Miriam Cohen | University of California, San Diego (original) (raw)

Papers by Miriam Cohen

Current Herpetology, 2005

Cannibalistic behaviour in seven Salamandra salamandra infraimmaculata half-sib cohort larvae (ea... more Cannibalistic behaviour in seven Salamandra salamandra infraimmaculata half-sib cohort larvae (each born to a single female and at the same time) and in juveniles was studied under different food and density conditions. The level of cannibalistic behaviour (tails bitten off or larvae eaten) changed as the larvae grew, from a low level during the first week to a peak at five weeks, regardless of differences in mass between the experimental larvae. No cannibalistic behaviour was observed in post-metamorphic salamanders even if they were cannibalistic as larvae. Significant differences in levels of cannibalism were found among different cohorts. Whereas in one cohort only 7% of the larvae were cannibalistic, in another, the cannibalism level peaked at 70% thereby indicating a possible maternal effect. However, cannibalistic behaviour in salamander larvae was apparently not related to the mother's age. The effect of food and density on cannibalism seems to be indirect or of secondary importance. Thus, cannibalism level was similar when food was scarce or when fed ad-libitum, whereas larvae offered a high level of food were significantly more cannibalistic. This could indicate that an optimum food level triggers cannibalism. When food becomes abundant the need for cannibalism ceased to persist. Under xeric conditions, ponds dry out rapidly; consequently rapid development through cannibalism results in earlier metamorphosis essential for this species' survival because of the limited time for dispersal of juveniles.

Development, Growth and Differentiation, 2006

In this study we describe the growth of several different larval cohorts (i.e. half-siblings of t... more In this study we describe the growth of several different larval cohorts (i.e. half-siblings of the same mother born on the same day) of a rare, xeric-adapted salamander Salamandra s. infraimmaculata Martens, 1885, under constant density and food conditions from birth to metamorphosis. The larvae spend the critical first phase of their lives in water, mostly in temporary ponds. Age and weight at metamorphosis were highly affected by varying food conditions. We have identified six different growth modes that these larvae use, both fast growing and slow growing. Each larval cohort was found to use 2-4 different such growth modes regardless of their initial weight. Fast growing modes (I-III) will enable larvae to survive dry years, and metamorphose bigger. Slow growing modes (IV-VI), used by 8% of the larval population, will enable survival only in rainy years. These last growth modes effect differential temporal dispersal in wet years by delaying the emergence of postmetamorphs onto land. Distribution of growth modes in the larval population is affected by food but not by density conditions. Late-born, fast-growing larvae will have an advantage in dry years being able to metamorphose and disperse, whereas the slow-growing larvae will survive only in wet years.

Cancer Research, 2005

Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of... more Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of the extracellular matrix. High molecular weight hyaluronan is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated breakdown of hyaluronan correlates with aggressiveness and invasiveness of ovarian cancer metastasis and with tumor angiogenesis. The goal of this work was to develop a novel smart contrast material for detection of hyaluronidase activity by magnetic resonance imaging (MRI). Gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) covalently linked to hyaluronan on the surface of agarose beads showed attenuated relaxivity. Hyaluronidase, either purified from bovine testes or secreted by ES-2 and OVCAR-3 human epithelial ovarian carcinoma cells, activated the hyaluronan-GdDTPA-beads by rapidly altering the R 1 and R 2 relaxation rates. The change in relaxation rates was consistent with the different levels of biologically active hyaluronidase secreted by those cells. Hyaluronan-GdDTPAbeads were further used for demonstration of MRI detection of hyaluronidase activity in the proximity of s.c. ES-2 ovarian carcinoma tumors in nude mice. Thus, hyaluronan-GdDTPAbeads could allow noninvasive molecular imaging of hyaluronidase-mediated tilt of the peritumor angiogenic balance. (Cancer Res 2005; 65(22): 10316-23) Requests for reprints: Michal Neeman, Department of Biological Regulation, The

Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to ... more Humans lack the common mammalian cell surface molecule N-glycolylneuraminic acid (Neu5Gc) due to a CMAH gene inactivation, which occurred approximately three million years ago. Modern humans produce antibodies specific for Neu5Gc. We hypothesized that anti-Neu5Gc antibodies could enter the female reproductive tract and target Neu5Gc-positive sperm or fetal tissues, reducing reproductive compatibility. Indeed, female mice with a human-like Cmah(−/−) mutation and immunized to express anti-Neu5Gc antibodies show lower fertility with Neu5Gc-positive males, due to prezygotic incompatibilities. Human anti-Neu5Gc antibodies are also capable of targeting paternally derived antigens and mediate cytotoxicity against Neu5Gc-bearing chimpanzee sperm in vitro. Models of populations polymorphic for such antigens show that reproductive incompatibility by female immunity can drive loss-offunction alleles to fixation from moderate initial frequencies. Initially, the loss of a cell-surface antigen can occur due to drift in isolated populations or when natural selection favors the loss of a receptor exploited by pathogens, subsequently the same loss-offunction allele can come under sexual selection because it avoids being targeted by the female immune system. Thus, we provide evidence of a link between sexual selection and immune function: Antigenicity in females can select against foreign paternal antigens on sperm and rapidly fix loss-of-function alleles. Similar circumstances existed when the CMAH null allele was polymorphic in ancestral hominins, just before the divergence of Homo from australopithecines.

Embo Journal, 2006

Membrane-bound hyaluronan mediates the initial adhesive interactions between many cell types and ... more Membrane-bound hyaluronan mediates the initial adhesive interactions between many cell types and external surfaces. In RCJ-P chondrocytes, such early contacts are mediated through a thick hyaluronidase-sensitive coat. The early adhesion is followed by integrin-mediated interactions and the formation of stable focal adhesions. During this process, the distance between the cell membrane and the surface is reduced from micrometers to few tens of nanometers. The transition from hyaluronan-to integrinmediated adhesion was studied on glass surfaces by total internal reflection fluorescence microscopy. Hyaluronanmediated adhesion precedes focal adhesions formation by 2-10 min. After these initial interactions, the pericellular hyaluronan remains sequestered into discrete pockets between the cell and the surface, which are a few hundreds nanometers thick and a few micrometers wide, and are flanked by focal adhesions. The hyaluronan coat facilitates the nucleation of small paxillin-rich contacts, which later mature into focal adhesions. These dynamic studies demonstrate that pericellular hyaluronan mediates initial cell-surface adhesion, and regulates the formation of focal adhesions.

Biophysical Journal, 2003

Hyaluronan is a megadalton glycosaminoglycan composed of repeating units of D-N-acetylglucosamine... more Hyaluronan is a megadalton glycosaminoglycan composed of repeating units of D-N-acetylglucosamine-β−D-Glucuronic acid. It is known to form a highly hydrated pericellular coat around chondrocytes, fibrosarcoma, and smooth muscle cells. Using environmental scanning electron microscopy we detected fully hydrated hyaluronan pericellular coats around rat chondrocytes (RCJ-P) and epithelial cells (A6). Hyaluronan mediates early adhesion of both chondrocytes and A6 cells to

International review of cell and molecular biology, 2014

All cells in nature are covered with a dense and complex array of glycan chains. Specific recogni... more All cells in nature are covered with a dense and complex array of glycan chains. Specific recognition and binding of glycans is a critical aspect of cellular interactions, both within and between species. Glycan-protein interactions tend to be of low affinity but high specificity, typically utilizing multivalency to generate the affinity required for biologically relevant binding. This review focuses on a higher level of glycan organization, the formation of clustered saccharide patches (CSPs), which can constitute unique ligands for highly specific interactions. Due to technical challenges, this aspect of glycan recognition remains poorly understood. We present a wealth of evidence for CSPs-mediated interactions, and discuss recent advances in experimental tools that are beginning to provide new insights into the composition and organization of CSPs. The examples presented here are likely the tip of the iceberg, and much further work is needed to elucidate fully this higher level o...

Influenza viruses bind to mucosal glycans to gain entry into a host organism and initiate infecti... more Influenza viruses bind to mucosal glycans to gain entry into a host organism and initiate infection. The target glycans are often displayed in multivalent arrangements on proteins; however, how glycan presentation influences viral specificity is poorly understood. Here, we report a microarray platform approximating native glycan display to facilitate such studies.

World journal of gastroenterology : WJG, Jan 28, 2014

To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helico... more To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers. We studied a cohort of randomly selected patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for MUC1, MUC4, MUC17, and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin (SNA) lectins was performed on sections from the ulcer margins. Staining intensity of MUC17 was higher in H. pylori ulcers (group 1) than in idiopathic ulcers (group 4), 11.05 ± 3.67 vs 6.93 ± 4.00 for foveola cells, and 10.29 ± 4.67 vs 8.00 ± 3.48 for gland cells, respectively (P < 0.0001). In contrast, MUC1 expression was higher in group 4 compared group 1, 9.89 ± 4.17 vs 2.93 ± 5.13 in foveola cells a...

Journal of Visualized Experiments, 2012

Mucins are complex and heavily glycosylated O-linked glycoproteins, which contain more than 70% c... more Mucins are complex and heavily glycosylated O-linked glycoproteins, which contain more than 70% carbohydrate by weight [1][2][3] . Secreted mucins, produced by goblet cells and the gastric mucosa, provide the scaffold for a micrometers-thick mucus layer that lines the epithelia of the gut and respiratory tract 3,4

Virology Journal, 2013

Background: Influenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. ... more Background: Influenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. Inhibiting NA with oseltamivir suppresses both viral infection, and viral release from cultured human airway epithelial cells. The role of NA in viral exit is well established: it releases budding virions by cleaving Sias from glycoconjugates on infected cells and progeny virions. The role of NA in viral entry remains unclear. Host respiratory epithelia secrete a mucus layer rich in heavily sialylated glycoproteins; these could inhibit viral entry by mimicking sialylated receptors on the cell surface. It has been suggested that NA allows influenza to penetrate the mucus by cleaving these sialylated decoys, but the exact mechanism is not yet established. Methods: We tested IAV interaction with secreted mucus using frozen human trachea/bronchus tissue sections, and bead-bound purified human salivary mucins (HSM) and purified porcine submaxillary mucins (PSM). The protective effect of mucus was analyzed using MDCK cells coated with purified HSM and PSM with known Sia content. Oseltamivir was used to inhibit NA activity, and the fluorescent reporter substrate, 4MU-Neu5Ac, was used to quantify NA activity. Results: IAV binds to the secreted mucus layer of frozen human trachea/bronchus tissues in a Sia dependent manner. HSM inhibition of IAV infection is Sia dose-dependent, but PSM cannot inhibit infection of underlying cells. HSM competitively inhibits NA cleavage of 4MU-Neu5Ac, reporter substrate. Human IAV effectively cleaves Sias from HSM but not from PSM, and binds to HSM but not to PSM. Conclusion: IAV interacts with human mucus on frozen tissue sections and mucus-coated beads. Inhibition of IAV infection by sialylated human mucus is dose-dependent, and enhanced when NA is inhibited with oseltamivir. Thus NA cleaves sialylated decoys during initial stages of infection. Understanding IAV interactions with host mucins is a promising new avenue for drug development.

The FASEB Journal, 2003

Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate and is implicated in dive... more Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate and is implicated in diverse physiological and pathological processes. In this study we report on a novel direct involvement of heparanase in cell adhesion. We demonstrate that expression of heparanase in nonadherent lymphoma cells induces early stages of cell adhesion, provided that the enzyme is expressed on the cell surface. Heparanase-mediated cell adhesion to extracellular matrix (ECM) results in integrin-dependent cell spreading, tyrosine phosphorylation of paxillin, and reorganization of the actin cytoskeleton. The surface-bound enzyme also augments cell invasion through a reconstituted basement membrane. Cell adhesion was augmented by cell surface heparanase regardless of whether the cells were transfected with active or point mutated inactive enzyme, indicating that heparanase functions as an adhesion molecule independent of its endoglycosidase activity. The combined feature of heparanase as an ECM-degrading enzyme and a cell adhesion molecule emphasizes its significance in processes involving cell adhesion, migration, and invasion, including embryonic development, neovascularization, and cancer metastasis.

The EMBO Journal, 2006

Soft Matter, 2007

... Miriam Cohen‡a, Derk Joesterb, Ilana Sabanayc, Lia Addadib and Benjamin Geigera. a Department... more ... Miriam Cohen‡a, Derk Joesterb, Ilana Sabanayc, Lia Addadib and Benjamin Geigera. a Department of Molecular Cell Biology ... in regulating the organization of the hyaluronan coat, A6 epithelial cells were treated with the actin-disrupting agent latrunculin A (LatA) and then ...

Proceedings of the National Academy of Sciences, 2011