103 research outputs found
In Full Force. Mechanotransduction and Morphogenesis during Homeostasis and Tissue Regeneration
No full textThe interactions of form and function have been the focus of numerous studies in the context of development and more recently regeneration. Our understanding on how cells, tissues and organs sense and interpret external cues, such as mechanical forces, is becoming deeper as novel techniques in imaging are applied and the relevant signaling pathways emerge. These cellular responses can be found from bacteria to all multicellular organisms such as plants and animals. In this review, we focus on hemodynamic flow and endothelial shear stress during cardiovascular development and regeneration, where the interactions of morphogenesis and proper function are more prominent. In addition, we address the recent literature on the role of extracellular matrix and fibrotic response during tissue repair and regeneration. Finally, we refer to examples where the integration of multi-disciplinary approaches to understand the biomechanics of cellular responses could be utilized in novel medical applications
On Zebrafish Disease Models and Matters of the Heart
No full textCoronary artery disease (CAD) is the leading form of cardiovascular disease (CVD), which is the primary cause of mortality worldwide. It is a complex disease with genetic and environmental risk factor contributions. Reports in human and mammalian models elucidate age-associated changes in cardiac function. The diverse mechanisms involved in cardiac diseases remain at the center of the research interest to identify novel strategies for prevention and therapy. Zebrafish (Danio rerio) have emerged as a valuable vertebrate model to study cardiovascular development over the last few decades. The facile genetic manipulation via forward and reverse genetic approaches combined with noninvasive, high-resolution imaging and phenotype-based screening has provided new insights to molecular pathways that orchestrate cardiac development. Zebrafish can recapitulate human cardiac pathophysiology due to gene and regulatory pathways conservation, similar heart rate and cardiac morphology and function. Thus, generations of zebrafish models utilize the functional analysis of genes involved in CAD, which are derived from large-scale human population analysis. Here, we highlight recent studies conducted on cardiovascular research focusing on the benefits of the combination of genome-wide association studies (GWAS) with functional genomic analysis in zebrafish. We further summarize the knowledge obtained from zebrafish studies that have demonstrated the architecture of the fundamental mechanisms underlying heart development, homeostasis and regeneration at the cellular and molecular levels
Zebrafish Angiogenesis and Valve Morphogenesis: Insights from Development and Disease Models
No full textIdentifying methods of gathering and sharing hazardous air containment information
No full textPlan BFor the past five years, air contaminants at Spectro Alloys have been a major source of employee concern. In these same five years, Spectro Alloys has seen high turnover and low employee morale. The purpose of this study was to assess and describe ways in which organizational trust-building can be enhanced by identifying effective methods of gathering and sharing information related to occupational exposure to air contaminants at Spectro Alloys Corporation. Based on employee feedback and past air sampling data, the two major air contaminants at Spectro Alloys are hydrogen chloride and aluminum dust. For this study, the health hazards associated with aluminum and hydrogen chloride were researched. Additionally, the value of trust in organizations, and methods of health hazard communication were described.
Air sampling performed at processes associated with high levels of air contaminants showed results to be acceptable compared to OSHA’s Permissible Exposure Limits. The information was shared with employees, supervisors and management for the purpose of pre-testing material, soliciting feedback and gaining participation in the process from all levels of Spectro employees. The information sharing sessions concentrated on the material, its health hazards, signs and symptoms of exposure, permissible exposure limits, concentrations found at Spectro, and controls associated with reducing employee exposure to the contaminants studied.
Methods of gathering and sharing information included personal communication, literature reviews, air sampling and the creation of materials with which to share the air contaminant information in an effective manner. Informal feedback from employees showed that trust, which is based on the relationship between the source and the recipient of the message, will take time to build Spectro Alloys. Effective information sharing methods, combined with air sampling data gives Spectro Alloys management an opportunity to begin trust-building and create a more favorable relationship with its employees
role of SUMO protein in the regulation of the yeast Chromosome Passenger Complex
No full textProgression of cells into anaphase occurs only when microtubules are correctly attached to chromosome kinetochores, a process that is frequently error-prone in eukaryotic cells. In yeast, where kinetochores interact with a single microtubule, attachment errors may result from mechanical or molecular disruptions.
The spindle assembly checkpoint (SAC) monitors and resolves these errors by halting anaphase onset until all chromosomes are properly attached and bioriented. Misattachments can lead to aneuploidy, characterised by deviations in chromosome number, which is associated with tumorigenesis and cancer. The kinase Ipl1/Aurora B, a pivotal component of the Chromosomal Passenger Complex (CPC) is essential for correcting these attachment errors, cooperating with SAC.
During metaphase to anaphase progression, the CPC translocates from centromeres to the spindle midzone, fulfilling critical roles in maintaining chromosomal stability, ensuring accurate segregation.
It has been suggested that the localization and activity of Ipl1 are influenced by CPC sumoylation. Sumoylation is a post-translational modification involving the attachment of the ubiquitin-like protein SUMO to specific protein targets. This study investigates the role of CPC sumoylation in the localization and activation of its components, as well as its impact on cell growth and spindle dynamics in Saccharomyces cerevisiae cells.
The results indicate that while the sumoylation of other CPC components does not significantly affect S. cerevisiae growth, Ipl1 sumoylation appears to be essential, as cells lacking this modification were non-viable. Additionally, there is strong evidence that SUMO does not influence the localization of the CPC in S. cerevisiae, as localization experiments in loss-of-sumoylation mutants showed no significant difference compared to wild-type cells.
However, SUMO may affect Ipl1 activity, as an increase in final spindle length was observed in S. cerevisiae mutants lacking CPC sumoylation. Equivalent differences in spindle size were observed in previous studies, suggesting that loss of Ipl1 function results in spindle elongation. However, these particular findings observed that the loss of Ipl1 function leads to an extension in spindle elongation time, something that was not observed in our findings. This suggests that sumoylation may influence phosphorylation of specific substrates by Ipl1 that are involved in spindle size, rather than its overall activity.Η είσοδος των κυττάρων στην ανάφαση πραγματοποιείται μόνο όταν οι μικροσωληνίσκοι είναι σωστά συνδεδεμένοι με τους κινητοχώρους των χρωμοσωμάτων, μία διαδικασία που συχνά παρουσιάζει σφάλματα στα ευκαρυωτικά κύτταρα. Στο ζυμομύκητα, όπου οι κινητοχώροι συνδέονται με μόνο ένα μικροσωληνίσκο, τα σφάλματα μπορεί να προκύψουν από μηχανικές ή μοριακές διαταραχές.
Το Σημείο Ελέγχου της Ατράκτου -Spindle Assembly Checkpoint (SAC)- παρακολουθεί και επιλύει αυτά τα σφάλματα, σταματώντας την έναρξη της ανάφασης μέχρι όλα τα χρωμοσώματα να είναι σωστά συνδεδεμένα με τους μικροσωληνίσκους και σωστά προσανατολισμένα. Λάθη σύνδεσης μπορούν να οδηγήσουν σε ανευπλοειδία, μία κατάσταση που χαρακτηρίζεται από διαφορές και αποκλίσεις στον αριθμό των χρωμοσωμάτων και συνδέεται με την καρκινογένεση. Η κινάση Ipl1/Aurora B, η οποία είναι βασικό μέλος του συμπλόκου Chromosome Passenger Complex (CPC), είναι απαραίτητη για την διόρθωση αυτών των σφαλμάτων, συνεργαζόμενη με το SAC.
Κατά την διάρκεια της μετάβασης από την μετάφαση στην ανάφαση, το CPC μετατοπίζεται από τα κεντρομερή στην μέση ζώνη (midzone) της ατράκτου, πραγματοποιώντας σημαντικές λειτουργίες στην σταθερότητα των χρωμοσωμάτων και στην εξασφάλιση του σωστού διαχωρισμού τους.
Έχει προταθεί ότι ο εντοπισμός και η δραστικότητα της Ipl1 επηρεάζονται από την σουμοϋλίωση του συμπλόκου CPC. Η σουμοϋλίωση είναι μια μετα-μεταφραστική τροποποίηση που περιλαμβάνει την δέσμευση της πρωτεΐνης SUMO σε συγκεκριμένα σημεία στις πρωτεΐνες. Η παρούσα μελέτη ερευνά τον ρόλο της SUMO στον εντοπισμό και στην ενεργοποίηση των μελών του CPC, καθώς και την επίδρασή της στην ανάπτυξη των κυττάρων και στην δυναμική της ατράκτου σε κύτταρα ζύμης Saccharomyces cerevisiae.
Τα αποτελέσματα δείχνουν ότι ενώ η σουμοϋλίωση των άλλων συστατικών του CPC δεν επηρεάζει σημαντικά την ανάπτυξη του S. cerevisiae, φαίνεται ότι για την Ipl1 είναι απαραίτητη, καθώς κύτταρα στα οποία η Ipl1 δεν τροποποιείται από την SUMO δεν ήταν βιώσιμα. Επίσης υπάρχουν ισχυρές ενδείξεις ότι η SUMO δεν επηρεάζει τον εντοπισμό του CPC στο S. cerevisiae, καθώς δεν παρατηρήθηκε διαφορά στον εντοπισμό του εν λόγω συμπλόκου σε μεταλλαγμένα κύτταρα που δεν είχαν αυτή τη σουμοϋλίωση συγκριτικά με κύτταρα φυσικού τύπου.
Ωστόσο, η SUMO ίσως επηρεάζει την δραστικότητα της Ipl1, καθώς παρατηρήθηκε αύξηση στο τελικό μήκος της ατράκτου σε μεταλλαγμένα κύτταρα S. cerevisiae που δεν φέρουν σουμοϋλίωση στο CPC. Αντίστοιχες διαφορές στο μέγεθος της ατράκτου παρατηρήθηκαν και σε προηγούμενες μελέτες, που υποδηλώνουν ότι η απώλεια λειτουργίας της Ipl1 οδηγεί σε επιμήκυνση της ατράκτου. Ωστόσο, στις μελέτες αυτές παρατηρήθηκε επίσης ότι η απώλεια λειτουργίας της Ipl1 οδηγεί και σε παράταση του χρόνου επιμήκυνσης της ατράκτου, κάτι το οποίο δεν παρατηρήθηκε στα ευρήματά μας. Αυτό υποδηλώνει πως ίσως η σουμοϋλίωση επηρεάζει την φωσφορυλίωση από την Ipl1 μόνο συγκεκριμένων υποστρωμάτων που εμπλέκονται στο μέγεθος της ατράκτου, και όχι την ενεργότητά της γενικότερα.12
Am J Physiol supplemental figures
No full textThese are supplementary data to a research paper on the role of receptor protein tyrosine phosphatase zeta 1 in heart development
supplementary movies
No full textThese are supplementary movies to a paper published at Am J Physiol - Heart and Circulatory Physiolog
Explosives Use in Decommissioning—Guide for Assessment of Risk (EDGAR) : I Determination of Sound Pressure Levels for Open Water Blasts and Severance of Conductors and Piles from Below the Seabed
No full textAcknowledgments: The author is grateful for the feedback from the EDGAR Stakeholder Group: Sarah Canning (JNCC), Julie Cook (BEIS), Ewan Edwards (Marine Scotland Science), Phillip Thomp- son (Thornton Tomasetti) and David Lindsay (SPEX). Funding: This research received no external funding. This work was supported by a Knowledge Exchange Award from the University of Aberdeen [Grant number RG13483].Peer reviewe
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