performance whose acquirement becomes difficult due to unavailability of labeled data as well as the time and process heads involved. The paper puts forward multi-objective social spider optimization (MOSSO) based efficient clustering technique to detect clouds in the visible range. This paper explains the proposed MOSSO algorithm along-with the analysis carried on 14 benchmark two-objective test problems against MOEA/D, MODE, MOPSO and SPEA2 multi-objective algorithms. Further, the strengths and weaknesses of the proposed algorithm are analyzed and have been used for the implementation of an efficient clustering technique named as MOSSO-C. Optimal centroid matrix for clustering is attained in MOSSO-C through environmental selection whose performance evaluation has been done on six synthetic databases and are compared with above mentioned conventional multi-objective algorithms. The obtained results encourage the use of MOSSO-C technique to get labeled data for training process of neural network classifier. This approach efficiently classifies the cloudy pixels against various Earth's surfaces (water, vegetation and land). The paper also discusses the performance evaluation of proposed technique on four Landsat 8 data which shows on an average 96.37% performance accuracy in detecting cloudy pixels. • Multi-objective social spider optimization (MOSSO) is proposed. • A Roulette wheel switching technique is proposed to obtain fittest striplings. • Cloud detection technique is formulated as a multi-objective clustering problem using MOSSO algorithm. • To select optimal centroid, an environmental selection method is proposed. • The optimal centroid act as target vector for a NN classifier to detect cloud. [ABSTRACT FROM AUTHOR]

Addictive behaviors are influenced both by impulsive processes headed toward consumption, and by higher-order, reflective, control-oriented processes. Our objective here was to (i) change automatically-activated action tendencies and explicit attitudes toward alcohol and softdrinks, as well as fat and healthy food through evaluative conditioning (EC) and (ii) investigate the role of contingency awareness in producing an EC effect. In the EC conditions, alcohol-related stimuli or fat foods (CS) were associated with negative pictures (US), while stimuli related to softdrinks or healthy foods (CS) were associated with positive pictures (US). In the control conditions, CSs were paired with neutral pictures (US). Measures of explicit attitudes and approach tendencies (AAT) were assessed before and after the EC procedure. Participants (n = 95) then indicated whether they remembered, for each CS, the valence of the associated US. Significant EC effects were found on explicit attitudes toward alcohol and marginally significant change on attitudes toward fat foods. The effect on alcohol appeared to depend on awareness of CS-US contingencies. No effects of EC were found on approach tendencies. Difficulties to find EC effects on action tendencies can be attributed to structural features of the AAT and strategies during EC. We conclude that EC alone may not be efficient in reducing addictive behaviors in populations with reduced capacity to process CS-US pairs and for which impulsive behaviors are strong predictors of consumption. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of cervical vertebral anomalies (CVA) in a group of patients presenting with cleft lip and palate (CLP) and to compare with a non-cleft population. Material and methods: The sample comprised of 150 lateral cephalograms of non-syndromic patients with CLP and 150 noncleft age-matched controls. The age range of both groups covered 6 to 20 years. An expert radiologist blinded to the cleft status evaluated the cephalograms for CVA and categorised them into normal, fusion, dehiscence and multiple cervical anomalies. The cleft group was subdivided according to the types of cleft (UCLP/BCLP/CPO) and gender (male/female). The CVA prevalence was compared between the cleft and non-cleft patients. Results: The prevalence of CVA was 37.7% and 20.7% in cleft and non-cleft patients, respectively. The difference was statistically significant with a p-value <0.01. Of the types of clefts, a left UCLP had the highest prevalence of CVA (47.2%), with fusion (35.8%) most commonly seen. On comparing CLP with CPO, no significant variation was observed between the types of anomalies. Conclusions: A high prevalence of CVA was observed in cleft patients compared with non-cleft subjects. The prevalence of CVA was similar between males and females. The practitioner should carefully evaluate the lateral cephalogram of CLP patients for CVA, which otherwise may remain undetected and lead to neurological symptoms later in life. [ABSTRACT FROM AUTHOR]

In a multitude of organisms, transcription factors of the basic helix-loop-helix (bHLH) family control the expression of genes required for organ development and tissue differentiation. The functions of different bHLH transcription factors in the specification of nervous system and paraxial mesoderm have been widely investigated in various model systems. Conversely, the knowledge of the role of these regulators in the development of the axial mesoderm, the embryonic territory that gives rise to the notochord, and the identities of their target genes, remain still fragmentary. Here we investigated the transcriptional regulation and target genes of Bhlh-tun1, a bHLH transcription factor expressed in the developing Ciona notochord as well as in additional embryonic territories that contribute to the formation of both larval and adult structures. We describe its possible role in notochord formation, its relationship with the key notochord transcription factor Brachyury, and suggest molecular mechanisms through which Bhlh-tun1 controls the spatial and temporal expression of its effectors. • Bhlh-tun1 is part of the Ciona notochord regulatory network. • Bhlh-tun1 expression is dependent upon Brachyury. • In turn Bhlh-tun1 controls 21 notochord genes involved in notochord intercalation. [ABSTRACT FROM AUTHOR]

The elongation of embryo and tissue is a key morphogenetic event in embryogenesis and organogenesis. Notochord, a typical chordate organ, undergoes elongation to perform its regulatory roles and to form the structural support in the embryo. Notochord elongation is morphologically similar across all chordates, but ascidian has evolved distinct molecular and cellular processes. Here, we summarize the current understanding of ascidian notochord elongation. We divide the process into three phases and discuss the underlying molecular mechanisms in each phase. In the first phase, the notochord converges and extends through invagination and mediolateral intercalation, and partially elongates to form a single diameter cell column along the anterior-posterior axis. In the second phase, a cytokinesis-like actomyosin ring is constructed at the equator of each cell and drives notochord to elongate approximately two-fold. The molecular composition and architecture of the ascidian notochord contractile ring are similar to that of the cytokinetic ring. However, the notochord contractile ring does not impose cell division but only drives cell elongation followed by disassembly. We discuss the self-organizing property of the circumferential actomyosin ring, and why it disassembles when certain notochord length is achieved. The similar ring structures are also present in the elongation process of other organs in evolutionarily divergent animals such as Drosophila and C. elegans. We hereby propose that actomyosin ring-based circumferential contraction is a common mechanism adopted in diverse systems to drive embryo and tissue elongation. In the third phase, the notochord experiences tubulogenesis and the endothelial-like cells crawl bi-directionally on the notochord sheath to further lengthen the notochord. In this review, we also discuss extracellular matrix proteins, notochord sheath, and surrounding tissues that may contribute to notochord integrity and morphogenesis. • Ascidian notochord elongation experiences three distinct phases. • The circumferential actomyosin ring drives ascidian notochord cell elongation but not cell division. • Ascidian the notochord experiences tubulogenesis and cells crawl bi-directionally on the sheath to further lengthen the notochord. [ABSTRACT FROM AUTHOR]

Locomotion by tail beating powered by a system of bilateral paraxial muscle and notochord is likely one of the key evolutionary innovations that facilitated the origin and radiation of chordates. The innovation of paraxial muscle was accompanied by gene duplications in stem chordates that gave rise to muscular actins from cytoplasmic ancestral forms, which acquired contractile capability thanks to the recruitment of the myosin motor-machinery. To better understand the role of actin diversification during the evolution of chordates, in this work we have characterized the complete actin catalogue of the appendicularian Oikopleura dioica , an urochordate that maintains a chordate body plan throughout its life, including the notochord in a muscled tail that confers an active free-living pelagic style. Our genomic survey, phylogenetic analyses and Diagnostic-Actin-Values (DAVs) reveal that O. dioica has four muscular actins (ActnM1–4) and three cytoplasmic actins (ActnC1–3), most of which originated by independent gene duplications during the evolution of the appendicularian lineage. Detailed developmental expression atlas of the complete actin catalogue of O. dioica reveals differences in the temporal-regulation and tissue-specificity of different actin paralogs, suggesting complex processes of subfunctionalization during the evolution of urochordates. Our results suggest the presence of a "cardio-paraxial" muscular actin at least in the last common ancestor of Olfactores (i.e. vertebrates+urochordates). Our results reveal highly dynamic tissue-specific expression patterns for some cytoplasmic actins, including the notochord, ciliated cells and neurons with axonal projections, which challenge the classic housekeeping notion ascribed to these genes. Considering that previous work had demonstrated the existence of notochord-specific actins in cephalochordates, the tissue-specific expression of two cytoplasmic actins in the notochord of O. dioica suggests that this pattern plausibly reflects the ancestral condition of chordates, and provides new insights to better understand the evolutionary origin of the notochord. fx1 • Stem Olfactores (vertebrates+urochordates) had a "cardio-paraxial" muscular actin. • Tissue-specificity of cytoplasmic actins challenges their classic housekeeping notion. • Expression of O. dioica cytoplasmic actins correlates with axons and cilia. • Notochord-specificity of cytoplasmic actins is an ancestral condition of chordates. [ABSTRACT FROM AUTHOR]

The gene regulatory networks underlying Ciona notochord fate specification and differentiation have been extensively investigated, but the regulatory basis for regionalized expression within the notochord is not understood. Here we identify three notochord-expressed genes, C11.331 , C12.115 and C8.891 , with strongly enriched expression in the secondary notochord cells at the posterior tip of the tail. C11.331 and C12.115 share a distinctive expression pattern that is highly enriched in the secondary notochord lineage but also graded within that lineage with the strongest expression at the posterior tip. Both genes show similar responses to pharmacological perturbations of Wnt and FGF signaling, consistent with an important role for Wnt and FGF ligands expressed at the tail tip. Reporter analysis indicates that the C11.331 cis -regulatory regions are extensively distributed, with multiple non-overlapping regions conferring posterior notochord-enriched expression. Fine-scale analysis of a minimal cis -regulatory module identifies discrete positive and negative elements including a strong silencer. Truncation of the silencer region leads to increased expression in the primary notochord, indicating that C11.331 expression is influenced by putative regulators of primary versus secondary notochord fate. The minimal CRM contains predicted ETS, GATA, LMX and Myb sites, all of which lead to reduced expression in secondary notochord when mutated. These results show that the posterior-enriched notochord expression of C11.331 depends on multiple inputs, including Wnt and FGF signals from the tip of the tail, multiple notochord-specific regulators, and yet-to-be identified regulators of regional identity within the notochord. • C11.331, C12.115 and C8.891 are strongly enriched in the Ciona 2° notochord lineage. • Drug treatments support a role for tail-tip expressed Wnts and FGFs. • Quantitative analysis of C11.331 cis -regulation reveals extensive apparent redundancy. • A silencer element represses C11.331 expression in 1° notochord. • Predicted LMX, Myb, GATA and ETS sites contribute to 2°-specific expression. [ABSTRACT FROM AUTHOR]

The sensor network that contains sensor nodes equipped with cameras, microphones and other sensors producing multimedia content is known as wireless multimedia sensor network (WMSN). In WMSN, battery energy and network lifetime are the real requirements of research for the transmission of multimedia information needs more energy. This research paper proposes a soft computing-based approach for optimizing the cluster head selection process to decide upon the optimal path of transmission, and SGP approach is used for cluster formation. A three-layer ANN model trained using back propagation has been proposed in this paper, and comparative analysis is performed among existing techniques such as LEACH, Q-LEACH, C-LEACH and SGP algorithms. It is found from the observations that proposed neural hybrid approach exhibits superior performance while exhibiting marginal improvement over SGP due to the training process where the error is minimized. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the natural history of intervertebral disk (IVD) and characterize its embryonic beginnings and age-related degeneration.Methods: Coronal sections of embryonic (E13.5-neonatal) and postnatal (4-60-week-old) Sprague-Dawley rat IVD were stained by a series of histological stainings (hematoxylin and eosin, Alcian blue, Picrosirius red, Masson, Periodic acid-Schiff). Growth kinetics within embryonic IVD were evaluated by immunohistochemical staining of Ki67 and proliferating cell nuclear antigen. Postnatal maturation and degeneration of IVD were visualized on radiology by X-ray, CT, and MR imaging.Results: During the formation of rat IVD, inner annulus fibrosus (AF) and cartilaginous endplate (CEP) shared similar cell density, extracellular matrix, and potential of growth kinetics; notochord provided increased and enlarged cytoplasmic vacuoles to generate nucleus pulposus (NP), part of which was retained within CEP. Postnatally, vacuolated notochord cells were reduced by devacuolation, while chondrocytic NP cells increased; cartilaginous layers of CEP were narrowed by vertebrae growth and secondary ossification; fibrotic portion of AF decreased as cartilaginous matrix accumulated and infiltrated outward. In aged and degenerated IVD, large longitudinal fissures were detected near the boundaries between inner and outer AF, whereas both reduced cellularity and accumulated cell clusters were evident within the dehydrated NP; only part of these histocytological changes could be reported on radiology.Conclusions: By showing that the natural history of IVD is orchestrated by a dynamic histocytological regulation, our study may facilitate better understanding of the developmental defects, cellular heterogeneity, age-related degenerative mechanisms, and biological regeneration of IVD. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Hypertext comprehension often suffers from inadequate representation of the text's structure. Explication of the local paragraph macrostructure within each node might help to overcome this obstacle. As headings show several deficits, especially in digital text, marginalia are considered a promising alternative in signaling hypertext structure as they should foster interactive processing. 41 participants learned with a hypertext with identical macropropositions presented as either macropropositional marginalia (EG 1), paragraph-initial topic sentences (EG2) or with an unsignaled placing of the macropropositions at the end of each paragraph (CG). All three experimental texts contained identical information. Results revealed increased inference performance for marginalia and increased factual recognition for topic sentences, confirming the assumptions that marginalia foster interactive processing but suffer the same oversignaling deficit as headings concerning the processing of factual information. [ABSTRACT FROM AUTHOR]

Calcium and phosphorus (P) are the main bone minerals, and P deficiency can cause hypomineralized bones (osteomalacia) and malformations. This study used a P-deficient salmon model to falsify three hypotheses. First, an extended period of dietary P deficiency does not cause pathologies other than osteomalacia. Second, secondary mineralization of non-mineralized bone is possible. Third, secondary mineralization can restore the bones' mineral composition and mechanical properties. For 7 weeks, post-smolt Atlantic salmon (Salmo salar) received diets with regular P content (RP) or with a 50% lowered P content (LP). For additional 9 weeks, RP animals continued on the regular diet (RP-RP). LP animals continued on the LP diet (LP-LP), on a regular P diet (LP-RP) or on a high P diet (LP-HP). After 16 weeks, animals in all groups maintained a non-deformed vertebral column. LP-LP animals continued bone formation albeit without mineralization. Nine weeks of RP diet largely restored the mineral content and mechanical properties of vertebral bodies. Mineralization resumed deep inside the bone and away from osteoblasts. The history of P deficiency was traceable in LP-RP and LP-HP animals as a ring of low-mineralized bone in the vertebral body endplates, but no tissue alterations occurred that foreshadow vertebral body compression or fusion. Large quantities of nonmineralized salmon bone have the capacity to re-mineralize. If 16 weeks of P deficiency as a single factor is not causal for typical vertebral body malformations, other factors remain to be identified. This example of functional bone without minerals may explain why some teleost species can afford to have an extremely low mineralized skeleton. [ABSTRACT FROM AUTHOR]

The origin of the notochord is a central issue in chordate evolution. This study examined the development of the acorn worm pygochord, a putative homologue of the notochord. Because the pygochord differentiates only after metamorphosis, the developmental was followed process by inducing regeneration after artificial amputation in Ptychodera flava. It was found that although the regeneration of the posterior part of the body did not proceed via formation of an obvious regeneration bud, pygochord regeneration was observed within a few weeks, possibly via trans‐differentiation of endoderm cells. The expression of the fibrillary collagen gene (Fcol) and elav in the pygochord during regeneration was detected. This indicates that pygochord cells are not part of gut epithelial cells, but that they differentiated as a distinct cell type. Our gene expression analyses do not provide supporting evidence for the homology between the pygochord and notochord, but rather favored the convergent evolution between them. This study examined the regeneration of the acorn worm pygochord, a putative origin of the notochord. We detected the expression of the fibrillary collagen gene and elav in the pygochord during regeneration. [ABSTRACT FROM AUTHOR]

Abstract slc7a5 (also known as LAT1), largely accepted as an amino acid transporter, has been shown to play important roles in cancer and developmental processes. Because knockout mice of Slc7a5 are embryonically lethal due to placental defects, it is difficult to evaluate its role in early development. In this study, expression and function of slc7a5 were evaluated in Xenopus laevis embryos that develop without a placenta. Expression of slc7a5 was detected in the notochord and in the eye and it was not co-localized with slc3a2 , which helps slc7a5 to localize at the plasma membrane, before the late neurula stage. Loss-of-function experiment with a morpholino antisense oligonucleotide led to defect of neural and non-neural patterning, inhibition of primary neurogenesis, and disruption of eye development. Disruption of neural development and primary neurogenesis was likely due to impaired notochord development as sonic hedgehog (shh) signaling pathway was compromised in slc7a5-inhibited embryos. These results suggest that slc7a5 is required for notochord development and subsequent primary neurogenesis via shh/gli signaling and for eye development. These novel developmental roles of slc7a5 appeared to be independent of transport function at least before the late neurula stage. Highlights • Xenopus slc7a5 expressed in the notochord and the eye. • Inhibition of slc7a5 disrupted early neural development and interfered with eye development • slc7a5 inhibition disrupted normal retinal morphogenesis • slc7a5 depletion disrupted neural- and non-neural patterning and primary neurogenesis • slc7a5 was essential for shh/gli signaling to induce proper notochordal and neural development [ABSTRACT FROM AUTHOR]

Abstract Introduction This study reports the clinicopathological characteristics and the perioperative and long-term treatment outcomes after aggressive surgical resection in solid pseudopapillary tumor (SPT) of the pancreas performed at a high volume center for pancreatic surgery in India. Materials and methods We analyzed a prospectively maintained database of the patients operated for SPT at Tata Memorial Hospital, India over a period of 11 years from February 2007 to February 2018. Results Fifty consecutive patients operated for SPT, during the study period were included. The median age at presentation was 24 years. Majority of the patients (43/50) were female (86%). Disease was predominantly localized in the head and uncinate process of pancreas (66%). Median tumor size was 7.7 cm (Range 1.6–15 cm). Tumor extent was radiologically defined as borderline resectable or locally advanced in 48% (n = 24) patients. Forty-six major pancreatic resections were performed, which included 10 (21%) vascular resections, 2 synchronous liver metastasectomies, 1 multi visceral resection and 5 total pancreaticosplenectomies. Five of these resections were reoperations in patients deemed inoperable on exploration at other centers. R0 resection was achieved in 47 patients (98%). Postoperative major morbidity was 19% and there was no mortality. At a median follow-up of 29 months (Range, 1–121 months), all patients were alive without any recurrence. Conclusion Aggressive complete surgical resection of SPT achieves excellent long-term survival. Surgery, especially for large and borderline resectable tumors, can be potentially complex and should be performed at high-volume centers to provide the best chance of cure. [ABSTRACT FROM AUTHOR]

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Highlights • Thiram toxicity was stage-dependent, earlier exposures resulted in greater effects. • Both Thiram and methimazole (a TPO inhibitor) caused notochord curvature. • Effects may be due to regulation of thyroid genes including TPO and Deiodinase 3. • Early life stage exposure may be responsible for adverse effects seen later. Abstract Thiram, a pesticide in the dithiocarbamate chemical family, is widely used to prevent fungal disease in seeds and crops. Its off-site movement to surface waters occurs and may place aquatic organisms at potential harm. Zebrafish embryos were used for investigation of acute (1 h) thiram exposure (0.001–10 µM) at various developmental stages. Survival decreased at 1 µM and 10 µM and hatching was delayed at 0.1 µM and 1 µM. Notochord curvatures were seen at 0.1 and 1 μM thiram when exposure was initiated at 2 and at 10 hpf. Similar notochord curvatures followed exposure to the known TPO inhibitor, methimazole (MMI). Changes were absent in embryos exposed at later stages, i.e., 12 hpf. In embryos exposed to 0.1 or 1 μM at 10 hpf, levels of the thyroid enzyme, Deiodinase 3, increased by 12 hpf. Thyroid peroxide (TPO), important in T4 synthesis, decreased by 48 hpf in embryos exposed to 1 µM at 10 hpf. Thiram toxicity was stage-dependent and early life stage exposure may be responsible for adverse effects seen later. These effects may be due to impacts on the thyroid via regulation of specific thyroid genes including TPO and Deiodinase 3. [ABSTRACT FROM AUTHOR]

The elongating mouse anteroposterior axis is supplied by progenitors with distinct tissue fates. It is not known whether these progenitors confer anteroposterior pattern to the embryo. We have analysed the progenitor population transcriptomes in the mouse primitive streak and tail bud throughout axial elongation. Transcriptomic signatures distinguish three known progenitor types (neuromesodermal, lateral/paraxial mesoderm and notochord progenitors; NMPs, LPMPs and NotoPs). Both NMP and LPMP transcriptomes change extensively over time. In particular, NMPs upregulate Wnt, Fgf and Notch signalling components, and many Hox genes as progenitors transit from production of the trunk to the tail and expand in number. In contrast, the transcriptome of NotoPs is stable throughout axial elongation and they are required for normal axis elongation. These results suggest that NotoPs act as a progenitor niche whereas anteroposterior patterning originates within NMPs and LPMPs. [ABSTRACT FROM AUTHOR]

This paper presents a novel method that utilizes in-process measurements of product quality and models that relate those measurements with the underlying manufacturing process parameters to drive down the product quality errors via strategic adjustments of the controllable process parameters. Uniqueness of the new method is its robustness to inevitable inaccuracies in the underlying models, as well as the absence of traditional, but restrictive assumptions of Gaussianity and independence of measurement and process noise terms. The new approach was demonstrated using models and data from an automotive cylinder head machining process and an industrial-scale semiconductor lithography overlay process. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is beginning to transform IMRT treatment planning for head and neck patients. However, the complexity and novelty of AI algorithms make them susceptible to misuse by researchers and clinicians. Understanding nuances of new technologies could serve to mitigate potential clinical implementation pitfalls. This article is intended to facilitate integration of AI into the radiotherapy clinic by providing an overview of AI algorithms, including support vector machines (SVMs), random forests (RF), gradient boosting (GB), and several variations of deep learning. This document describes current AI algorithms that have been applied to head and neck IMRT planning and identifies rapidly growing branches of AI in industry that have potential applications to head and neck cancer patients receiving IMRT. AI algorithms have great clinical potential if used correctly but can also cause harm if misused, so it is important to raise the level of AI competence within radiation oncology so that the benefits can be realized in a controlled and safe manner. [ABSTRACT FROM AUTHOR]

Existence and biomedical relevance of the neurenteric canal, a transient midline structure during early neurulation in the human embryo, have been controversially discussed for more than a century by embryologists and clinicians alike. In this study, the authors address the long-standing enigma by high-resolution histology and three-dimensional reconstruction using new and historic histological sections of 5 human 17- to 21-day-old embryos and of 2 marmoset monkey embryos of the species Callithrix jacchus at corresponding stages. The neurenteric canal presents itself as the classical vertical connection between the amniotic cavity and the yolk sac cavity and is lined (a) craniolaterally by a horseshoe-shaped "hinge of involuting notochordal cells" within Hensen's node and (b) caudally by the receding primitive streak epiblast dorsally and by notochordal plate epithelium ventrally, the latter of which covered the (longitudinal) notochordal canal on its ventral side at the preceding stage. Furthermore, asymmetric parachordal nodal expression in Callithrix and morphological asymmetries within the nodes of the other specimens suggest an early non-cilium-dependent left-right symmetry breaking mode previously postulated for other mammals. We conclude that structure and position of the mammalian neurenteric canal support the notion of its homology with the reptilian blastopore as a whole and with a dorsal segment of the blastopore in amphibia. These new features of the neurenteric canal may further clarify the aetiology of foetal malformations such as junctional neurulation defects, neuroendodermal cysts, and the split notochord syndrome. [ABSTRACT FROM AUTHOR]

Endocrine disruptors have been demonstrated to exert adverse effects on growth and development of amphibians by disrupting hormone levels. Tail resorption, which is one of the most remarkable events during amphibian metamorphosis, is closely associated with thyroid hormones levels. However, limited research has been conducted on the effects of endocrine disruptors on tail resorption in amphibians. This study explored the effects of NaClO 4 and T4 on the growth, development and tail resorption during the metamorphosis of Rana Chensinensis. The results demonstrated that exposure to NaClO 4 led to an increase in body size and a delay in metamorphosis of R. Chensinensis tadpoles. Histological analysis revealed that both NaClO 4 and exogenous T4 exposure resulted in thyroid gland injury, and NaClO 4 treatment delayed the degradation of notochord and muscles, thereby delaying tail resorption. Moreover, transcriptome sequencing results showed that apoptosis-related genes (APAF1 , BAX and CASP6) and cell component degradation-related genes (MMP9 and MMP13) were highly expressed in the T4 exposure group, and the expression of oxidative stress-related genes (SOD and CAT) was higher in the NaClO 4 exposure group. Taken together, both NaClO 4 and exogenous T4 affect tail resorption in R. Chensinensis , thereby affecting their adaptation to terrestrial life. The present study will not only provide a reference for future experimental research on the effects of other endocrine disruptors on the growth, development and tail resorption of amphibians but will also provide insights into environmental protection and ecological risk assessment. [Display omitted] • NaClO 4 and T4 effects on tail resorption of Rana chensinsnsis were assessed • NaClO 4 exposure increased body size and delayed metamorphosis of Rana Chensinensis • NaClO 4 and exogenous T4 exposure both caused thyroid gland injury • NaClO 4 and T4 delayed and accelerated tail resorption, respectively [ABSTRACT FROM AUTHOR]

It is well established that Hensen's nodes can induce the formation of supernumerary digits after grafting into the anterior margin of the developing limb bud. The recent finding that distinct mesodermal cell populations are segregated within the node has made it possible to isolate different prospective cell types in an attempt to correlate digit-inducing ability with cell fate. We find that the prospective notochord cells contained within Hensen's node are able to induce supernumerary digits, whereas presumptive somite cells cannot. This early difference in inducing ability persists into later stages of development: epithelial somites are unable to induce while notochord from all lengths of the neuraxis continues to induce. Using probes to retinoic acid receptor-beta 2 and sonic hedgehog (shh) we find no evidence to support the idea that inducing tissues generate extra digits by releasing retinoic acid into adjacent limb tissue but find that the inducing ability of a tissue correlates with its expression of shh.

It is well established that Hensen's nodes can induce the formation of supernumerary digits after grafting into the anterior margin of the developing limb bud. The recent finding that distinct mesodermal cell populations are segregated within the node has made it possible to isolate different prospective cell types in an attempt to correlate digit-inducing ability with cell fate. We find that the prospective notochord cells contained within Hensen's node are able to induce supernumerary digits, whereas presumptive somite cells cannot. This early difference in inducing ability persists into later stages of development: epithelial somites are unable to induce while notochord from all lengths of the neuraxis continues to induce. Using probes to retinoic acid receptor-beta 2 and sonic hedgehog (shh) we find no evidence to support the idea that inducing tissues generate extra digits by releasing retinoic acid into adjacent limb tissue but find that the inducing ability of a tissue correlates with its expression of shh.

Notochord is an axial structure derived of embryonic mesoderm and in addition to structural supporting role in inducing nearby germinal layers, it has a basic role in formation of organs such as vertebral column, axial vessels, neural tube and primitive gut. This organ undergoes essential changes during the development process. First, arises from the primitive node and terms notochordal process, while containing a central canal. Then, transforms to notochordal plate and thereafter, changes to a cord called definitive notochord. Finally, it degenerates in centra and remains in intervertebral discs and makes its nucleus pulposus. Glycoconjugates are macromolecules containing carbohydrates that interfere in some biological phenomena such as cell proliferation, differentiation, migration and apoptosis during the development of numerous organs. The terminal sugars of carbohydrate chains are mainly responsible for these duties. These sugars are identifiable by using some polypeptides derived from plants and animals sources termed lectins. Lectins are linked exclusively to these sugars and the applied technique is called lectin histochemistry. Investigation of the developmental changes of notochord using this technique has shown that different glycoconjugates with divers terminal sugars such as N-acetylgalactoseamine (GalNac), N-acetylclucoseamine (GlcNac), galactose (Gal), fucose (Fuc), mannose (Man) and neuraminic acid (NeuAc) and also Gal-GalNac and GalGlcNac disaccharides are expressed during morphogenesis period in this organ of different animal species. Review of extensive studies carried out on development of notochord and its inductive role on nearby tissues has revealed that it is a highly glycosylated tissue and diverse glycoconjugates with different terminal sugars are expressed in it. Some of these molecules are probably involved in morphological changes of notochord while, the others are present in secreted substances from it and play key roles in its inductive effects on the nearby tissues.

Abstract Background Genomic analysis has upended chordate phylogeny, placing the tunicates as the sister group to the vertebrates. This taxonomic rearrangement raises questions about the emergence of a tunicate/vertebrate ancestor. Results Characterization of developmental genes uniquely shared by tunicates and vertebrates is one promising approach for deciphering developmental shifts underlying acquisition of novel, ancestral traits. The matrix glycoprotein Fibronectin (FN) has long been considered a vertebrate-specific gene, playing a major instructive role in vertebrate embryonic development. However, the recent computational prediction of an orthologous “vertebrate-like” Fn gene in the genome of a tunicate, Ciona savignyi, challenges this viewpoint suggesting that Fn may have arisen in the shared tunicate/vertebrate ancestor. Here we verify the presence of a tunicate Fn ortholog. Transgenic reporter analysis was used to characterize a Ciona Fn enhancer driving expression in the notochord. Targeted knockdown in the notochord lineage indicates that FN is required for proper convergent extension. Conclusions These findings suggest that acquisition of Fn was associated with altered notochord morphogenesis in the vertebrate/tunicate ancestor.

A sellar spine is a midline bony spur arising from the ventral aspect of the dorsum sellae. Representing a remnant of the anterior notochord, it is often an incidental finding and thought to be of no clinical significance. However, it has recently been suggested that a potential association may exist between sellar spine and pediatric pituitary endocrinopathies, possibly caused by deformation of the developing pituitary gland by the sellar spine. To our knowledge, this is the first case report demonstrating an association between sellar spine and clinical diabetes insipidus. • A sellar spine is a midline bony spur arising from the ventral aspect of the posterior clinoid process. • Sellar spine may potentially be associated with pediatric pituitary endocrinopathies. • Patients with unexplained or refractory DI may benefit from CT to assess for the presence of a sellar spine. [ABSTRACT FROM AUTHOR]

The founder cells of the Nucleus pulposus, the centre of the intervertebral disc, originate in the embryonic notochord. After birth, mature notochordal cells (NC) are identified as key regulators of disc homeostasis. Better understanding of their biology has great potential in delaying the onset of disc degeneration or as a regenerative-cell source for disc repair. Using human pluripotent stem cells, we developed a two-step method to generate a stable NC-like population with a distinct molecular signature. Time-course analysis of lineage-specific markers shows that WNT pathway activation and transfection of the notochord-related transcription factor NOTO are sufficient to induce high levels of mesendoderm progenitors and favour their commitment toward the notochordal lineage instead of paraxial and lateral mesodermal or endodermal lineages. This study results in the identification of NOTO-regulated genes including some that are found expressed in human healthy disc tissue and highlights NOTO function in coordinating the gene network to human notochord differentiation.

Chordomas are low-grade malignant tumours that arise from remnants of the notochord, usually from within the vertebral bodies It accounts for 1%-4% of malignant primary bone tumours, 50% of which are located in the sacrococcygeal region. It's annual incidence is 0.1/100 000 population. The greatest incidence was found between the fifth and the seventh decades with a male predominance. In spite of its slow-growing nature, chondroid chordoma tends to relapse, and it may eventually become malignant, often jeopardising the patient's prognosis. We report the case of sacrococcygeal chondroide chordoma and the treatment performed.

The patterning of the spine of a zebrafish is controlled by the notochord, a rod-like structure that supports and instructs the developing embryo.

Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmentation, yet observe a largely normal segmentation process of the chordacentra. We demonstrate that axial entpd5+ notochord sheath cells are responsible for chordacentrum mineralization, and serve as a marker for axial segmentation. While autonomous within the notochord sheath, entpd5 expression and centrum formation show some plasticity and can respond to myotome pattern. These observations reveal for the first time the dynamics of notochord segmentation in a teleost, and are consistent with an autonomous patterning mechanism that is influenced, but not determined by adjacent paraxial mesoderm. This behavior is not consistent with a clock-type mechanism in the notochord.

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments.