Our understanding of how complex carbohydrates function during embryonic development is still very limited, primarily due to the large number of glycosyltransferases now known to be involved in their synthesis. To overcome these limitations, we have taken advantage of the zebrafish system to analyze the function of complex carbohydrates during development by down-regulating the expression of specific glycosyltransferases. Herein, we report the identification of the zebrafish ortholog of mammalian beta1,4-galactosyltransferase I, beta4GalT1, and its requirement for proper convergent extension movements during gastrulation. beta4GalT1 is expressed in the oocyte and throughout the embryo during the first 24 h of development. Knockdown of zebrafish beta4GalT1 by two independent morpholino oligonucleotides results in embryos with a truncated anterior-posterior axis, as well as elongated somites and moderate defects in the patterning of the head mesenchyme. Co-injection of zebrafish beta4GalT1 mRNA returns galactosyltransferase activity to control levels and rescues the defects produced by morpholino oligonucleotides. In situ hybridizations of various molecular markers reveal that the axial mesoderm of epiboly stage embryos is abnormally widened in beta4GalT1 morphants, indicative of abnormal convergent extension. Consistent with this, the rate of anterior-posterior axis elongation is reduced relative to control-injected embryos, similar to that seen in known convergent extension mutants. Among the many potential substrates for beta4GalT1 is laminin, a principle component of the extracellular matrix that supports cell movements such as those that occur during convergent extension. Previous in vitro studies have shown that the galactosylation status of laminin directly influences its ability to support cell spreading and migration. In this regard, laminin isolated from beta4GalT1 morphant embryos is poorly galactosylated, which may contribute to defective cell migration during convergent extension movements. This work demonstrates that zebrafish can be used to identify critical developmental roles for specific glycosyltransferases that would not be obvious otherwise, such as an absolute requirement for beta4GalT1 during convergent extension movements.
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http://dx.doi.org/10.1016/j.ydbio.2006.05.024 | DOI Listing |
Elife
January 2025
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, Oeiras, Portugal.
During the trunk to tail transition the mammalian embryo builds the outlets for the intestinal and urogenital tracts, lays down the primordia for the hindlimb and external genitalia, and switches from the epiblast/primitive streak (PS) to the tail bud as the driver of axial extension. Genetic and molecular data indicate that Tgfbr1 is a key regulator of the trunk to tail transition. Tgfbr1 has been shown to control the switch of the neuromesodermal competent cells from the epiblast to the chordoneural hinge to generate the tail bud.
View Article and Find Full Text PDFBiophys J
January 2025
Department of Biology, New York University, New York, New York, 10003, USA. Electronic address:
The outer membrane is the defining structure of Gram-negative bacteria. We previously demonstrated that it is a major load-bearing component of the cell envelope and is therefore critical to the mechanical robustness of the bacterial cell. Here, to determine the key molecules and moieties within the outer membrane that underlie its contribution to cell envelope mechanics, we measured cell-envelope stiffness across several sets of mutants with altered outer-membrane sugar content, protein content, and electric charge.
View Article and Find Full Text PDFBMJ Open
January 2025
Azrieli Research Center UHC Sainte-Justine, Montreal, Quebec, Canada.
Introduction: Precision health can be described as the right intervention, at the right time, for the right person, with a focus on monitoring and maintaining health in a longitudinal approach. Despite an increasing focus on precision approaches in medicine, their application in a rehabilitation context remains unexplored. As such, a greater understanding of the current state of the literature is required, in combination with clinician, researcher and healthcare manager perspectives regarding barriers and facilitators to the practical implementation of precision rehabilitation in clinical practice.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, ON, Canada.
Lower-limb exoskeletons have demonstrated great potential for gait rehabilitation in individuals with motor impairments; however, maintaining human-exoskeleton coordination remains a challenge. The coordination problem, referred to as any mismatch or asynchrony between the user's intended trajectories and exoskeleton desired trajectories, leads to sub-optimal gait performance, particularly for individuals with residual motor ability. Here, we investigate the virtual energy regulator (VER)'s ability to generate coordinated locomotion in lower limb exoskeleton.
View Article and Find Full Text PDFJ Chem Theory Comput
January 2025
Department of Chemistry, University of California, Berkeley, California 94720, United States.
Energy decomposition analysis (EDA) based on density functional theory (DFT) and self-consistent field (SCF) calculations has become widely used for understanding intermolecular interactions. This work reports a new approach to EDA for post-SCF wave functions based on closed-shell restricted second-order Mo̷ller-Plesset (MP2) together with an efficient implementation that generalizes the successful SCF-level second-generation absolutely localized molecular orbital EDA approach, ALMO-EDA-II, and improves upon MP2 ALMO-EDA-I. The new MP2 ALMO-EDA-II provides distinct energy contributions for a frozen interaction energy containing permanent electrostatics and Pauli repulsions, polarized energy-yielding induced electrostatics, dispersion-corrected energy, and the fully relaxed energy, which describes charge transfer.
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