Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements

During the early stages of infection, Neisseria gonorrhoeae triggers a phosphotyrosine-dependent Cav1-Vav2-RhoA signaling cascade that promotes the pathogen's extracellular state

Unconstrained three-dimensional reaching in Rhesus monkeys

To better understand normative behavior for quantitative evaluation of motor recovery after injury, we studied arm movements by non-injured Rhesus monkeys during a food-retrieval task. While seated, monkeys reached, grasped, and retrieved food items. We recorded three-dimensional kinematics and muscle activity, and used inverse dynamics to calculate joint moments due to gravity, segmental interactions, and to the muscles and tissues of the arm. Endpoint paths showed curvature in three dimensions, suggesting that maintaining straight paths was not an important constraint. Joint moments were dominated by gravity. Generalized muscle and interaction moments were less than half of the gravitational moments. The relationships between shoulder and elbow resultant moments were linear during both reach and retrieval. Although both reach and retrieval required elbow flexor moments, an elbow extensor (triceps brachii) was active during both phases. Antagonistic muscles of both the elbow and hand were co-activated during reach and retrieval. Joint behavior could be described by lumped-parameter models analogous to torsional springs at the joints. Minor alterations to joint quasi-stiffness properties, aided by interaction moments, result in reciprocal movements that evolve under the influence of gravity. The strategies identified in monkeys to reach, grasp, and retrieve items will allow the quantification of prehension during recovery after a spinal cord injury and the effectiveness of therapeutic interventions

Targeted Disruption of the Ceacam1 (MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection

The CEACAM1 glycoproteins (formerly called biliary glycoproteins; BGP, C-CAM, CD66a, or MHVR) are members of the carcinoembryonic antigen family of cell adhesion molecules. In the mouse, splice variants of CEACAM1 have either two or four immunoglobulin (Ig) domains linked through a transmembrane domain to either a short or a long cytoplasmic tail. CEACAM1 has cell adhesion activity and acts as a signaling molecule, and long-tail isoforms inhibit the growth of colon and prostate tumor cells in rodents. CEACAM1 isoforms serve as receptors for several viral and bacterial pathogens, including the murine coronavirus mouse hepatitis virus (MHV) and Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis in humans. To elucidate the mechanisms responsible for the many biological activities of CEACAM1, we modified the expression of the mouse Ceacam1 gene in vivo. Manipulation of the Ceacam1 gene in mouse embryonic stem cells that contained the Ceacam1a allele yielded a partial knockout. We obtained one line of mice in which the insert in the Ceacam1a gene had sustained a recombination event. This resulted in the markedly reduced expression of the two CEACAM1a isoforms with four Ig domains, whereas the expression of the two isoforms with two Ig domains was doubled relative to that in wild-type BALB/c (+/+) mice. Homozygous (p/p) Ceacam1a-targeted mice (Ceacam1aΔ4D) had no gross tissue abnormalities and were viable and fertile; however, they were more resistant to MHV A59 infection and death than normal (+/+) mice. Following intranasal inoculation with MHV A59, p/p mice developed markedly fewer and smaller lesions in the liver than +/+ or heterozygous (+/p) mice. The titers of virus produced in the livers were 50- to 100-fold lower in p/p mice than in +/p or +/+ mice. p/p mice survived a dose 100-fold higher than the lethal dose of virus for +/+ mice. +/p mice were intermediate between +/+ and p/p mice in susceptibility to liver damage, virus growth in liver, and susceptibility to killing by MHV. Ceacam1a-targeted mice provide a new model to study the effects of modulation of receptor expression on susceptibility to MHV infection in vivo