Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell function and fate

The aim of the present study was to examine the roles of l-fucose and the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan sulfate (CS/DS) with selected functional molecules in neural tissues. Cell surface glycans and GAGs have evolved over millions of years to become cellular mediators which regulate fundamental aspects of cellular survival. The glycocalyx, which surrounds all cells, actuates responses to growth factors, cytokines and morphogens at the cellular boundary, silencing or activating downstream signaling pathways and gene expression. In this review, we have focused on interactions mediated by l-fucose, KS and CS/DS in the central and peripheral nervous systems. Fucose makes critical contributions in the area of molecular recognition and information transfer in the blood group substances, cytotoxic immunoglobulins, cell fate-mediated Notch-1 interactions, regulation of selectin-mediated neutrophil extravasation in innate immunity and CD-34-mediated new blood vessel development, and the targeting of neuroprogenitor cells to damaged neural tissue. Fucosylated glycoproteins regulate delivery of synaptic neurotransmitters and neural function. Neural KS proteoglycans (PGs) were examined in terms of cellular regulation and their interactive properties with neuroregulatory molecules. The paradoxical properties of CS/DS isomers decorating matrix and transmembrane PGs and the positive and negative regulatory cues they provide to neurons are also discussed

A Study of the Factors That Influence Consumer Attitudes Toward Beef Products Using the Conjoint Market Analysis Tool

This study utilizes an analysis technique commonly used in marketing, the conjoint analysis method, to examine the relative utilities of a set of beef steak characteristics considered by a national sample of 1,432 US consumers, as well as additional localized samples representing undergraduate students at a business college and in an animal science department. The analyses indicate that among all respondents, region of origin is by far the most important characteristic; this is followed by animal breed, traceability, animal feed, and beef quality. Alternatively, the cost of cut, farm ownership, the use (or nonuse) of growth promoters, and whether the product is guaranteed tender were the least important factors. Results for animal science undergraduates are similar to the aggregate results, except that these students emphasized beef quality at the expense of traceability and the nonuse of growth promoters. Business students also emphasized region of origin but then emphasized traceability and cost. The ideal steak for the national sample is from a locally produced, choice Angus fed a mixture of grain and grass that is traceable to the farm of origin. If the product was not produced locally, respondents indicated that their preferred production states are, in order from most to least preferred, Iowa, Texas, Nebraska, and Kansas.

Immunolocalization of keratan sulfate in rat spinal tissues using the keratanase generated BKS-1(+) neoepitope: correlation of expression patterns with the slass II SLRPs, lumican and keratocan

This study has identified keratan sulfate in fetal and adult rat spinal cord and vertebral connective tissues using the antibody BKS-1(+) which recognizes a reducing terminal N-acetyl glucosamine-6-sulfate neo-epitope exposed by keratanase-I digestion. Labeling patterns were correlated with those of lumican and keratocan using core protein antibodies to these small leucine rich proteoglycan species. BKS-1(+) was not immunolocalized in fetal spinal cord but was apparent in adult cord and was also prominently immunolocalized to the nucleus pulposus and inner annulus fibrosus of the intervertebral disc. Interestingly, BKS-1(+) was also strongly associated with vertebral body ossification centers of the fetal spine. Immunolocalization of lumican and keratocan was faint within the vertebral body rudiments of the fetus and did not correlate with the BKS-1(+) localization indicating that this reactivity was due to another KS-proteoglycan, possibly osteoadherin (osteomodulin) which has known roles in endochondral ossification. Western blotting of adult rat spinal cord and intervertebral discs to identify proteoglycan core protein species decorated with the BKS-1(+) motif confirmed the identity of 37 and 51 kDa BKS-1(+) positive core protein species. Lumican and keratocan contain low sulfation KS-I glycoforms which have neuroregulatory and matrix organizational properties through their growth factor and morphogen interactive profiles and ability to influence neural cell migration. Furthermore, KS has interactive capability with a diverse range of neuroregulatory proteins that promote neural proliferation and direct neural pathway development, illustrating key roles for keratocan and lumican in spinal cord development

Perlecan in pericellular mechanosensory cell-matrix communication, extracellular matrix stabilisation and mechanoregulation of load-bearing connective tissues

In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes to regulate tissue homeostasis. Thus perlecan plays a key regulatory role in chondrocyte metabolism, and in chondrocyte differentiation. Perlecan acts as a transport proteoglycan carrying poorly soluble, lipid-modified proteins such as the Wnt or Hedgehog families facilitating the establishment of morphogen gradients that drive tissue morphogenesis. Cell surface perlecan on endothelial cells or osteocytes acts as a flow sensor in blood and the lacunar canalicular fluid providing feedback cues to smooth muscle cells regulating vascular tone and blood pressure, and the regulation of bone metabolism by osteocytes highlighting perlecan\u27s multifaceted roles in load-bearing connective tissues

Probing the Evolution of the Galaxy Interaction/Merger Rate Using Collisional Ring Galaxies

We present the results from our program to determine the evolution of the galaxy interaction/merger rate with redshift using the unique star-forming characteristics of collisional ring galaxies. We have identified 25 distant collisional ring galaxy candidates (CRGCs) in a total of 162 deep Hubble Space Telescope Wide Field/Planetary Camera-2 images obtained from the HST Archives. Based on measured and estimated redshifts, these 25 CRGCs all lie in the redshift interval of 0.1 < z < 1. Using the local collisional ring galaxy volume density and the new ``standard'' cosmology, we find that in order to account for the number of identified CRGCs in our surveyed fields, the galaxy interaction/merger rate, parameterized as (1 + z)^m, must increase steeply with redshift.We determine a minimum value of m = 5.2 $\pm$ 0.7, though m could be as high as 7 or 8. We can rule out a non-evolving (m = 0) and weakly evolving (m = 1-2) galaxy interaction/merger rate at greater than the 4 sigma level of confidence.Comment: Accepted in the Astrophysical Journal (11 pages, 4 figures). Higher resolution version of the figures is available at http://www.astro.cornell.edu/~vassilis/papers

Making the most of time in quantum metrology: concurrent state preparation and sensing

A quantum metrology protocol for parameter estimation is typically comprised of three stages: probe state preparation, sensing and then readout, where the time required for the first and last stages is usually neglected. In the present work we consider non-negligible state preparation and readout times, and the tradeoffs in sensitivity that come when a limited time resource T must be divided between the three stages. To investigate this, we focus on the problem of magnetic field sensing with spins in one-axis twisted or two-axis twisted states. We find that (accounting for the time necessary to prepare a twisted state) no advantage is gained unless the time T is sufficiently long or the twisting sufficiently strong. However, we also find that the limited time resource is used more effectively if we allow the twisting and the magnetic field to be applied concurrently, which possibly represents a more realistic sensing scenario. We extend this result into an optical setting by utilizing the exact correspondence between a spin system and a bosonic field mode as given by the Holstein-Primakoff transformation

3D immuno-confocal image reconstruction of fibroblast cytoskeleton and nucleus architecture

Computational models of cellular structures generally rely on simplifying approximations and assumptions that limit biological accuracy. This study presents a comprehensive image processing pipeline for creating unified three‐dimensional (3D) reconstructions of the cell cytoskeletal networks and nuclei. Confocal image stacks of these cellular structures were reconstructed to 3D isosurfaces (Imaris), then tessellations were simplified to reduce the number of elements in initial meshes by applying quadric edge collapse decimation with preserved topology boundaries (MeshLab). Geometries were remeshed to ensure uniformity (Instant Meshes) and the resulting 3D meshes exported (ABAQUS) for downstream application. The protocol has been applied successfully to fibroblast cytoskeletal reorganisation in the scleral connective tissue of the eye, under mechanical load that mimics internal eye pressure. While the method herein is specifically employed to reconstruct immunofluorescent confocal imaging data, it is also more widely applicable to other biological imaging modalities where accurate 3D cell structures are required

Neural tissue homeostasis and repair is regulated via CS and DS proteoglycan motifs

Chondroitin sulfate (CS) is the most abundant and widely distributed glycosaminoglycan (GAG) in the human body. As a component of proteoglycans (PGs) it has numerous roles in matrix stabilization and cellular regulation. This chapter highlights the roles of CS and CS-PGs in the central and peripheral nervous systems (CNS/PNS). CS has specific cell regulatory roles that control tissue function and homeostasis. The CNS/PNS contains a diverse range of CS-PGs which direct the development of embryonic neural axonal networks, and the responses of neural cell populations in mature tissues to traumatic injury. Following brain trauma and spinal cord injury, a stabilizing CS-PG-rich scar tissue is laid down at the defect site to protect neural tissues, which are amongst the softest tissues of the human body. Unfortunately, the CS concentrated in gliotic scars also inhibits neural outgrowth and functional recovery. CS has well known inhibitory properties over neural behavior, and animal models of CNS/PNS injury have demonstrated that selective degradation of CS using chondroitinase improves neuronal functional recovery. CS-PGs are present diffusely in the CNS but also form denser regions of extracellular matrix termed perineuronal nets which surround neurons. Hyaluronan is immobilized in hyalectan CS-PG aggregates in these perineural structures, which provide neural protection, synapse, and neural plasticity, and have roles in memory and cognitive learning. Despite the generally inhibitory cues delivered by CS-A and CS-C, some CS-PGs containing highly charged CS disaccharides (CS-D, CS-E) or dermatan sulfate (DS) disaccharides that promote neural outgrowth and functional recovery. CS/DS thus has varied cell regulatory properties and structural ECM supportive roles in the CNS/PNS depending on the glycoform present and its location in tissue niches and specific cellular contexts. Studies on the fruit fly, Drosophila melanogaster and the nematode Caenorhabditis elegans have provided insightful information on neural interconnectivity and the role of the ECM and its PGs in neural development and in tissue morphogenesis in a whole organism environment

What are the potential roles of nuclear perlecan and other heparan sulphate proteoglycans in the normal and malignant phenotype

The recent discovery of nuclear and perinuclear perlecan in annulus fibrosus and nucleus pulposus cells and its known matrix stabilizing properties in tissues introduces the possibility that perlecan may also have intracellular stabilizing or regulatory roles through interactions with nuclear envelope or cytoskeletal proteins or roles in nucleosomal-chromatin organization that may regulate transcriptional factors and modulate gene expression. The nucleus is a mechano-sensor organelle, and sophisticated dynamic mechanoresponsive cytoskeletal and nuclear envelope components support and protect the nucleus, allowing it to perceive and respond to mechano-stimulation. This review speculates on the potential roles of perlecan in the nucleus based on what is already known about nuclear heparan sulphate proteoglycans. Perlecan is frequently found in the nuclei of tumour cells; however, its specific role in these diseased tissues is largely unknown. The aim of this review is to highlight probable roles for this intriguing interactive regulatory proteoglycan in the nucleus of normal and malignant cell types