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C D Marion

Publications and source records attributed to C D Marion.

5 recordsLinked to original sources

Primary structure requirements for Xenopus nodal-related 3 and a comparison with regions required by Xenopus nodal-related 2.

Transforming growth factor-beta superfamily members play important roles in the early development of animals. Activin and the Xenopus nodal related proteins 1, 2, and 4 induce muscle actin from Xenopus ectodermal explants, whereas the bone morphogenetic proteins 4 and 7 induce ectoderm to differentiate as epidermis. Bone morphogenetic proteins are antagonized by soluble binding proteins such as noggin and chordin, which leads to expression of neural cell adhesion molecule in animal caps. The transforming growth factor-beta superfamily member Xenopus nodal-related 3 also induces the neural cell adhesion molecule through inhibition of bone morphogenetic proteins. Therefore, whereas Xenopus nodal-related 2 and 3 share a high amount of sequence homology, they lead to very different cell fates. This study investigates the functional domains that distinguish the activities of these two factors. It was found that mutually exclusive regions of nodal-related 2 and 3 were required for activity. The central region of the mature domain is required for nodal-related 2 to induce muscle actin, whereas the N- and C-terminal ends of the mature domain are required for nodal-related 3 to induce neural cell adhesion molecule. These results help to define the minimal domains required for the unique activities of these factors.

Actins↗

Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3.

During gastrulation in amphibians, secreted factors from Spemann's organizer act on dorsal ectoderm to induce the central nervous system. A number of secreted factors produced by Spemann's organizer have recently been identified. The TGFbeta family member Xnr3 is similar in amino acid sequence to the mouse factor nodal and is expressed in a restricted group of cells in the superficial layer of Spemann's organizer. Xnr3, unlike the related factors nodal, Xnr1 and Xnr2, lacks mesoderm-inducing activity. We report here that Xnr3 can directly induce neural tissue in Xenopus ectoderm explants (animal caps). Injection of animal caps with either Xnr3 RNA or plasmids induces the expression of the pan-neural genes NCAM and nrp1, as well as the anterior neural marker Cpl1. A growing body of evidence suggests that neural induction in Xenopus proceeds as the default in the absence of epidermis inducers. The best candidates for the endogenous epidermis inducers are BMP-4 and BMP-7. The neural inducing activity of Xnr3 can be inhibited by overexpression of BMP-4, as has been observed with the neural inducers noggin, chordin and follistatin. Furthermore, Xnr3 can block mesoderm induction by BMP-4 and activin, but not by Xnr2. The structural basis underlying the divergent activities of Xnr2 and Xnr3 was analyzed using site-directed mutagenesis. Mutations introduced to the conserved cysteine residues characteristic of the TGFbeta family were found to inactivate Xnr2, but not Xnr3. The most unique feature of Xnr3 is the absence of a conserved cysteine at the C terminus of the protein. This feature distinguishes Xnr3 from other TGFbeta family members, including Xnr2. However, we observed that changing the C terminus of Xnr3 to more closely resemble other TGFbeta family members did not significantly alter its activity, suggesting that other structural features of Xnr3 distinguish its biological activity from Xnr2.

Amino Acid Sequence↗

Focus on autonomy: supporting an innovative, empowered staff.

Current nursing literature documents the benefits of nurse autonomy with evidence of increased job satisfaction. Health care organizations can support autonomous behavior through empowerment. This article reports how one hospital is responding to nurses' requests for empowerment. The request to focus the nursing division's efforts to enable an innovative empowered staff was initiated during an annual planning session with clinical and administrative staff participation. The first phase of the project involved baseline measurements of autonomy and strategic planning for empowerment through education and leadership modeling. Initial autonomy studies were conducted in 1994 and will be repeated at 18, 36, and 48 months.

Humans↗

Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections.

E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV.

Amino Acid Sequence↗